JOHN R. FEUSSNER, M.D.
CHIEF RESEARCH AND DEVELOPMENT OFFICER
VETERANS HEALTH ADMINISTRATION
DEPARTMENT OF VETERANS AFFAIRS
BEFORE THE NATIONAL SECURITY, VETERANS AFFAIRS AND
INTERNATIONAL RELATIONS SUBCOMMITTEE
COMMITTEE ON GOVERNMENT REFORM
U. S. HOUSE OF REPRESENTATIVES
RESEARCH AND TREATMENT OF GULF WAR VETERANS' ILLNESSES
January 24, 2002
Mr. Chairman and members of the Subcommittee, thank you for providing VA this opportunity to discuss the current status of the federal research program on Gulf War veterans' illnesses. I serve as the Department of Veterans Affairs' ( VA) Chief Research and Development Officer and the Chairperson of the Research Working Group ( RWG) of the Military and Veterans Health Coordinating Board ( MVHCB). I am accompanied today by Dr. Mark Brown, Director, Environmental Agents Service, and Dr. Han Kang, Director, Environmental Epidemiology Service.
In your invitation letter, you indicated that the purpose of the hearing was to assess the status of research and treatment of Gulf War veterans' illnesses among U.S. and coalition forces. You also requested follow-up of the recent General Accounting Office (GAO) report, Coalition Warfare: Gulf War Allies Differed in Chemical and Biological Threats Identified and in Use of Defensive Measures.
As you know, the United States deployed nearly 700,000 military personnel during the Gulf War from August 1990 to the cease-fire on February 28, 1991. Within months of their return, some Gulf War veterans reported various symptoms and illnesses that they believed were related to their service. Veterans, their families, and the VA have been concerned about possible health effects from exposures during the Gulf War.
Overview of the Research Portfolio on Gulf War Veterans' Illnesses
To date, the Federal government is projecting cumulative expenditures of $174 million for research related to Gulf War veterans from FY 1994 through FY 2001. There are 193 projects at various stages of completion in the research portfolio on these veterans' illnesses. In FY 1999 and FY 2000, 43 new projects were added to this portfolio. Research projects have been funded in the categories of basic research and applied research, such as clinical epidemiology and population-based epidemiologic research. To date, 116 federally funded projects have been completed. All projects and their focus areas are described in detail in annual reports to Congress.
An important role of the RWG is programmatic review and recommendations to funding agencies on research proposals that have been competitively and scientifically reviewed. The RWG continues to work diligently to foster the highest standards of competition and scientific merit review for all research on illnesses in Gulf War veterans.
Mr. Chairman, I will highlight the following topics in my testimony today: 1) an update on the status of several major research and treatment initiatives; 2) the status of two major Institute of Medicine studies; and 3) a brief description of our collaboration on research and other initiatives with our Gulf War coalition partners.
Status Report on Research and Treatment of Gulf War Veterans' Illnesses
We know that combat casualties do not always result in visible wounds, and that historically after all conflicts, some veterans have returned with debilitating health problems. VA recognizes its responsibility for developing effective treatments and prevention strategies for service-related diseases. Studies clearly show that some Gulf War veterans report a variety of chronic and ill-defined symptoms including fatigue, cognitive problems, and musculoskeletal problems, at significantly higher rates than the rates reported by non-deployed veterans.
Four National Research and Treatment Initiatives on Illnesses in Gulf War Veterans
Highlights of the ongoing research efforts include Phase III of the VA National Health Survey of Gulf War Era Veterans and Their Families, an epidemiological study of amyotrophic lateral sclerosis ( ALS) in Gulf War veterans, and two major treatment trials.
The VA National Health Survey of Gulf War Veterans and Their Families began in 1995 when health surveys were mailed to 15,000 Gulf War veterans and 15,000 non-deployed veterans. The self-reported survey results have been published and provided to the Subcommittee. Results from the initial two phases of this study show that Gulf War veterans are reporting significantly higher rates of diverse symptoms, including joint, muscle, respiratory, gastrointestinal, and skin problems. This population also reports higher rates of chronic fatigue and symptoms of post-traumatic stress disorder (PTSD).
In 1998, the third phase of this study began, which was designed to perform medical evaluations on a randomly selected subgroup of the veterans who completed the earlier mailed surveys. Phase III included 1,061 Gulf War veterans and their spouses and children, and 1,128 non-deployed veterans and their spouses and children. Veterans and spouses were examined for illnesses that had frequently been reported by Gulf War veterans in previous studies, namely, chronic fatigue syndrome, fibromyalgia, post-traumatic stress disorder, neurological abnormalities (including cognitive dysfunction and peripheral neuropathy), arthritis, hypertension, asthma, and chronic bronchitis. Children were examined for birth defects, which were diagnosed through pediatric examinations.
Each individual received a complete physical examination, including a neurological exam. In addition, veterans received several blood tests, neuropsychological testing, nerve conduction velocity tests, and pulmonary function tests. The preliminary results show that Gulf War veterans demonstrated significantly increased rates of two disorders, compared to non-deployed veterans. These were chronic fatigue syndrome (1.6% vs. 0.4%) and post-traumatic stress disorder (10.1% vs. 3.2%). There were no observed differences in veterans in the rates of fibromyalgia, cognitive dysfunction, peripheral neuropathy, arthritis, hypertension, asthma, and chronic bronchitis. There were no observed differences in the rates of the primary or secondary outcomes among the spouses of Gulf War veterans and non-deployed veterans.
Gulf War veterans have voiced concerns about a possible association between ALS and service in the war. This fatal neurological disease is also called Lou Gehrig's disease. Neither a cause nor an effective treatment for ALS is known. Preliminary data suggested that the age distribution of cases of ALS in Gulf War veterans appeared to be younger than the age distribution of cases of ALS in the general U.S. population. Accordingly, in March 2000, VA began a research effort to identify all cases of ALS, occurring among Gulf War veterans deployed to the Gulf during Operations Desert Shield/Desert Storm and non-deployed veterans. VA collaborated with the Department of Defense ( DoD), and the Centers for Disease Control and Prevention ( CDC), university experts, and the ALS Association to determine the veterans' health status and to describe their exposures to potential risk factors for ALS, based on clinical examinations at centers of excellence in neurological diseases. The case-finding and medical confirmation of cases was recently completed.
The preliminary results show that Gulf War veterans deployed to Operations Desert Storm and Desert Shield had almost a two-fold increased rate of ALS, compared to non-deployed veterans. There were 40 cases of ALS diagnosed among almost 700,000 Gulf War veterans. There were 67 cases among almost 1.8 million non-deployed veterans. The next step in this investigation will involve careful evaluation of possible risk factors in the veterans, including family history, military occupation, injuries and trauma, and exposures to hazardous chemicals.
As a result of the study, the Secretary of Veterans Affairs decided to take steps to compensate veterans with ALS who were deployed to the Gulf region during Operations Desert Shield/Desert Storm. VA has contacted the Gulf War veterans identified in the study to help them file new claims or to expedite existing claims.
In 1998, the VA Cooperative Studies Program initiated planning for two treatment trials, known as the "ABT" (antibiotic treatment) and "EBT" (exercise-behavioral therapy) trials. Patient characteristics for entry into both trials were similar. All veterans who served in the Gulf War between August 1990 and August 1991 were eligible for the studies. Patients were eligible if they had at least two of three symptoms (fatigue, musculoskeletal pain, and cognitive dysfunction) that began after August 1990. In addition, patients had to be symptomatic when the study began with symptoms that had lasted for more than six months.
The ABT trial initiated its enrollment of 491 Gulf War veterans in May 1999 at 26 VA sites and 2 DoD sites. The primary hypothesis of the study was that antibiotic treatment, with doxycycline for 12 months, would improve the health status of patients with chronic symptoms who tested positive for Mycoplasma infection at baseline. The secondary hypotheses were that doxycycline treatment would reduce symptoms of fatigue, pain, and memory problems; and that doxycycline treatment would convert patients who were Mycoplasma positive to Mycoplasma negative. The trial was completed in December 2001, when patient follow-up was finished.
Of the patients enrolled in the ABT study, 84% exhibited all three symptoms of fatigue, pain, and neurocognitive difficulties. The preliminary results show that doxycycline was not an effective treatment. The antibiotic did not lead to an improvement of physical function or to reductions in fatigue, pain, or memory problems. In addition, this study does not support a possible relationship between chronic symptoms experienced by some Gulf War veterans and persistent Mycoplasma infections.
The EBT trial initiated enrollment of 1,092 Gulf War veterans in April 1999 at 18 VA sites and 2 DoD sites. The primary hypotheses of the study were that both aerobic exercise and cognitive behavioral therapy ( CBT) would significantly improve physical function in veterans, and that the combination of exercise and CBT would be more beneficial than either treatment alone. The secondary hypotheses were that treatment would lead to improvement in mental health function, and to improvement in symptoms of fatigue, pain, and memory problems. The EBT trial was completed in December 2001.
After 12 months of treatment, the functional status and symptoms of each individual were compared to his or her baseline. The preliminary results show that exercise and/or CBT did not improve physical function. However, exercise, CBT, or the combination did lead to significant improvements in mental health function. In addition, exercise, with or without CBT, lead to significant improvements in symptoms of fatigue and memory problems. Aerobic exercise appears to be a promising treatment for Gulf War veterans who have chronic symptoms of fatigue and memory problems.
Longitudinal Studies to Determine the Long-Term Health of Gulf War Veterans
The Research Working Group determined that continuing longitudinal studies that evaluate the health status of Gulf War veterans are a high priority, to determine whether their health is getting better or worse over time. There are five ongoing studies, which are supported by VA, DoD, and CDC. The five studies in Boston, New Orleans, New Jersey, Iowa, and the United Kingdom are following approximately 18,000 veterans, altogether. Each of these studies has included questionnaires on physical symptoms, psychological symptoms, and exposures during the Gulf War. The New Jersey, Iowa, and U.K. studies have also included comprehensive medical histories and physical examinations. The Boston and New Orleans scientists have evaluated their cohorts at four time points, beginning soon after service personnel returned from the war. The British scientists have evaluated their cohort at three time points, and the New Jersey and Iowa scientists have evaluated their cohorts at two time points. The RWG continues to be committed to facilitating the long-term monitoring of the health of Gulf War veterans. To aid in such an assessment, the VA Office of Research and Development released a Request for Proposals in 2000. Multiple proposals were submitted in response to this solicitation in 2001. DoD funding has recently been approved to perform a longitudinal study of the participants of the VA National Health Survey of Gulf War Era Veterans and Their Families.
In addition to the follow-up of the health of Gulf War veterans, the RWG has made a commitment to monitor the health of service members after future deployments. The Millennium Cohort Study is a prospective study of U.S. military forces, which was designed to collect population-based demographic and health data systematically to evaluate the health of service personnel throughout their military careers and after leaving military service. This study is a cross-sectional sample of 100,000 military personnel who will be followed prospectively by mail surveys every three years over a 21-year period, starting in 2001. In 2004 and 2007, 20,000 new personnel will be added to the cohort. The total of 140,000 veterans will be followed until 2022. The principal objective of the study is to evaluate the impact of military deployments on various measures of health over time, including chronic diseases such as cancer, heart disease, and diabetes. This ambitious study requires the collaboration of DoD and VA scientists over an extended period of time.
Other Research Initiatives on Illnesses in Gulf War Veterans
VA recently established two new Centers for the Study of War-Related Illnesses at the VA Medical Centers in East Orange, New Jersey and Washington, D.C. These new Centers will assist VA in the development of appropriate preventive strategies to minimize illness following future conflicts, including both combat and peacekeeping operations, and to develop new approaches for improving the treatment of active-duty and veteran patients with war-related illnesses. Each Center will focus on medical care and risk communication for veterans, education for health care providers, and center-initiated research.
In September 2001, CDC funded two research projects designed to develop and implement more effective methods of risk communication for active-duty service members, veterans, and their health care providers. The project at Rutgers University is entitled "Improving Health Risk Communications to Prevent Unexplained Illnesses Related to Military Deployments." The project at the Jackson Foundation and Walter Reed Army Medical Center is entitled "Health-e VOICE: Optimized Implementation of a Stepped Clinical Risk Communications Guideline." These two projects will be funded for three years.
In 2000, DoD published three Broad Agency Announcements to announce the availability of research funding. The review of projects and awarding of funds were completed in 2001. The number of new projects funded in each area is:
A study at the University of California at San Francisco and the San Francisco VA Medical Center, which DoD recently funded for five years, will focus on neuroimaging of veterans with symptoms of central nervous system dysfunction. A preliminary study of 12 ill Gulf War veterans in Texas suggested that these individuals showed normal brain anatomy on magnetic resonance imaging (MRI), but showed biochemical abnormalities on magnetic resonance spectroscopy (MRS). This study was limited because of the small sample size and because there was no control for alcoholism, depression, PTSD, or drug treatments. The San Francisco study will carefully evaluate 200 Gulf War veterans and 200 non-deployed veterans, through neurological exams and neuropsychological testing. Then, MRI and MRS will be performed to detect anatomical and biochemical abnormalities, while controlling for the effects of other concurrent illnesses.
Institute of Medicine Studies Related to Gulf War Veterans' Illnesses
In 1998, VA contracted with the Institute of Medicine (IOM) to perform periodic reviews of the scientific and medical literature regarding adverse health effects associated with the exposures experienced during the Gulf War. The first phase of this study focused on pyridostigmine bromide, depleted uranium, sarin, cyclosarin, and the anthrax and botulinum toxoid vaccines. This first phase was funded for 27 months, and a report on this first phase was published in September 2000, entitled Gulf War and Health: Volume I. Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines.
The IOM has already begun its next two-year review, focusing on health effects from pesticides and solvents used during the Gulf War. That report is expected to be completed in August 2002.
In 1999, VA requested the IOM to perform a study to identify effective treatments for health problems in Gulf War veterans. The IOM Committee's charge was as follows:
In July 2001, IOM published the results of this study, entitled Gulf War Veterans: Treating Symptoms and Syndromes. IOM stated that difficult-to-diagnose symptoms experienced by some Gulf War veterans have a large overlap with the following seven diagnoses: chronic fatigue syndrome, depression, fibromyalgia, headache, irritable bowel syndrome, panic disorder, and PTSD. A major focus of the report was the evaluation of proven treatments for these recognized diagnoses, and IOM provided recommendations for improving health care for patients with these disorders. It concluded that available studies of proven therapies for persons with these disorders are a valuable resource for deriving effective treatments for undiagnosed illnesses. VA has already implemented many of IOM recommendations. For example, VA is developing clinical practice guidelines for chronic fatigue syndrome, fibromyalgia, and depression.
Collaboration on Research and Other Initiatives with Gulf War Coalition Partners
There has been extensive international coordination and collaboration on research between the United States and its Gulf War coalition partners. For example, there have been three research conferences that were organized by the Persian Gulf Veterans Coordinating Board (now called the Military and Veterans Health Coordinating Board, or MVHCB). British scientists have provided presentations at all 3 conferences in 1998, 1999, and 2001. The 2001 Conference had extensive international participation. The participants included 400 scientists and clinicians from Great Britain, France, Canada, Australia, the Netherlands, Denmark, and Israel.
Research scientists from the U.S. and the UK are in continual communication. DoD funded the first large British study of Gulf War veterans in 1996, which has been directed by Dr. Simon Wessely. DoD is now funding a joint research project on the health of Gulf War veterans in Iowa and Great Britain, which includes the cohort studied by Dr. Wessely. Dr. Wessely, who is an expert in cognitive behavioral therapy, is on the Data Safety Monitoring Board of the EBT study. Since 1998, a British medical officer from the Ministry of Defence has been based at the office of the MVHCB. In addition, another British medical officer is an ex officio member of the Research Working Group of the MVHCB. Research scientists from the U.S. and Canada are also in frequent communication, particularly in regard to the potential health effects of exposure to depleted uranium. In addition, scientists working for the Canadian Department of National Defence adopted the questionnaire developed by Iowa scientists for a survey of all Canadian Gulf War veterans, which was published in 1998.
As the Chair of the Research Working Group, I was asked to brief a French scientific delegation on April 4, 2001. Several of the issues discussed at that briefing were related to the findings in an 135-page report on illnesses in Gulf War veterans that was published a few weeks later. This French report was entitled: Mission Report from the Working Group responsible for analyzing health data relating to French veterans of the Gulf War. This report reviewed 350 American and British studies of illnesses in Gulf War veterans. The conclusions of this exhaustive review by the French Working Group were as follows:
The French Working Group concluded, "The medical data pertaining to French Veterans are not accessible. Thus, it prevents us from upholding or overturning the findings drawn from the international [American and British] literature. . . The questions that are being asked about the Gulf War have revealed, or confirmed, to the members of the Working Group that epidemiological monitoring in France for war veterans is totally inadequate."
The recommendations for a health study of French Gulf War veterans were: "In order to bring reliable and clear answers to questions raised by public debate and to concerns expressed by soldiers deployed in the Gulf, we are adamant in proposing several projects that we have classified as epidemiological studies, other research and mid-term and long-term monitoring. We feel it is essential to carry out an in-depth study using a questionnaire for all the veterans who participated in the Gulf War."
A comprehensive epidemiological study will begin with the evaluations of approximately 25,000 French Gulf War veterans in February 2002, and is planned to take two years. Dr. Roger Salamon, a professor at the University of Bordeaux, is directing the study, which will include a comprehensive questionnaire covering a full range of health effects, and a medical examination in a civilian or military medical facility.
Mr. Chairman, you also requested follow-up of the recent General Accounting Office (GAO) report, Coalition Warfare: Gulf War Allies Differed in Chemical and Biological Threats Identified and in Use of Defensive Measures. This report summarized the experience of troops from the U.S., UK, and France during the Gulf War. It outlined each country's approach to "chemical, biological, and radiological defense, including their use of protective gear and specific drugs and vaccines." One of GAO's major conclusions was that "owing to the number of differences in the experience of the three sets of veterans, they do not point unambiguously to any single cause for the reported illnesses." The GAO report drew "no conclusions regarding the cause or causes of health problems reported by veterans of the Gulf War." GAO also stated that they could "not preclude the possibility that additional time or more thorough examination could yield additional reports of health problems among French veterans." Indeed, plans for a "more thorough examination" of the 25,000 French Gulf War veterans are being implemented.
Summary of Major Research Findings To Date
The Federal research program has yielded several important results, as follows:
As the federal research program continues to provide more results, we will substantially increase our understanding of Gulf War veterans' illnesses, which, in turn, will enhance our ability to diagnose and treat them. In addition, this newly gained knowledge may enhance prevention and intervention in illnesses in participants of future deployments.
Mr. Chairman, thank you again for providing this opportunity to summarize our work to date to understand the health problems of Gulf War veterans. You have my assurance that we will continue this effort to resolve or ameliorate health problems in this population to the greatest extent possible. Mr. Chairman, this concludes my testimony. My colleagues and I are ready to answer any questions that you, the other subcommittee members, or the distinguished guests may have.