[House Hearing, 111 Congress]
[From the U.S. Government Publishing Office]
INNOVATIVE TECHNOLOGIES AND TREATMENTS HELPING VETERANS
=======================================================================
HEARING
before the
COMMITTEE ON VETERANS' AFFAIRS
U.S. HOUSE OF REPRESENTATIVES
ONE HUNDRED ELEVENTH CONGRESS
FIRST SESSION
__________
MAY 13, 2009
__________
Serial No. 111-18
__________
Printed for the use of the Committee on Veterans' Affairs
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COMMITTEE ON VETERANS' AFFAIRS
BOB FILNER, California, Chairman
CORRINE BROWN, Florida STEVE BUYER, Indiana, Ranking
VIC SNYDER, Arkansas CLIFF STEARNS, Florida
MICHAEL H. MICHAUD, Maine JERRY MORAN, Kansas
STEPHANIE HERSETH SANDLIN, South HENRY E. BROWN, Jr., South
Dakota Carolina
HARRY E. MITCHELL, Arizona JEFF MILLER, Florida
JOHN J. HALL, New York JOHN BOOZMAN, Arkansas
DEBORAH L. HALVORSON, Illinois BRIAN P. BILBRAY, California
THOMAS S.P. PERRIELLO, Virginia DOUG LAMBORN, Colorado
HARRY TEAGUE, New Mexico GUS M. BILIRAKIS, Florida
CIRO D. RODRIGUEZ, Texas VERN BUCHANAN, Florida
JOE DONNELLY, Indiana DAVID P. ROE, Tennessee
JERRY McNERNEY, California
ZACHARY T. SPACE, Ohio
TIMOTHY J. WALZ, Minnesota
JOHN H. ADLER, New Jersey
ANN KIRKPATRICK, Arizona
GLENN C. NYE, Virginia
Malcom A. Shorter, Staff Director
Pursuant to clause 2(e)(4) of Rule XI of the Rules of the House, public
hearing records of the Committee on Veterans' Affairs are also
published in electronic form. The printed hearing record remains the
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of converting between various electronic formats may introduce
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current publication process and should diminish as the process is
further refined.
C O N T E N T S
__________
May 13, 2009
Page
Innovative Technologies and Treatments Helping Veterans.......... 1
OPENING STATEMENTS
Chairman Bob Filner.............................................. 1
Prepared statement of Chairman Filner........................ 36
Hon. Harry E. Mitchell, prepared statement of.................... 36
WITNESSES
Alkermes, Inc., Cambridge, MA, David A. Broecker, President and
Chief Executive Officer........................................ 6
Prepared statement of Mr. Broecker........................... 50
BrainCells Inc., San Diego, CA, James A. Schoeneck, Chief
Executive Officer.............................................. 29
Prepared statement of Mr. Schoeneck.......................... 71
Brainport Technologies, Wicab, Inc., Middleton, WI, Robert A.
Beckman, President and Chief Executive Officer................. 5
Prepared statement of Mr. Beckman............................ 41
Fate Therapeutics, Inc., La Jolla, CA, David Scadden, M.D.,
Scientific Founder............................................. 12
Prepared statement of Dr. Scadden............................ 59
Federoff, Howard J., M.D., Ph.D., Executive Vice President for
Health Sciences, Executive Dean of the School of Medicine,
Georgetown University Medical Center, Washington, DC........... 25
Prepared statement of Dr. Federoff........................... 68
Harmonex, Inc., CliniCom, Atlanta, GA, Nelson M. Handal, M.D.,
FAPA, Founder, Chairman, and Medical Director, Board Certified
Child, Adolescent and Adult Psychiatrist, and Fellow, American
Psychiatric Association........................................ 27
Prepared statement of Dr. Handal............................. 69
Mobile Medical International Corporation, St. Johnsbury, VT, Mark
Munroe, Senior Vice President, Sales and Marketing............. 8
Prepared statement of Mr. Munroe............................. 55
Sidransky, David, M.D., Director, Head and Neck Cancer Research
Division, Johns Hopkins University School of Medicine, and
Professor of Oncology, Otolaryngology-Head and Neck Surgery,
Cellular and Molecular Medicine, Urology, Genetics, and
Pathology, Johns Hopkins University and Hospital, Baltimore, MD 4
Prepared statement of Dr. Sidransky.......................... 39
TeleMed Network, Ross, CA, Stanley Stern, President.............. 10
Prepared statement of Mr. Stern.............................. 56
Zila, Inc., Scottsdale, AZ, David R. Bethune, Executive Chairman
and Chief Executive Officer.................................... 2
Prepared statement of Mr. Bethune............................ 36
SUBMISSIONS FOR THE RECORD
Balanoff, William L., DDS, MS, FICD, SmilePerfect, Fort
Lauderdale, FL, statement...................................... 73
Califano, Joseph, III, M.D., Professor, Department of
Otolaryngology-Head and Neck Surgery and Oncology, Johns
Hopkins Medical Institutions, Baltimore, MD, statement......... 75
Epstein, Joel, DMD, MSD, FRCD(C), FDS RCS, Director,
Interdisciplinary Program in Oral Cancer Biology, Prevention
and Treatment, College of Medicine, Chicago Cancer Center,
University of Illinois, Chicago, IL, statement................. 77
MATERIAL SUBMITTED FOR THE RECORD
Post-Hearing Questions and Responses for the Record:
Hon. Bob Filner, Chairman, Committee on Veterans' Affairs to
Hon. Eric K. Shinseki, Secretary, U.S. Department of
Veterans Affairs, letter dated May 14, 2009, and VA
responses.................................................. 79
INNOVATIVE TECHNOLOGIES AND TREATMENTS HELPING VETERANS
----------
WEDNESDAY, MAY 13, 2009
U.S. House of Representatives,
Committee on Veterans' Affairs,
Washington, DC.
The Committee met, pursuant to notice, at 10:00 a.m., in
Room 334, Cannon House Office Building, Hon. Bob Filner
[Chairman of the Committee] presiding.
Present: Representatives Filner, Mitchell, Hall, Perriello,
Teague, Donnelly, McNerney, Walz, and Adler.
OPENING STATEMENT OF CHAIRMAN FILNER
The Chairman. Good morning. I apologize for being late. I
call this hearing of the House Veterans' Affairs Committee to
order.
If the first panel can take their seats while I am just
doing a little introduction, that would be great.
I ask unanimous consent that all Members have 5 legislative
days in which to revise and extend their remarks. Without
objection, so ordered.
I want to thank you all for being here. The purpose of this
hearing is very simple. In my job, and I am sure every one of
my colleagues has the same experience, we meet constituents who
have had contact, have invented, or have manufactured
instruments, technologies, or treatments which would seem to
have a great benefit for our veterans.
Yet, many have had a frustrating experience of dealing with
a bureaucracy that just does not seem to react very quickly to
new ideas and new treatments, and people are frustrated. They
have things to help, whether it is a device for early detection
of oral cancer, for example, or correction of vision for those
who are brain injured.
You would think the U.S. Department of Veterans Affairs
(VA) would jump on these inventions and, yet, for some reason
that is the law of bureaucracies, it is easier to say no.
What I wanted to do today is highlight a series of
different medical technologies, treatments, inventions, and
discoveries that would seem to me, and to many people that I
have talked to, to have great relevance for our veterans. Yet,
somehow, they do not seem to have been introduced into the VA
system.
I would ask each of our panelists to summarize the medical
situation for a layman as succinctly as possible and talk about
some of the frustration you have had with trying to get it
introduced into the VA system.
I think people are going to be really startled by some of
the things that we can do as a Nation which our veterans can,
in fact, increase the quality of their lives and the degree of
their health care. Yet, we seem not to have done it and I just
want to highlight the fact that there are so many of these
around.
I have no special interest in any company per se. I am not
trying to get anybody a job or a contract. I just feel it is
imperative that the ingenuity of our Nation be more recognized
and that the sense that we can do better for our veterans comes
out. Somehow, maybe we can change things by having all of you
here together showing what we can do as a Nation and hopefully
encourage the more quick acceptance of this for treatments.
I thank you for being here. I would welcome panel number
one. It is comprised of companies that will discuss a wide
range of technologies and treatments that are either ready for
use or are currently in development.
[The prepared statement of Chairman Filner appears on p.
36.]
Are you in the same order that I have here? Mr. Bethune, we
thank you. You are Chairman and Chief Executive Officer of
Zila, Incorporated. Dr. Sidransky is the Director of the Head
and Neck Cancer Research Division of Johns Hopkins University
School of Medicine joining him. Mr. Beckman is the President
and Chief Executive Officer for BrainPort Technologies, Wicab,
Incorporated. Mr. Broecker is the President and Chief Executive
Officer for Alkermes, Incorporated. Mr. Munroe is the Senior
Vice President of Mobile Medical International Corporation. Mr.
Stern is the President of TeleMed Network. And, Dr. Scadden is
the Founder of Fate Therapeutics, Incorporated.
I would like you to try to summarize the medical knowledge
for a layman. Be as dramatic as you would like and give us some
sense of what happened when you brought this to the VA's
attention, either locally or nationally.
We will start with Mr. Bethune. Thank you.
STATEMENTS OF DAVID R. BETHUNE, EXECUTIVE CHAIRMAN AND CHIEF
EXECUTIVE OFFICER, ZILA, INC., SCOTTSDALE, AZ; DAVID SIDRANSKY,
M.D., DIRECTOR, HEAD AND NECK CANCER RESEARCH DIVISION, JOHNS
HOPKINS UNIVERSITY SCHOOL OF MEDICINE, AND PROFESSOR OF
ONCOLOGY, OTOLARYNGOLOGY-HEAD AND NECK SURGERY, CELLULAR AND
MOLECULAR MEDICINE, UROLOGY, GENETICS, AND PATHOLOGY, JOHNS
HOPKINS UNIVERSITY AND HOSPITAL, BALTIMORE, MD; ROBERT A.
BECKMAN, PRESIDENT AND CHIEF EXECUTIVE OFFICER, BRAINPORT
TECHNOLOGIES, WICAB, INC., MIDDLETON, WI; DAVID A. BROECKER,
PRESIDENT AND CHIEF EXECUTIVE OFFICER, ALKERMES, INC.,
CAMBRIDGE, MA; MARK MUNROE, SENIOR VICE PRESIDENT, SALES AND
MARKETING, MOBILE MEDICAL INTERNATIONAL CORPORATION, ST.
JOHNSBURY, VT; STANLEY STERN, PRESIDENT, TELEMED NETWORK, ROSS,
CA; AND DAVID SCADDEN, M.D., SCIENTIFIC FOUNDER, FATE
THERAPEUTICS, INC., LA JOLLA, CA
STATEMENT OF DAVID R. BETHUNE
Mr. Bethune. Thank you, Mr. Chairman.
I am a proud U.S. Navy veteran and I am Chairman and CEO of
Zila, developer and marketer of the innovative ViziLite Plus
technology for the early detection of oral cancer and
precancerous abnormalities.
Private citizens around the world and even prisoners in our
Federal prisons enjoy the life-saving benefits of ViziLite Plus
screening.
The VA has repeatedly resisted efforts to understand the
great value of ViziLite Plus.
Oral cancer kills one American every hour, but veterans are
2.8 times more likely to get oral cancer than the general
public, partly due to the higher rates of smoking, chewing, and
drinking.
In 2006, the VA diagnosed 1,704 oral cancers, 5 percent of
all U.S. cases. Surviving this disease depends upon detection.
In the VA, their own data shows that 70 percent of oral
cancers are diagnosed at late stage when the 5-year survival
rate is just 26 percent, which is worse than our general
population results.
ViziLite Plus has received FDA clearance to aid in the
detection of early stage oral abnormalities including precancer
and cancer.
Some clinical studies on oral cancer screening, which when
dentists use their unaided eyes and fingertips have shown that
up to one-third of serious cancers and lesions are missed.
Supplementing the exam with ViziLite Plus has shown to
produce 100 percent screening effectiveness. ViziLite Plus is
an adjunctive screening technology similar to the mammogram,
PAP smear, or PSA test. They all promote early detection,
leading to fewer deaths, enhanced quality of life, and
significantly lower health care costs.
The treatment of late-stage oral cancer typically costs
$200,000 per patient and while treating a precancerous lesion,
it costs less than $1,500.
Zila provides the VA with ViziLite Plus at a deeply
discounted $12 per test. Screening all veterans seen in VA
facilities yearly would cost about $60 million, a sum that
would easily be recouped by the reduction in surgeries, long-
term care, suffering and death.
ViziLite Plus is backed by eight published studies,
recognized by the American Dental Association through their
Dental Procedure Code, adopted by the Federal Bureau of
Prisons, used by dentists worldwide, and covered by numerous
health insurance plans.
The decision to implement ViziLite Plus exams should be
universal in all VA facilities. Congress should urge the
Secretary of Veterans Affairs to immediately implement annual
ViziLite plus oral cancer screening of all veterans who are
seen at VA facilities nationwide. This is the best way to
assure the consistent delivery of quality life-saving care to
our veterans.
Thank you.
[The prepared statement of Mr. Bethune appears on p. 36.]
The Chairman. I would now like to introduce Dr. David
Sidransky. He is the Director of the Head and Neck Cancer
Research Division at Johns Hopkins University, School of
Medicine and Professor of Oncology, Otolaryngology-Head and
Neck Surgery, Cellular and Molecular Medicine, Urology,
Genetics, and Pathology at Johns Hopkins University and
Hospital. He is also one of the world's most cited cancer
researchers and author of over 340 peer-reviewed publications.
Dr. Sidransky.
STATEMENT OF DAVID SIDRANSKY, M.D.
Dr. Sidransky. Thank you.
The mission is to try and identify and treat oral cancer
and its precursors as early as possible. Historically this has
put a premium on the thorough and meticulous initial
examination.
However, clinical studies designed to test the
effectiveness of visual examination in identifying dysplasia,
the earliest cells that turn or can turn into cancer and cancer
itself, say otherwise.
In the meta-analysis of six worldwide studies, it was
reported that the weighted sensitivity of visual examination in
identifying oral cancer and precancerous lesions was under 80
percent.
Visual examination by untrained examiners often misses the
earliest more curable lesions. These results demonstrate that
disease remained undiagnosed by conventional examination.
By contrast, published studies reporting sensitivity values
from ViziLite are consistent. To date, the sensitivity of
ViziLite examination in identifying dysplasia and cancer is
nearly perfect.
According to published literature, pharmaceutical-grade
toluide blue, such as that included in the ViziLite Plus test
kit, preferentially stains lesions consistent with severe
dysplasia, carcinoma in situ and cancer.
In one study, we find that a TBlue application correlated
to a reduction of false positives by more than 50 percent. As
such, ViziLite Plus has adequate sensitivity to find the
meaningful number of individuals with disease while having
sufficient specificity to not falsely identify individuals
without disease as being positive for cancer.
It is within this framework that ViziLite Plus fits into
clinical practice. No other medical device has sufficient
sensitivity and specificity to meet the requirement of early
detection of oral cancer among veterans.
Other dyes and devices cannot precisely identify
precancerous lesions and early invasive cancers while excluding
healthy patients who need no further intervention.
Indeed ease of use makes ViziLite appropriate for use by
all oral disease health care professionals including dentists,
periodontists, oral surgeons, otolaryngologists, and even
primary care physicians.
In conclusion, ViziLite Plus is an easy-to-use, sensitive,
and specific medical device to help both relatively untrained
and expert examiners both identify oral lesions in their
patients who are in the high risk group for oral cancer.
Additionally, in an aging patient population, this product
can bring diagnostic power to physicians outside the dental
specialties for greater value and potentially more savings in
hospitalization.
Inclusion in VA oral cancer screening protocols would
improve screening efficacy for lesions suspicious for both
precancer and cancer and ultimately reduce the terrible
morbidity and mortality of this disease that our veterans
suffer.
Thank you.
[The prepared statement of Dr. Sidransky appears on p. 39.]
The Chairman. Thank you so much.
Mr. Beckman.
STATEMENT OF ROBERT A. BECKMAN
Mr. Beckman. Good morning. I am Robert Beckman, the CEO of
Wicab, Inc., a medical device company based in Madison,
Wisconsin.
I want to thank the Committee for inviting me to present
information on two innovative medical devices we are
developing. Both devices are available today for further
clinical testing that could ultimately lead to unique benefits
for some of our wounded or disabled veterans.
We are developing sensory substitution technology invented
by Dr. Paul Bach-y-Rita at the University of Wisconsin. Before
he passed away, Paul famously said, ``We see with our brains
and not with our eyes and the brain is not hardwired.''
What he meant is that if your eye is not functional, an
alternate sensor such as a digital camera can be used. And
because the brain is not hardwired, alternative neuro channels
such as the tongue can transmit the impulses.
Wicab is developing and testing two unique medical devices
based on this invention, one for balance and one for vision.
First, the BrainPort vision device, which I brought with me
today, consists of a small digital camera with zoom capability.
The user controls the intensity of the stimulation on their
tongue and the zoom feature. The image is transmitted real time
and displayed on the user's tongue through this 20-by-20 array
of stainless steel pins.
So our device provides a streaming video image on the
tongue for blind people. With the BrainPort vision device,
users are able to identify and navigate complex paths,
doorways, and objects.
For example, one blind user with two glass eyes was able to
successfully shoot a basketball and another used the BrainPort
vision device at an indoor rock climbing gym to see the next
rock holds and at home with his daughter to play tic-tac-toe.
The BrainPort vision device will not replace the cane or
the sight dog, but it will become an important additional tool
to improve the safety, mobility, and quality of life for blind
users.
Some examples, finding the open seat on a crowded bus or
train, identifying the direction to the target building in a
confusing parking lot, finding the handle in order to remove a
hot pot from the stove.
Wicab recently sponsored clinical testing of the BrainPort
vision device at the Atlanta VA. Dr. Michael Williams, the PI,
``concluded bottom line the device performs remarkably well for
the tasks that we looked at in phase one.''
To optimize the device, we need feedback from a much larger
pool of users who are blind. We would welcome the opportunity
to further test the BrainPort vision device at VA sites.
Perhaps those willing soldiers who are blind as a result of a
blast injury should be first inline to test this new
technology.
Now I would like to turn your attention to the BrainPort
balance device. This devise uses an accelerometer mounted
within the intra-oral device to sense head position
information. An accelerometer is like a digital carpenter's
level which senses tilt information as the patient's head
moves.
This tilt information is displayed on the patient's tongue
in the form of an electrical signal which feels like a bubble
moving on their tongue.
We trained patients with chronic balance disorders to
maintain their balance by keeping the bubble on the center of
their tongue. This training is intuitive. On day one, patients
learn to maintain their balance simply by keeping the signal in
the center of their tongue. More importantly, within 3 to 5
days after patients start training, they start to experience
improved balance even after the device is removed.
Patients perform most of the training at home during two
20-minute sessions per day. This is an important feature
because patients with chronic balance disorders cannot easily
travel to a clinic.
Early patient results after BrainPort balance device
training are very promising. For instance, a traumatic brain
injury (TBI) patient in Madison, Wisconsin, has now used our
device for 2 and a 1/2 years. His physician, his mother, and
the patient all agree that his recent improvement dramatically
exceeds the gains he achieved in the first 13 years after his
injury.
University of Wisconsin investigators recently analyzed
data from 26 stroke patients, all of whom continued to
experience significant balance disorders despite extensive
vestibular rehabilitation. The results of the training with the
BrainPort balance device over 8 weeks were quite promising both
statistically and clinically according to the PI, Dr. Mary Beth
Badke.
The BrainPort vision device and the BrainPort balance
device have both been hindered by limited funding available to
run clinical studies necessary to demonstrate the efficacy to
the standards of the medical community.
The VA could help accelerate adoption of both devices into
standard medical care by prioritizing and sponsoring further
clinical studies within the VA system, especially in cases
where the overall target populations are relatively small such
as people who are blind or have a balance disorder related to a
traumatic brain injury. VA funding could make the difference
for those deserving veterans.
Mr. Chairman, thank you for inviting me to make this
presentation to the Committee Members today.
[The prepared statement of Mr. Beckman appears on p. 41.]
The Chairman. Thank you so much.
I have to get my list here. Next, we will have, Mr.
Broecker.
STATEMENT OF DAVID A. BROECKER
Mr. Broecker. Thank you, Chairman Filner. I really
appreciate you inviting me here today to address the Committee.
My name is David Broecker and I am the President and CEO of
a small biotechnology company in Cambridge, Massachusetts,
called Alkermes. At Alkermes, we are dedicated to developing
medicines that make a difference in patients' lives.
I am pleased to be with you here today and appreciate the
time you have given me to share the story of a breakthrough
medicine that we believe can make a tremendous difference in
the lives of numerous veterans suffering from alcohol
dependence.
The medicine is call VIVITROL. But before telling you about
VIVITROL and how it might benefit veterans, I would first like
to highlight the problem of alcohol dependence.
As you are well aware, alcohol dependence is a huge public
health problem, especially among people who have served in the
military. It is a disease that not only hurts the patient but
also affects the lives of family and friends. Unlike other
illnesses, most alcohol dependent people do not seek treatment
unless confronted by family or friends and many times treatment
only occurs after a patient is in some sort of crisis
situation.
Nationally, there are approximately 20 million people who
abuse or have become dependent on alcohol. Of these, fewer than
10 percent are actually in treatment for their disease.
Today treatment consists almost exclusively of counseling
or talk therapy aimed at changing the behaviors of alcohol
dependent patients. Fewer than ten percent of these people in
treatment are actually offered any sort of addiction medicine
in the ongoing treatment of their disease.
Unfortunately, without medication-assisted therapy, the
relapse rates of 1 year of treatment are extremely high.
Tragically the problem of alcohol dependence is intensified in
military personnel, particularly combat personnel who are often
subjected to extremely difficult circumstances.
According to estimates from the Substance Abuse and Mental
Health Services Administration, approximately 650,000 veterans
suffer from alcohol dependence. When you combine the diagnosis
of alcohol abuse with alcohol dependence, the number jumps to
approximately seven and a half percent of all veterans or
nearly 1.9 million people.
Despite these challenges, there are ways to dramatically
improve care for our alcohol dependent veterans. Current
treatment guidelines issued by the National Institute on
Alcohol Abuse and Alcoholism call on providers to consider
medically assisted treatment in addition to counseling on an
ongoing basis for all patients.
Currently there are only four medicines approved by the FDA
for the treatment of alcohol dependence, Antabuse, ReVia,
Campral, and our product called VIVITROL.
Unlike the other medicines which must be taken on a daily
basis to have a clinically significant effect, VIVITROL is
unique in that it is an injection that delivers medicine over
an entire month.
For alcohol dependent patients struggling with their
addiction and trying to change their behaviors in profound
ways, the challenges associated with adhering to daily
medications are significant, and this is what often leads to
relapse.
These are fragile patients, particularly in the early
stages of treatment. This is why VIVITROL represents a
breakthrough in the treatment of this disease.
With VIVITROL, patients receive medicine for an entire
month allowing them to focus on changing their behavior through
counseling and other psychosocial support.
VIVITROL was developed in conjunction with support from the
National Institutes of Health (NIH) and was approved by the FDA
in 2006 for the treatment of alcohol dependence. It was shown
in a large, multi-center, placebo-controlled study to
dramatically reduce drinking among dependent patients. It has
also been shown to prolong abstinence and prevent relapse,
especially among severely dependent patients.
Since launch, we have heard numerous stories that tell us
that this medicine does indeed make a difference in patients'
lives.
In addition, we know of large managed care organizations
that have done their own assessments and concluded that
VIVITROL works well and reduces the utilization of other health
care services within their system.
Our belief is that veterans would benefit significantly
from widespread adoption of VIVITROL within the VA for the
treatment of alcohol dependence.
The utilizations of medicines in general, and VIVITROL in
particular, within the VA has been extremely limited. I believe
there are several reasons for this.
First, the current VA/U.S. Department of Defense (DoD)
guidelines for the use of medically assisted treatment for
alcohol dependence were written in 2001. VIVITROL was launched
after these guidelines were developed. These guidelines need to
be updated and disseminated throughout the VA.
Second, metrics and targets need to be established and
tracked for the screening and treatment of alcohol dependence.
Make the metrics simple so that no one can argue with them. I
believe that the systems are in place to do this.
And, finally, make the treatment of alcohol dependence
within the VA, and with our current service personnel, a real
priority. The benefits for patients and their families will be
dramatic.
And we look forward to working collaboratively to see that
these goals are achieved.
Again, I would like to thank the Committee for letting me
share the story of Alkermes and VIVITROL and, at the
appropriate time, I would like to answer any questions you
might have.
[The prepared statement of Mr. Broecker appears on p. 50.]
The Chairman. Thank you.
Mr. Munroe.
STATEMENT OF MARK MUNROE
Mr. Munroe. Good morning. First I want to thank Chairman
Filner and the Committee for allowing me to testify here today
on behalf of my employer, Mobile Medical International
Corporation of St. Johnsbury, Vermont.
My name is Mark Munroe, Senior Vice President of Mobile
Medical. My sole purpose here today is to explain how Mobile
Medical is using an innovative approach to help Veterans Health
Administration (VHA) medical centers provide top-flight
surgical care, keep VA surgeons engaged with their patients,
and save a significant amount of time and money associated with
the refurbishment of VA operating rooms.
It is important to note that this is not a new concept. We
have been engaged with the private sector over 14 years and our
solutions with VA medical centers for more than 3.
Mobile Medical is an international company that develops
and manufactures commercial and military mobile surgical
hospitals which meet all U.S. health care standards. These
mobile health care solutions are rapidly deployable, fully
integrated, self-contained, and present innovative solutions
for today's health care delivery needs.
To illustrate the versatility of this technology in various
markets, please note that Mobile Medical has responded to a
Federal Emergency Management Agency (FEMA) request to support
the University of Texas medical branch in Galveston after
Hurricane Ike.
We provide on-site surgery at a maximum security prison in
North Carolina with a Mobile Medical staffed unit and have
delivered eye care and surgical care units to Armenia, Saudi
Arabia, Oman, and Iraq.
As a point of reference, about 6 weeks ago, Mobile Medical
was featured on the international television program Little
People, Big World where Iraqi dwarf children were shown
receiving care on the mobile unit in southern Iraq.
Our flagship product, the mobile surgery unit, can be
driven to any VA hospital location and upon deployment, triples
in size to become a mobile surgical hospital that meets all
U.S. health care standards.
These standards include those required for State licensure,
Medicare certification, and Joint Commission on the
Accreditation of Health care Organizations. Mobile Medical
units meet all three of these standards.
Mobile Medical has provided mobile surgical capability to
private, nonprofit, and university medical centers for over 12
years from California to Virginia, and beyond. This service has
most often been provided on a rental basis and contract periods
last anywhere from 6 months to several years.
The primary reasons hospitals opt for this mobile solution
are that it eliminates the cost of contracting out surgical
cases to other hospitals and saves additional resources by
trimming months from the duration of the project.
Over the past 18 months, Mobile Medical has successfully
brought this cost-saving innovation to VA medical centers which
are undergoing hospital operating room renovations.
Our conservative estimates indicate that VA medical centers
can save on average $12,000 per surgical case by maintaining
control of their cases rather than contracting them out to
local or regional hospitals. This approach also assures VA
management that VA surgeons are handling the cases and
maintaining their skills.
Mobile Medical has successfully utilized this approach at
the VA medical center in White River Junction, Vermont, and has
a unit actively working on endoscopic cases at the VA medical
center in Martinsburg, West Virginia.
Mobile Medical is preparing to provide several units to
cover a major operating room renovation project at the Miami VA
and is currently working on similar opportunities at VA
facilities in New Orleans, Kansas City, San Diego, Clarksburg,
and Fayetteville.
Many facility leaders have indicated interest in utilizing
our units for the purpose I have described in a streamlined
contractual process administered by the VA headquarters.
In order to address these concerns, Mobile Medical
submitted an unsolicited proposal to VA's National Acquisition
Center in 2008. This submission proposed a pilot project using
three mobile surgery units over 3 years, saving $90 million.
Those savings are summarized in the attached two page executive
summary I have provided. This request was ultimately denied.
Mobile Medical estimates that a more robust project using
20 mobile surgery units for currently scheduled operating room
projects could result in a total cost avoidance of nearly $700
million over a 5-year period. We have also attached a document
that supports that information as well.
Mobile Medical continues to attempt a dialog with the
National Acquisition Center (NAC) in order to emphasize the
significance of the cost savings this approach offers. The
benefits of keeping patients and staff inside the VA system for
their surgeries and the difficulties VA medical center
contracting officers face as they attempt to fashion
appropriate contract vehicles for this service.
Mobile Medical stands ready to provide the VA and the
veterans it serves with cost-effective solutions for complex
health care delivery concerns. We would be happy to provide
private sector references as well as VA references if so
desired.
Thank you for taking the time to learn about our innovative
work. It has been a pleasure being here today.
[The prepared statement of Mr. Munroe appears on p. 55.]
The Chairman. Thank you so much.
Mr. Stern.
STATEMENT OF STANLEY STERN
Mr. Stern. Chairman Filner, Members of the Committee, thank
you for the opportunity to testify today on behalf of TeleMed
Network.
My name is Stanley Stern. I am the President of TeleMed
Network.
Our team has the singular goal to reduce the shocking rate
of veteran suicides. As you know, suicide is a solitary and
misguided act. Our technology addresses this issue directly,
confronting isolation with connectivity to both the VA and
other veterans, especially those who are isolated because of
geography or health status.
Further, our technology can provide direct and indirect
guidance to avert these misguided decisions. Our technology
team is led by Ed Yoon, the former Engineer of the Year for
Microsoft, and Dr. Mervyn Silverman, an internationally
recognized leader in the fight against AIDS, provides public
health guidance.
Our technology provides veterans with video
teleconferencing capability in their home. Teleconferencing is
not new, but it is expensive and complicated to install,
costing boardrooms hundreds of thousands of dollars per room, a
cost that can be justified, but cannot be done on a large
scale.
Our TeleMed Internet Endpoint known as a TIE costs less
than $1,000. It is designed to scale. It is small, three
pounds, portable, mailable, and provides a brilliant
videoconferencing image on a veteran's home television display.
The TIE and its secure network are mutually optimized for
video. There is no installation. It is plug and play. Just plug
it into the TV, connect it to the Internet, and turn it on. In
order to scale, it has to be simple.
Let me explain how being visually connected benefits a
veteran. First, with just one touch on a wireless keyboard, a
veteran sees and speaks with a VA health care service provider
whenever he or she needs help. The health care worker
immediately appears full screen and the call can be initiated
by the VA or the veteran.
A second button connects the veteran to a 24/7 group
therapy session. The caller can participate or simply observe
his peers speaking about issues he also confronts. It is an
ever-accessible confirmation that he is not alone and that
there are solutions available.
With this technology, these benefits can be available
without an appointment, without travel, and, most important,
without stigma because these conversations do not need to be
part of a medical record. They just need to help the veteran.
TIE provides many other communication benefits. After an
18-month deployment, close friends are dispersed across the
country. TIEs allow veterans to see and converse with each
other again.
For example, squad or platoon meetings every Tuesday night.
Local veterans can meet on Wednesday nights and there can be
various interest group meetings as well. TIE connects vets from
their homes to their veteran peers and professionals at the VA.
It directly confronts isolation and misguided decisions.
Help is the least accessible for our rural veterans who
must often drive hours to receive care. Inaccessibility
compounds the medical problem and many choose just not to get
the needed attention.
Our focus remains suicide prevention, but a TIE unit is
also an excellent vehicle for medical checkups, evaluation,
counseling, and eliminating the driving, the waiting, and the
mileage expense to the VA.
The TIE can benefit spouses left at home who will be able
to communicate with each other for support and learn from the
successes of those who have already had these experiences
themselves.
Accessible marriage counseling is just another benefit. Job
training, classes, even interviews will be available to provide
new directions, possibilities, and hope for returning veterans.
The network also creates cost-saving efficiencies. An
available health care provider in Nevada can answer an urgent
call from busy New York.
TIE is a conduit that connects the VA to its veterans,
allowing the VA to provide its best Post Traumatic Stress
Disorder (PTSD) remedies 24/7 to a veteran's home.
Our technology provides the quality, simplicity, and cost
that allow these advantages to be scalable, benefiting both
rural and urban veterans.
We will measure these improvements with independent
research that will quantitatively demonstrate reduced suicide
rates and intentions, improved medical benefits and access, and
lower costs all within 1 year.
Mr. Chairman, that completes my statement. I will be happy
to answer any questions. Thank you.
[The prepared statement of Mr. Stern appears on p. 56.]
The Chairman. Thank you.
Dr. Scadden.
STATEMENT OF DAVID SCADDEN, M.D.
Dr. Scadden. Mr. Chairman, Members of the Committee, thank
you very much for the opportunity to speak with you today.
I am here as a representative and scientific founder of
Fate Therapeutics, which is a new biotech company started in
San Diego, California.
My day job is as a physician. I am a hematologist/
oncologist. I run the Center for Regenerative Medicine at the
Massachusetts General Hospital. I am the Jordan Professor of
Medicine at Harvard, where I co-founded and co-direct the
Harvard Stem Cell Institute and the Department for Stem Cell
and Regenerative Biology.
Fate Therapeutics is a company that is dedicated to taking
advantage of the explosive new information about stem cell
biology as a way to induce regeneration and thereby reduce
disability.
The technology of stem cells is something that has become
available now as a modality by which we can approach problems
of chronic disability as a means to try to reverse, not simply
forestall, the development of disease.
Stem cells that we are approaching are really of two types.
The first is the adult stem cell population that resides in all
of us, that is in most of our tissues. And our approach is to
identify compounds that have the capacity to turn these cells
on as a means to enhance the body's ability to repair itself.
We have identified drugs that are capable of doing this,
and are entering into clinical trials to do so, and have, as a
number of different opportunities, ways in which we can take
advantage of learning about the stem cells that, for example,
make up our musculoskeletal system and turn them on with
medications as a way to improve the outcome of blast injury to
limbs, an important aspect of veteran care.
In addition, another stem cell technology that we focus on
is the ability to take cells from any one of us simply by
plucking a hair, exposing them to particular compounds in a
laboratory, and reversing the history of those cells so that
they become essentially an embryonic-like cell.
They are clearly not derived from an embryo. They can be
derived from any of us, but they have the full capability of
being able to serve as a source of any cell type.
The advantage of this cell is that it then becomes
essentially an identical reproduction of the cells that we all
have and, therefore, it could be potentially used as a tool kit
for each of us as a way to potentially replace injured tissue.
That would be accomplished without the potential for
immunologic rejection.
These cells also have the capacity to be used as a model
for the development of new medications. Again, an emphasis of
our company is to try to design ways in which we can identify
molecules that could be used as a way to enhance regeneration,
to induce an ability to restore function of damaged tissues.
So we are an early stage company that has focused on the
two different types of stem cells using essentially the
strength of the pharmaceutical approach to now develop
strategies to improve the ability of regenerative capabilities
in settings that are particularly relevant for veterans
including those of limb injury, with blasts to musculoskeletal
tissues, as well as neurologic regeneration in the setting of
hearing loss and visual loss.
So our company is one that tries to take advantage of the
necessary need for the innovations in the academic setting,
coupled with the commercial enterprise, and we hope with
government partnership.
Thank you for your attention.
[The prepared statement of Dr. Scadden appears on p. 59.]
The Chairman. Thank you so much.
In a conversation with the Secretary of the Department of
Veterans Affairs, I asked him to send somebody to this hearing.
Is there a representative from the VA here? Thank you so much,
we have a representative. I appreciate you being here.
Both the Secretary, in his use of the word transformative,
and the Deputy Secretary's understanding of innovation bode
well for the future, but we wanted to make sure people were all
aware of this.
Mr. Mitchell, do you have any questions?
Mr. Mitchell. Thank you, Mr. Chairman. I would like to ask
a couple questions of Mr. Bethune.
What makes the use of ViziLite Plus by the VA such a high
priority?
Mr. Bethune. Well, I would ask Dr. Sidransky to answer that
if you do not mind.
Dr. Sidransky. Yes. The bottom line is that veterans are at
great risk for oral cancer. And while we all accept screening
for various types of cancer like cervical cancer, colon cancer,
et cetera, we sometimes neglect this important disease which is
really a plague for veterans.
By using this technology, lesions that are curable,
resectable, and would impact these veterans. It would be
available to them, and that is the main reason to really
approach and use this technology with the veterans.
Mr. Mitchell. I have one other question of Mr. Bethune.
In your prepared testimony, you argue that this Committee
should call upon the VA's headquarters to implement ViziLite
Plus exams across the VA system despite objections raised by
senior VA dental officers. However, you also mention six
facilities in the VA system are already using ViziLite.
What feedback have you received from those VA offices who
have decided to utilize your product and does it square with
the assessments of the senior VA officials?
Mr. Bethune. Congressman, I believe that they do agree that
it is a very worthwhile test to be performed routinely. We
have----
The Chairman. I am sorry. Can you put the microphone in
front of you?
Mr. Bethune. Yes. Those that we have contacted and talked
to about this product found it very important to implement.
Our problem is as a very small company, we do not have the
resources to call on all of the many VA hospitals and clinics
around the United States and it would take us years to have
each of these institutions look at this technology and then
make the decision. That is why we are urging the head of the VA
here, General Shinseki, to look at it as a universal program
for all of the VA hospitals.
Mr. Mitchell. But the feedback you have gotten from the six
VA hospitals so far has been very positive?
Mr. Bethune. Pretty much so, yes, sir.
Mr. Mitchell. Thank you, Mr. Chairman.
The Chairman. Thank you, Mr. Mitchell.
Mr. McNerney.
Mr. McNerney. Thank you, Mr. Chairman.
Well, I have to say I found all of your testimony very
exciting. And this is the kind of thing I want to see happen.
Mr. Bethune, the ViziLite Plus, how intrusive is it to
administer this test? Is it just a swab or how is the test
administered?
Mr. Bethune. We have a person out here. Dr. Balanoff is a
practicing dentist and he uses this routinely in his practice.
Dr. Balanoff, could you answer that question, please?
Dr. Balanoff. Yes. It is a very simple test. You have a
patient rinse with an acetic acid rinse----
The Chairman. Sir, we have a microphone at the end of the
dais. If you could use that one? Thank you.
Dr. Balanoff [continuing]. You have the patient rinse with
an acetic acid rinse which has kind of a vinegar taste to it.
And the most important thing is to use a light. And this light
will identify all abnormalities. And this is really important
for the general dentist, which is going to be screening the VA
population.
So it is just a very simple, easy test that takes less than
2 minutes to do and is noninvasive and is 100 percent accurate
to all leukoplakias, white lesions, inside the mouth.
And then the follow-up to that would be if you found
something abnormal to use the blue, the tolonium chloride that
we have as part of our kit and, again, noninvasive.
Mr. McNerney. So you rinse out the mouth and then look at
it with a light or something?
Dr. Balanoff. That is correct. That light is a special
wavelength. White light which will allow the dentist to find
something abnormal and then once they find something abnormal
to refer it off to the appropriate specialist. And what this
light does, it is an adjunctive test, which just makes it
easier.
It would be kind of equivalent to going to a medical doctor
and not allowing the medical doctor to use a stethoscope or a
blood pressure cuff. You want something adjunctive to help you
diagnose the health of the patient and that is what the light
does.
Mr. McNerney. All right. Thank you. Thank you.
Mr. Beckman, the BrainPort vision device, this sounds
very--how intrusive is the device that is on the tongue? Are
you able to eat? Do you have to remove it for different
activities or how intrusive is this?
Mr. Beckman. Well, for vision, the device does rest on top
of the tongue. And so, yes, indeed, in its current form, you
would have to remove the device when you were eating, talking,
et cetera.
However, with additional funding, there are no
technological barriers to making this device totally wireless
so that the intra-oral device could be mounted on the upper
palate. And blind people using wireless technology would be
able to use the device without anybody even knowing that they
actually have the technology available to them.
Mr. McNerney. Well, that is pretty exciting. I am kind of
thrilled by the technical aspect of this rather than the
administrative aspect, if you cannot tell.
Mr. Broecker, the drug that you are talking about, how does
it work? Does it make you nauseous when you have alcohol or how
does it work?
Mr. Broecker. No. You know, one of the very first medicines
that was developed was a drug called Antabuse and that is the
one that if you take it and you drink alcohol, it makes you
sick.
Our drug, VIVITROL, is a monthly injection. And what is
thought is that this diminishes the cravings that occur in
alcohol dependent patients by blocking your opiate receptors.
And so that is how the drug works.
Mr. McNerney. Are there any side effects?
Mr. Broecker. Some minor nausea, but that quickly goes away
after a couple days.
Mr. McNerney. And do you have to continue the usage of
VIVITROL for a long period of time or is a couple months
sufficient?
Mr. Broecker. Well, in the studies that we have done, we
have monitored patients over a 6-month period of time. So the
clinical studies we have done have been over 6 months of time.
However, we do know of patients that have been on it for, you
know, 2, 3 years.
But it is very important that, you know, the patient not
only get the drug but they are engaged in an active counseling,
you know, a program to deal with the behavioral aspects of
alcohol dependence. So the medicine addresses the biological
urge and craving to drink while the counseling addresses the
behavioral change that is required.
Mr. McNerney. Well, thanks.
Again, I want to thank the panel for their testimony and
for the Chairman for the insight to bring this panel together.
The Chairman. Thank you.
Mr. Walz.
Mr. Walz. Thank you, Mr. Chairman.
And thank you to each of you for coming in and, as my
colleague from California said, sharing with us some very
exciting and innovative technology.
Obviously the goal of this Committee and I would say the
goal of all Americans is to provide for the highest quality of
life for our veterans after they serve our Nation. It is an
honorable goal and also if it is done right, and we have heard
many of you say this, it is not only doing morally the right
thing, it is going to save us money in the long run.
So my question to you, and I am with Mr. McNerney, I like
the technology side, too, but I also know that it is not the
technology that stops this from happening, it is bureaucracy
that stops it from happening in many cases.
So that is the part I want to talk about a little bit,
about acquisition reform and contracting reform because we
heard the President talk last week, just in cost overruns at
DoD, if we do this right in acquisition reform, we can save up
to $300 billion.
I do not think people realize what we are talking about.
That is the entire pay of our entire military and the health
care for their families for 2\1/2\ years in cost overruns, not
cutting weapon system, just cost overruns.
So my issue on this is, I wanted to ask each of you, we all
understand that the reason we have a lot of these things in
place is to prevent fraud, waste, and abuse. Obviously it is
not totally doing that, at least from an efficiency standpoint
in DoD. The same might be true of the VA. Those procedures were
never put into place to stop innovative and life-saving
technologies from getting to our veterans.
So I would like each of you to just take, you know, a few
seconds or whatever. What has been your experience? And some of
you, you are obviously coming from the private sector, too, so
you are dealing with private institutions.
I say this because I always ask all of my questions against
a backdrop that I represent the Mayo Clinic and I ask them how
does it work for you as opposed to the VA. And we all agree the
VA does many, many, many things as well as anybody in the world
in terms of the care.
This is the part I want to understand: are we nimble enough
to innovate or are we behind the curve in that? So why don't
each of you just give your input as you see this. Are we
inhibiting it and not really protecting the taxpayer dollars in
the right way?
So if we just start with Mr. Beckman and go around, that
would be great.
Mr. Beckman. Neither the BrainPort balance device nor the
BrainPort vision device are cleared by the Food and Drug
Administration (FDA) at this time. So we are not in the process
of attempting to commercialize or market our devices to the VA.
On the other hand, I think that the VA could take a
leadership role, especially when you consider that people with
traumatic brain injury represent a very small population
overall and within the military. And, secondly, people that are
blind, especially people that are totally blind with no better
than light perception are also a very small population.
So, again, it would, I think, make sense for the Veterans
Affairs to take a leadership role so that the people, for
instance, who have been blinded or who have suffered traumatic
brain injury as a result of the most recent conflicts would be
the first in position to be able to test these technologies
rather than being the last.
Mr. Broecker. When it comes to alcohol dependence, as I
mentioned in my testimony, the latest guidelines that have been
adopted by the VA were in 2001. And, since that time, not only
has our drug been approved by the FDA, but there has been
another drug called Campral that has been approved by the FDA.
So, as it relates to adoption of innovative treatments for
a disease like alcohol dependence, these guidelines need, you
know, continued to be updated and then disseminated within the
VA system.
My understanding is that there were recent guidelines that
were developed last spring that still have not been
disseminated. So, I think something that they need to do is
clearly, you know, the expert groups and the key opinion
leaders within the VA should see to it that these things get
adopted and get put into practice within the VA system.
I think the other thing is, you get the results you
measure. And, I know that the VA is a big, complex system, but
if you could, develop very simple measures that could be
adopted across the VA about things like alcohol dependence or,
the variety of the diseases that are represented up here with
all the various technologies and hold the people accountable
for implementing some of these new technologies.
And then the final thing I would say is, make funding
available. If there are certain funding pools that could be
allocated to the adoption of certain technologies, as you
mentioned about sight and things like that, there is no better
testing ground than the VA for some of these innovative
therapies.
Mr. Munroe. Congressman, we are in a little bit of a
different category here with Mobile Medical in that we
currently work with the VA. We are on an innovative technology
track, which is answering a question that exists today and that
is that with the current state of the VA facilities and the
need for operating room renovation, the facilities really have
two options when it comes to doing that.
The first is they close their operating rooms altogether
and they send their patients outside into the private health
care sector. When you do that, you lose all control. And
certainly from a cost perspective, now you are in the
commercial setting paying commercial rates. You are not in the
existing setting which is really health care at cost.
The second option that they have is they can close a
portion of their operating rooms and essentially phase a
renovation project. If they do that, two major things happen.
One is the construction and renovation of that project doubles
and sometimes triples in length, i.e., it triples in cost.
The second thing that happens is you are always concerned
about infection control. And we have seen some of that very
recently in the VA setting because when you are doing
construction in an operating room theater on one side of a wall
and you are treating a patient on another side of a wall, I am
sure some of the surgeons here could say, you know, that is not
the most conducive environment.
Additionally you have staff that now have to work different
shifts, overtime, double time in order to cover that type of
schedule.
So to answer your question of the bureaucracy component of
this, just today we received an e-mail from one of the VA
facilities that says our renovation project is approved. It is
part of the stimulus bill. We forgot how we are going to treat
our patients when we close our operating rooms.
We did not put that on the front end of our project plan.
We just said we need to fix the hardware, the operating room.
So now the contracting officer has to scramble and they have to
scramble to take operating dollars to solve that problem. That
issue is apparent at every VA facility I go to and visit when
they talk to us about operating room renovations.
So as you can see in some of the numbers we have presented,
our objective and our goal with our unsolicited proposal was to
show the VA that the request is there. The contracting
officers, the chiefs of surgery, have the need for this
solution. The projects are scheduled. The facilities need to be
renovated.
If there was a pool of units such as ours that they could
now say, okay, this project now receives two, three, four
mobile surgery units, all that bureaucracy goes away because
now they have access to the tool that they need, no different
than having access to the drug that they need or anything else
to help the veterans in that setting.
Mr. Walz. I appreciate it. I went over my time. I will wait
if we get a chance to come back around again to let the four of
you take that on too.
So, Mr. Chairman, I yield back.
The Chairman. Mr. Walz, why don't we just try to finish?
Mr. Walz. Thank you, Mr. Chairman. I appreciate that.
Mr. Stern, go ahead.
Mr. Stern. Well, I will be brief. In our case, this is a
dramatic reduction in cost for communication and communicating
with veterans about their real psychological needs early will
truncate many years of therapy thereafter. So it has to stand
up to the cost benefits and I am sure that it does.
That said, for many of the technologies we have heard about
today, there is also a social benefit that often transcends the
economic parts. And I think that somehow, even though it cannot
be quantitative, has to be measured.
Dr. Scadden. I will just say that in the setting of
rehabilitation, the VA is clearly very strong, but its emphasis
is largely on device and engineering-based approaches.
And one of the things that I think stem cell biology
represents is a way to try to take advantage of cellular
components that may enhance the ability of such devices to be
functional.
And to have the VA be involved in bringing together teams
of individuals who have the perspective and expertise that the
VA system represents coupled with those who have the expertise
in cell biology, I think, could actually be a very productive
area of developing new approaches to rehabilitation
regeneration.
Mr. Bethune. Yes, sir, Congressman. Our product, ViziLite
Plus, has been approved by the FDA. It has been awarded a
special government award contract for use in any Government
Federal facility. So there is no impediment for this product to
be used.
The impediment, I believe, is that we do not have a
universal requirement that this be administered around all of
the VAs. It is a decentralized decision now being made where
the local VA can make the decision.
And most of the VAs, you asked this morning, Congressman
Mitchell, about what do they think about this product is that
many of them say, well, we do not have the funds earmarked for
this product.
So many VAs report that they don't have available money to
spend, although they tell me they do have the funding for other
projects, but they do not have a special earmark fund for
ViziLite Plus to administer this oral cancer screening exam.
Mr. Walz. Thank you, Mr. Chairman.
The Chairman. Thank you, Mr. Walz.
Mr. Donnelly.
Mr. Donnelly. Thank you, Mr. Chairman.
Dr. Scadden, this area of stem cells is really interesting.
What can it be rewound to do? There are a couple of specifics
that you mentioned, but what is the overall feel that is out
there?
Dr. Scadden. So right now we have the ability to take a
cell that is defined as being something like a skin cell or a
blood cell and essentially have it be able to forget all of its
history. It no longer identifies itself as such and it can
become any one of the different cell fates. There are over 200
cell types that make up our body.
So the potential is to be able to now say, well, maybe from
this population of cells that we derived from here, we could
now make a cell population that makes insulin and that could be
used for individuals with diabetes or we could make things like
muscle and potentially have it be useful in that context.
So I think the range of possibilities is quite enormous.
The technology is obviously very, very early and the question
of how to do it in a way that gets predictable outcomes, that
is safe, all of these things are still in need of development.
But it is, I think, something that we should frankly be
driving full speed ahead because this is really a very
transformative technology and the ability to potentially
reverse, not just forestall, the outcome of injury and disease.
Mr. Donnelly. So while you talk in the documents we
received about three specific applications, the applications
are basically limitless?
Dr. Scadden. Yeah. I mean, we do not know now whether or
not we will be able to create all of the different cell types
of the body, but certainly this potential is something that
when tested has been possible to achieve. And I think a lot of
it is more technical than it is in biologic terms.
Mr. Donnelly. And this is simply just one of our skin cells
from our hand?
Dr. Scadden. Right. So what is done now is either biopsy
from the arm, for example, you can literally pluck a hair, you
can take a blood sample.
Mr. Donnelly. Thank you.
Thank you, Mr. Chairman.
The Chairman. Mr. Hall.
Mr. Hall. Thank you, Mr. Chairman.
And thank you to all of our panelists. I am sorry to have
missed the first part of the testimony, but I have a couple
questions.
Mr. Beckman, I wonder if you could tell us why BrainPort
devices are not implantable and is that something that could
change?
Mr. Beckman. I think one of the key advantages of the
BrainPort device is the fact that it is not implantable. In
fact, it is a portable device where there is no need to implant
the technology.
Other technologies for vision such as retinal implants are
being developed, but I think the fact that they involve
surgery, that they are invasive means that those technologies
will likely not be available for probably 10 years or more. Our
technology is available today.
Mr. Hall. I understand that. And I can see the advantages
to either, or both. But cochlear implants, for instance, have
been and are being used by large numbers of people with some
success.
Is it because of the location in the brain of the nerves
that one would need to get at, the nerve centers one would need
to get at, that it is more difficult or is this something that
you see happening in the future?
Mr. Beckman. That goes back to my testimony. One of Dr.
Paul Bach-y-Rita's main hypotheses is that the brain is not
hardwired. So, in other words, you can use an alternate sensor
and also an alternate path to send that signal to the brain.
And we have demonstrated that, for instance, people who are
blind who perform a certain task with our device and while they
are performing that task, they are analyzed with PET imaging,
we have demonstrated that those people process the visual
information in the visual cortex of their brain.
On the other hand, people who are sighted that perform the
exact same task process that same information in the
somatoesensory region of their brain. So, in other words, the
brain is masterful in the way that it can process the
information in the appropriate area.
Mr. Hall. And it can change, it can switch and adapt from
one pathway to another?
Mr. Beckman. Yes.
Mr. Hall. What is the typical training, you may have said
this in response to a question before I got here, what is the
typical training time for someone to be able to use, to adapt
to the BrainPort?
Mr. Beckman. I think that is also an amazing part about
this technology. We train blind people, literally in hours they
start to recognize symbols, pathways, doorways, et cetera. We
have not so far had anybody except for one blind person, Eric
Weihenmayer, use the device for more than 10 hours.
We have videos on our Web site that show some of the
benefits. All of those people are performing the tasks with
less than 10 hours of training.
And I think what is most interesting is what will happen
when we get this technology into the hands of many, many
adults, letting them take it home, use it on their own, explore
the potential benefits of the technology on their own. That is
where we will start to really discover what the advantages and
possibilities are for this technology.
Mr. Hall. Thank you.
Regarding the use of, I believe it is Mobile Medical and
TeleMed, well, certainly, you know, having just come back from
Afghanistan and Iraq as many of us did on our so-called break
at the end of last month, we are all very much in favor of and
encouraged by the work that you are doing to make the treatment
of our wounded service men and women faster and more effective.
And we realize the conundrum of battlefield medicine saving
more lives but then leaving more grievously wounded people for
us to treat when they get home.
I read something here, I believe it was Mr. Stern, the
TeleMed testimony, about remote computer provided sessions for
group therapy counseling, et cetera.
What are the limitations of that? I mean, there are
inherent, I believe there are inherent limits to what a soldier
will diagnose him or herself with or how--the interpersonal
reaction between therapists and patient or a room full of
participants face to face is different. There is body language.
Well, it is harder to just get up and walk out the door. It is
easier to log off. How do you address that or can you address
that problem?
Mr. Stern. Yes, Congressman.
Mr. Hall. Would you push your microphone there, please.
Thank you.
Mr. Stern. How is it now?
Mr. Hall. That is fine. Thank you.
Mr. Stern. The idea behind a group session is, there are a
number of types. I only had 5 minutes to explain there and so I
welcome the question.
There is absolutely room for private group therapy session
where somebody can be there as an individual or anonymously.
That is all right, too, because the stigma is a big part of
this.
But I think the thing that will benefit most people is
having the ability for, with the knowledge of those
participating, with their full knowledge, having others observe
them passively.
You know, it is not unlike what we see in talk radio where
you will have a psychologist or a doctor explaining a problem
to one person who knows they are being heard nationally, but
many of us just listen in the car and listen and think, well,
that relates to me. I have had those problems and I like
hearing that solution.
But we would not have gone to a psychologist or a doctor to
get that solution. This offers that benefit, but it has to
always be very clear. You need to know if it is public or
private and it is easy to do both.
I hope that answers your question, sir.
Mr. Hall. It does. Thank you.
I yield back, Mr. Chairman.
The Chairman. Mr. Perriello.
Mr. Perriello. Just quickly. Thank you very much, Mr.
Chairman, for holding this hearing.
I think this intersection of innovative technologies and
treatment of our veterans is a very exciting area and obviously
in many ways, the VA system itself is in a great position to
deal with this given the issues that we face. But we also know
so many independent private-sector groups are at the cutting
edge of this.
So not only helping us to understand where the technology
is and where it can go, but also addressing some of these
issues of the dynamic relationship between the VA system itself
and independent companies is very important.
So I enjoyed reading your statements even though I missed
many of them here. I really just want to say how important this
is as an issue and something we want to push on.
There are not many questions I have. I just wanted quickly
to understand a little bit more from you, Mr. Bethune, about
what some of the real world experiences have been with doctors
and health care providers with the ViziLite Plus innovative
technology. It is just something I wanted to understand a
little more about how that has played out in the real world
applications.
Mr. Bethune. Well, thank you for that question. I have a
person here in the audience who would be great for that
question, Dr. Joel Epstein. He is Professor of Oral Medicine
and also Oral Cancer at the University of Illinois. So he might
be able to answer that question more.
Dr. Epstein. Thank you for your question. It is nice to be
here with you.
The real world utilization requires increasing education
for utilization of detection adjuncts based upon the principle
that early detection of any cancer is critical. It is critical
more from the standpoint of diagnosis and preventing reducing
the morbidity of more intensive therapy that is required for
advanced disease management.
In addition, there are the cost savings in terms of quality
of life impact which is dramatic for head, neck and oral cancer
and from the standpoint of cost of care.
Early detection that is being promoted on an ongoing basis
in the community and to a large degree the dental community
because currently we see earlier stage disease being diagnosed
by dental providers rather than medical providers. This relates
in part to the way in which patients present.
For example, if it is weight loss or voice changes occur,
those patients may present at a late stage to a physician's
office rather than a dentist's office.
But certainly, all health care providers should be involved
in early detection procedures and this can and has been shown
to enhance the early detection of oral cancers.
Mr. Perriello. Let me ask one other question that is
hypothetical. It came up anecdotally talking to some of the
doctors, but more the troops when I was over in Afghanistan,
was this issue about whether we are sufficiently prescreening
folks. And it was all anecdotal in terms of a propensity for
PTSD.
And there was no evidence, and I am not claiming that there
is such a thing, but do we think that down the road, there may
be some way to look at this from the front end of being able to
identify more accurately potential predisposition in some of
these directions before we send people into conflict or is that
really something that will continue to play out as sort of myth
among folks at the battlefront but not real medicine?
Dr. Sidransky. Hi. Yeah. So this probably goes away from
the area of expertise of the people that are here. I am
actually also a geneticist.
And I think that in general, that is the way the medicine
is going, but it will be a period of time. We will understand
more the makeup of individuals as well as some of the risk
factors perhaps with questionnaires and other things that they
fill out.
And I think for any type of disease, whether it be cancer,
post-traumatic stress or anything else, I think there will be
an interaction between the genetic information that the veteran
comes with as well as some of the environment that can be
related and the questionnaire is some sort of intake.
And I think it can. I think for many of these diseases that
interaction, if you can actually take it out and implement some
way of actually looking at it, we will be able to identify some
of these individuals, to identify them as being potentially at
risk or basically, you know, for therapy or something else or
actually not able to be able to participate because of that.
We are not quite there yet, I think, for a lot of the
mental and the psychiatric issues, but I think there is a lot
of movement in that direction.
Mr. Stern. And I agree with Dr. Sidransky on this point,
that this is solvable. And right now it is being done in a very
crude way, I am afraid.
I mean, I know an anecdote that was told to me by the
person in charge of suicide prevention at the Palo Alto VA. She
was telling me the story of a sergeant who on the day they were
being deployed had questions about one of his troops and his
behaviors and really did not know how to diagnose it.
And it was happening at that level and clearly it could be
done before that by professionals, not the sergeant ready to
board the plane, but by professionals before that, as long as
you have the communication ability or some other mode to get
people in and diagnose them. So I think it is very solvable.
The Chairman. We need to go for votes. We have been called
for votes and we are going to have to take a recess for about
15 minutes. I will dismiss the first panel after I just ask
some quick questions.
I want to thank you all, I think everybody who has heard
you was blown away by the excitement of what new technology can
really do. You represent just a slice of what is happening in
America with new innovations.
I am confident that our new Administration will be more
open on the various levels you talked about, not only in
testing, but if you need a centralized decision, for example,
or more openness.
I had a long talk with Secretary Shinseki and Mr. Gould,
the Deputy Secretary, and they are very aware of how an agency
needs to have a way to innovate. I think we are going to have a
much more flexible, nimble VA to make use of some of the
innovations very much more quickly. We will be testing that by
your experiences.
I just again want to make it clear for the record, you see
that none of our Republican colleagues are here. They decided
that somehow special interests were invited, somehow that we
were promoting this or that company. That was not the
intention. We are trying to take a cross-section of what is
available. Nobody here is pushing for a contract, just a sense
of ideas that are available and how we might respond as an
institution.
I just want to make sure, since this always comes up, that
none of the witnesses have ever given me or anybody else up
here a campaign contribution.
This is a hearing to talk about the excitement and the
possibilities of new innovations. I see someone who might want
to say a few words, from the Blinded Veterans Association, of
what this might mean for someone who is blind.
The opening up of fields of vision for people who have eye
injuries, or brain injuries is exciting. It is a tool where
people can read, with a non-invasive technology that has been
shown to us and, yet, the VA does not have it for some reason.
I want to thank you all for helping us generate that
excitement and to make sure the new Administration understands
that we have to look at this in a much more nimble fashion.
We have the second biggest bureaucracy in the government,
but it has to move faster because it affects our patients' care
and their quality of life. Every one of you talked about how we
could save hundreds of millions, if not billions, of dollars.
This is not rocket science to say if it works, let us use it.
Just one quick question. Mr. Munroe, you talked about the
mobile surgical unit to help when there are problems, for
example, refurbishing a VA facility.
How about access into rural areas? That is one of the
biggest problems faced by the VA. I assume we can adapt this
and take that to the veterans in rural areas as opposed to
forcing them to go 200, 300, 400, 500 miles.
Mr. Munroe. Mr. Chairman, understanding one thing. The
genesis of Mobile Medical was exactly that, was that there are
patients in the private sector and in the VA setting that spend
hours traveling for procedures and having a mobile solution
that can go to a community, draw from that pool while it is
there, and then travel to another community is exactly the
reason that the mobile surgery unit was created in the first
place.
The Chairman. Thank you.
Mr. Munroe. You are welcome.
The Chairman. Again, we have to run for some votes. We will
be back in 15 minutes. I will dismiss the first panel. Ask the
second panel to approach the witness table.
Again, thank you so much for sharing these innovations.
Some of this is proprietary, but I really appreciate you
sharing with us the excitement and to demonstrate the kinds of
changes that we can make to better serve our veterans. We will
start panel two in 15 minutes.
[Recess.]
The Chairman. I apologize again for the interruption, we
have no control over when votes are held. We thank you for your
patience and look forward to panel number two. I hope that in
your presentation you answer the question that Mr. Walz asked,
which is, ``What do you need from the VA to make this a reality
for the veterans we are responsible for?''
I appreciate your being here. Dr. Howard Federoff is the
Executive Vice President for Health Sciences at Georgetown
University, Dr. Nelson Handal is the Founder and Medical
Director of Harmonex, Inc., Clinicom, and James Schoeneck is
the Chief Executive Officer of Braincells Inc.
Dr. Federoff.
STATEMENTS OF HOWARD J. FEDEROFF, M.D., PH.D., EXECUTIVE VICE
PRESIDENT FOR HEALTH SCIENCES, EXECUTIVE DEAN OF THE SCHOOL OF
MEDICINE, GEORGETOWN UNIVERSITY MEDICAL CENTER, WASHINGTON, DC;
NELSON M. HANDAL, M.D., FAPA, FOUNDER, CHAIRMAN, AND MEDICAL
DIRECTOR, HARMONEX, INC., CLINICOM, ATLANTA, GA, BOARD
CERTIFIED CHILD, ADOLESCENT AND ADULT PSYCHIATRIST, AND FELLOW,
AMERICAN PSYCHIATRIC ASSOCIATION; AND JAMES A. SCHOENECK, CHIEF
EXECUTIVE OFFICER, BRAINCELLS INC., SAN DIEGO, CA
STATEMENT OF HOWARD J. FEDEROFF, M.D., PH.D.
Dr. Federoff. Good afternoon Chairman Filner and Members of
the Committee, thank you for holding this hearing, for the work
you are doing on behalf of America's brave veterans, and for
allowing me to testify this morning.
I will be focusing on innovative work that from my
perspective is critically important to addressing the long-term
implications of traumatic brain injury both to ensure that we
are serving the long-term needs of returning veterans who have
experienced TBI and also to do so in ways that are wise for the
Department of Veterans Affairs Health Care Programs.
The Defense in Veterans Brain Injury Center makes the point
on its Web site that America's armed forces are sustaining a
tax from explosions or blasts almost daily in Iraq and
Afghanistan. It also notes that screenings at Walter Reed have
found that 32 percent of servicemembers evacuated from theater
had traumatic brain injury. Those statistics obscure the
reality.
Also referenced on that Web page that sometimes in the
setting of mild traumatic brain injury there may be no outward
sign of injury. Over 90 percent of combat-related TBIs are
close brain injuries.
Indeed, TBI has been termed the silent epidemic. While 1.4
million Americans suffer from TBI from a variety of sources
each year, many of these injuries with potential long-term
consequences are not reported. Even in mild cases of trauma the
central nervous system can suffer permanent, often debilitating
damage.
There can be no dispute that our military is moving
aggressively to respond as best as they can to the flood of
very visible and tragic traumatic brain injuries that our men
and women in uniform are experiencing in these 21st century
conflicts.
Just as the nature of these injuries has changed from shell
shock suffered by those serving in earlier conflicts, medical
science has made significant strides. But we owe it to those
who are serving and those who have served our Nation in uniform
to act on the important realization that notwithstanding the
attention they are receiving, there are all too many who have
suffered mild to moderate traumatic brain injuries that pose
serious but hidden threats to their long-term well-being. We
need to act.
Developing methodologies for more rapid and accurate
diagnosis of traumatic brain injury and its associated risk
determine the most effective approaches to triaging patients
with traumatic brain injury.
Pursue the rational design and screening of new therapies,
including novel drug discovery and development targeting the
prevention or minimizing of cognitive impairments which can
impact learning capabilities, the ability to hold down a job,
and to predispose to post-traumatic stress disorders.
Years of neurologic research has taught us a great deal
about the human brain, and therefore there is information that
is relevant to TBI victims.
First, the plasticity of the human brain permits unique
recuperative responses to trauma. We must fully understand
these responses to better understand when to intervene and when
to allow the body to heal itself.
Second, research to date indicates that unlike in the case
of stroke in at least some forms of TBI there is a longer time
frame from the time of injury for possible therapeutic
intervention before permanent loss of brain function.
And third, research in other areas. Alzheimer's and
Parkinson's disease makes clear that blood in its circulating
cells may serve as an important window into the human brain
helping us to better understand the impact of neurologic
disease and injury.
For example, understanding the neuropathology of brain
inflammation through the analysis of blood-based proteins and
distinct populations of white blood cells called leukocytes may
help us to determine the extent to which the brain has been
injured and the degree to which the body is responding and
possibly recovering.
These observations are generally invisible, absent a
molecular analysis of the blood of an injured person, but they
potentially hold the key to effective and timely interventions.
Recently the Department of Defense, through its Neurotoxin
Exposure Treatment Program, NETRP, has awarded a 5-year grant
to Georgetown University Medical Center neuroscientists to
perform systematic and extensive biomolecular profiling of
brain tissues and peripheral blood to identify and validate
robust and sensitive and specific markers for traumatic brain
injury. These signatures can be read from the blood, and early
on may aid in the diagnosis of a variety and severity of brain
injuries and guide therapeutic responses.
Indeed this research I am confident will inform the
rational design of new drugs and therapies to prevent both
short-term and lasting brain damage.
Our work will be carried out in conjunction with the
Seattle-based Institute of Systems Biology and researches at
the University of Rochester.
As someone who believes in the tremendous benefits of
possible collaboration, I am pleased that we are working with
the Uniform Services Universities of the Health Sciences as
they pursue their direction from Congress to focus on TBI, as
well as the National Institute for Nursing Research, the
National Institute of Neurologic Disorders and Stroke, and the
Washington Hospital Center.
Our research for the Department of Defense will rely
critically on first the civilian-sector TBI patients for our
initial studies in recognition of the reality that we will be
able to recruit these individuals without delays that are
inherent in working with patients injured in combat.
However, I am following up with the recommendations from
Chairman Filner that we reach out to the DC VA Medical Center
to pursue approaches to ensure longitudinal followup between
the care received in these cases from the military and the
ongoing Department of Veterans Affairs military care.
Given the ongoing work of traumatic brain injury at the
Washington VA Medical Center, as well as over 30 Georgetown
Medical Center faculty who hold appointments there, I am
confident that we will actively engage the Washington VA
Medical Center in this research to provide the best possible
care for traumatic brain injury patients now relying on the
Department of Veterans Affair for medical services. Ongoing
monitoring of their conditions and well documented longitudinal
followup will be critical; it will likewise enrich our
research.
Members of the Committee know very well that the vast
majority of military personnel who are returning from the field
who have experienced TBI are very young. God willing, they have
long lives ahead, therefore it is incumbent upon us to ensure
that we are aggressive in this kind of research endeavor that
looks beyond the immediate consequences of even mild TBI. With
this type of research we can address the silent epidemic before
it takes a toll on the long-term quality of life of those
serving our country.
I urge the Department of Veterans Affairs, in close concert
with the Department of Defense and Department of Health and
Human Services, to remain vigilant in pursuing the
identification of both these biomolecular signatures and of
effective therapeutic responses to traumatic brain injury.
Again, thank you for giving me this opportunity.
[The prepared statement of Dr. Federoff appears on p. 68.]
The Chairman. Thank you. Dr. Handal.
STATEMENT OF NELSON M. HANDAL, M.D., FAPA
Dr. Handal. Mr. Chairman, Members of the Committee, thank
you for the opportunity to share information about innovative
treatments and technologies that are serving to enhance quality
of care, especially in our area of mental health. I am a board
certified psychiatrist.
As you know, information, and the way it is used, is at the
core of psychiatrist assessment and diagnosis. Typically
patients requiring mental health care are interviewed in what
is commonly referred to as a traditional face-to-face
psychiatric interview. Practicing medical health clinicians
know that too often time constraints, volume and complexity of
the information, limited access to care, and other factors, if
not properly identified and addressed, end up limiting the
accuracy of their face-to-face interview.
The key question is how to gather information
comprehensively in a reasonable amount of time utilizing an
easy to use tool that generates a valuable report to facilitate
disposition and the clinician's initial face-to-face interview?
Our organization, Harmonex, is the developer of a patient
self-administered and computer-based assessment tool known as
CliniCom. CliniCom is comprehensive, easy to use, and allows
the clinician to verify suggested diagnosis. The technology
resides in a secure platform that comprehensively screens for
56 mental illnesses and traumatic brain injury. CliniCom also
includes a powerful suicide alert. CliniCom is based on the
DSM-IV standard and incorporates clinical research and widely
accepted community standards of care.
CliniCom is being used successfully across our Nation at
private outpatient clinics and hospital settings alike. The
technology can be equipped to run in most clinical environments
using tablets, desktops, and kiosks. CliniCom evokes the
appropriate question sets based on the user type and the
patient's age. It does not replace the mental health
professional, it simply allows them to significantly enhance
the face-to-face interview, its outcomes, and quality of care.
CliniCom does not forget to ask pertinent mental health
questions each and every time. It gathers complete medical,
social, and family histories and can also identify concerns
associated with suicide, violence, and traumatic events.
CliniCom will also quantify severity of symptoms and severity
of conditions automatically. It allows for secure and uniform
documentation by organizing clinical information in the
standard history and physical format.
Once patients complete the assessment, clinicians can
devote much of their interview toward building rapport,
validating the clinical report, and helping patients understand
the nature of their condition. It is very difficult to gather
all of this information during a single traditional face-to-
face psychiatric interview. Our technology can gather
clinically relevant and necessary information in a reasonable
and quantifiable manner.
The clinical decisionmaking process overall is
significantly enhanced by allowing CliniCom to identify
individuals that may have co-morbid conditions, meaning the
presence of one or more disorders or diseases in addition to a
primary disease or disorder. An example would be an individual
with depression, in addition to PTSD and substance abuse. With
CliniCom clinicians can better ensure that both primary and
comorbid problems are identified simultaneously, leaving no
stone unturned.
A recent independent survey of 1,109 CliniCom users
identified that 92 percent of users reported that CliniCom was
very easy to use. In addition, survey results indicate that 87
percent of the users found CliniCom to be very easy to
understand, while 88 percent found it to be very thorough.
Seventy percent of users completed the assessment in 60 minutes
or less. This is a function of the severity of their case.
While CliniCom has served to enhance care to the private
sector, we have confidence that the technology can also serve
to enhance care within military mental health. CliniCom has
unique characteristics that make it well suited for use both as
pre- and post-deployment screening tool and also as a
comprehensive mental health assessment tool.
By implementing a technology like CliniCom, DoD and the VA
can use this valuable clinical resource to help mitigate the
overarching issues of stigma and access to care, an issue that
every member of our armed forces is given a complete
comprehensive and responsible mental health assessment.
In summary, CliniCom is a unique information gathering tool
designed to assess mental health conditions, TBI, and
suicidality. The technology is comprehensive, easy to use, and
its conclusions can be easily verified by mental health
professionals.
In addition, what is learned from these cases can be used
to conduct research that could lead to even greater advantages
in mental health care. Truly modernizing the way we help people
of all walks of life, who today suffer from mental illness.
We are grateful to the Members of this Committee for the
work you do on behalf of our veterans and soldiers. Thank you
for your time and the opportunity to introduce to you CliniCom.
We look forward to answering your questions and are prepared to
help in any way we can.
[The prepared statement of Dr. Handal appears on p. 69.]
The Chairman. Thank you very much. Mr. Schoeneck.
STATEMENT OF JAMES A. SCHOENECK
Mr. Schoeneck. Chairman Filner and Members of the
Committee, thank you for your opportunity and the honor of
being able to appear before this distinguished Committee today.
And I wish to commend you for your attention to the compelling
issues surrounding military post-traumatic stress disorder or
PTSD.
I have served as CEO of BrainCells since 2005 and have
worked on successful drugs in both the biotech and
pharmaceutical industry for almost 30 years. BrainCells is a
San Diego based biotech founded on the discovery made only 10
years ago that new nerve cells grow in certain parts of the
human brain. In fact, new neuron production, a process known as
neurogenesis, is a requirement for the normal emotional
responses that mentally healthy people take for granted.
By way of ground breaking studies from our founding
scientists from Columbia University and the Salk Institute, we
have demonstrated that stress can arrest the formation of these
new cells resulting in immeasurably shrunken site within the
brain called the hippocampus.
We now have the first physical understanding of the
biologic processes that are involved in psychiatric diseases.
Image studies performed on PTSD patients confirm that they also
suffer abnormal changes in the hippocampus. And although these
methods are not yet available to diagnose and study progress of
all clinical PTSD patients, they may some day soon be
available.
Importantly, BrainCells has designed a drug screening
platform to search for new classes of drugs that will help this
nerve cell growth function return to normal, restoring
neurogenesis with the intention of improving emotional
integration with fewer side effects. BrainCells believes that
its compounds provide alternatives to the traditional anti-
depressant and anti-anxiety drugs by directly increasing
neurogenesis.
Expanded screening and treatment for PTSD and depression
and new efforts to reduce the stigma surrounding mental illness
among servicemembers are to be commended. But since October
2001, approximately 1.6 million U.S. troops have been deployed
for Operations Enduring Freedom and Iraqi Freedom, and
according to last year's Rand Study, one in seven
servicemembers is returned from deployments with symptoms of
PTSD.
PTSD can be regarded parenthetically as a chronic wounding
of the brain just as traumatic brain injury bruises the brain.
Violence, divorce, domestic abuse have skyrocketed among
returnees and suicide rates in the military now exceed those in
the civilian population; unheard of as a historic suicide rate
has always been much lower among soldiers, sailors, Marines,
and airmen.
PTSD is classified as an anxiety disorder with symptoms of
chronic anxiety and fear that serve no purpose. It is often
accompanied by typical or atypical depression. Non-drug
treatment is regarded as the first line option for PTSD and is
routinely incorporated in the management plans for patients.
Many do not achieve a response from this non-drug therapy.
The selective serotonin reuptake inhibitors, or SSRIs, are
used as first line pharmacological treatments. These are
familiar classes of anti-depressants like Prozac and Paxil.
Response rates for these medications rarely exceed 20 to 30
percent of PTSD patients. In fact, this class of drug routinely
causes side effects like insomnia, weight gain, and most
significantly for young returnees, sexual dysfunction. This is
because of the increased serotonin resulting from the
medication that can affect many parts of the brain and the
body, many of which do not need to extra serotonin.
Less than 40 percent of servicemembers diagnosed with PTSD
receive mental health care, and some of those voluntarily forgo
treatment or compliance because of sexual functional effects or
those worries. Many soldiers use alcohol and illegal drugs to
deal with the symptoms rather than take their SSRIs.
Combat veterans are now thought to suffer a more severe
form of PTSDs than civilian victims of trauma. Military stress
is generally associated with greater depression, more anger,
irritability, more aggression, and a far greater tendency
toward suicide or violence as illustrated by the deaths in Iraq
this week. Additional studies are needed, but experts are
moving to the conclusion that military PTSD is both different
from civilian trauma and also it is more difficult to treat.
Methods used to treat civilian PTSD are at times inadequate
to address military syndromes. It is disturbing to realize that
we still have thousands of Vietnam veterans in the full throws
of chronic PTSD and simultaneously we are being advised by the
military that currently deployed troops are experiencing severe
problems in record numbers, and if left untreated PTSD is a
lifetime disorder.
Probably because of the nature of this unique physiological
insult, combats for PTSD is different than the mental syndrome
that civilians suffer. It has its own symptoms that require
medications designed and tested for military and veteran
populations.
It is unlikely that the civilian pharmaceutical industry
can or will invest resources to address this as it is a
specialized orphan-like condition that suffers from anxiety,
depression, memory, and memory processing disorders.
The investors at BrainCells, for example, anticipate that
we will use our resources to develop drugs for large civilian
populations, like major depressive disorder. This market may
provide investors with their anticipated return on the
investment in exchange for the high financial risks taken in
drug development.
Unless the government provides collaboration incentives and
funding directly to biotech and pharmaceutical industry to
deliver to the FDA-approved drugs labeled for military post-
traumatic stress disorder, clinicians will be left with a
combination of existing drugs tested and approved for people
with a different medical condition.
Members of our military who voluntarily protect our Nation
from harm are deserving of well funded pharmaceuticals that are
directly and specifically directed to the disease of military
PTSD.
Congress has generously funded significant amounts into the
research of determining the organic causes and best practices
for treating PTSD, but its yet to fully engage those of us who
are singularly and professionally dedicated to identifying and
testing safe new compounds.
Members of the Committee are undoubtedly aware of the
myriad of ways that private enterprise can be provided
incentives as exemplified by orphan drug laws that offer tax
credits and patent extensions to illnesses affected by small
populations. Tragically, military PTSD has already exceeded the
statutory 200,000 patients that define orphan drug laws, but
surely our war fighters are deserving of the best that our
creative laboratories can provide.
In closing, I wish to summarize the following thoughts and
recommendations.
PTSD is a disease that dramatically impacts the lives of
our troops and returning veterans and their families. There are
wonderful new developments in the field of neuropharmacology
that could make a huge difference to sufferers of PTSD with
fewer side effects. We must respond with a sense of urgency
around testing new classes of drugs to treat the patients with
military PTSD. Our collective goal should be to have new
medications for the veterans of these conflicts, not the next.
And a public private pathway to drug development is necessary,
including regulatory and financial incentives for orphan-like
drug development, including supporting clinical trials.
Thank you once again for the opportunity to speak before
the Committee.
[The prepared statement of Mr. Schoeneck appears on p. 71.]
The Chairman. I thank you all and appreciate all the
thought that has gone into this.
If I can just go back. Mr. Schoeneck, have you brought up
these suggestions directly with the VA or have you been in
contact with the VA Central Office?
Mr. Schoeneck. We have not talked directly with the VA
Central Office. We have previously spoken more with the DoD
than with the VA around these problems.
The Chairman. You want direct support, either money or some
of the other incentives you talked about for research into
these areas?
Mr. Schoeneck. That is correct, that is correct.
The Chairman. Just for the layman here, I know it in
general, but give me a more specific definition of the orphan-
drug incentive. What is an orphan-drug incentive?
Mr. Schoeneck. When you are designated as an orphan drug
you get 7 years of market exclusivity on the back end of the
approval for the drug. And particularly if we are using drugs
that may have already exhausted some of their normal patent
life that becomes very important in terms of having a time that
the risk for the investment can be paid back for those that
have taken that risk.
The Chairman. What is the criteria?
Mr. Schoeneck. It is 200,000.
The Chairman. Is it a small population?
Mr. Schoeneck. Yes, small populations that are 200,000 or
less.
The Chairman. So that number needs to be revisited as one
of the things you are suggesting.
Mr. Schoeneck. Exactly.
The Chairman. Is the VA research process big enough? Is
there enough money? Is it open enough? Are you aware of what is
available now and how they go about that?
Mr. Schoeneck. The dollars that are available now tend to
be more toward treatment or exploring treatments with existing
medications, not things that are novel and in development. And
the drug development process and the requirements that are
there from the FDA, which should be there in terms of
protecting the safety of Americans, those are not things in
general that the VA pays for. Those are generally paid for by
some outside source or by a more specific funding source.
The Chairman. Does NIH do any of this?
Mr. Schoeneck. The NIH, to my knowledge, is not doing
anything directly on PTSD. There is a Congressionally directed
consortium that is working on PTSD, but they are looking more
at the currently available compounds and how they may be able
to be used together rather than looking at things that are
truly novel.
The Chairman. Could the VA use the NIH as an agent to make
sure there is specific granting authority or amounts of money
available for things that the VA wants? Is that a model that we
could use?
Mr. Schoeneck. I think it is possible. I would have to
think about it more, but I think it is possible.
The Chairman. If the NIH system works, and I don't know if
it does, but let us assume it does, some of the money from VA
could be put in NIH or NIH money could be targeted to the areas
of research that the VA needs as opposed to forming a
bureaucracy within the VA to deal with it. If you think it is a
good idea, let me know.
Dr. Handal, have you dealt with the VA in trying to get
CliniCom used or have you dealt with the Department of Defense?
Dr. Handal. I have talked with several people.
The Chairman. I assume this is a computer program?
Dr. Handal. Yes. It is software that has been developed
over the past 5 years, and we have implemented the technology
in 13 States.
The issue with DoD or the VA is, I think, the same as what
we heard this morning. It is very difficult, I think, for--
specially for innovative technologies to, you know, have some
audience, and that is why I really appreciate the opportunity
today.
The Chairman. Are the people you deal with afraid that it
is not proven or that they are going to buy something that is
not worth it or proves to be wrong or what is the problem?
Dr. Handal. No. I think everybody gets very, very
interested and very excited about it. I think part of it is the
bureaucracy.
Now you were mentioning, you know, the fact that there are
ways to probably get application, and those ways we have tried,
many of those ways, and still I think we have had difficulty. I
would like to have Ms. Sharon Allred, she is our CEO, and maybe
she can give you a little bit more information about how that
pathway went.
The Chairman. If you can just use that microphone there?
Whom do you go to in the VA and what occurs when you get there?
Give me a sense of what is going on.
Ms. Allred. Well we have tried a lot of local approaches
working with chief of psychiatry at Walter Reed and we have
worked with Fort Rucker and several of the places where we have
actually gone to where the psychiatrists themselves and the
medical professionals believe very strongly in what we have
developed and built. But when you start trying to put it into
place, then you start hitting some of the red tape type issues.
You know, they have to get approval and they can't necessarily
get approval at the local level, and they have to, you know, it
has to be a top down type process.
You know, we have tried to look for solicitations and other
things that actually deal directly with this, but again those
are very difficult to find. And as we were talking with the
gentlemen here earlier that represent the VA, a lot of times it
is just difficulty in trying to find who the right person to
talk to within the VA that handles the type of technology that
we are dealing with.
We are tried, true, and proven in the private sector. We
have definitely done our research on the security. We have
actually had it analyzed by personnel from the military. So we
feel like we are ahead of the curve, we are just not exactly
sure how to get directly into the right people.
The Chairman. Okay, thank you.
Ms. Allred. Uh-huh.
The Chairman. You need a little revolutionary cadre on the
side that is working constantly at subversive activities. Of
course, I will chair that.
I am only being half facetious. Any big bureaucracy needs
to institutionalize a way to undermine it to institutionalize
change. That is to find ways that somehow don't get through the
normal processes.
As I said, I had a long conversation with the Secretary and
the Deputy Secretary, and they seem to understand that. As the
Deputy Secretary said, you want to have openness, but you have
to have some constraint on it as well.
There has been FDA approval of a lot of innovations we have
heard and there has been other peer reviewed innovations. It
seems to me that risk is minimized with all these other things
that are going on.
We have, as everybody pointed out, many cases of PTSD and
TBI. We need all the help we can get and I will look at
anything. Particularly with PTSD as you point out--as everybody
has pointed out--it would be good to have pre-deployment and
post-deployment data to see what kinds of differences there
are. If you have a tool to do that, I don't know why we don't
use it.
The numbers are so high, and I think that the numbers that
we have used here tend to underestimate it. As policy makers,
we should say prove to me you don't have TBI or PTSD before you
leave, rather than us having to prove you have it. Make a
mandatory physical evaluation for everybody. Whether you are
using something like CliniCom, or a personal interview with a
psychiatrist or other medical professional. We don't do that.
We have all these self-administered questionnaires that are
gained, and they are not comprehensive anyway.
We are letting servicemembers who can explode at any time,
and it is up to us to minimize that. You all have given us some
ways to help them. It seems that the military and the VA should
be looking at all these innovations. By not doing so, we get
two statistics. Half of the homeless on the street tonight are
Vietnam veterans, because we did not look at PTSD, and the
suicide rate of Vietnam veterans now outnumber those killed on
the battlefield.
We have done something wrong there. We can't keep repeating
that mistake, and yet it seems that we are. We have far less
numbers in Iraq and Afghanistan, but the percentages are as
high or higher in all the things we don't want to happen.
As we proceed as a Committee and as a VA with new
leadership, what is the first thing each of you would like to
see happen? What is the key thing that you would like--a new
VA, a transformed VA, an innovated VA, how could it help what
you all are thinking? If each of you would take a turn at that?
Give me one thing.
Dr. Federoff. In the current context being able to engage
the spectrum of health care professionals in longitudinal
follow up. Particularly now that it is clear that there is some
elements of blast-related head injury that distinguishes itself
from other forms of head injury.
Without that natural history work and a commitment to
support it long term, some of the answers that are needed will
not be known, and it may well be the case in citing the Vietnam
example that some of those answers may not be known for
decades. But commitment long term for follow up--careful follow
up is, I think, warranted.
The Chairman. And, the VA is about the only institution
that can do that?
Dr. Federoff. Yes.
The Chairman. Or, can provide you with the subjects for
such research?
Dr. Federoff. Correct.
The Chairman. Yes.
Dr. Handal. One idea would be the creation of an office for
innovative technology, and that would basically be where people
who develop technology, especially in health care, would
approach that office and present to them whatever claims they
have, and then that office probably should be responsible for
carrying this information through the VA and DoD, and then
replying back to whoever is interested in working with the VA.
I think it sounds to me, and I am not a businessman in the
true sense, I am a physician, but it really sounds to me that
there are so many ways that you can try to approach the VA and
the DoD, but there really is no one door where you can go and
say okay I have this technology and I want you to look at it
and talk to me about it and I can describe it and then you can
carry it forward and see who is interested in the VA.
And we can claim for instance that we have a hospital in
our area that could use it. The director for instance of the
program, with the Behavioral Health Program, Dr. Barry
Frankhauser, he told me I want to use it. And he wanted to use
it at that particular military hospital. And you know, it was
very difficult to convince other people to do it, despite the
fact that they thought it was a very appropriate thing to do.
The Chairman. Yes, you are getting back to my revolutionary
cadre of subversives. I put it a little differently than you.
Of course, setting up that office will go through a
bureaucratic process which will take 7 years and which will
only be staffed by those who have given adherence to the
bureaucracy.
You have to almost institutionalize a revolutionary part of
your--I mean, how does IBM or how does Microsoft innovate? They
are big bureaucracies. Our new Deputy Secretary of the VA comes
from IBM, so I think he can give us some help on that. How do
those big bureaucracies constantly innovate? There is probably
a secret little room with a lot of young geeks in jeans, who
are thinking things through all the time to undermine
Microsoft, then they adopt them, and then they make another
$500 billion. It seems to me we have to do that if you want to
carry back that message somewhere. Of course, that will go
through your bureaucratic process and may never get to the
Secretary.
I am sorry, am I pronouncing your name right by the way?
Mr. Schoeneck. Schoeneck.
The Chairman. Schoeneck. Okay, thank you.
Mr. Schoeneck. So I think just two brief things. One is
access to VA populations with PTSD and funding to look at and
examine truly novel medications in this area.
We have been stuck in the same cycle of medications coming
off of the Prozac-like spins for the last 25 years and it is
time for this population to have an opportunity to get
something truly novel that might be able to treat the disease
in a different way.
I think the other one is to potentially think about an
orphan-drug exception that designates military PTSD as an
orphan drug. You would definitely get the attention of more an
industry by doing that.
The Chairman. So just by doing that, that makes incentive
to----
Mr. Schoeneck. Absolutely.
The Chairman. Well, I appreciate all of your thoughts. We
look forward to working with you in the future. We will follow
up on all this and hope that we can make the quality of life
for our veterans a lot better, quicker and cheaper.
Thank you so much. This hearing is adjourned.
[Whereupon, at 12:40 p.m., the Committee was adjourned.]
A P P E N D I X
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Prepared Statement of Hon. Bob Filner,
Chairman, Full Committee on Veterans' Affairs
I would like to thank everyone for attending this hearing today.
The purpose of today's hearing is to be made aware of, and learn about,
the innovative technologies and treatments which are currently
available or are in development to help veterans.
We will hear from companies that have devoted many resources into
researching the unique maladies that affect veterans of all conflicts.
While I applaud the VA for being the leader in research and
treatment of such conditions as Traumatic Brain Injury and Post
Traumatic Stress Disorder, it is important that our veterans have
access to other ground-breaking treatment modalities which have been
developed in the private sector.
As the Chairman of the Veterans' Affairs Committee, I have learned
about many exciting developments in technology and treatments that can
help our deserving veterans. However, it has come to my attention that
the developers of these new technologies and treatments face many
barriers. For example, it is a challenge to add a new treatment tool to
the VA's supply schedule and there is yet another obstacle of the VA
not making active use of the treatment tool on the supply schedule.
In the end, this affects veterans who cannot access the best
technologies and treatments that are available in the market. Just as
our veterans bravely risked their lives for our country, it is our duty
to ensure that they have access to the latest and the most effective
treatments.
Prepared Statement of Hon. Harry E. Mitchell
Thank you, Mr. Chairman, for calling this hearing. We live in the
most innovative country in the world and at a time of unprecedented
technological advancement. I am pleased that we will have the
opportunity to review a number of cutting-edge products and treatments
that can help save lives--and improve the quality of life--of many of
our veterans.
Before I yield back my time, I'd like to thank David Bethune--the
Chairman of Scottsdale's Zila, Inc.--for appearing before the Committee
today. Zila develops and markets the ViziLite Plus Technology, which
provides a method for detecting oral cancer. This product is already in
use at a number of VA facilities, and I look forward to learning about
its results at the VA.
Thanks also to Vomaris Innovations--who produces a bio-electric
wound care product in Chandler, Arizona--for submitting testimony to
the Committee. And finally, thank you to the rest of our panelists. I
look forward to hearing about new tools and methods we may use in the
care of America's veterans. I yield back.
Prepared Statement of David R. Bethune, Executive Chairman
and Chief Executive Officer, Zila, Inc., Scottsdale, AZ
Thank you, Mr. Chairman and Members of the Committee, for inviting
us to participate in today's important hearing on Innovative Technology
and Treatments Helping Veterans. I am David R. Bethune, a proud navy
Veteran and Chairman and Chief Executive Officer of Zila, Inc., the
developer and marketer of the ViziLite Plus technology for the early
detection of oral abnormalities that could lead to cancer.
It has been said that without change, there is no innovation. With
respect to the Department of Veterans Affairs, I would modify that:
Without change, our Nation's Veterans will not enjoy the life-saving
benefits of innovation.
Innovation has already brought an effective, fast and low-cost
screening technology to dental offices throughout America and the
world. And yet our Veterans, who are among the most in need and most
deserving of this technology, are being denied its benefits. In this
respect, our Veterans receive inferior care to the inmates in our
Federal prisons. Why? Because the VA has not added a 5-minute procedure
to routine dental check-ups, that could save lives, improve the quality
of life, and prevent costly surgeries and long-term care.
The Tragedy of Oral Cancer
Oral cancer is a killer. Yet while it claims one American life
every hour, it flies under the radar for most Americans. In times past,
oral cancer was thought to be a disease of old men who had smoked all
their lives. Today, with oral cancer rates increasing among women, and
striking both women and men in their 20's and 30's, we know that
virtually everyone is at risk. Tobacco and alcohol are confirmed
causes, and now, thanks to Johns Hopkins research, it is becoming clear
that the HPV virus, long known as the primary cause of cervical cancer,
is emerging as a leading cause of mouth cancer. Seventy-five percent of
all people carry the HPV virus at some point in their lives, and it is
easily spread to the mouth through oral sex.
Oral cancer is the eighth most common type of cancer among males in
the United States. 34,000 new cases are reported yearly, and
regrettably, most are discovered at later stages, when the outlook is
most grim. This helps explain the surprisingly high death rate
associated with this disease. The tragedy is that because oral cancer
occurs in the mouth, which is totally accessible to the eyes of
dentists and physicians, it should be one of the most avoidable and
manageable forms of cancer.
Based on available statistics, Veterans are especially susceptible
to oral cancer. In 2006, 1,704 cases of oral cancer were diagnosed
within the VA. That's 5 percent of all annual cases in the U.S. Given
that the VA treats about 5.5 million patients per year, Veterans are
almost 3 times more likely to be diagnosed with oral cancer than are
members of the general public. And now we know that the conflicts in
Iraq and Afghanistan are producing another generation of tobacco-using
Veterans. A survey of Marines and sailors shows they are using tobacco
at more than twice the rate of other Americans--64 percent vs. 30
percent.\1\ If there was any doubt that oral cancer is a real and
growing threat for vets, this should put it to rest.
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\1\ Tobacco use in Iraq vets--http://www.medpagetoday.com/
MeetingCoverage/CHEST/11520 accessed 5/4/09.
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As with most other types of cancer, chances of surviving this
disease depend largely on how early it is detected. In the VA system,
the record for detection and survival is dismal. Seventy percent of VA
oral cancers are diagnosed at late stage, when the 5-year survival rate
is just 26 percent. Early stage detection occurs only 30 percent of the
time; those lucky patients have an 82 percent 5-year rate of survival.
The goal, however, should be detection of pre-cancerous tissue--cells
on the pathway to cancer. Identifying these abnormalities offers the
best chance of avoiding the often horrific or fatal consequences of
oral cancer itself. And this--the early detection of oral abnormalities
that could lead to cancer--is exactly what ViziLite Plus was cleared by
the FDA to do.
The hardworking and highly professional dentists of the VA should
not be faulted for these poor cancer detection statistics; after all,
their record closely aligns with that of the historical record of
dentists who serve the public. A primary reason that so many cancers go
undetected for so long is that the conventional examination method is
far from perfect. Dentists have long been taught to use their trained
eyes and fingertips to conduct a conventional visual exam. Yet studies
to date of the conventional visual exam have demonstrated that it is
only effective in identifying suspicious lesions about two-thirds of
the time; in other words, it misses suspicious lesions one-third of the
time. When you supplement the conventional visual exam with ViziLite
Plus, you increase screening effectiveness to 100 percent.
Adjunctive Screening Technology Makes Sense: Fewer Deaths, Enhanced
Quality of Life, Lower Healthcare Costs
ViziLite Plus falls into a category of medical devices called
adjunctive screening technologies. It is similar in function to
(although less expensive than) the mammogram for breast cancer; the Pap
smear for cervical cancer; and the PSA test for prostate cancer. The
rationale for adjunctive screening technologies comes down to this:
They promote early detection, which leads to fewer deaths, enhanced
quality of life, and significantly lower healthcare costs.
There is ample evidence that adjunctive screening technologies save
lives. From 1972-1992, breast cancer deaths declined 45 percent with
mammograms. From 1950-1990, the Pap smear helped reduce cervical cancer
deaths by over 70 percent. And from 1993-2002, prostate cancer deaths
declined 18 percent, thanks to the PSA test.
It's hard to put a valuation on the dramatic reduction in pain and
suffering that is achieved through early detection, especially with
oral cancer. When a pre-cancerous lesion is identified, it and the
threat of imminent cancer can be eliminated in a quick out-patient
procedure. That contrasts with gross surgical removal of large segments
of the tongue, cheek or jaw bone for patients with late-detected mouth
cancer. With such extensive surgery, and accompanying radiation and
chemotherapy, quality of life plummets as simple, everyday tasks like
talking, eating and sleeping are made near-impossible.
As for cost savings, we have solid evidence that early detection of
oral cancer dramatically reduces the need for expensive surgery,
chemotherapy and long-term care. Analysis by the Delta Dental insurance
company shows that treatment of late stage oral cancer typically
exceeds $200,000 per patient, while treatment of pre-cancerous lesions
costs only $500-$1,500. For patients, early detection means a faster
return to the workplace, which reduces lost wages and improves
productivity.
Even in these challenging economic times, the VA can afford wide-
scale implementation of ViziLite-assisted oral cancer screening exams.
Zila Pharmaceuticals has contracted to provide ViziLite Plus to the
government at a deeply discounted price of approximately $12 per test.
If the VA were to provide a potentially life-saving ViziLite Plus exam
to every Veteran receiving VA services (5.5 million in 2007), the cost
would total only $66 million--a meager amount compared to the agency's
$41.2 billion budget \2\, and a sum that would be totally eclipsed in
cost by the reduction in surgeries and long-term care.
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\2\ VA budget--http://www.whitehouse.gov/omb/budget/fy2009/
Veterans.html accessed 5/4/09.
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The military should also provide ViziLite Plus-assisted oral cancer
exams to all personnel undergoing medical exams as they end their
active duty.
Adjunctive Technology for Oral Cancer Screening is Widely Utilized
ViziLite Plus screening is gaining wide acceptance as an adjunctive
technology, advancing the standard of care. This is confirmed by:
American Dental Association recognition (through their dental procedure
code); adoption by the Federal Bureau of Prisons; acceptance by
dentists; approval for reimbursement coverage by numerous commercial
health insurance carriers; and contractual inclusion in the Federal
Supply Schedule.
Recognizing the need for an adjunctive screening technology to
fight oral cancer, the American Dental Association in 2005 created a
new procedure code for this type of screening. ViziLite clinical
evidence was the sole data supporting the ADA's decision to create the
Code, which facilitates insurance billing.
The Federal Bureau of Prisons (BOP) has embraced ViziLite Plus. The
BOP strongly encourages every Federal prison facility to incorporate
ViziLite into their care protocols, both for new prisoners at intake
and for those already incarcerated. The BOP recognizes the economic
benefits of early detection and treatment, and ultimately, the
importance of being fiscally responsible with moneys provided to it.
Dentists across the United States and the world are incorporating
ViziLite Plus into their oral cancer screening protocols. Patients are
benefiting from the technology in Canada, the UK, France, Germany,
Spain, Portugal and beyond.
A growing number of health insurance carriers provide coverage for
the ViziLite Plus screening exam. These include Guardian, UnitedHealth
care Dental, Humana Dental, Northeast Delta Dental, Essex Dental
Benefits, SafeGuard and many self-insured employer and union groups.
Altogether, some 24 million people are enrolled in plans that offer
ViziLite Plus coverage.
ViziLite Plus is available to all VA facilities through a Federal
Supply Schedule (FSS) contract (V797P-3158M) administered by the VA
National Acquisition Center (VA NAC).
Zila's Experience Encouraging Use of ViziLite Plus in the Veteran's
Administration
ViziLite Plus has been or is currently being utilized at six
facilities out of the entire national VA system. Other than these
facilities the VA has been slow in their response to our wanting to
describe the system and its potential benefits to the Veteran. Given
the ability of all facilities to readily purchase ViziLite Plus through
the Federal Supply Schedule contract, I strongly recommend that this
technology be made available to all that visit the VA clinics.
One of the unique aspects of oral cancer is that screening and
detection are typically performed by a dental professional, while
treatment is administered by a medical professional. As a result, a
simple budgetary fact may be undercutting care: The VA's dental budget
bears the cost of using innovative technology to help identify oral
cancer, but the economic benefit of early detection is shifted to the
medical budget.
To underscore this, our company has had far greater success in
securing coverage for ViziLite Plus from those national insurance
carriers that provide both dental as well as medical coverage, because
they take a comprehensive look at costs and have come to the conclusion
that ViziLite Plus saves money.
Some dentists say, ``Your technology is not proven,'' or ``We'll
consider using ViziLite Plus when it has matured.'' Rejecting
innovation this way endangers lives. The ViziLite technology has been
cleared by FDA and thoroughly vetted by scientists, regulators and
private practitioners. Eight peer reviewed papers have been published
demonstrating the efficacy of ViziLite and ViziLite Plus. This
extensive research supports sensitivity of 100 percent--where oral
cancer was present, ViziLite Plus detected it every time. A clinical
study published in the journal Oral Oncology (using a high-risk patient
population similar to that served by the VA) demonstrated a reduction
of false positives by 55 percent--suggesting the potential of reducing
unnecessary biopsies by half.
We have been told by senior VA dental officers, ``My dentists don't
have time to do a ViziLite exam,'' and ``We don't have the budget to
purchase it.'' The exam takes only 5 minutes, so that should not be an
issue. The cost savings of early detection vs. late detection have
already been explained.
Innovative technologies like ViziLite Plus are sometimes resisted
by professionals who are set in their ways. VA leaders need to break
through such resistance and bring this important and economical
technology to our Veterans. Allow me to emphasize: The decision to
implement ViziLite Plus exams should not be left to individual VA
hospitals; it should be directed by VA's headquarters here in
Washington.
Without ViziLite Plus screening, cancers could grow, metastasize
and wind up costing the VA extraordinary amounts of money, and could
subject Veterans to gross physical distress, for no good reason.
This Committee should urge the Secretary of Veterans Affairs to
immediately implement annual ViziLite Plus oral cancer screening of all
Veterans who are seen at VA facilities nationwide. This is the best way
to assure the consistent delivery of quality life-saving care to our
Veterans.
In accepting the nomination to be Secretary of Veterans Affairs,
General Eric Shinseki said, ``I can think of no higher responsibility
than ensuring that the men and women who have served our Nation in
uniform are treated with the care and respect that they have earned.''
Mr. Chairman, our Veterans deserve state-of-the-art innovative
technologies like ViziLite Plus.
On behalf of all the employees of Zila, Inc., I thank you and the
Committee for your concern about this important matter, and I urge you
to exercise continuing close oversight of this issue going forward.
Thank you.
Prepared Statement of David Sidransky, M.D., Director, Head and Neck
Cancer Research Division, Johns Hopkins University School of Medicine,
and Professor of Oncology, Otolaryngology-Head and Neck Surgery,
Cellular and Molecular Medicine, Urology, Genetics, and Pathology,
Johns Hopkins University and Hospital, Baltimore, MD
Mr. Chairman and Members of the Committee, I am Dr. David
Sidransky, M.D.:
Oral cancer (squamous cell carcinoma of the head and neck, SCCHN)
remains a significant cause of morbidity and mortality among Americans.
While the death rate for many other cancers has improved, the mortality
from advanced head and neck cancer has not changed in decades. Although
90 percent of patients with SCCHN are often diagnosed over the age of
40, the diagnosis of SCCHN is often delayed at all ages and the even
with the best treatment, death in advanced cases of oral cancer does
not spare any age group. Specific risk factors have been linked to the
development of this cancer, including the use of tobacco products and
excessive alcohol intake. However, about 25 percent of those diagnosed
do not share any of these behaviors. A portion of these cancers are
also associated with a virus, called the human papilloma virus or HPV.
These cancers often strike the young in our society and their treatment
leads to severe deformity, impairment of swallowing and drinking, and
death. There is little hope of this society abandoning the major
behavioral risks, specifically smoking or drinking. Moreover, HPV
infection will not be controlled for decades even with the advent of
new vaccines. Thus, oral cancer will continue to cause significant
morbidity and mortality in our population.
Most cancers, including SCCHN develop over a long period of time
and arise from early precursor lesions. Most cancers in the oral cavity
are not found at this precursor stage and are already invasive at the
time of diagnosis. Clinical outcomes in advanced cancers depend on the
histological type of cancer, the size of the tumor at presentation,
spread to local draining lymph nodes and how aggressively the tumor is
attacking the body and spreading throughout other organs as metastases.
When cancers are small and have not spread the chances of cure are much
higher. Thus, morbidity and mortality can be impacted by effective
identification of cancer at early enough stages to be more easily
cured, or at least halted, and by use of effective therapeutic
modalities to remove or kill the cancer cells. Today, these
interventional options depend on surgery to remove as much of a tumor
as possible, and then radiation therapy or chemotherapy to attempt to
prevent the smaller tumor foci from seeding distant locations and
enabling metastatic disease. These latter approaches are fairly
burdensome interventions, which are most effective before cancer cells
spread to multiple, more distant sites in the body.
Doctors have now known for decades that early detection is the best
chance to impact the death rate from this disease (50-60 percent over 5
years). A cancer that is caught early enough is often curable. The
problem is that patients with oral cancer do not present to their
health care professional with readily visible signs or symptoms of
their cancer until the disease has advanced to a late stage. Thus,
clinicians strive to identify and treat individuals with SCCHN as early
as possible. This puts a premium on identification tools that can be
easily integrated into clinical practice, that are relatively non-
invasive and also inexpensive, so they can be applied to large
populations. Perhaps most importantly, early detection tools must have
adequate sensitivity to find a meaningful number of such individuals
while having sufficient specificity to not falsely identify individuals
without disease as being positive for cancer.
In a meta-analysis of six worldwide studies it was reported that
the weighted sensitivity of visual examination in identifying oral
cancer and precancerous lesions was 79.6 percent. Visual examination by
untrained examiners often misses the earliest more curable lesions.
These results demonstrate that disease remained undiagnosed by
conventional examination. By contrast, published studies reporting
sensitivity values for ViziLite are consistent. To date, the
sensitivity of ViziLite examination in identifying dysplasia and cancer
is reported as 100 percent.
According to published literature, pharmaceutical-grade toluidine
blue, such as that included in the ViziLite Plus test kit,
preferentially stains lesions consistent with severe dysplasia,
carcinoma in situ and cancer. In one study we find that a TBlue
application correlated to a reduction in False Positives by 55 percent.
As such, ViziLite Plus has adequate sensitivity to find a meaningful
number of individuals with disease while having sufficient specificity
to not falsely identify individuals without disease as being positive
for cancer.
It is within this framework--early identification in high-risk
populations; use of accessible, inexpensive yet effective diagnostics;
demonstrated clinically relevant diagnostic sensitivity and acceptable
specificity--that the ViziLite Plus by Zila finds its niche. No other
medical device has sufficient sensitivity and specificity to meet the
requirement of early detection in oral cancer. Other dyes and device
can not precisely identify precancerous lesions and early invasive
cancers while excluding healthy patients that need no further
intervention. Indeed, the ease of use of the ViziLite product makes it
appropriate for use by dentists, periodontists, oral surgeons,
otolaryngologists, and primary-care physicians.
Considering the demographics of the U.S. military, past and
present, one can see that risk factors such as alcohol consumption,
cigarette smoking and advancing age imply that military members and
veterans of military service are at elevated risk of developing SCCHN
whether they are young or old. Clearly, having a product that can be
used to screen for oral cancer by any number of physician or dental
specialists as well as generalists, makes this a valuable and necessary
tool in the early diagnosis of oral cancer among military Veterans.
The FDA has cleared this combination device with an indication for
use to assist in the evaluation of oral mucosal lesions for patients at
increased risk for oral cancer. This is the intended use of the
product, which has been studied in clinical trials in the United States
and abroad and data reviewed by FDA. Interestingly, research and
clinical studies by oral surgeons and dental research scientists has
shown that this product is capable of much more. While it is not proper
for any FDA-regulated company to make references to claims for which
the product is not cleared, it is interesting to note the publications
regarding the tolonium chloride component of ViziLite Plus.
There is a great deal published in the literature which suggests
that the identification of oral premalignant lesions by this product,
in conjunction with use of ViziLite, may identify lesions that are a
greater risk to the patient, perhaps by virtue of identifying specific
changes in the DNA of the tumor cells that indicate a more aggressive
cancer. The tolonium chloride dye has demonstrated relatively high
values for sensitivity and specificity. Thus, arrays of intriguing
molecular studies have shown that the lesions that tolonium chloride
(TBlue) detects are those that will become or are already aggressive
cancers.
Probably at least partially because of the strength of the
literature in support of tolonium chloride (TBlue) and the use of
chemiluminescence (ViziLite), the ViziLite Plus system was selected to
assist in the identification of precancerous lesions in a National
Institutes of Health-funded, Phase II study of Cetuximab
(Erbitux', ImClone Systems Inc.) in upper aerodigestive
precancer. Its inclusion is to identify those patients meeting the
eligibility requirements of molecular changes consistent with oral
lesion likely to progress to cancer. Because of unique characteristics,
ViziLite use in this trial also allows the physician to clearly mark
the boundaries of the lesion to determine the efficacy of the tested
drug.
In conclusion, ViziLite Plus is an easy to use, sensitive and
specific medical device to help both relatively untrained and expert
examiners to identify oral lesions in their patients, who by virtue of
their lifestyle choices regarding tobacco smoking and alcohol use, are
in a high risk group for oral cancer. Additionally, in an aging patient
population similarly at high risk of developing this cancer, use of
this product can bring diagnostic power to physicians outside the
dental specialties for greater value and potentially more savings in
hospitalization. It is anticipated that inclusion into oral cancer
screening protocols within the VA clinics would help to improve
screening efficacy for lesions suspicious for precancer and cancer, and
ultimately reduce the morbidity and mortality of this disease.
Prepared Statement of Robert A. Beckman, President and Chief Executive
Officer, Brainport Technologies, Wicab, Inc., Middleton, WI
Purpose of this Testimony
The BrainPort vision device and the BrainPort balance device
represent novel technologies with the potential to address certain
needs of soldiers who have suffered vision loss due to eye trauma or
balance disorders related to traumatic brain injuries, as well as those
veterans who experience chronic balance disorders after a stroke. Both
devices are available today for further clinical testing. VA
participation and sponsorship of such studies would accelerate the
introduction of these devices into standard rehabilitation practices.
Background on Sensory Substitution
Sensory substitution is based on the premise that the input sensors
for the human senses can be augmented or substituted by alternate
sensors. Cochlear implants are an early example of sensory
substitution. Miniature electrical components attached to an external
microphone are implanted in people who are totally deaf. With training,
people learn to interpret the electrical impulses as sound, which
enables them to hear. Wicab, Inc., founded by the late Dr. Paul Bach-y-
Rita, is developing sensory substitution technology for patients with
chronic balance disorders and people who are blind or vision impaired.
Unlike cochlear implants, BrainPort devices are not implantable.
Instead, the electrical signals are effectively transmitted from the
sensor to the brain through the tongue. The tongue is a uniquely
qualified target for electrical impulses because of 1) the density and
sensitivity of nerve fibers 2) the suitability of the tongue's chemical
environment to receive and maintain contact and 3) the rapid transfer
of information from the tongue to the brain.
For people with balance disorders, the BrainPort balance device
uses an accelerometer to provide accurate head position information.
For people who are blind or vision impaired, the BrainPort vision
device uses a digital camera to provide visual images. In both cases,
the sensory information is provided via a substitute channel, an
electrical impulse on the surface of the tongue.
BRAINPORT VISION DEVICE
Description of Vision Device Technology
The BrainPort vision device provides information to blind
individuals via a neuro-stimulating array placed on the tongue. This
unique device provides immediate benefits to its blind users in areas
of safety, mobility, and recreation and opens a new world of sensory
experience and exploration.
The BrainPort vision device operates by acquiring an image stream
from a camera, similar to a camcorder. Like a camcorder, the moving
images are sent to a display, which, in this case, is the electrode
array on the tongue. The image stream is displayed on the tongue by
converting light information to electrical stimulation, which feels
like microscopic bubbles to the user. With minimal training, users
learn to interpret the images on their tongue as information about the
scene in front of them.
The BrainPort vision device includes an imaging system capable of
working both indoors and outdoors, with a field of view spanning 3-75
degrees (magnified versus wide angle views). The tongue array contains
400 electrodes and is connected to the controller via a flexible cable.
The control system is approximately the size of a PDA and runs for
about 3 hours per charge, with swappable batteries.
An artist's concept of the tongue array (or Intra-Oral Device, IOD)
and camera mounting is shown below alongside the device. The IOD is
attached to a flexible boom by a thin wire. The camera unit is mounted
on a pair of eyeglasses frames. The user controls and the power supply
are connected to a belt-worn, pager-style, controller.
[GRAPHIC] [TIFF OMITTED] T9916A.001
[GRAPHIC] [TIFF OMITTED] T9916A.002
Who would benefit from the BrainPort Vision Device?
According to the American Federation for the Blind, there are 1.3
million people in the U.S. who are legally blind, of which 20 percent,
or 260,000 have no better than light perception. Considering the
current resolution of the tongue display, the BrainPort vision device
is most applicable to this subset of people who are blind, with no
better than light perception. The BrainPort vision device is not
intended as a replacement for the guide dog or the cane. However, blind
users can use the BrainPort vision device independently--at home, at
work, and in public spaces indoors and out as a tool for improved
safety, mobility and object recognition. Secondary benefits include
applying the technology toward specific hobbies and recreational
situations. These benefits enable greater independence at home, school
and in business, greatly improving quality of life.
The following list of product benefits was compiled from survey
responses gathered from blind individuals who have used and know the
capabilities of BrainPort technology.
Safety
Navigating difficult environments, such as parking lots, traffic
circles, complex intersections
Recognizing quiet moving objects like hybrid cars or bicycles
Crossing the street and staying within the lines of a crosswalk
Avoiding unexpected overhead obstacles like tree branches, low
signs, doorways, and holiday decorations
Mobility
Finding doorways, hall intersections, lobby or restaurant in an
office or hotel
Finding continuous sidewalks, sidewalk intersections and curbs
Finding and navigating to buildings in school or business campus
environment
Avoiding obstacles on sidewalks and in hallways
Finding stairwells and recognizing if they go up or down
Object Recognition
Spot reading signs, mail, book titles, etc
Locating people
Locating known objects such as shoes, cane, coffee mug, keys
Discriminating between empty and occupied chairs on a bus or in a
conference room
Finding the trash can, the restroom, kitchen
Orienting oneself in a new environment, finding where objects are
within a room
Recognizing graphics: web pages, mathematical graphs, photos
Signing documents such as checks and legal documents
Recreation
Playing off-the-shelf board and card games
Walking in the woods
Finding a wayward basketball
Running a road race
Cross-country skiing
Rock climbing
Computer games
Current Status of Vision Device Product Development
The development of the BrainPort vision device to its current state
has been enabled by funding provided from the National Eye Institute
and DARPA. The technology has evolved dramatically as a result of this
funding and accomplishments by our engineering and neuroscience teams.
Four years ago, the vision device required a desktop computer, employed
a camera that had no zoom capability, a limited field of view and was
only functional indoors. Today the device for the first time is small,
versatile and user-friendly enough to enable blind users to explore the
capabilities of the device both indoors and outdoors, without active
supervision.
Although the BrainPort vision device is not yet commercially
available, Wicab plans to file for FDA clearance shortly. Nevertheless,
the BrainPort vision device is nowhere near optimized. The current
resolution on the tongue is limited by the density of the electrical
tactors on the tongue array. The current density is 20 times 20 pixels,
effectively 20 DPI resolution. Wicab projects users would experience
increased perception by increasing the resolution, up to a limit of
approximately 150 DPI. With technology adapted from high definition
television displays, this improved resolution is feasible today, but
would cost approximately $1 million to implement. Wireless technology
could eliminate the current requirement for cables running from the
control unit to the user's mouth--another advance that is feasible
today, but expensive to implement.
Beyond the physical aspects of BrainPort device design, there are
more effective methods for information transfer (luminance or
otherwise) through the tongue. These techniques include: Advanced Image
Processing (pattern recognition, image stabilization, optical flow,
etc); Context aware computing--adaptive algorithms to automatically
adjust for visual task, reading a book versus walking down the street,
for example; Proactive guidance--providing attentive signaling to
important items in a scene (a `do not walk' sign is flashing); Directed
guidance--to allow a blind user to query about items in a scene--`are
my shoes in this room' (and highlight everything in the scene that
looks like a shoe); and Information Stream Synergy--Integration of
image data with external data, to overlay or interleave data from
multiple sensors or data sources (the Internet, for example), with the
image data.
BrainPort Vision Device Preliminary Clinical Results
Over the past 2 years, Wicab has developed clinical tests to
understand the capabilities of blind individuals while using the
BrainPort device, and to develop product features based upon user
performance and requests. Two years ago, the BrainPort vision device
consisted of a 100-pixel tongue display and a narrow fixed field of
view webcam. During testing, we noticed that subjects moved closer or
farther away from an object for recognition. Based on this observation
and suggestions from users, we incorporated user controlled zoom
magnification. With this feature, users could magnify small
characteristics (like letters on a page) or reduce large objects like
buildings for appropriate recognition. In mobile situations, we noticed
that users made repeated head movements to gather enough information to
avoid obstacles, make turns, judge distance, etc. We found that
expanding the camera's effective field of view enabled more comfortable
use and better judgment of distance. In the last year, we have improved
the resolution of the tongue display, from 100 pixels to 611 pixels.
User feedback and performance confirms that more resolution provides
crisper and clearer information to the user, especially when conveying
curves and diagonal line features. Moreover, it enables object
identification without reducing the field of view due to magnification.
During studies with the 100-pixel tongue display, 10 participants
accurately reported the orientation of a 10-inch line presented on a
wall 2 feet in front of them, approximately 80 percent of the time.
Participants also accurately sorted cards with squares and circles of
varying sizes into their respective categories, again >80 percent
correct performance. From a distance of 5 feet and utilizing the
BrainPort zoom magnification features, participants could report the
orientation of the `gap' in a rotating letter C, a controlled visual
acuity test with a mean ``acuity'' of 20/135. To test orientation and
mobility with the device, participants were placed in a large room, 15-
20 feet away from a wall that displayed a variety of shapes.
Participants could accurately identify shapes from a distance, using
zoom, as well as navigate to the targeted shape (85 percent and 95
percent success rates, respectively). These high success rates
demonstrate that with as little as 100 points of information, the
BrainPort device enabled both identification of key features and the
formation of a spatial reference for that information.
The next experiments represent more recent work with five subjects
and a higher resolution tongue display of 611-pixel, identifying moving
balls. One hundred four-alternative forced choice (4AFC) trials were
presented on a LCD computer display. In each trial, a filled in circle/
ball of three different sizes (small, medium and large) traveled in one
of four directions (up, down, left, right). The subjects were to
indicate with a button press on a numeric keypad which direction they
perceived the motion of the circle or ball. As the graph below
illustrates, all subject performed with greater than 90 percent
accuracy within 3-4 seconds of trial presentation. This indicates that
in the absence of other sensory input, participants using the BrainPort
are quite sensitive to motion.
[GRAPHIC] [TIFF OMITTED] T9916A.003
Another computerized experiment focused on object recognition,
specifically letter matching. Fifty two-alternative forced choice
(2AFC) letter stimuli were presented to all participants with a high
resolution LCD video display system. Participants were instructed to
respond, as quickly and accurately as possible, which of two letters
matched the target item above the pair. Difficulty was manipulated by
making the incorrect foil either visually similar to the correct answer
in the hard condition, or dissimilar in the easy condition.
[GRAPHIC] [TIFF OMITTED] T9916A.004
As the graph below illustrates, all subjects responded with greater
than 90 percent accuracy, regardless of difficulty level within 25-35
seconds. Participants responded faster to ``easy'' letter matches than
for the ``difficult'' matching, while maintaining accuracy. With
practice and experience, we expect response times would decrease.
[GRAPHIC] [TIFF OMITTED] T9916A.005
Wicab is also conducting clinical studies of the BrainPort vision
device at the Atlanta VA under the direction of Dr. Michael Williams.
According to a recent preliminary report, Dr. Williams concluded
``Bottom line, the device performs remarkably well for the tasks we
looked at in Phase I, and substantially enhances subjects' ability to
accurately identify a variety of shapes at varying distances, this is
statistically significant at the .001 level, and not a random or chance
finding.''
Recommendations
The BrainPort vision device is now available for the next phase of
clinical testing. One of the populations that may benefit from
participating in these studies are soldiers who are blind, including
those soldiers that lost their vision due to a traumatic injury. Wicab
is very interested in obtaining further user feedback regarding the
overall usefulness of the device in performing everyday tasks.
BRAINPORT BALANCE DEVICE
The BrainPort balance device provides change in head position
information to the brain through electrical impulses directed to the
tongue. The device consists of: (1) an intraoral device, which contains
an accelerometer for sensing head tilt and an electrode array for
transmitting the signal to the tongue; and (2) a control unit, which
contains the micro controller, signal processors, memory, battery, user
controls and associated driver electronics. The signal on the tongue
moves in relation to the patient's head position. Patients are trained
to maintain their balance while standing with their eyes closed by
focusing on keeping the signal in the center of their tongue. As the
patient feels the stimulus move on their tongue, they can adjust their
body to move the stimulation toward the center of the tongue.
Training protocols typically require the patient to use the device
during two 20-minute sessions each day. Within a few days, most
subjects learn to use the signal on their tongue to help maintain their
balance and, more importantly, start to experience retention of the
therapeutic effect, improved balance, after the training session ends.
Preliminary clinical data has demonstrated impressive results in
treating the symptoms in a wide range of subjects with central or
peripheral vestibular balance disorders.
[GRAPHIC] [TIFF OMITTED] T9916A.006
Who would benefit from the BrainPort Balance Device
The prevalence of balance and/or vestibular disorders is
significant:
At least half of the overall U.S. population is affected
by a balance or vestibular disorder sometime during their lives.
Vestibular disorders (or dizziness) affect about 20
percent of the general population. Prevalence increases with age:
approximately \1/4\ to \1/3\ of the elderly complain of some form of
dizziness, and by age 75 this proportion approaches 50 percent.
Approximately 12.5 million Americans over the age of 65
and 6 million under age 65 experience balance or dizziness problems
that significantly interfere with their lives.
Fifty percent of falls suffered by the elderly are
associated with vestibular problems.
The annual cost of medical care for U.S. patients with
balance disorders exceeds $1 billion.
Each year, over 700,000 people suffer a new or recurring
stroke in the U.S.
About 5.7 million U.S. stroke survivors are alive today,
many of them with permanent stroke-related disabilities.
Over 70 percent of military individuals involved in blast
injuries have a resultant balance disorder.
The conventional treatment for individuals with vestibular
dysfunction is vestibular rehabilitation. Vestibular rehabilitation is
effective for many vestibular disorders, however, approximately 30
percent of all vestibular patients do not derive meaningful benefit
from vestibular rehabilitation; instead, they rely solely on
compensatory strategies. Furthermore, most vestibular disorders are not
amenable to surgical treatment. Pharmacological management of these
conditions with vestibular suppressants often retards the recovery
process or is associated with adverse side effects such as drowsiness.
Consequently, many people are left to manage their lives with
inadequate therapeutic intervention. These people represent the target
market for the BrainPort balance device.
Chronic balance disorders can dramatically alter a person's ability
to engage in daily activities, greatly diminishing their quality of
life. Because both vestibular and visual cues for postural control are
compromised, patients with chronic balance disorders are often at
greater risk of falling, and must rely on constant vigilance and
restricted physical activity to avoid instability and falls.
Preliminary patient results indicate the BrainPort balance device
will be useful in treating a broad population of patients that suffer
balance disorders related to vestibular dysfunction. Target etiologies
are both unilateral and bilateral vestibular dysfunction, including
such specific vestibular disorders as ototoxicity, vestibular neuritis,
and perilymphatic fistula, as well as a wide variety of disorders that
affect vestibular function, such as balance deficits due to stroke or
brain injury.
Current Status of Device Development and Regulatory Process
The development of the BrainPort balance device and preliminary
clinical studies have been funded by the National Institute of Deafness
and other Communicative Disorders and private investors. Wicab received
the CE Mark for the balance device in January 2006, and has commenced
limited commercial activities in Europe, Canada, Brazil and Russia.
Wicab expects initial sales will be modest, because most people in
these countries rely on government reimbursement to cover the cost of
medical devices such as the BrainPort balance device.
Wicab is currently conducting a controlled clinical study in an
effort to secure FDA 510(k) clearance. Wicab anticipates study
completion by March 2010.
Medical devices intended for commercialization in the United States
must be designed under established Design Control procedures that meet
the FDA Quality System Regulations. Wicab quality system includes
design controls, supplier controls, manufacturing and post-market
surveillance in accordance with FDA's QSR and the European standard ISO
13485. The BrainPort balance device also complies with national
standards such as Underwriters Laboratory and the EU Medical Device
Directive.
BrainPort Balance Device Preliminary Clinical Results
Peripheral and Central Vestibular Dysfunction Study
Wicab studied the benefits of training with the BrainPort balance
device in 112 subjects with vestibular dysfunction at 17 clinical
sites. Etiologies of the subjects include peripheral vestibular
dysfunction (bilateral vestibular dysfunction, unilateral vestibular
dysfunction, post acoustic neuroma resection), central vestibular
dysfunction (stroke, brain injury and age related changes), and mixed
etiologies. These prospective studies designed to measure short-term
and long-term balance-related changes that resulted from training with
the BrainPort balance device. The BrainPort device training procedure
was consistent across all sites.
Subjects received clinical training for 3-5 consecutive days (2 1-
hour sessions each day) with the BrainPort balance device. Subjects
then continued training at home for two 20-minute sessions each day for
the duration of the study and were assessed at the end of the at-home
period. Subjects did not use the BrainPort device during the
assessments.
Changes in balance were measured using clinically accepted
standardized outcome measures including Computerized Dynamic
Posturography Sensory Organization Test, Dynamic Gait Index,
Activities-specific Balance Confidence Scale and the Dizziness Handicap
Inventory.
Subjects showed statistically significant improvement in all
measures. Almost all of the study subjects had received prior
conventional rehabilitation and had reached a plateau. This improvement
is in addition to that reached by traditional rehabilitation.
Atlanta VA Pilot Traumatic Brain Injury Study Summary
Patients with traumatic brain injury (TBI) frequently have problems
with balance and walking due to problems of integration of sensory
inputs. Under sponsorship from Wicab, the Atlanta VAMC Rehab R&D Center
is conducting a study to investigate the effects of the BrainPort
balance device with patients with a traumatic brain injury and balance
deficits.
Standard physical therapy tests of balance and walking, including
Computerized Posturography testing, and Dynamic Gait Index are used to
measure of fall risk. After completing the testing, subject are trained
to use the device while trying to maintain balance while standing with
eyes closed and feet in a challenging position (such as together or
heel-to-toe) and on altered surfaces, such as a foam cushion. Training
occurs over 5 days. Subjects then take the device home to use twice
daily for 20 minutes. Subjects return to the Atlanta VAMC for follow up
testing to see if balance and walking improve after a 12-week period of
home training.
This project is still in the very early stages. Measures of balance
confidence, computerized posturography and fall risk improved in the
three subjects trained thus far. These data, while preliminary,
suggests a positive effect of the BrainPort balance device on balance
in individuals with TBI.
Traumatic Brain Injury Case Study
One of the patients participating in a study with the device is a
39-year-old male who sustained a severe traumatic brain injury due to a
motor vehicle accident in 1993. Following his accident, he completed
the full range of conventional rehabilitation including inpatient and
outpatient physical therapy, occupational therapy and speech therapy.
His balance and walking improved to where he could walk using a walker,
but required supervision to navigate outside of his home and
occasionally fell when walking or trying to do an activity. His
cognitive function improved to the point where he was able to live
independently and work part-time, but he felt like his head was never
quite clear. He continued to have difficulty with balance, walking, and
daily activities due to ataxia and impaired motor control on his right
side, caused by damage to the left midbrain and cerebellum. After
extensive rehabilitation, he had reached a plateau in his recovery. In
2006, 13 years after his injury, he began using the BrainPort balance
device.
He has been training with the BrainPort balance device consistently
for the past 2\1/2\ years. After the initial week of clinic training
sessions, the majority of his training is completed in his home. He
returns to the clinic for modifications to his training approximately
every 3 months. He has demonstrated ongoing improvements in his balance
since enrolling in the BrainPort study. His score on a standardized
balance confidence scale improved from 74 percent confidence to 94
percent confidence at 1 year, where it remains. Though he continues to
use his walker, he demonstrates a much more upright posture with
decreased dependence on the walker. He no longer falls and does not
require supervision to walk in the community. He is transitioning to
walking with a quad cane, which is much less cumbersome for daily use.
He is able to walk longer distances both with and without his assistive
devices. When he has a loss of balance, he is able to regain his
equilibrium independently. He reports that he is more confident in his
balance, and his activities do not require as much effort, which
results in an increase in his energy level. The patient, his mother and
his doctor attribute the improvements in his posture, standing balance,
ataxia, and gait over the last 2\1/2\ years to training with the
BrainPort balance device.
Stroke Pilot Study Summary
A pilot study with 26 patients who have a balance problem due to
stroke was conducted at 5 clinical sites. Participants learned to use
the BrainPort device over a 5 day (10 hours total) clinic training
period. Following clinic training, each participant continued their
training in their home, independently for 8 weeks. Participants were
assessed at baseline and at 8 weeks to compare their balance and
mobility before and after training.
Training with the BrainPort device for 8 weeks, seven of which were
at home, yielded statistically significant (p values less than .05)
improvements on the Dynamic Gait Index (DGI), Berg Balance Scale (BBS)
and the Timed Up and Go Test (TUG), three valid objective measures used
to assess balance and ambulation. With the BBS, this statistically
significant change was over two times the minimal criteria established
for clinically significant improvement. For the TUG, the degree of
improvement also exceeded the minimal difference for clinical
significance.
Consistent with these objective findings, participants showed
statistically significant improvement on the Activities-Specific
Balance Confidence Scale, a self-report measure. This improvement was
over two times the minimal criteria established for clinically
significant improvement. Similarly, on the Stroke Impact Scale,
patients demonstrated statistically significant improvement on their
ratings of mobility, activities of daily living, social participation
and overall rating of stroke recovery. Importantly, no statistically
significant changes were obtained with measures of memory,
communication and emotions, all subjective measures that were not
anticipated to be affected by BrainPort training.
Taken together, these data provide both objective and participant
endorsement of the BrainPort device in the treatment of balance,
mobility and function among individuals with stroke.
Early studies with the BrainPort balance device demonstrate the
potential for helping patients with stroke and traumatic brain injury
improve their balance and motor control. Ultimately, the device could
become a key component of a comprehensive rehabilitation program.
Recommendations
The medical community requires rigorously planned controlled
clinical data prior to adopting new technologies such as the BrainPort
balance device. Wicab is sponsoring such a study in patients with
peripheral vestibular dysfunction. Based on the early promising results
in traumatic brain injury, we would welcome the opportunity to work
with soldiers who have a balance disorder related to a blast injury to
incorporate BrainPort balance training as a part of their
rehabilitation regimen. VA leadership is appropriate, given the
relatively small patient population with traumatic brain injuries,
which hinders funding by commercial entities. Finally, the preliminary
results in stroke warrant the initiation of a controlled clinical study
in that target patient population, and Wicab would similarly welcome VA
participation in this patient study.
Prepared Statement of David A. Broecker, President and
Chief Executive Officer, Alkermes, Inc., Cambridge, MA
Mr. Chairman, Ranking Member Buyer and Members of the Committee,
thank you for inviting me to testify here today on behalf of Alkermes.
Overview
Alkermes is pleased to have the opportunity to submit testimony on
innovative technologies and treatments for veterans. Given the personal
sacrifice that our brave service men and women have made, we believe
that it is important to give them access to the best medicines and
treatments currently available to help them get the care they need to
live happy, healthy and productive lives. Using innovative drug
delivery technology, Alkermes has developed a unique medicine for the
treatment of alcohol dependence, called VIVITROL'
(naltrexone for extended-release injectable suspension). VIVITROL is a
breakthrough medicine that, when combined with counseling, has the
potential to greatly reduce the human and financial toll associated
with alcohol dependence.
Alkermes
Alkermes is a small biotechnology company located in Cambridge,
Massachusetts. As a company, we are committed to developing medicines
that make a difference in patients' lives. Our products, which use
novel molecules and innovative drug delivery technologies, target the
unmet medical needs of patients suffering from diseases like
schizophrenia, bipolar disorder, addiction and diabetes. We approach
the drug development process with patients as our top priority,
beginning with a thorough understanding of the challenges they face on
a day-to-day basis. Our products are designed with patient needs and
behaviors in mind, with the goal of dramatically improving therapeutic
outcomes.
Substance Use Disorders Among OEF/OIF Veterans
Alcohol dependence is a major problem among military veterans. In
2003, a survey conducted by the Substance Abuse and Mental Health
Services Administration (SAMHSA) estimated the veteran population in
the United States to be 25 million, or roughly 11.5 percent of the
entire non-institutionalized civilian population.\1\ Approximately 7.5
percent, or nearly 1.9 million, of these veterans reported drinking
heavily in the month prior to being surveyed (compared to 6.5 percent
of comparable nonveterans). SAMHSA estimated that approximately 650,000
veterans (2.6 percent) were alcohol dependent. By 2006, the VA's own
data showed that only 175,268 veterans were actually receiving
treatment for their alcohol abuse or alcohol dependence within the VA
system.\2\ In addition to post-traumatic stress disorder (PTSD),
alcohol abuse and alcohol dependence are consistently among the most
prevalent psychological disorders in male veterans of the Vietnam
era.\3\ In female veterans of Vietnam, alcohol abuse and dependence are
second only to depression and generalized anxiety.
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\1\ U.S. Department of Health and Human Services, Substance Abuse
and Mental Health Services Administration, National Survey on Drug Use
and Health, November 10, 2005.
\2\ U.S. Department of Veterans Affairs, Health Services for VA
Substance Use Disorder Patients--Comparison of Utilization in Fiscal
Years 2005, 2004, 2003, and 2002, June 2006.
\3\ U.S. Department of Veterans Affairs, National Center for
Posttraumatic Stress Disorder, Findings from the National Vietnam
Veterans' Readjustment Study, available at http://www.ncptsd.va.gov/
ncmain/ncdocs/fact_shts/fs_nvvrs.html?opm=1&rr=rr45&srt=d&echorr=true.
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Since the start of Operations Enduring Freedom (OEF) and Iraqi
Freedom (OIF), over 1.8 million American military personnel have been
deployed, with nearly a third coming from the National Guard and
Reserves.\4\
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\4\ Legal residence/home address for servicemembers currently
deployed as of December 31, 2008. (2009) Defense manpower data center.
Retrieved April 8, 2009 from: dva.state.wi.us/WebForms/Data_Factsheets/
ResDistribution_Dec08.pdf
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In 2006, the New Jersey Department of Military and Veterans
Affairs, in conjunction with the University of Medicine and Dentistry
of New Jersey and the Bloustein Center for Survey Research at Rutgers
University, surveyed New Jersey National Guard members who had returned
from Iraq within the past year. The results of the study were
striking--37 percent of those surveyed reported problem drinking in the
year following their deployment. Even more troubling, 55.3 percent of
the veterans with PTSD reported problem drinking.\5\
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\5\ Kline, A. & Falca-Dodson, M. (2007) Presentation on substance
abuse and mental health problem in returning Iraqi veterans.
---------------------------------------------------------------------------
In a study published in the Journal of the American Medical
Association, Hoge et al. of the Walter Reed Military Research Institute
administered anonymous surveys and assessed 2,530 U.S. combat duty
personnel before their deployment to Iraq and 3,671 troops three to 4
months after their return from combat duty in Iraq or Afghanistan. Over
35 percent of Marines reported experiencing at least one symptom of
alcohol dependence (drinking more than intended) after deployment, and
over 29 percent reported that they felt they needed to cut down on
their drinking.\6\
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\6\ Hoge, C., Auchterlonie, J. & Milliken, C. (2006). Military
mental health problems: Use of mental health services, and attrition
from military services after returning from deployment to Iraq or
Afghanistan. Journal of the American Medical Association, 295(9), 1023-
1032.
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To put the seriousness of these alcohol problems in perspective,
Hoge et al. found substantially lower rates for depression (7.1
percent), anxiety (6.6 percent) and PTSD (12.2 percent). Only PTSD
showed a comparable rate of increase (pre-deployment to post-
deployment)--an expected finding given that over 90 percent of the
combat duty personnel had been directly involved in gun battle and/or
handling the bodies of fellow service men and women, killed in the line
of duty.\7\
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\7\ Hoge, C.W., Castro, C.A., Messer, S.C., McGurk, D., Cotting,
D.I. & Koffman, R.L. (2004). Combat duty in Iraq and Afghanistan,
Mental Health Problems, and Barriers to Care. New England Journal of
Medicine, 351(1), 13-22.
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The incidence of alcohol dependence symptoms appears to be the most
common problem facing returning combat duty personnel. Alcohol
dependence exacerbates other psychiatric and medical problems and
undermines treatment. Combat duty personnel may be particularly likely
to use alcohol to self-medicate their psychiatric problems, resulting
in worsened overall mental health and alcohol dependence. The strong
reluctance to seek professional help may be a particularly important
factor contributing to the misuse and ultimate dependence on alcohol.
While the incidence of mental health and alcohol problems within a
few months of returning from combat is high, alcohol problems in
particular often take years to manifest. For this reason it is
important to consider research from past military conflicts.
Specifically, the National Vietnam Veterans Adjustment Survey found 40
percent of male veterans reported lifetime alcohol problems post-
deployment. In 2000, the Department of Defense's Alcohol Abuse and
Tobacco Use Reduction Committee reported that, even prior to the start
of the conflict, 21 percent of servicemembers admitted to drinking
heavily, costing the Department of Defense more than $600 million each
year in terms of medical care and lost productivity.\8\
---------------------------------------------------------------------------
\8\ Rhem, K. (2000, June 6) Alcohol abuse costs DoD Dearly.
American Forces Press Service. Retrieved May 7, 2009 from: http://
www.defenselink.mil/news/newsarticle.aspx?id=45284.
---------------------------------------------------------------------------
A February 2007 report by the American Psychological Association on
the mental health needs of returning veterans found a variety of
barriers are preventing military personnel from accessing much needed
mental health and alcohol treatment. The report cited stigma and a lack
of availability of services as the primary reasons why personnel and
their families are not accessing care.\9\ Shortages of trained
uniformed personnel, high burn out rates among providers and
difficulties in referring military personnel to civilian providers
often mean long waits for care. Moreover, in other reports and
testimony before this Committee, providers have reported significant
recent decreases in the availability of inpatient beds for alcohol
dependence treatment. During these high service utilization periods,
medication assisted treatment for alcohol dependence may improve VA
care delivery by integrating primary care and behavioral health care
and providing immediate help upon substance use disorder diagnosis
during high volume periods.
---------------------------------------------------------------------------
\9\ Johnson, S. et al (2007) The psychological needs of U.S.
military servicemembers and their families: a preliminary report.
Retrieved May 7, 2009 from: http://www.apa.org/releases/
MilitaryDeploymentTaskForceReport.pdf.
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Vivitrol
As researchers have gained a deeper understanding of the complex
brain mechanisms that trigger alcohol dependence, medications are
increasingly considered to be important treatment options for this
disease. In 2005, the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) issued guidelines, recommending the combination of
medications and psychosocial support as part of an integrated treatment
program.\10\
---------------------------------------------------------------------------
\10\ U.S. Department of Health and Human Services, National
Institutes of Health, Helping Patients Who Drink too Much: A
Clinician's Guide, 2005.
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One of the products currently approved by the U.S. Food and Drug
Administration (FDA) for the treatment of alcoholism is VIVITROL, an
extended-release naltrexone product developed and manufactured by
Alkermes. Naltrexone is a non-addictive, non-aversive agent that binds
to opioid receptors in the brain. In people with alcohol dependence, it
is believed that this blockade diminishes craving for alcohol and leads
to a greater ability to resist urges to drink excessively.\11\
Eliminating the urge to drink allows patients the stability they need
to focus on the psychosocial therapy component of their recovery.\12\
---------------------------------------------------------------------------
\11\ Oswald LK, Wand GS. Opioids and Alcoholism. Physiology &
Behavior 2004; 81: 339-358.
\12\ Vivitrol [prescribing information]. Cambridge, MA: Alkermes,
Inc; 2007.
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Approved by the FDA in April 2006, VIVITROL is the first and only
once-monthly injectable medication for the treatment for alcohol
dependence. It is intended for patients who are able to abstain from
drinking in an outpatient setting in the week prior to initiation of
treatment with VIVITROL; patients using VIVITROL in combination with
psychosocial support have demonstrated significantly increased
abstinence and decreased both drinking and heavy drinking days beyond
what was achieved with counseling and placebo alone.\13\
---------------------------------------------------------------------------
\13\ Garbutt JC, Kranzler H, O'Malley S, Gastfriend D, Pettinati H,
Silverman BL, et. al. Efficacy and Tolerability of Long-Acting
Injectable Naltrexone for Alcohol Dependence: A Randomized Controlled
Trial. Journal of the American Medical Association; 2005; 293:1617-
1625.
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In a 2005 study in the Journal of the American Medical Association,
authors reported on the results of a 6-month phase III clinical trial
on extended-release naltrexone. When extended-release naltrexone was
added to counseling alone, the average patient experienced a 48-percent
reduction in heavy drinking days compared to counseling plus placebo
alone.\14\ For those who had abstained from alcohol in the week prior
to receiving their first dose of medication, there was a 90 percent or
better reduction in heavy drinking, a two to three times greater
likelihood of maintaining continuous abstinence and a 90-percent
reduction in drinking days compared to the counseling plus placebo
group over the 6-month period. VIVITROL is the only pharmacologic
treatment for alcohol dependence that extends a medication's release
over 30 days, which assures that measurable blood plasma concentrations
are present in the patient's bloodstream every day during the expected
treatment period.
---------------------------------------------------------------------------
\14\ Garbutt, J. et al (2005). Efficacy and tolerability of long-
acting injectable naltrexone for alcohol dependence: a randomized
controlled trial. Journal of the American Medical Association; 293:
1617-1625.
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In fact, studies show that VIVITROL, when combined with
psychosocial therapy, triples the duration of initial abstinence and
nearly triples the proportion of patients who maintain total abstinence
over 6 months.\15\ Even at times when alcoholics are most at risk for
drinking--for example, the ten deadliest U.S. national holidays due to
drunk driving--this once-monthly medication has been found to reduce
the median level of drinking to virtually zero.16,17
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\15\ O'Malley SS, Garbutt JC, Gastfriend DR, Dong Q, Kranzler H.R.
Efficacy of extended-release naltrexone in alcohol-dependent patients
who are abstinent before treatment. J Clin Psychopharmacol 2007
Oct;27(5):507-12.
\16\ Lapham S, Forman R, Alexander M, Illeperuma A, Bohn MJ. The
effects of extended-release naltrexone on holiday drinking in alcohol-
dependent patients. J Subst Abuse Treat 2009 Jan;36(1):1-6.
\17\ Rosenbloom DL. Holidays, triggers, and willpower--is there a
role for medications? A commentary on ``The effects of extended-release
naltrexone on holiday drinking in alcohol-dependent patients''. J Subst
Abuse Treat 2009 Jan;36(1):7.
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While there are other pharmacologic treatments for alcohol
dependence, a SAMHSA study found that the vast majority of patients
with this disease have difficulty adhering to an alcohol
pharmacotherapy that requires them to take a pill every
day.18,19 Anticipating this challenge, the National
Institute on Drug Abuse (NIDA) issued two reports in 1976 and 1981
calling for the development of sustained-release
preparations.20,21 The VIVITROL clinical development program
was funded in part with a Small Business Innovation Research Program
grant from NIAAA. The proprietary Medisorb' drug delivery
technology in VIVITROL allows the medication to be gradually released
into the body at a controlled rate, delivering the naltrexone
throughout the bloodstream and to the brain for 30 days after each
injection. It provides patients the convenience of monthly dosing,
which alleviates the difficulty of adhering to a daily medication
regimen.
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\18\ Other pharmacologic interventions to treat alcohol dependence
include: oral naltrexone, acamprosate, and disulfuram.
\19\ Harris KM, DeVries A, Dimidjian K (2004). Trends in naltrexone
use among members of a large private health plan. Psychiatric Services.
http://ps.psychiatryonline.org. 55(3):221.
\20\ Willette R, Barnett G, editors (1976). Narcotic Antagonists:
The Search for Long-Acting Preparations. NIDA Res Monogr DHEW
Publication No. (ADM) 76-296. http://www.drugabuse.gov/pdf/monographs/
04.pdf.
\21\ Willette R, Barnett G, editors (1981). Narcotic antagonists:
naltrexone pharmacochemistry and sustained-release preparations. NIDA
Res Monogr 28:1-273. http://www.drugabuse.gov/pdf/monographs/28.pdf.
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Veterans Access to Vivitrol
While Alkermes is pleased that many top tier addiction treatment
centers have now adopted Vivitrol on their formularies as a first-line
treatment for patients with alcohol dependence, the Committee should be
aware that our Nation's veterans do not have the same access to the
latest alcohol pharmacotherapies.\22\
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\22\ Alcoholism and Drug Abuse Weekly; 2007; 19(23).
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The VA conducted a clinical review of VIVITROL from January 2007
through February 2008 and declined to grant the product formulary
status. Although VA providers may prescribe non-formulary products for
their patients, significant barriers may prevent VA patients from
receiving treatment with VIVITROL. A longstanding VA directive limits
the interaction that companies can have with VA physicians to discuss
non-formulary products. This type of restriction may limit provider
education and hamper patient access to novel therapies. Although some
providers within the VA have fought for access to VIVITROL and have
prescribed it for their patients with great success, the usage rate for
VIVITROL within the VA is effectively zero.
To the credit of the VA, the agency published policy guidance,
Uniform Mental Health Services in VA Medical Centers and Clinics, in
June 2008. This document promotes the use of medication assisted
treatment for alcohol dependent individuals; however, to date, few
veterans have been able to obtain access to VIVITROL. While there are
approximately 650,000 veterans who meet the criteria for alcohol
dependence, only about one quarter of those individuals actually
receive SUD treatment within the VA system.\23\ In 2008, our estimates
suggest that fewer than 125 patients in the entire VA system (less than
0.07 percent) have received VIVITROL.
---------------------------------------------------------------------------
\23\ U.S. Department of Veterans Affairs, supra note 2.
---------------------------------------------------------------------------
In March 2008, the VA testified before this Committee that the VA/
DoD Clinical Practice Guidelines for Substance Use Disorders would be
published within 6 months.\24\ These guidelines are a necessary element
of educating providers about SUD treatment, which is key to broadening
patient access and eliminating the stigma associated with this
devastating disease. The guidelines were last updated in 2001 and,
since their initial release, new medications for the treatment of
alcohol dependence have been approved by the FDA. Nevertheless, in the
absence of updated guidelines, our veterans appear to have enormous
difficulty accessing these newer agents.25,26
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\24\ John Paul Allen, Ph.D., Associate Chief Consultant for
Addictive Disorders, Veterans Health Administration, U.S. Department of
Veterans Affairs, in testimony before the House Committee on Veterans'
Affairs Subcommittee on Health, March 11, 2008, available at http://
veterans.house.gov/hearings/transcript.aspx?newsid=187.
\25\ CAMPRAL' (acamprosate calcium) Delayed-Release
Tablets were approved by the FDA on July 29, 2004.
\26\ VIVITROL' (naltrexone for extended-release
injectable suspension) was approved by the FDA on April 13, 2006.
---------------------------------------------------------------------------
The VA has outlined a performance measure to assess its success in
continuity of care for veterans in treatment for SUD; however, by the
VA's own admission, ``Many VA SUD programs have found it difficult to
meet the Office of Quality and Performance's Continuity of Care
performance measure. The measure requires that patients entering a new
episode of specialty SUD treatment receive at least two VA substance
abuse clinic visits for each of three successive 30-day periods after
qualifying as a new patient.'' \27\ VIVITROL is a powerful tool that
could improve continuity of care for veterans being treated for SUD and
bring VA closer to meeting this performance measure.
---------------------------------------------------------------------------
\27\ Schaefer J et al. (2007). Program and Patient Factors that
Influence Continuity of Care Performance Measure Outcomes in VA
Substance Use Disorder Treatment Programs, available at http://
www.chce.research.va.gov/docs/pdfs/CoC_Providers_Survey.pdf.
---------------------------------------------------------------------------
Many people outside of the VA have had access to VIVITROL for some
time. Beneficial results have been reported in state public treatment
systems, in many other community-based treatment programs throughout
the U.S., in primary care settings, in DUI and drug courts and in
private commercial insurance patients.28-32 In these
privately insured patients, this medicine was associated with the
greatest reduction in hospitalization and emergency room visits while
simultaneously increasing patients' utilization of counseling--leading
Aetna Behavioral Health to introduce disease management with the
medicine before patients even leave alcohol rehabilitation programs.
Similar cost benefits were reported by a major state-wide Blue Cross
Blue Shield health plan--a 49-percent reduction in hospital and
pharmacy costs after VIVITROL treatment.\33\ Improved outcomes and
reduced costs are significant and attainable, but the VA must make SUD
treatment a priority--both in policy and in funding.
---------------------------------------------------------------------------
\28\ Colston S. Florida Advancing Recovery Project Implementing
Medication Assisted Treatment using Vivitrol: November 2006-October
2008 Preliminary Results. Available from: Florida Substance Abuse
Program Office, [email protected].
\29\ Abraham AJ, Roman PM. Early Adoption and Implementation of
Vivitrol. Addiction Health Services Research Annual Conference, Boston
MA, Oct 21, 2008.
\30\ Un H. Medication Assisted Treatment for Alcohol Use Disorder.
SAMHSA/CSAT Invitational Conference on Economic Access to Treatment,
Washington DC, Nov 3, 2008.
\31\ Lee JD, Grossman E, DiRocco D, Truncalil A, Rotrosen J, Hanley
K, Stevens D, Gourevitch MN. Extended-release Naltrexone Injectable
Suspension for Treatment of Alcohol Dependence in Urban Primary Care--A
Feasibility Study: Preliminary Analysis. Addiction Health Services
Research Annual Conference, Boston MA, Oct 21, 2008.
\32\ Hon J Kandrevas, Hon D Gruenburg. Testimony on Use of
Medication in Selected Michigan DUI Courts to State of Michigan House
Subcommittee on Corrections, March 6, 2008.
\33\ Borawala AS, Gill P, Jan S. Utilization Patters of
Vivitrol' (naltrexone for extended-release injectable
suspension) for Alcohol Dependence. Horizon Blue Cross Blue Shield of
New Jersey, Newark NJ and Rutgers U. Poster presented at Academy of
Managed Care Pharmacy 21st Annual Meeting, April 17, 2009, Orlando FL.
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Real Patients, Real Success
I would like to share with you a story, told to me by a physician,
about the success one patient realized with VIVITROL. The patient's
name is Chris, and he is currently 26 years old. Chris started drinking
when he was in high school, on Friday nights after football games with
his friends and fellow band members. After graduating from high school,
Chris enrolled as a college freshman and soon found himself drinking
more and more. Pretty soon, he started skipping classes and instead
spent all his time drinking with his new friends. Unfortunately, Chris
dropped out of school before the end of his freshman year and moved
back to his father's home in Nashville, Tennessee.
Chris enrolled in a local community college, but his drinking
continued to get out of control. Every day, he would take a cooler of
beer with him to school in the back of his car, drinking between
classes and later showing up to work drunk. During the summers, he
would visit his mother and stepfather in Dallas, Texas, where his
drinking led to arguments and a concern that he might assault his
mother. His anger and drinking led to a total of six arrests for
driving under the influence (DUI)--three in Texas and three in
Tennessee--and one arrest for aggravated assault. Chris would get sober
during his times in jail, and he attempted to get longer-term treatment
through the Salvation Army and numerous half-way houses. Each time he
would ``dust himself off'' and try to stay sober, but, unfortunately,
he relapsed every time. Finally, someone he knew convinced him to try
VIVITROL.
Chris was hesitant at first, but he quickly saw the benefits of the
medicine. He liked being able to see a doctor once a month to receive
his injection, without having to worry about taking his medicine every
day. He was able to get into and stay in counseling. Currently, he is
back in school. He was recently invited to his family reunion for the
first time in 4 years, and he has re-established good relationships
with both his parents. He has a new girlfriend, is holding down a job
and has remained sober for more than a year. Chris says that VIVITROL
really helped him get back on the right track, and now he can't wait to
get up and enjoy each day. The reason this physician's story means so
much to me is because Chris is his son.
Conclusion
Alkermes and its investors took a risk in pursuing a difficult
manufacturing process to produce medicines with innovative delivery
systems in order to treat the unmet needs of patients with devastating
diseases. If the company's work were assuredly profitable, companies
much larger than ours would pursue the same approach. Patients, not
profits, are the driving force behind what we do. Since 1987, Alkermes
has continually focused on one goal--improving the lives of patients by
developing therapies that improve outcomes. What started as a small
research company is now a company that develops and manufactures
treatments for diseases that others in the industry have largely
ignored. The Federal Government, through NIH and NIDA, partnered with
Alkermes in development of VIVITROL many years ago, but the government
must remain an active partner, following through on its commitment to
assist patients with accessible, affordable SUD pharmacotherapy. Our
company is focused on the devastating problem of alcohol dependence
among our veterans, and we believe that the VA must be equally
committed. Meaningful clinical guidelines must be published and
regularly updated to reflect emerging therapies; performance measures
must be developed, communicated and enforced in order to promote
accountability; and the VA must make treatment of addiction among our
Nation's veterans a real priority before we lose even one more veteran
to the disease. In closing, thank you again for the opportunity to
testify here today about the Alkermes story. We believe we offer a
product that can dramatically improve the lives of our Nation's
veterans; they deserve no less than the very best innovative
technologies and treatments available.
Prepared Statement of Mark Munroe, Senior Vice President, Sales
and Marketing, Mobile Medical International Corporation,
St. Johnsbury, VT
Good day. First, I want to thank Chairman Filner and Congressman
Buyer for allowing me to testify here today on behalf of my employer,
Mobile Medical International Corporation, Inc. (MMIC) of St. Johnsbury,
Vermont. My name is Mark Munroe, Senior Vice President of MMIC. My sole
purpose here today is to explain how MMIC is using an innovative
approach to help Veterans Health Administration Medical Centers provide
top-flight surgical care, keep VHA surgeons engaged with their patients
and save significant amounts of time and money associated with the
refurbishment of VHA operating rooms.
Mobile Medical is an international company that develops and
manufactures commercial and military mobile surgical hospitals which
meet U.S. health care standards. These mobile health care solutions are
rapidly deployable, fully integrated, self-contained and present
innovative solutions for today's health care delivery needs. To
illustrate the versatility of this technology in various markets, note
that MMIC has responded to a FEMA request to support the University of
Texas Medical Branch (UTMB) in Galveston Texas after Hurricane IKE;
provides on-site surgery at a maximum security prison in North Carolina
with an MMIC staffed mobile unit; and has delivered eye-care and
surgical care units to Armenia, Saudi Arabia, Oman and Iraq. As a point
of reference, about 6 weeks ago Mobile Medical was featured on the
international television program, Little People, Big World, where Iraqi
dwarf children were shown receiving care on the MMIC mobile surgical
unit in Southern Iraq.
Our flagship product, the Mobile Surgery Unit, can be driven to any
VHA location and upon deployment triples in size to become a mobile
surgical hospital that meets U.S. health care standards. These
standards include those required for State licensure, Medicare
Certification and Joint Commission on the Accreditation of Healthcare
Organizations (JCAHO). MMIC's units meet all three of these standards.
MMIC has provided mobile surgical capability to private, non-profit and
university medical centers for over 12 years from California to
Virginia and beyond. This service has most often been provided on a
rental basis, and contract periods last anywhere from 6 months to
several years. The primary reasons hospitals opt for this mobile
solution are that it eliminates the cost of contracting out surgical
cases to other hospitals and saves additional resources by trimming
months from the duration of the project.
Over the past 18 months MMIC has successfully brought this cost-
saving innovation to VHA medical centers which are undergoing hospital
operating room renovations. Our conservative estimates indicate that
VHA Medical Centers can save on average $12,000 per surgical case by
maintaining control of these cases rather than contracting them out to
local or regional hospitals. This approach also assures VHA management
that VHA surgeons are handling the cases and maintaining their skills.
MMIC has successfully utilized this approach at the VAMC in White
River Junction, Vermont, and has a unit actively working on endoscopic
cases at the VAMC in Martinsburg, WV. MMIC is preparing to provide
several units to cover a major operating room renovation project in
Miami and is currently working on similar opportunities at VHA
facilities in New Orleans, LA, Kansas City, MO, San Diego, CA,
Clarksburg, WV and Fayetteville, NC. Many VHA facility leaders that
have indicated interest in utilizing our units for this purpose have
expressed a desire for a streamlined contractual process administered
by VHA headquarters.
In order to address these expressed concerns, MMIC submitted an
``Unsolicited Proposal'' to the VA's National Acquisition Center in
2008. This submission proposed a pilot project utilizing 5 MSU's over 3
years saving $90 million. Those savings are summarized in the attached
two-page executive summary. This request was ultimately denied. MMIC
estimates that a more robust project utilizing 20 MSUs for currently
scheduled operating room projects could result in total cost avoidance
of nearly $700M over a 5-year period. (See one-pager also attached).
MMIC continues to attempt a dialog with the National Acquisition
Center in order to emphasize the significance of the cost savings this
approach offers, the benefits of keeping patients and staff inside the
VHA system for their surgeries and the difficulties VHA Medical Center
contract officers face as they attempt to fashion appropriate contract
vehicles for this service.
Mobile Medical International Corporation stands ready to provide
the Veterans Health Administration and its patients/clients with cost
effective solutions for complex health care delivery concerns.
Thank you for taking the time to learn about MMIC's innovative work
within the VHA system. It has been a pleasure being here today and an
honor to testify before the Committee. Thank you.
Prepared Statement of Stanley Stern, President,
TeleMed Network, Ross, CA
Chairman Filner, Ranking Member Buyer, and Members of the
Committee, thank you for the opportunity to testify today on behalf of
TeleMed Network. My name is Stanley Stern; I am President of TeleMed
Network.
I want to outline for you today a technology that my company
believes can significantly improve the treatment of behavioral health
problems among veterans by better connecting them to the medical and
community support they deserve.
A recent study by RAND estimated that 18.5 percent of troops
returning from the wars in Iraq and Afghanistan--about 300,000 people--
suffered symptoms of post-traumatic stress disorder.\1\ Other studies
have suggested that similarly large numbers of veterans show signs of
depression, often in conjunction with PTSD.\2\
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\1\ T. Tanielian and L. Jaycox, eds, Invisible Wounds of War:
Psychological and Cognitive Injuries, The Consequences, and Services to
Assist Recovery, 2008.
\2\ D.G. Campbell et al., ``Prevalence of Depression-PTSD
Comorbidity; Implications for Clinical Practice Guidelines and Primary
Care-Based Interventions,'' Journal of General Internal Medicine 22.
no. 6 (2006); N. Breslau et al., ``A Second Look at Comorbidity in
Victims of Trauma: The Postraumatic Disorder-Major Depress
Connection,'' Biological Psychiatry, 48, no. 9 (200), as referenced in
M. Audrey Burnam et al., ``Mental Health Care for Iraq and Afghanistan
War Veterans,'' Health Affairs, 28, no. 3, (2009), p. 773.
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The Departments of Defense and Veterans Affairs, with the
consistent support of this Committee, have dramatically increased
efforts to restore our wounded, regardless of whether they were damaged
in body or mind. Sometimes it has taken bad news to spur a response,
but ultimately, I and most Americans believe, this Country does do the
right thing for our veterans.
Unfortunately, the challenges to treating those warriors who are
now fighting their own private battles against mental health conditions
are complicated by culture, demographics, and geography.
Mental illness encourages isolation and flourishes in it, and the
internal and external forces that drive troubled veterans into
isolation are very strong. This is particularly sad when their illness
is something like PTSD, which may respond better to personal therapy
and interaction with veterans' groups than to drugs.\3\
---------------------------------------------------------------------------
\3\ Institute of Medicine, Crossing the Quality Chasm: A New Health
System for the Twenty-first Century (Washington: National Academies
Press, 2001), as referenced in M. Audrey Burnam et al., ``Mental Health
Care for Iraq and Afghanistan War Veterans,'' Health Affairs, 28, no.
3, (2009), p. 776.
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Nationwide, relatively few Americans, compared with past
generations, have been exposed to military life and its shared
experiences, both good and bad. That's an unfortunate side effect of
America's all-volunteer military. So when soldiers go home after
battle, fewer and fewer people understand what they've been through.
That goes for psychological counselors as much as anybody.
After being steeped in the pride and self-reliant ethos of
America's Services, many veterans are understandably reluctant to admit
their need for help, particularly when the wounds are invisible. They
may even think, albeit incorrectly, that VA hospitals exist mainly for
those graying veterans of past wars, not for otherwise healthy young
men and women.\4\
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\4\ Tanielian and Jaycox, eds., Invisible Wounds of War, referenced
in M. Audrey Burnam et al., ``Mental Health Care for Iraq and
Afghanistan War Veterans,'' Health Affairs, 28, no. 3, (2009), p. 774.
---------------------------------------------------------------------------
The isolation can be even worse for those who served with the
Reserves or National Guard, particularly when they go home to a small
town or a community that's isolated by geography or culture. Qualified
help, where caregivers understand what happens to men and women in war,
may be miles away, compounding the self-protecting urge to stick it
out, go it alone, to be a ``soldier.''
Two years ago, the Department of Defense Task Force on Mental
Health took a broad look at psychological care for veterans and
candidly admitted that ``the Military Health System lacks the fiscal
resources and the fully trained personnel to fulfill its mission to
support psychological health in peacetime or fulfill the enhanced
requirements imposed during times of conflict.'' \5\
---------------------------------------------------------------------------
\5\ Report of the Department of Defense Task Force on Mental
Health, June (2007), Executive Summary, Findings.
---------------------------------------------------------------------------
The Task Force reported that about one-third of the 686,306
veterans discharged between 2002 and 2006 who were eligible sought care
at a VA facility. Of those, more than one-third were diagnosed or
evaluated for mental disorders (17 percent PTSD, 14 percent drug
problems, and 12 percent depression).
Among the specific failures in mental health care were an inability
to overcome the stigma that veterans attach to reaching out for mental
health care, the inaccessibility of qualified service providers,
insufficient collaboration among providers, and other problems having
to do with communication.
Indeed, the crux of many of the problems in dealing with military
mental health problems is communication. So, why not use modern
technology to relink the suffering veteran back into a supportive
community that understands his or her problems and has the proper tools
to solve them?
Simply put, TeleMed's system can provide veterans with a video
teleconferencing capability in their homes, using a simple, scaleable,
and affordable version of the technology common in corporate business.
Our TeleMed Internet Endpoint, what we call ``TIE,'' currently
costs less than $1,000, with the price expected to drop significantly.
It is small, just three pounds, so it is portable and can be mailed.
Yet, it provides a brilliant video conferencing image on a home
television. The TIE and its secure network are mutually optimized for
video. Simply plug it into a TV, connect it to the Internet and an
inexpensive digital camera, and turn it on.
I invite you to imagine how this two-way visual and audio
communication could be used.
First, with just one touch on a wireless keyboard, the veteran sees
and speaks with a VA health care service provider whenever he or she
needs help. The health care worker immediately appears full screen. The
contact could be initiated by the veteran or the VA.
A second button could connect the veteran to an ongoing group
therapy session, say on substance abuse or suicide prevention, perhaps
one operating 24/7 with participants from around the globe. The caller
might choose to participate, or simply observe his peers speaking about
issues he also confronts. Imagine the psychological reassurance of this
always-accessible confirmation that he is not alone. Help is available
without an appointment, without travel, and most without stigma.
In recent months, increased attention has been paid to suicide
among veterans. I have no way of knowing if the rates of suicide have
gone up because of our wars in Afghanistan and Iraq and the increased
deployments associated with them, but I do know that a functioning TIE
Network could be ready when a potentially suicidal patient needs help
most, at the moment of crisis, in the middle of the night.
Such group therapy conversations need not become part of a
permanent medical record, and we know for certain that a major reason
some military people are reluctant to seek help is because they fear a
record of their outreach could damage their careers.
At the same time, the Obama Administration has placed a major
emphasis on systematized electronic medical records as a way to improve
care and drive down health costs. The VA has already taken the lead in
this field, and the TIE Network takes this initiative even further.
Doctors could record sessions with patients for later review and
consultation. Patients could access medical records, receive reminders
on medications, see instructional or inspirational videos. TIE is
secure, encrypted, and data transmission is fully compliant with HIPAA.
The system is ready to interface with VA electronic medical records.
Help, of course, is least accessible for our rural veterans who
often must drive for hours to receive care. But studies have shown that
mental health professionals in general are not distributed evenly
across the county.\6\ TIE offers a chance to link those best qualified
to provide evidence-based quality therapy to those who need it most.
Concurrently, it offers a chance for the government to use cost-
effective treatment and not be tied to caregivers in specific areas.
---------------------------------------------------------------------------
\6\ IOM, ``Increasing Workforce Capacity for Quality Improvement,''
in Improving the Quality of Health Care for Mental and Substance-Use
Conditions, Quality Chasm Services (Washington: National Academies
Press, 2006), and President's New Freedom Commission on Mental health,
``Subcommittee on Rural Issues: Background Paper'' (Rockville, Md.:
U.S. HHS, June 2004), as referenced in M. Audrey Burnam et al.,
``Mental Health Care for Iraq and Afghanistan War Veterans,'' Health
Affairs, 28, no. 3, (2009), p. 775.
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My emphasis here today is on the many ways that the TIE Network can
solve the difficult problems of treating the psychological problems of
veterans, but TIE units are excellent vehicles for many other uses.
They could be used for medical check-ups, evaluations, and counseling,
while eliminating the driving, the waiting, and the mileage expense to
the VA.
TIE is a conduit that connects the VA to its veterans, allowing the
VA to provide its best treatments for PTSD, depression, and other
problems directly to the vet's home. Our technology provides the
quality and simplicity at a cost that allows these advantages to be
scalable, benefiting both rural and urban veterans. We will measure
these improvements with independent research that I am confident will
quantitatively demonstrate improved medical benefits and access, and
lower costs--all within 1 year.
__________
TeleMed Network is led by:
The Executive Team
Stanley Stern-President
Founder of two companies:
Cobalt Communications-video conferencing integration
PRN-largest in-store advertising network
Janette Gitler-COO
Senior Program Director-Gordon and Betty Moore Foundation
Responsible for $300M Environmental Fund
Director of Programming-KRON & KQED (2 largest media in
SF Bay Area)
Dr. Mervyn Silverman-SVP & Medical Director
Director of Health, City of San Francisco
President, American Foundation for Aids Research
Director Consumer Affairs, U.S. FDA
Awarded: Public Health Hero, ``Heroes in Medicine Award,
Award of Courage''
David Wellstone-Director
National spokesperson on health care & mental health
The Technical Team
Ed Yoon-CTO
Chief Technology Officer-Gordon & Betty Moore Foundation
(Intel)
Senior Technology Evangelist for Microsoft
Developed/installed communication systems for Congress,
FBI, CIA, DoD, NATO
Microsoft-Senior Consultant to CINCPACFLT (Commander-in-
Chief, U.S. Pacific Fleet)-developed technology road-map for next
decade
Awarded: Architectural Engineer of the Year from
Microsoft's executive Committee
Ken Novak
25 years of experience in Wide Area Network (WAN) design
and implementation
Digital Vision Fellow at Stanford University
Chief Technology Officer at CGNET-IT services to non-
profits around the globe
Bill Lattin
Chief Technology Officer, Certicom Corporation
Managing Director of SecureField, an information security
consultancy that specializes in cryptographic design and network
security.
Chair of the Standards for Efficient Cryptography Group
(SECG)
Advisory Board
Jim Omura
Professor of electrical engineering at UCLA for 15 years
Designer of a number of spread spectrum communications
systems, and the Massey-Omura cryptosystem
Fellow of the IEEE and a member of the National Academy
of Engineering
Awarded the IEEE Alexander Graham Bell Medal
Scott Minick
Board Chairman-California Pacific Medical Center
Board Member of approx. 12 biotech companies
Susan Porth
20 years with Kaiser Permanente
10 years as SVP & CFO for 10 years
Prepared Statement of David Scadden, M.D., Scientific Founder,
Fate Therapeutics, Inc., La Jolla, CA
Mr. Chairman, ladies and gentlemen of the Committee, on behalf of
Fate Therapeutics, I would like to thank all of the Members for
inviting Fate Therapeutics to testify today. We would like to ask that
this document be considered our formal testimony and have it submitted
into the record through David Scadden, Founder, Fate Therapeutics.
CREATING TOMORROW'S MEDICINES FOR WOUNDED SOLDIERS
USING THE MOST ADVANCED STEM CELL TECHNOLOGY
Executive Summary:
Many diseases and injuries involve the death of cells that the body
cannot naturally replace. Sometimes cell death can occur suddenly, as
when a soldier sustains traumatic injuries in the battlefield. Other
times it is slow and inexorable, as in Parkinson's disease; a
consequence that can be attributed to the exposure to chemical agents
used in warfare. The great promise of stem cells--the body's equivalent
of renewable energy--is that they could be coaxed into becoming and
then replacing cells lost to disease or injury. While initial efforts
centered on the use of embryonic stem cells, we believe the
breakthrough creation of induced pluripotent stem cells (known as iPS
cells) and deeper understandings in adult stem cell biology have
enabled us to create and develop tomorrow's medicines for veterans.
The transformative discoveries that led to the creation of iPS
cells occurred in parallel with new understandings of adult stem cells
and their roles in developmental and regenerative biology. iPS cells
are created by using technologies that can turn a mature adult cell--
like a skin cell--into a cell that has similar properties of self-
renewal and pluripotency as embryonic stem cells, without using human
embryos. Adult stem cells are found in almost all the tissues or organs
in the body and are primarily responsible for maintaining and repairing
the tissue in which they reside. Specifically, it was found that adult
stem cells essentially lie in a reactive state; triggered into action
by disease or injury. These remarkable discoveries were the basis for
Fate Therapeutics' drug discovery and development strategy to create
new medicines.
Scientists at Fate Therapeutics are working to quickly unlock the
true potential of iPS and adult stem cells by using a two-prong
approach. Fate is establishing technologies to ensure safe, efficient
methods to create iPS cells to enable disease modeling, drug discovery
and development and personalized cell replacement therapy. The second
approach is to apply conventional drug approaches, whether in the form
of pills or by injection, to activate specific mature adult cells to
restore health. By leading this area of research, Fate is answering the
underlying questions of how cells in the body activate and transform in
normal, disease or injured states and then applying these
understandings to develop tomorrow's medicines for veterans and the
general public.
For veterans, we believe the near term applications for such a
strategy to generate wound healing therapies are especially applicable.
While improved technological advances in armor have increased the
survivability of our soldiers, it has come with the unintended cost of
our armed service men and women sustaining more severe injuries.
Traumatic brain injury, non-union bone fractures, deafness and
blindness are unfortunately injuries that are found to be commonplace
in today's battlefields and unfortunately have limited to no treatment
options. Programs underway at Fate Therapeutics have indicated that
cells in the areas of the body that suffer damage from such wounds, can
be activated through the traditional applications of medicines to guide
the body to heal itself. While these initiatives are in the early
stages, we continue to strive to fully realize the potential of the
discoveries in stem cell biology and develop them as safe and curative
therapies for our wounded soldiers who so honorably deserve them.
Fate Therapeutics:
Founded in 2007 on the leading stem cell and developmental biology
research, Fate Therapeutics is using the fundamental biological
mechanisms that guide cell fate to develop regenerative medicines. The
company has brought together the foremost scientists from the Nation's
research hotbeds (Boston, San Francisco, San Diego and Seattle) who
have demonstrated the potential to create and modulate stem cells to
restore health. While embryonic stem cells opened the possibility for
regenerative medicine, Fate Therapeutics is focusing on adult stem
cells and induced pluripotent stem cells (iPSCs). Adult stem cells
naturally exist in tissues or organs and are responsible for
maintaining and repairing the tissue in which they are found. iPSCs are
stem cells created from fully mature differentiated cells, like a skin
cell, and are being developed as personalized cell replacement
therapies (See Background on Stem Cell Research below for more on stem
cell types and applications). Fate is using conventional drug discovery
and iPSC technology to identify small molecules that can specifically
activate these stem cells to repair and regenerate tissue for veterans'
health.
Scientific Founders of Fate Therapeutics:
Fate's scientific founders are working with the company to
collaboratively research and develop innovative therapeutics to
modulate cell fate. By partnering with the leading academic labs in
stem cell and developmental biology, Fate has exclusive access to the
most advanced biological assays, models and research to illuminate the
biology of stem cells and deliver on the promise of regenerative
medicine.
Philip Beachy, Ph.D.-Ernest and Amelia Gallo Professor of
Developmental Biology at Stanford University School of Medicine and an
Howard Hughes Medical Institute (HHMI) Investigator
Randall Moon, Ph.D.-William and Marilyn Connor Chair and
director of the Institute for Stem Cell and Regenerative Medicine at
University of Washington and an HHMI investigator
David Scadden, M.D.-Gerald and Darlene Jordan Professor
at Harvard Medical School, co-director of Harvard Stem Cell Institute,
and director of Massachusetts General Hospital Center for Regenerative
Medicine
Leonard Zon, M.D.-Grousbeck Professor of Pediatric
Medicine at Harvard Medical School, director of the Stem Cell Program
at Children's Hospital Boston, and an HHMI Investigator
Sheng Ding, Ph.D.-Associate professor in the departments
of chemistry and cell biology at The Scripps Research Institute
Rudolf Jaenisch, M.D.-Founding member of the Whitehead
Institute, professor of biology at MIT, and member of the National
Academy of the Sciences
Drs. Beachy and Moon are leading developmental biologists who
understand how to activate specific stem cell pathways to differentiate
stem cells in vivo and in vitro. Drs. Scadden and Zon are renowned
scientists and doctors who are researching ways to guide cells to treat
various diseases and identifying means to explore the adult stem cell
niche, locations where naturally occurring stem cells are found in the
body. Drs. Ding and Jaenisch are the foremost investigators finding
small molecules and other non-genetic methods to guide cell fate.
DIRECTING CELLS TO RESTORE HEALTH:
FATE THERAPEUTICS' REGENERATIVE MEDICINE PROGRAMS
FOR SOLDIERS AND VETERANS
Hearing Restoration
Among veterans, hearing loss is the most common service-connected
disability.\1\ A 2004 survey showed that 28 percent of troops coming
home from a war zone have diminished hearing.\2\ In 2004, the Veterans
Administration (VA) paid $633.8 million to 378,982 veterans whose main
disability was hearing loss, according to the Army's Center for Health
Promotion and Preventive Medicine (Figure 1). That number has since
grown to more than $1.2 billion annually in compensation costs for
hearing loss and hearing related injuries.
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\1\ Fausti SA, et al. Hearing health and care: The need for
improved hearing loss prevention and hearing conservation practices. J
Rehabil Res Dev. 2005 Jul-Aug; 42(4 Suppl 2):45-62.
\2\ Schulz, TY. Troops Return with Alarming Rates of Hearing Loss.
Hearing Health vol 20:3; Fall 2004.
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In a 2005 study, the Center for Naval Analyses found that permanent
hearing loss is one of the most common disabilities among sailors and
recommended expansion of active military hearing-conservation programs
that work to reduce noise exposure.\3\ In 2005, it may have not seemed
possible to recommend funding research to restore hearing, but today
stem cell research and its applications in regenerative medicine offer
that opportunity. Fate Therapeutics, a private biotechnology company,
has converged the leading scientific expertise and research in stem
cell and developmental biology to discover and develop regenerative
medicines to treat a number of diseases and conditions that currently
have little to no therapeutic options, including acute hearing loss.
---------------------------------------------------------------------------
\3\ Geoffrey B. Shaw and Robert P. Trost. ``Statistical Analysis of
Hearing Loss Among Navy Personnel.'' February 2005. CRM D0011228.A2.
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Fate's Program to Cure Acute Deafness:
Hair cells in the ear are specialized cells responsible for sensing
sound and transmitting those signals to the brain. Once damaged,
usually due to loud or sustained noise exposure, these specialized
cells die and are not replaced, causing deafness; however, stem cells
have been identified in the adult ear (Figure 3).
[GRAPHIC] [TIFF OMITTED] T9916A.007
Figure 3a: Cross section through the ear anatomy; 3b: Expanded
depiction of red box in 3a to show cochlear structure and hair cells
(orange cell), the specialized sensory cell for hearing; 3c: Supporting
cells upon activation can divide and differentiate into hair cells
(blue cells); 3d: Supporting cells have also been seen to change form
or transdifferentiate into hair cells (Images: University of
Washington).
Research in cell culture and animal models has shown that upon
activation these stem cells can differentiate into the specialized
cells needed to restore hearing. Fate Therapeutics has proprietary
research around the pathways that modulate stem cell activation and
differentiation and is evaluating the company's library of drug
candidates to identify ways to efficiently activate these pathways. We
are currently performing preclinical validation experiments in cochlear
explant cultures to confirm our small molecule drug candidates activate
progenitor cells in the inner ear to grow and differentiate into hair
cells. We hope to advance the development of therapeutics to regenerate
cochlear hair cells, which are lost as a result of noise damage
sustained during military service.
Vision Restoration
One in 10 veterans from military operations in Iraq and Afghanistan
have sustained serious traumatic eye injuries, which is the highest
percentage for eye wounds among any other major conflict dating to
World War I.\4\ In 2007, it was reported that more than 1,100 veterans
from these two military conflicts have undergone surgery for damaged
eyes.\5\ While body armor improvements are saving more lives, eyes,
limbs and heads still remain extremely vulnerable. In fact, eye wounds
occur at almost twice the rate as wounds that require amputations.
Moreover, troops who sustain combat injuries leading to sudden
blindness lose a greater degree of independence and have a much longer
rehabilitation time to regain the ability to perform simple life tasks.
---------------------------------------------------------------------------
\4\ Wong, TY, et al. ``Eye Injuries In Twentieth Century Warfare: A
Historical Perspective.'' (1997) Survey of Ophthalmology. (1997)
41:433-459.
\5\ Zoroya, G. ``Blinded by War: Injuries Send Troops into
Darkness.'' USA Today. November 14, 2007.
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While science is still a long way from regrowing new limbs, stem
cell research and its applications in regenerative medicine can now
offer an opportunity to restore sight. Fate Therapeutics, a private
biotechnology company, has converged the world's leading scientific
expertise and research in stem cell and developmental biology to
discover and develop regenerative medicines to treat a number of
diseases and conditions that currently have little to no therapeutic
options, including acute blindness.
Fate's Program to Cure Acute Blindness:
Rods and cones in the eye are specialized cells responsible for
sensing light and transmitting those signals to the brain. Once
damaged, these specialized cells die and are not replaced, causing
blindness; however, stem cells have been identified in the adult eye
(Figure 2).
a.
[GRAPHIC] [TIFF OMITTED] T9916A.008
b.
[GRAPHIC] [TIFF OMITTED] T9916A.009
Figure 2a: Location of stem cells in the eye; 2b: Expanded
depiction of red box in 2a to show a Muller glial cell (arrow: orange
cell), a type of stem cell in the eye that can upon activation divide
and differentiate into rods (light blue cells) (Images: Nature).
Research in cell culture and animal models has shown that upon
activation of the Wnt or Hedgehog pathway these stem cells can
differentiate into the specialized cells needed to restore sight. Fate
Therapeutics has proprietary research around the pathways that modulate
these stem cells and is evaluating the company's library of drug
candidates to identify ways to efficiently activate these pathways. We
are currently performing preclinical validation experiments in retinal
explant cultures to confirm our small molecule drug candidates activate
progenitor cells in the eye to grow and differentiate into rods and
cones. We hope to advance the development of therapeutics to regenerate
photoreceptors lost as a result of choroidal hemorrhage and retinal
detachment consequent to traumatic eye injury sustained in combat.
Bone Regeneration
Advances in medical care and improvements in both body and vehicle
armor have resulted in increased soldier survival, from 76.4 percent
during the Vietnam War to 90.4 percent in Iraq. However, the price of
this survival has led to the rise in soldiers sustaining more severe,
traumatic injuries: orthopedic musculoskeletal injuries account for
approximately 70 percent of war wounds; fractures account for 26
percent of combat injuries; and 82 percent of all fractures are open
fractures.\6\ Most civilian orthopaedic treatment approaches cannot be
applied to battlefield medicine because combat injuries often involve
high-velocity shells or explosives, which injuries are generally very
different from low velocity bullet wounds more often seen in civilian
trauma centers. The challenge in these battlefield injuries is the high
degree of tissue loss and contamination combined with limited treatment
resources. The specific treatment protocol includes surgical
debridement, leaving all wounds open, early fracture stabilization,
broad-spectrum antibiotics, and rapid evacuation to higher levels of
care.
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\6\ Peter Pollack and Carolyn Rogers. ``A brief background of
combat injuries.'' AAOS NOW. March/April 2007. American Association of
Orthopaedic Surgeons.
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While science is still a long way from regrowing new limbs, stem
cell research and its applications in regenerative medicine can now
offer an opportunity to develop therapeutics that can activate the
body's own stem cells to advance healing and repair of bone and
cartilage. A regenerative medicine treatment supplement to support
orthopedic medicine at either battlefield or surgical care level could
provide quicker healing times and better overall recovery. Fate
Therapeutics, a private biotechnology company, has converged the
leading scientific expertise and research in stem cell and
developmental biology to discover and develop regenerative medicines to
treat a number of diseases and conditions that currently have little to
no therapeutic options, including traumatic orthopedic injuries.
Fate's Program for Non-Union Fracture:
Non-union bone fractures are large breaks in the bone that cannot
heal without further intervention. These fractures represent a major
challenge for battlefield medicine because treatment often requires
multiple surgeries and medical procedures (Figure 2a).
a.
[GRAPHIC] [TIFF OMITTED] T9916A.010
b.
[GRAPHIC] [TIFF OMITTED] T9916A.011
Figure 2a: Except for oblique, these different types of fractures
take longer to heal and often need surgeries and other medical
interventions to heal properly. 2b: A schematic of bone graft.
The most common means of fixing a non-union fracture is to add a
bone graft taken from the patient's own pelvis (Figure 2b). However,
this increases pain, medical procedures, hospital time and potential
complications, such as donor site wound infection, bleeding or
numbness. The most advanced FDA-approved product, a bone growth factor,
reduces the usage of bone graft but does not reduce healing time.
Developing small molecule drugs that can selectively activate and guide
stem cells in the body will be the best chance at a successful solution
to reduce non-union fracture healing time. We hope to advance the
development of therapeutics to regenerate bone in cases of high energy
weapon injuries and blast injuries. These combat injuries are often
associated with highly fragmented fractures and infection that increase
the failure rate of bone to heal.
Background on Stem Cell Research
Embryonic Stem Cells:
In 1998, the first human embryonic stem cell (hESC) line was
created from a fertilized egg. This was a significant milestone in
regenerative medicine because hESCs are pluripotent, meaning they can
become any cell in the body, and stem cells could conceivably be grown
and differentiated into replacement cells for any applicable
therapeutic need (Figure 1).
[GRAPHIC] [TIFF OMITTED] T9916A.012
All the Cells in the Body to Restore Health
Figure 1: The promise of regenerative medicine
However, the seemingly unlimited therapeutic potential associated
with hESCs were tempered with the sobering safety issues that hESCs
presented. Specifically, because of the limited population source from
which hESCs are derived, potential patients would be exposed to similar
immune rejection risks as those of organ transplant recipients when
receiving organs from donors of not identical genetic matches.
Moreover, hESC recipients would face increased risks to potentially
unknown genetic diseases of the donor. Accordingly, the ability to
generate patient-specific replacement cells with pluripotent
capabilities became the next sought after milestone to fully realize
the therapeutic potential of regenerative medicine.
Scientists tried to address this hurdle with a technique that
replaces an egg cell's nucleus with the nucleus from a patient's skin
cell (Figure 2). Since the nucleus of an adult skin cell has a full set
of chromosomes, the egg cell would in a sense be fertilized with an
exact copy of the patient's DNA. The embryonic stem cell line derived
from this ``fertilized'' egg cell would be a genetic match to the
patient and likely to not be rejected. However, this technique was
highly inefficient and relied on donated egg cells, which are from a
limited population source and difficult to obtain.
[GRAPHIC] [TIFF OMITTED] T9916A.013
2Figure 2: Schematic of nuclear transfer, a previously explored
method to generate genetically matched stem cells.
Induced Pluripotent Stem Cells (iPS cells):
In 2007, in separate publications Drs. Yamanaka and Jaenisch, the
later a scientific founder of Fate Therapeutics, reported that fully
differentiated adult cells, such as a skin cell, could be
``reprogrammed'' to become embryonic-like stem cells by forcing
expression of four transcription factors (Figure 3). Called induced
pluripotent stem cells (iPS cells), as iPS cells were derived from the
potential patient's own cells, the issue of creating patient specific
cells was addressed. Furthermore, ethical issues involving the use of
embryos or eggs had been avoided.
[GRAPHIC] [TIFF OMITTED] T9916A.014
Figure 3: A schematic of creating iPS cells, a more efficient and
reproducible process for generating personalized cell replacement
therapies.
iPS cells were first created by genetic manipulation using viruses,
which carry risks from insertion and makes the cells unsuitable for
clinical use. Fate Therapeutics and the company's scientific founders
have found safer and more efficient ways to create iPS cells using non-
genetic methods, such as small molecules and biologics. As iPS cells
can potentially be made from any adult cell and differentiate into any
cell type, iPS cells are considered to be the best means to create
personalized cells for regenerative medicine. Beyond cell therapy, Fate
Therapeutics believes iPS cells are of essential importance to research
how to control cell fate with small molecules to develop conventional
therapeutics.\7\ These small molecules could potentially be applied to
modulating adult stem cells to stimulate the body's own healing process
to repair and regenerate tissues.
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\7\ All drugs in pill form, like aspirin, are composed of small
molecules. Small molecules are easier to turn into drugs because they
can be tested for safety and efficacy. Thus, they follow a conventional
pharmaceutical drug development approach with a well-defined regulatory
and commercialization path.
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Adult Stem Cells Are Naturally Found in the Body:
While ESCs and iPS cells are types of stem cells made in the lab,
adult stem cells naturally occur in the human body. Adult stem cells
are found in tissues or organs and primarily maintain and repair the
tissue in which they are found. Some populations of adult stem cells
are also thought to remain quiescent (non-dividing) in areas of the
body called ``niches'' until they are activated by disease or tissue
injury. Adult stem cells can renew themselves and can differentiate to
yield the major specialized cell types of the tissue or organ. Some
researchers are trying to grow adult stem cells in the laboratory for
cell replacement therapy; however Fate Therapeutics is taking a
different approach. Fate is using conventional drug discovery\8\ and
iPS cell technology to identify small molecules that can specifically
activate these adult stem cells in the body to repair and regenerate
tissue.
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\8\ Conventional drug discovery relies on a deep understanding of
the biological pathways and mechanisms which control a specific cell or
cellular process. Small molecules and biologics are developed into
drugs based on their selectivity to modulate these cellular processes
in a way that has therapeutic benefit.
Prepared Statement of Howard J. Federoff, M.D., Ph.D., Executive Vice
President for Health Sciences, Executive Dean of the School
of Medicine, Georgetown University Medical Center, Washington, DC
Chairman Filner, Ranking Member Buyer and Members of the Committee.
Thank you for holding this hearing, for the work you are doing on
behalf of America's brave veterans, and for allowing me to testify this
morning. I will be focusing on innovative work that from my perspective
is critically important to addressing the long term implications of
traumatic brain injury (TBI) both to ensure that we are serving the
long term needs of returning veterans who have experienced TBI and to
do so in ways that are wise for the Department of Veterans Affairs
health care programs.
The Defense and Veterans Brain Injury Center makes the point on its
Web site that ``America's armed forces are sustaining attacks from
explosions or blasts . . . almost daily in Iraq and Afghanistan.'' It
also notes that screenings at Walter Reed have found that 32 percent of
servicemembers evacuated from theater had TBI. Those statistics obscure
the reality, also referenced on that webpage, that ``Sometimes, in the
case of mild TBI, there may be no outward sign of injury. Over 90
percent of combat-related TBI's are closed brain injuries.''
Indeed, TBI has been termed ``the silent epidemic.'' While 1.4
million Americans suffer from TBI from a variety of sources each year,
many of these injuries--with potential long term consequences--are not
reported. Even in mild cases of trauma, the central nervous system can
suffer permanent, often debilitating damage.
There can be no dispute that our military is moving aggressively to
respond as best they can to the flood of very visible and tragic
traumatic brain injuries that our men and women in uniform are
experiencing in these 21st century conflicts. Just as the nature of
these injuries has changed from the ``shell shock'' suffered by those
serving in earlier conflicts, medical science has made significant
strides. But we owe it to those who are serving and have served our
Nation in uniform to act on the important realization that,
notwithstanding the attention they are receiving, there are all too
many who have suffered mild to moderate traumatic brain injuries that
pose serious, but hidden threats to their long term well-being. We need
to act to:
Develop methodologies for more rapid and accurate
diagnosis of TBI and its associated risks;
Determine the most effective approaches to triaging TBI
patients; and
Pursue the rational design and screening of new
therapies, including novel drug discovery and development targeting the
prevention or minimizing of cognitive impairments which can impact
learning capabilities, the ability to hold down a job, and predispose
to post-traumatic stress disorders.
Years of neurological research have taught us a great deal about
the human brain, and, therefore, there is information relevant for TBI
victims:
First, the plasticity of the human brain permits unique
recuperative responses to trauma. We must fully understand these
responses to better understand when to intervene and when to allow the
body to heal itself.
Second, research to date indicates that, unlike in the
case of a stroke, in at least some types of TBI, there is a longer
timeframe from the time of injury for a possible therapeutic
intervention before permanent loss of brain function.
And, third, research on Alzheimer's and Parkinson's
diseases makes clear that blood and its circulating cells may serve as
an important window into the human brain, helping us better understand
the impact of neurological disease and injury. For example,
understanding the neuropathology of brain inflammation through analysis
of blood based proteins and distinct populations of leukocytes may help
us better determine the extent to which the brain has been injured and
the degree to which the body is responding and possibly recovering.
These observations are generally invisible absent a molecular analysis
of the blood of an injured person, but they potentially hold the key to
effective and timely interventions.
Recently, the Department of Defense through its Neurotoxin Exposure
Treatment Program (NETRP) has awarded a 5-year grant to Georgetown
University Medical Center neuroscientists to perform systematic and
extensive bio-molecular profiling of brain tissues and peripheral blood
to identify and validate robust, specific and sensitive biomarkers for
TBI. Those bio-molecular ``signatures'' can be read from the blood and,
early on, may aid in diagnosis of the variety and severity of brain
injuries and guide therapeutic responses. Indeed, this research, I am
confident, will inform the rational design of new drugs and therapies
to prevent both short-term and lasting brain damage. Our work will be
carried out in conjunction with the Seattle-based Institute for Systems
Biology and researchers at the University of Rochester. As someone who
believes in the tremendous benefits that are possible through broad
collaborations, I am pleased that we are planning to work with the
Uniformed Services University of the Health Sciences as they pursue
their direction from Congress to focus on TBI, as well as with the
National Institute for Nursing Research, the National Institute of
Neurological Disorders and Stroke, and the Washington Hospital Center.
Our research for the Department of Defense will initially rely on
civilian sector TBI patients for our clinical studies in recognition of
the reality that we will be able to recruit civilian patients without
the delays that are inherent in working with patients injured in
combat. However, I am following up on a recommendation from Chairman
Filner that we reach out to the DC VA Medical Center (WVAMC), to pursue
approaches to ensure longitudinal follow up between the care received
in the cases from the military and ongoing DVA medical care. Given the
on-going work on traumatic brain injury at WVAMC, as well as the over
30 Georgetown Medical Center faculty who hold joint appointments with
WVAMC, I am confident that we will actively engage WVAMC in this
research. To provide the best possible care for TBI victims now relying
on the Department of Veterans Affairs for medical services, ongoing
monitoring of their conditions and well-documented longitudinal follow
up will be critical. It will likewise enrich our research.
Members of this Committee know very well that the vast majority of
military personnel who are returning from the field having experienced
TBI are very young. God willing, they have long lives ahead. Therefore
it is incumbent upon us to ensure that we are aggressive in just this
kind of research endeavor that looks beyond the immediate consequences
of even mild TBI. With this kind of research, we can address the
``silent epidemic'' before it takes a toll on the long-term quality of
life of those who are serving our country. I urge you to ensure that
the Department of Veterans Affairs, in close concert with both the
Department of Defense and the Department of Health and Human Services,
remain vigilant in pursuing the identification both of these bio-
molecular signatures and of effective therapeutic responses to TBI.
Again, thank you for giving me this opportunity to testify before
you.
Prepared Statement of Nelson M. Handal, M.D., FAPA, Founder, Chairman,
and Medical Director, Harmonex, Inc., CliniCom, Atlanta, GA,
Board Certified Child, Adolescent and Adult Psychiatrist,
and Fellow, American Psychiatric Association
[Good Morning.] Mr. Chairman, Members of the Committee, thank you
for the opportunity to share information about innovative treatments
and technologies that are today serving to enhance quality of care in
mental health.
As you know, information and the way it is used is at the core of
psychiatric assessment and diagnosis. Typically patients requiring
mental health care are interviewed in what is commonly referred to as a
traditional face-to-face psychiatric interview. Practicing mental
health clinicians know that too often, time constraints, volume and
complexity of the information, limited access to care, and other
factors, if not properly identified and addressed, often end up
limiting the accuracy of their face-to-face assessments.
The key question is how to gather information comprehensively, in a
reasonable amount of time, utilizing an easy to use tool that generates
a valuable report to facilitate disposition and the clinician's initial
face-to-face interview.
Our organization, Harmonex is the developer of a patient self
administered and computer based assessment tool known as CliniCom.
CliniCom is comprehensive, easy to use and allows the clinician to
verify suggested diagnoses. The technology resides in a secure platform
that comprehensively screens for 56 possible mental illnesses and
Traumatic Brain Injury (TBI). CliniCom also includes a powerful suicide
alert that is unlike anything available in mental health today.
CliniCom is based on the DSM-IV standard and incorporates clinical
research and widely accepted community standards of care.
CliniCom is being used successfully across our Nation at private
outpatient clinics and hospital settings alike. The technology can be
equipped to run in most clinical environments using tablets, desktops
or kiosks. CliniCom evokes the appropriate question sets based on the
user type and the patient's age. It does not replace the mental health
professional. It simply allows them to significantly enhance the face-
to-face interview, its outcomes, and quality of care.
CliniCom does not forget to ask pertinent mental health questions
each and every time. It gathers complete medical, social, and family
histories and can also identify concerns associated with suicide,
violence, and traumatic events. CliniCom will also quantify severity of
symptoms and conditions automatically. It allows for secure and
uniformed documentation by organizing clinical information in a
standard History and Physical (H&P) format.
Once patients complete the assessment, clinicians can devote much
of their initial interview toward validating the CliniCom report and
helping patients understand the nature of their condition. It is very
difficult to gather all of this information during a single,
traditional face-to-face psychiatric interview. Our technology can
gather all clinically relevant and necessary information in a
responsible and quantifiable manner.
The ``Clinical Decision Making Process'' overall is significantly
enhanced by allowing CliniCom to identify individuals that may have
``co-morbid conditions,'' meaning the presence of one or more disorders
(or diseases) in addition to a primary disease or disorder. An example
would be an individual with depression in addition to PTSD and
Substance Abuse. With CliniCom, clinicians can better ensure that both
primary and co-morbid problems are identified simultaneously, leaving
no stone unturned.
A recent independent survey of 1109 CliniCom users indicated that
92 percent of users reported that CliniCom was very easy to use. In
addition, survey results indicated that 87 percent of users found
CliniCom to be very easy to understand, while 88 percent found it to be
extremely thorough. Seventy percent of users completed the assessment
in 60 minutes or less. This is a function of the severity of their
case.
While CliniCom has served to enhance care in the private sector, we
have confidence that the technology can also serve to enhance care
within military mental health. CliniCom has unique characteristics that
make it well suited for use both as a pre- and post-deployment
screening tool and also as a comprehensive mental health assessment
tool.
Soldiers can effectively be screened with CliniCom prior to
deployment to establish a mental health base-line. The technology can
then be used in-theatre, to address any changes to that base-line or
post-deployment in an effort to identify any changes in mental health
status. As a post-deployment screening measure, CliniCom's methodology
offsets some of the drawbacks inherent in screening methods currently
in use; most of which are simply paper or online checklists consisting
of only a few questions. We believe CliniCom would also assist the
clinical assessment and care of soldiers in outpatient and inpatient
behavioral health settings.
CliniCom works to identify individuals with possible Post Traumatic
Stress Disorder (PTSD), Traumatic Brain Injury (TBI) or suicidality in
a thorough manner. Certain algorithms are triggered if the individual
endorses trauma of any sort in the social history items; so for
example, PTSD is identified not just by combat related trauma but also
trauma that may have existed prior to deployment, even traumas
occurring earlier in life.
Another very important benefit of CliniCom is its suicide alert
capabilities. When an individual endorses suicide presenting complaints
or screening items, a complex algorithm for suicide assessment is
automatically engaged.
By implementing a technology like CliniCom, DoD and VA can use this
valuable clinical resource to help mitigate the overarching issues of
stigma and access to care and ensure that every member of our armed
forces is given a complete, comprehensive and responsible mental health
assessment.
In summary, CliniCom is a unique, information gathering tool
designed to assess mental health conditions, TBI and suicidality. The
technology is comprehensive, easy to use and its conclusions can easily
be verified by mental health professionals. In addition, what is
learned from these cases can be used to conduct research that could
lead to even greater advances in mental health care, truly modernizing
the way we help people of all walks of life, who today suffer with
illness.
We are grateful to the Members of this Committee for the work you
do on behalf of our veterans and soldiers. Thank you for your time and
for the opportunity to introduce you to CliniCom. We look forward to
answering your questions and are prepared to help in any way we can.
Prepared Statement of James A. Schoeneck, Chief Executive Officer,
BrainCells Inc., San Diego, CA
Chairman Filner, Ranking Member Buyer, Ladies and Gentlemen of the
Committee:
Thank you for the opportunity and the honor of appearing before
this distinguished Committee today. I wish to commend you for your
attention to the compelling issues surrounding Military Post Traumatic
Stress Disorder, or PTSD.
I have served as Chief Executive Officer of BrainCells Inc since
2005, and have worked on successful drugs in the biotech and
pharmaceutical industry for almost 30 years. BrainCells is a San Diego
biotech founded on the discovery made only 10 years ago that new nerve
cells, specifically neurons, grow in certain parts of the human brain.
This new science of neurogenesis has linked emotional disorders to the
failure to create and develop new cells located in a specialized part
of the brain. In fact, new neuron production is a requirement for
normal emotional responses that mentally healthy people take for
granted. By way of groundbreaking studies, the founding scientists of
BrainCells from Columbia University and the Salk Institute have
demonstrated that stress can arrest the formation of these new cells
(neurogenesis) resulting in a measurably shrunken site within the brain
called the hippocampus. We now have the first physical understanding of
biologic processes involved in psychiatric diseases. Image studies
performed on PTSD patients confirm that they, also suffer from abnormal
changes in the hippocampus. Although these methods are not yet
available to diagnose and study the progress of all clinical PTSD
patients, they will be someday soon.
Importantly, BrainCells has designed a drug screening platform to
search for new classes of drugs that will help this nerve cell growth
function return to normal--restoring neurogenesis with the intention of
improving emotional integration with few side effects. BrainCells
believes that its compounds provide alternatives to traditional anti-
depressants and anti-anxiety drugs by directly increasing neurogenesis.
BrainCells believes we have excellent drug candidates to treat PTSD.
Over the past few years, the U.S. Department of Defense and the
Veterans Health Administration have taken steps to improve mental
health services for personnel returning from deployments and veterans.
Expanded screening and treatment for PTSD and depression and new
efforts to reduce the stigma surrounding mental illness among
servicemembers are to be commended. But since October 2001,
approximately 1.6 million U.S. troops have been deployed for Operations
Enduring Freedom and Iraqi Freedom in Afghanistan and Iraq, and
according to last year's Rand Study one in seven servicemembers has
returned from deployments with symptoms of PTSD. That leaves us 230,000
service men and women and veterans known to be suffering from mental
injuries. (PTSD can be regarded parenthetically as a chronic wounding
of the brain just as Traumatic Brain Injury bruises the brain.) Recent
reports published in the Journal of the American Medical Association
placed numbers even higher.i The radiating social effects of
so many PTSD sufferers are mind-boggling when one considers that
families also must experience the impact of their loved ones returning
with mental illness. Violence, divorce, and domestic abuse have
skyrocketed among returnees and suicide rates in the military now
exceed those in the civilian population--unheard of as historic suicide
rates have always been lower among soldiers, sailors, marines, and
airmen.
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\i\ Bridget M. Keuhn, ``Soldier Suicide Rates Continue to Rise''
JAMA March 18, 2009 301 (11): 1111-1113.
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PTSD is classified as an anxiety disorder with symptoms of chronic
anxiety and fear that serve no purpose. It is often accompanied by
typical or atypical depression. Treatments for PTSD have had mixed
results. Non-drug treatment is regarded as the first-line option for
PTSD and is routinely incorporated into management plans for patients
with PTSD. Many patients do not achieve a sufficient response to non-
drug therapy or are left with disabling residual symptoms.ii
The selective serotonin reuptake inhibitors (SSRIs) are considered the
first-line pharmacological treatments. These are the familiar class of
anti-depressants like Prozac or Paxil. Response rates for these
medications rarely meet 60 percent in the general population, and less
than 20-30 percent of PTSD patients achieve remission.iii
This class of drugs routinely causes side effects like insomnia, weight
gain, and most significantly for young returning servicemembers, sexual
dysfunction. This is because the increased serotonin resulting from
this medicine affects many tissues in the brain and body--most of which
do not need extra serotonin. Less than 40 percent of servicemembers
diagnosed with PTSD receive mental health care--and some of those
voluntarily forego treatment or compliance because of sexual function
effects or worries. Many soldiers use alcohol or illegal drugs to deal
with symptoms rather than take SSRI anti-depressants.
---------------------------------------------------------------------------
\ii\ Expert Review of Clinical Pharmacology January 2009, Vol. 2,
No. 1, Pages 77-86.
\iii\ William Berger et al., ``Pharmacologic alternatives to
antidepressants in posttraumatic stress disorder: A systematic
review'', Dec. 24, 2008, Progress in Neuro-Psychopharmacology and
Biological Psychiatry Volume 33, Issue 2, 17 March 2009, Pages 169-180.
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Combat veterans are now shown to suffer a more severe form of PTSD
than civilian victims of trauma. Military trauma is generally
associated with greater depression, more anger and irritability, more
aggression, more problems with one's sense of personal identity, and a
far greater tendency toward suicide or violence.iv
Additional studies are needed, but experts are moving to the conclusion
that military PTSD is both different from civilian trauma, and it is
also more difficult to treat. Methods used to treat civilian PTSD are
at times inadequate to address military syndromes. The numbers of
refractory or resistant cases are rising. It is disturbing to realize
that we still have thousands of Viet Nam veterans in the full throws of
chronic PTSD and simultaneously we are being advised by the military
that currently deployed troops are experiencing unprecedented severity
and incidence of the condition. Often if left untreated, PTSD is a
lifetime disorder.
---------------------------------------------------------------------------
\iv\ Naifeh, James et al., ``Clinical Profile Differences Between
PTSD-Diagnosed Military Veterans and Crime Victims,'' Journal of Trauma
and Dissociation, 9(3): 321-334.
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Probably because of the nature of the unique psychological insult,
military PTSD is a different mental syndrome than civilian trauma
induced PTSD. It is not just depression and anxiety combined, but has
its own set of symptoms that require medicines designed for and tested
in the affected population. Presently, it is unlikely that the civilian
pharmaceutical industry can or will invest resources to address this
specialized ``orphan-like'' condition of military PTSD that includes
suffering from extreme anxiety, depression and memory processing
disorders. Our investors at BCI, for example, anticipate that we will
use our resources to develop drugs to treat the large civilian market
for major depressive disorder. This market may provide investors with
their anticipated return on investment in exchange for the high
financial risks taken in the development of new drugs. Unless the
government provides collaboration, incentives and funding directly to
the biotech and pharmaceutical industry to deliver FDA approved drugs
labeled for military Post Traumatic Stress Disorder, clinicians will be
left with combinations of existing drugs tested in and approved for
people with different medical conditions. I wish to respectfully
suggest to the Committee that the members of our military who
voluntarily protect the Nation from harm are deserving of a well-funded
pharmaceuticals development program directed specifically to military
derived PTSD. The Congress has generously funded significant amounts
for research into determining organic causes and best existing
practices for treating PTSD, but has yet to fully engage those of us
who are singularly and professionally dedicated to identifying and
testing safe new compounds that treat tough diseases.
Members of the Committee are undoubtedly aware of the myriad ways
that private enterprise can be provided incentives, as exemplified by
the orphan drug laws that offer tax credits and patent extensions to
illnesses affecting small populations. Tragically, military PTSD has
already exceeded the statutory 200 thousand patients that define the
orphan drug laws, but surely our warfighters are deserving of the best
that our creative laboratories can provide.
I am deeply grateful for this opportunity to share my views with
the Committee. In closing I wish to summarize with the following
thoughts and recommendations:
1. PTSD is a disease with great personal and social cost that
dramatically impacts the lives of our troops and returning veterans,
their families and the society around them. Unfortunately, current
therapies fail to sufficiently treat a large proportion of those
afflicted with the disorder.
2. There are wonderful new developments in the field of
neurobiology and neuropharmaceuticals that may make a huge difference
to sufferers of PTSD and other mental disorders without some of the
side effects that dissuade veterans and military personnel from seeking
treatment.
3. We must respond with a sense of urgency around testing new
classes of drugs to treat the patients who do not respond to existing
therapies for military PTSD. Our collective goal should be to have new
medicines for the veterans of these conflicts, not future ones.
4. A clear pathway to new drug development engaging the
pharmaceutical industry as a full partner, including regulatory and
financial incentives for orphan-like drug development, including
clinical trials is required.
5. Improved screening of patients for early diagnosis and
treatment must continue and expand since early diagnosis predicts far
better outcomes.
6. We must also invest time and resources in improved tools to
diagnose and differentiate PTSD from TBI, and the creation of tools
that evaluate treatment effectiveness, thereby reducing treatment
failures and suicides.
Once again, my thanks for the opportunity to speak before you.
Statement of William L. Balanoff, DDS, MS, FICD,
SmilePerfect, Fort Lauderdale, FL
Mr. Chairman and Members of the Committee, I am William L.
Balanoff, DDS, MS, FICD.
Visual examination has often been referred to as the ``Gold
Standard'' examination for oral cancer screening, but has not been
successful at achieving early detection rates of pre-cancerous and
cancerous lesions to the point of reducing incidence and death. As
such, the incidence rate of oral cancer remains virtually unchanged and
mortality rates have not significantly decreased over the same time
period. I like to think that dental practitioners are not remiss and
don't want to do a thorough job of screening patients at increased risk
for oral cancer, but rather that it's just that we haven't had the
benefits of adjunctive screening technologies to help us identify early
cancers and precancerous lesions such as those used by our colleagues
in the medical community for other cancer types.
The reality is that the general practitioner is charged with the
responsibility of identifying potentially harmful lesions and referring
that patient to a specialist in oral diseases for further evaluation
and possible treatment. Whether it is private practice dentistry or VA
dentistry, the demands and complexities are great. Given the inherent
difficulties associated with oral soft tissue examination (patient's
ability to provide adequate access, pooling of saliva, multiple
structures of varying color and working knowledge of oral pathology),
the inclusion of a diagnostic adjunct is critical to ensure that all
abnormalities have been visually captured.
The idea of not using diagnostic adjuncts to screen patients for
oral abnormalities is the equivalent to a philosophy of a medical
doctor using only his eyes and hands to assess a patient's health when
diagnostic adjuncts are available. All patients expect their doctors to
use every tool and test available to assess their health. Much is the
same for the practicing dentist and the availability of medical devices
to assist in the screening for oral lesions which can be missed during
visual examination. Rates of death associated with cancers encountered
by my MD counterparts were not adequately reduced until adjuvant
screening devices were introduced. Cancer death rates from prostate,
breast and cervical cancer did not begin to show substantive decreases
until adjunctive screening technology allowed physicians to see or feel
things they could not see or feel with their unaided eyes or hands.
Mammograms, PAP smears and PSA tests have reduced death rates by 40
percent, 80 percent and 17 percent respectively. These dramatic
improvements in lives saved was only realized when physicians were
given scientifically based technological advancements to aid in the
discovery of these diseases.
Since leaving dental school, I have performed thousands of head and
neck examinations to detect the presence of disease which requires
treatment. Disease states such as periodontal disease and dental caries
(cavities) are diagnosed with the aid of adjunctive technology.
Periodontal probing, X-rays, and microbiology are standard regimens for
the diagnosis of periodontal disease and X-rays are at the heart of
diagnosing dental caries. As a dental professional, my decisions have
been grounded in science and research to help detect and treat these
disease states. Oral cancer and premalignancies can now be addressed in
the same manner with the advent of devices for improving the efficacy
of visual soft tissue examination.
Of concern to me are those professing to be pundits of oral cancer
screening and accepting the status quo as acceptable care. Of even
greater concern is during my routine research of new products available
to a practitioner that I read articles or reviews recommending that
diagnostic adjuncts not be used and that visual examinations remain the
only test required. Unfortunately, too often these recommendations are
made by those who have never tried oral cancer screening adjuncts and
are making recommendations based upon another's opinion or by those who
do not see patients and only write about that which they themselves are
inexperienced.
For the past 5 years, the use of chemiluminescence (ViziLite) has
allowed me to identify lesions that were otherwise missed during
previous conventional oral examination. This adjunctive screening
device is now the standard of care, along with conventional visual
examination, in my conduct of dentistry and its use is ideally suited
for patients identified at being at increased risk for oral cancer.
The technology was first tested on thousands of women in worldwide
clinical studies and was shown to significantly improve the sensitivity
for identifying cervical intraepithelial neoplasias, the precancerous
lesions of the female cervix. In four studies it was shown to improve
the sensitivity of identifying cervical pathology from 92 percent to
99.1 percent. The FDA cleared the light technology for dentistry in
2001 because the visual response to lesions treated with a mild acetic
acid followed by chemiluminescent illumination was nearly identical for
the same kind of cells making up both areas. More recently, a medical
grade toluidine blue (TBlue') was added to the ViziLite
light source and cleared by the FDA for use as the combination device
ViziLite Blue Oral Lesion Identification and Marking System (ViziLite
Plus)by Zila Pharmaceuticals, Inc.
Toluidine blue has been used clinically for many years and is well
documented in its utility for use in identifying high grade dysplasia.
It has been reported that toluidine blue may be preferentially retained
by nuclear and mitochondrial DNA associated with oral premalignant
lesions (OPLs) and ``frank'' cancer. It is because of this that
staining suspicious lesions differentially identified during ViziLite
examination is of great benefit to higher risk patients, such as those
found in the VA hospitals. It allows me to refer patients with a
greater likelihood of pathology present.
[GRAPHIC] [TIFF OMITTED] T9916A.015
[GRAPHIC] [TIFF OMITTED] T9916A.016
My job as a general dentist is to find everything ``abnormal'' in
my patients and to refer to specialists those conditions presenting
with a great deal of clinical suspicion. Primarily, clinical suspicion
is determined by direct visualization under normal patient lighting. As
an adjunct, ViziLite Plus is critical for 1) initial identification of
a lesion missed during visual examination and/or 2) to provide me with
additional information to make an informed referral.
General dentists, including those who treat our Nation's Veterans,
are responsible for the detection of abnormalities that present as
pathosis. And because there is a screening adjunct that has helped me
to identify precancerous lesions that I missed during visual
examination, I strongly recommend the ViziLite Plus system for use
within the Veterans Administration system.
Statement of Joseph Califano III, M.D., Professor,
Department of Otolaryngology-Head and Neck Surgery and Oncology,
Johns Hopkins Medical Institutions, Baltimore, MD
Mr. Chairman and Members of the Committee, I am Dr. Joseph
Califano, MD.:
As a Professor of Otolaryngology-Head and Neck Surgery and
Oncology, a researcher in Molecular Biology, and a practicing head and
neck surgeon, I routinely see patients who present at their initial
consultation with advanced head and neck cancers. Many head and neck
cancers are already at an advanced stage in the disease process before
the lesion is discovered during examination or the patient presents
with a specific complaint. As an example, 50 percent of cancers of the
tongue have already metastasized before they are diagnosed. It is
typically only at relatively advanced stages that most patients become
aware of any signs or symptoms associated with oral malignancies
(except for lip cancer, which is usually obvious because any change in
appearance is in a visually prominent area). While the survival rates
for breast, lung and prostate cancers have improved over the last three
decades, this is not true for oral cancer overall. Recurring and second
primary tumors contribute to the devastating mortality and morbidity
associated with oral cancers.
Late diagnosis contributes to the low 5-year relative survival
rates for all oral and oropharyngeal cancers, even as treatment
modalities have improved. For example, the 5-year relative survival
rate for localized cancer of the lip is 97 percent, but only 35.3
percent when distant metastases are present at the time of diagnosis.
For cancer of the tongue, the corresponding 5-year relative survival
rates are 73.6 percent and 25.9 percent. It is also difficult to
diagnose recurrent malignancies or second tumors close to a treated
site, since irradiation and surgery each result in changes to the
mucosa that could result in observed early pre-malignant and malignant
abnormalities being dismissed as scarring or radiation-induced changes.
For all types of oral cancers, the more localized the lesion at the
time of diagnosis the better the patient's chance of survival and the
less invasive and destructive treatment will be, leading to better
quality of life. A recent pilot study at the University of Washington
involving specialists trained to identify oral cancer found that their
sensitivity in detecting lesions with atypical cellular changes using
an unaided visual examination was just 21 percent, and 50 percent for
lesions with moderate or greater dysplasia or carcinoma. Techniques
with high sensitivity and specificity that aid earlier diagnosis of
oral cancer have the potential to reduce both mortality and morbidity.
Carcinogenesis: a molecular process characterized by genotypic changes
followed by phenotypic change
Malignancies develop through molecular changes at the cellular
level. Cell cycles become deregulated, with genetic changes and tissue
dysplasia of varying severity occurring. Loss of heterozygocity in pre-
malignant lesions, with chromosomal abnormalities and allelic loss on
specific arms of chromosomes, is predictive of malignant
transformation. Loss of heterozygocity in the 3p, 9p and 17p arms of
chromosomes in particular is predictive for malignant transformation,
and secondary malignancies are more likely in cases where multiple
chromosomal arms are affected.
ViziLite Plus
Adjunctive technology aids the detection of lesions at an early
stage. ViziLite Plus is used to help identify pre-malignant and
malignant lesions by differentially staining the tissues and has been
found to offer high sensitivity and specificity. The stain used is
pharmaceutical-grade toluidine blue (TBlue) which binds to a pre-
malignant or malignant lesion. Recent studies have shown that the
differential uptake of TBlue in lesions is associated with chromosomal
changes and loss of heterozygocity, and predictive of malignant
transformation. In addition to aiding the detection of lesions
requiring biopsy for histopathology and diagnosis, T-blue staining has
been shown to delineate the margins of lesions such that the area of
resection at the time of surgery encompasses the full extent of the
lesion and all identified abnormal tissue.
Use of ViziLite Plus in the Erbitux study
The ViziLite Plus system is currently being utilized as part of an
ongoing Phase II clinical trial at multiple cancer sites for
determining the efficacy of the head and neck cancer drug, Cetuximab
(trade name Erbitux). ViziLite Plus was selected as part of the
inclusion criteria for patient admittance into the study to identify
lesions consistent with specific chromosomal deletions in patients with
previous histories of oral and oropharyngeal cancer. Previous work with
this pharmaceutical-grade toluidine blue has demonstrated an affinity
for the dye to bind to sites of allelic loss that are consistent with
cancer progression of low-grade epithelial dysplasia. To be admitted,
positive differential staining must occur followed by histological and
molecular analyses. The role of the blue dye is to identify those
lesions with the greatest likelihood of presenting the necessary
allelic loss for progression.
The value of adjunctive screening technologies in the VA
Specific behaviors, and advancing age, increase an individual's
risk for oral cancer. Smoking tobacco or drinking alcohol increases an
individual's risk by up to 600 percent. Tobacco use is by far the
single greatest risk factor, with over 75 percent of all cases
occurring in tobacco users (smoking, spit, and chew tobacco). The
combination of smoking and drinking further increases risk, as
demonstrated by Mashberg's study on Veterans. The prevalence of tobacco
smoking has historically been higher among Veterans than in the general
population, and alcohol abuse is one of the most common mental health
problems Veterans experience. Veterans are therefore a high-risk
population for oral and oropharyngeal cancers.
Since earlier detection aids earlier treatment and would improve
patient outcomes and quality of life, adjunctive technology that
improves the rate of detection and that helps predict which lesions
will undergo malignant transformation is warranted. Screening
technologies such as ViziLite Plus help the examiner detect lesions
that would otherwise be missed, and help predict which lesions will
undergo transformation. It is strongly suggested that ViziLite Plus be
considered for inclusion into clinics examining high-risk populations,
such as the Veterans Administration, so that more effective examination
and biopsy procedures may be performed to diagnose disease earlier.
Thank you for the opportunity of sharing my views on this important
subject. I will be pleased to respond to any questions you may have.
Statement of Joel Epstein, DMD, MSD, FRCD(C), FDS, RCS,
Director, Interdisciplinary Program in Oral Cancer Biology,
Prevention and Treatment, College of Medicine, Chicago Cancer Center,
University of Illinois, Chicago, IL
Mr. Chairman and Members of the Committee, I am Dr. Joel Epstein,
DMD:
Over the past few years dentistry has been introduced to visual
diagnostic adjuncts to the conventional head and neck and oral
examination for oral cancers. Light-based technologies have been
developed with the goal of assisting practitioners in identification
and evaluation of mucosal changes that include premalignant lesions and
cancer. Health care providers have been and continue to be challenged
with identifying abnormal oral conditions, which may represent
premalignant and malignant disease. Until recently we have had to rely
solely on visual examination in order to identify these abnormal
changes and only through meticulous and time consuming oral
examination. The result has been that the majority of oral cancer is
not diagnosed until symptomatic and with advanced stage of disease,
when extensive treatment is required and prognosis is guarded. While
conventional visual examination remains the cornerstone for the oral
cancer screening process, adjuvants are available that may facilitate
lesion identification and guide subsequent testing for diagnosis and
may be of assistance to experienced health care providers and patients
such as those found in the VA system.
Worldwide clinical trials have been conducted to determine the
sensitivity of the visual examination in identifying neoplasias
presenting with precancerous dysplasia or invasive carcinoma.
Sensitivity is determined by number of true positive (dysplasias and
cancers identified) results and the number of false negative
(dysplasias and cancer missed) results recorded during visual
examination. A large general population in India was studied where an
oral examination was conducted and early detection of cancers was
shown, and reduced mortality was seen at 2 year follow-up. However,
oral lesions at early stage are subtle and may appear benign and have
few symptoms thereby limiting the attention of the examining health
care worker. The advanced stage of cancer at diagnosis in \2/3\ of the
population in studies in developed countries including the USA,
demonstrates the difficulty in detection and diagnosis of premalignant
lesions or early stage cancer.
The most widely used light technology available and supported with
the most peer-reviewed literature is chemiluminescence. Tissue
reflectance using a chemiluminescent light source
(ViziLite') emitting low-intensity, diffuse wavelengths of
light may provide additional information. The light is reflected off of
tissue surface and sub-layers, and is affected by keratin and tissues
that contain cells with nuclei that take up a larger volume of the cell
than normal (hallmark of dysplasia and cancer). Normal tissue absorbs
this light and abnormal tissues will reflect the light.
Chemiluminescent light is non-discriminatory and will be reflected by
nearly all abnormalities. Clinical studies to date conducted at
different centers show that approximately 60 percent of lesions will
show enhanced contrast, brightness and surface texture with
chemiluminescent light compared to standard white light illumination.
To date, the literature has demonstrated a sensitivity of 100 percent
for this type of technology in the detection of pathologic lesions. It
has been further demonstrated that increased brightness may reduce the
potential for not identifying a potentially significant mucosal lesion.
These studies were conducted in patient populations likely comparable
to those which are found in the VA to assess visibility and increased
visual characteristics that may increase detection, but were not
studies where identified lesions were biopsied to assess cellular
change (histopathology).
In studies involving oral chemiluminescence, lesions meeting the
definitions of `clinically suspicious' for dysplasia or cancer were
captured in lieu of biopsy and histological analyses, with the
exception of two studies, i,ii which had histological
outcomes. Additionally, all published studies have been conducted by
specialists in Oral Medicine, Oral Pathology and/or Oral Surgery. In
the majority of studies, chemiluminescence (ViziLite) examination
identified lesions suspicious for pathology that remained unidentified
after conventional visual examination. In four (4) studies involving
885 patients, thirteen (13) lesions in thirteen different patients
(1.46 percent) were not identified during visual examination and
categorized as clinically suspicious for dysplasia or worse. Further,
in one these studies iii an occult lesion detected by
ViziLite alone was later biopsied post-study during routine patient
care and proved to be squamous cell carcinoma of the lateral tongue.
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\i\ Ram S, Siar CH. Chemiluminescence as a diagnostic aid in the
detection of oral cancer and potentially malignant epithelial lesions.
Int J Oral Maxillofac Surg. 2005 Jul;34(5):521-7. Epub 2005 Jan 26.
ii Epstein JB et al. Analysis of oral lesion biopsies
identified and evaluated by visual examination, chemiluminescence and
toluidine blue. Oral Oncol. 2008 Jun;44(6):538-44.
\iii\ Epstein JB, et al. The Efficacy of Oral Lumenoscopy
(ViziLite) in Visualizing Oral Mucosal Lesions. Spec Care Dentist. 2006
Jul-Aug;26(4):171-4.
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Another adjunct for visualization and clinical assessment is vital
tissue staining, where a product is applied to the oral surface in
patients and evaluated. Toluidine blue has a long history of study.
More recently, a medical grade toluidine blue has been developed and
the more recent studies have used this product as a single agent for
detection and evaluation or in combination with chemiluminescence. As a
clinical researcher with experience in conducting research and
publishing study results on diagnostic aids for the detection of oral
cancer and its precursor lesions, it is clear from the literature that
the use of toluidine blue is the most reliable adjunct we employ to
assist in a differential diagnosis, biopsy site selection, to
accelerate the decision for biopsy, and to assist in detection of
lesion margins. Without performing tissue biopsy for H&E analysis,
toluidine blue and it's preferential staining of nucleic acids (DNA)
helps to identify lesions with the likelihood of presenting pathology.
Cross-sectional studies iv,v and a prospective study
vi have shown that toluidine blue binds to sites of genetic
change that predicts progression of premalignant lesions to cancer and
in lesions that already represent cancer at first diagnostic biopsy.
Toluidine blue has been shown to assist in clinical evaluation, biopsy
site selection and to provide guidance of the risk of progression of
premalignant lesions to cancer.
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\iv\ Epstein JB, Zhang L, Poh C, Nakamura H, Berean K, Rosin M.
Increased allelic loss in toluidine blue-positive oral premalignant
lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003
Jan;95(1):45-50.
v Guo Z, Yamaguchi K, Sanchez-Cespedes M, Westra WH,
Koch WM, Sidransky D. Allelic losses in OraTest-directed biopsies of
patients with prior upper aerodigestive tract malignancy. Clin Cancer
Res 2001;7(7):1963-1968.
\vi\ Zhang L, Williams M, Poh CF, et al. Toluidine blue staining
identifies high-risk primary oral premalignant lesions with poor
outcome. Cancer Res 2005;65(17):8017-8021.
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The screening technology utilizing chemiluminescence and
pharmaceutical-grade toluidine blue (TBlue) is ViziLite Plus. This
device has been studied in patient populations similar to those found
in the VA system. The combination device utilizes chemiluminescence for
the identification of abnormalities in patient populations at increased
risk for oral cancer (its FDA intended use). The ViziLite examination
is performed only after conventional visual examination. ViziLite Plus
also contains TBlue and is applied to those lesions differentially
identified by the ViziLite light source and present with clinical
suspicion.
Based upon the body of evidence in the peer-reviewed literature it
can be recommended that ViziLite Plus be used in a higher risk patient
population by experienced providers, as seen in VA clinics. ViziLite
Plus technology should be considered for clinical use in the evaluation
of lesions previously identified during conventional head and neck
examinations. Although this type of application may not realize the
full potential of the combination device, the Veteran population could
be well-served by reducing the number of false positive findings
associated with visual examination thus potentially reducing the number
of unnecessary biopsies. This outcome has been shown in a multicenter
study ii, in a risk population similar to the VA population,
where a reduction in the number of biopsies by approximately half would
have still identified clinically significant lesions. Additionally, the
system may be used in conjunction with clinical suspicion, for the
monitoring of pathologic lesions over time as an indicator for repeat
biopsy and histologic examination.
Thank you for the opportunity of sharing my views on this important
subject. I will be pleased to respond to any questions you may have.
MATERIAL SUBMITTED FOR THE RECORD
Committee on Veterans' Affairs
Washington, DC.
May 14, 2009
Honorable Eric K. Shinseki
Secretary
U.S. Department of Veterans Affairs
810 Vermont Avenue, NW
Washington, DC 20420
Dear Mr. Secretary:
In reference to our Full Committee hearing entitled ``Innovative
Technologies and Treatments Helping Veterans'' on May 13, 2009, I would
appreciate it if you could answer the enclosed hearing questions by the
close of business on June 27, 2009.
In an effort to reduce printing costs, the Committee on Veterans'
Affairs, in cooperation with the Joint Committee on Printing, is
implementing some formatting changes for materials for all full
Committee and Subcommittee hearings. Therefore, it would be appreciated
if you could provide your answers consecutively and single-spaced. In
addition, please restate the question in its entirety before the
answer.
Due to the delay in receiving mail, please provide your response to
Debbie Smith by fax at 202-225-2034. If you have any questions, please
call 202-225-9756.
Sincerely,
BOB FILNER
Chairman
__________
Questions for the Record
The Honorable Bob Filner, Chairman
House Committee on Veterans' Affairs
Innovative Technologies and Treatments Helping Veterans
May 13, 2009
During the Full Committee hearing on May 13, 2009, I received
testimony from Alkermes, a small biotechnology company that
manufactures a drug called VIVITROL. VIVITROL is an extended-release
naltrexone product. It is a non-addictive, non-aversive agent that
binds to opioid receptors in the brain. It was recently approved by the
U.S. Food and Drug Administration (FDA). It is my understanding the
drug VIVITROL was used on a limited basis in the Veterans Integrated
Service Network 8, particularly in the Gainesville facility. Please
provide answers to the following questions:
Context of Response: Vivitrol' is not on the Department
of Veterans Affairs (VA) formulary. Its use is very limited and VA does
not systematically collect patient data that would definitively respond
to several of the questions you raise. In these instances, we are
summarizing peer reviewed literature on Vivitrol'. At
present, no VA medical centers in the Veterans Integrated Service
Network (VISN) 8 are performing research on Vivitrol'.
Scientific Evidence: When the Food and Drug Administration (FDA)
approved Vivitrol', the Veterans Health Administration (VHA)
Pharmacy Benefits Management Service (PBM) initiated a review of the
scientific evidence to evaluate its efficacy and safety compared to
other standard therapies available to VA patients. VA formulary
committees, the PBM medical advisory panel (MAP) and VISN pharmacy
executives reviewed the scientific evidence supporting the use of
Vivitrol'. There are limited data showing better medication
adherence with injectable naltrexone relative to orally administered
naltrexone. Unfortunately, there is no definitive evidence showing that
injectable naltrexone is safer or results in better patient outcomes
compared with oral naltrexone. Very limited data suggest a possibility
that injectable naltrexone might be less safe than oral naltrexone. VA
also recognizes that patients must be amenable to traveling to a VA
clinic to receive intramuscular injections of naltrexone every month.
Overall, there is a lack of definitive evidence that injectable
naltrexone improves patient outcomes relative to oral naltrexone.
Availability: Vivitrol' is available for non-formulary
use and VHA PBM and the MAP/VISN pharmacist executives committee have
issued guidance for the non-formulary use of injectable naltrexone. VA
and Department of Defense (DoD) guidelines for the management of
substance use disorders provide recommendations for the use of both
oral and injectable naltrexone. Prior trials of oral naltrexone or
other anti-alcoholic agents (e.g., acamprosate or disulfiram) are not
required before injectable naltrexone can be considered. Further,
clinical guidelines recommend that addiction-focused counseling be
offered in addition to naltrexone, regardless of route of
administration.
The responses to the questions below reflect information based on
VA prescription data and a thorough literature review. As noted, there
are no systematically collected data available specific to VISN 8 that
can be used to respond to the questions.
Question 1: What is the total number of patients in your network
receiving VIVITROL as part of their treatment for alcohol dependence?
Response: Within VISN 8 the total number of patients receiving
Vivitrol' is 45. The James A. Haley Veterans' Hospital in
Tampa, Florida currently has one patient and the North Florida/South
Georgia Veterans Health System currently has 44 patients receiving
Vivitrol'. In fiscal year (FY) 2008, VA-wide, 71 Veterans
were prescribed Vivitrol'. Oral naltrexone is more widely
used, with 5,827 unique patients receiving it in FY 2008.
Question 2: Does VIVITROL improve the patients' urges to drink?
Response: Based on review of the available literature, both oral
naltrexone and Vivitrol' result in decreased urges to drink
for some patients.
Question 3: What percentage of patients experienced a decrease in
their urge to drink?
Response: The FDA approved labeling for Vivitrol'
suggests that it decreases heavy drinking (and, presumably, urges to
drink) in those patients who were able to achieve abstinence for at
least 1 week prior to starting treatment.
Question 4: Does VIVITROL decrease drinking?
Response: Review of the existing literature suggests that both oral
naltrexone and Vivitrol' are effective at decreasing rates
of heavy drinking among patients.
Question 5: Does VIVITROL promote abstinence from drinking?
Response: Both oral naltrexone and Vivitrol' are shown
to significantly reduce use of alcohol. Both medications are
appropriate for use in treatment programs that promote abstinence or
programs that promote decreased use of alcohol.
Question 6: What percentage of patients remain abstinent during
treatment?
Response: Based on findings from a small post-hoc subgroup analysis
of individuals included in an industry-sponsored clinical trial who
were able to achieve abstinence prior to drug treatment,
Vivitrol' treatment was associated with approximately 32
percent abstinence at 6 months, compared to 11 percent for those who
received placebo.
Question 7: What is the average duration of persistence on
VIVITROL?
Response: Vivitrol' is administered on a monthly basis.
Review of utilization data for FY 2007 indicates that approximately 50
percent of those Veterans who were prescribed Vivitrol'
received no more than 1 injection. We are not aware of any direct
research data on the average duration of persistence on
Vivitrol'.
Question 8: Do patients engage in behavioral counseling while
receiving VIVITROL? If so, what percentage of patients are receiving
counseling?
Response: Vivitrol is currently prescribed and administered within
VA specialty care for alcohol use disorders. Given that this treatment
is provided within a specialty care program, Veterans who have been
prescribed Vivitrol' would also receive counseling.
Question 9: What happens to hospital utilization (specifically
emergency department visits and inpatient admissions) in patients using
VIVITROL?
Response: We are not aware of any studies that have evaluated
emergency department visits and rates of hospital utilization among
patients using Vivitrol'.