Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report (2018)

Chapter: Attachment 2

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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Attachment 2

DEPARTMENT OF THE ARMY
OFFICE OF THE SURGEON GENERAL
7700 ARLINGTON BOULVARD
FALLS CHURCH, VA 22042-5140

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DASG-PPM-NC 14 February 2018

MEMORANDUM FOR Committee on Toxicology, National Academies of Medicine, Science and Engineering (Ms. Susan Martel), 2101 Constitution Avenue NW, Washington, DC 20418-0007

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

  1. Purpose. To provide information regarding the roles and responsibilities of the President and members of the Benefits Application Panel (BAP), and the process by which applications for health care (claims) will be adjudicated to determine if an individual applicant’s medical condition(s) is the proximate result of participation in Army, or Army sponsored, chemical or biological substance testing programs between 1942 and 1975 in order to determine eligibility for DoD provided health care for the a claimed condition(s).
  2. Introduction. As directed by court injunction, in order fulfill the obligations under Army Regulation 70-25 (AR 70-25) to provide medical care to former members of the armed forces who participated as research subjects in the Army’s chemical or biological substance testing programs, the U.S. Army has implemented a new program to facilitate health care for veterans who suffered injury or illness that was the proximate result of their participation in Army chemical and biological substance testing programs between 1942 and 1975 (hereinafter Veterans). To execute this program, under the authority of the U.S. Army Surgeon General (TSG), the U.S. Army Public Health Center (APHC) has established this BAP to adjudicate applications for medical care from veterans and make a proximate cause recommendation, based on the preponderance of the evidence, in order to determine an applicant’s eligibility to receive medical care at a Department of Defense (DoD) medical treatment facility.
  3. Eligibility Criteria. In order to apply and to be considered for eligibility, the Veteran must have or provide at a minimum the following:
    1. A Department of Defense (DoD) Form 214 or War Department (WD) discharge/separation form(s) or functional equivalent. Other confirming documentation of military service dates may be acceptable, and
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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DASG-PPM-NC

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

    1. Served as a research subject in a U.S. Army chemical or biological substance testing program between 1942 and 1975, including the receipt of medications or vaccines under the U.S. Army investigational drug review; and
    2. A diagnosed medical condition the veteran believes to be a proximate result of their participation in a U.S. Army chemical or biological substance testing program
  2. Application Contents. The following documents will be considered by the BAP in every case:
    1. Completed Form 840, Application for Medical Care, signed by a living Veteran, or authorized representative/agent
    2. Medical evaluations or diagnosis from treating physician;
    3. Any Military, Civilian, or Department of Veterans Affairs’ (VA) medical records, documenting a diagnosis the applicant believes is proximately caused by exposure to a substance or from participation in chemical or biological substance research;
    4. Military personnel records verifying the unit of assignment at the time of the research study; including annual training (AT), temporary tour of active duty (TTAD), active duty (AD), active duty for training (ADT), initial active duty for training (IADT), active duty for special work (ADSW), or full-time National Guard duty (FTNGD) orders, and all amendments thereto pertaining to the case being reviewed, if the applicant claims that the testing occurred while they were serving in an Active Duty or Reserve status.
    5. The veteran must provide proof of participation as a research subject in a testing program that was sponsored, overseen, directed, funded, and/or conducted by the Department of the Army or in the War Department, in which humans were exposed to a chemical or biological substance for the purpose of studying or observing the effects of such exposure.
    6. Line of duty investigation completed in accordance with AR 600-8-4, if applicable.
    7. Any VA service connection decision for the medical condition(s) being claimed.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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DASG-PPM-NC

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

    1. Previous findings of the BAP, if the applicant requests reconsideration and provides additional records or has a new medical condition, which they want the BAP to consider, if applicable.
    2. Human test subjects may have concerns regarding the consensual nature of their participation in testing. Many human test subjects were under a “secrecy oath” or other non-disclosure restrictions. This secrecy oath may have inhibited the Veterans from discussing health concerns with their providers or seeking compensation from the VA, or even omitting a discussion regarding any chemical and biological warfare test participation when seeking care or compensation. Evidence of such concerns or actions may be included in the application for consideration by the BAP.
    3. Any other documents submitted by the applicant.
  2. U.S. Army BAP Membership.
    1. U.S. Army Public Health Center (APHC) is responsible for establishing the BAP and administration of the BAP. The BAP will consist of medical professionals with expertise in chemical or biological agents from the Army Medical Corps or civilian employees from the Medical Research Institute of Chemical Defense (MR ICD), the Medical Research Institute of Infectious Diseases (MRIID), or the APHC, or other specialists as assigned.
    2. Membership of the BAP.
      1. The BAP president, or anyone performing duties as the BAP president, is a voting member and is assigned to serve on either a chemical or biological focused BAP on appointment orders signed by the Chief of Staff (CoS) of MEDCOM.
      2. Other voting members will be appointed on orders signed by the CoS of MEDCOM, and will consist of, but not limited to, the following specialties:
        1. Occupational and/or environmental medicine physician(s) proficient in chemical dose-response, toxicology, epidemiology, risk assessment and general causation:
        2. Physician(s) with expertise in assessing, diagnosing and treating the medical condition(s) listed by the veteran in the application for medical care.
Page 11 Cite Bookmark
Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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DASG-PPM-NC

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

    1. A legal advisor (nonvoting member), if required, will be provided by APHC.
    2. The BAP president may, in his/her discretion, invite (non-voting) physician(s) with competence in medical specially areas to advise in the review of issues which require expertise beyond or in addition to that available on the BAP.
    3. No BAP may have a voting member participate in the BAP’s adjudication of any application in which the member has a conflicting interest or cannot provide an unbiased & impartial opinion, except to provide information requested by the BAP. Appointed BAP members will recuse themselves if they have a conflict of interest or cannot provide and unbiased and impartial opinion.
    4. The BAP will meet at the call of the President and comply with all applicable policy guidance provided by APHC.
  2. BAP Guidance.
    1. All complete applications from eligible Veterans will be reviewed by the BAP for a decision on whether the claimed diagnosis(es) was the proximate result of the applicant’s participation in an Army chemical or biological substance testing program, by a preponderance of the evidence.
    2. A single or multiple diagnoses provided by the evaluating physician for the specific diagnoses indicated on the application for medical care is the diagnoses that the BAP will review. If the BAP believes that another diagnosed medical condition, other than the medical condition(s) claimed by the applicant, should be considered for review in the interest of equity, this will be discussed with PM and a decision will be made whether there is sufficient evidence to consider the condition or whether additional information is needed. If there is sufficient medical or documentary evidence for the BAP to consider another medical condition, that decision will be captured in writing. If there are questions or concerns regarding the specified diagnosis(es), the BAP may request additional information from the physician or recommend that the applicant receive another medical examination to support their application for medical care.
    3. The BAP may not substitute the claimed diagnosis(es) or introduce a diagnosis(es) based on BAP members’ opinion or clinical judgement, but may request additional information from the veteran’s physician. If additional information is requested, the 120 day processing time will be suspended.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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DASG-PPM-NC

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

    1. The BAP members are allowed and encouraged to introduce or discuss their own professional knowledge and evaluation of the medical diagnosis claimed by the applicant.
  2. Review and Adjudication Process. Only complete applications provided by the Program Manager will be reviewed and adjudicated by a BAP.
    1. Literature reviews previously conducted which describe exposures during testing and health outcomes during follow-up (Committee on Toxicology (COT) 1983, 1984, 1985, Institute of Medicine (IOM) 1993, Ho Chunk 2016, etc.) will be supplemented with specific reviews of the associations between the exposure agent(s) and the health outcome of interest for each applicant This information will be presented and discussed by the BAP members at the meeting for the claim under consideration.
    2. The BAP will conduct a record review of the application, extrinsic medical evidence, VA records, and Army records and will determine, by a preponderance of the evidence, whether the applicant’s diagnosed condition was a proximate result of his or her participation in the specific research program. The BAP review and results will be captured on Figure 1-1, and this form will be filed as discussed in paragraph 15 below.
    3. The BAP will be made up of a minimum of three voting members and the Panel’s decision will be based on a majority vote as to whether or not the health condition is considered the “proximate result”.
  3. Causation Methodology.
    1. The court has determined that the Army should provide health care for “any injury or disease that is the PROXIMATE result of their participation in the research”. The court defined proximate result as “any health condition having a sufficiently strong causal link such that a reasonable person could find that the injury or disease was caused by testing exposure or participation in research”.
    2. Established and generally accepted methods exist for determining whether an individual’s disease or adverse health effect was caused by an alleged exposure. In order to establish that a chemical or biological exposure resulted in any particular adverse health condition, two separate analyses must be performed: a general and a specific causation analysis.
Page 13 Cite Bookmark
Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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DASG-PPM-NC

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

  1. General causation is the scientific determination as to whether or not the chemical in question is capable of causing a particular condition in the general population at some specified dose. It is a determination of what toxicities the chemical is known to produce in humans (sometimes extrapolating from animal data). The issue addressed in a general causation analysis is: Has the chemical(s) in question been shown to cause the disease(s) in question in humans? The objective methodology for proving general causation, as currently practiced, has been continually refined for over a hundred years. One of the first efforts to formalize this process occurred when scientists and physicians sought to establish the cause of diseases induced by infectious agents whose presence could not easily or readily be identified with the naked eye, which resulted in Koch’s postulates. In the 1960’s, when scientists were evaluating the role of chemicals in the environment or workplace, or the role of smoking and other habits on disease, criteria that should be considered when assessing causation were identified by the Surgeon General in the assessment of smoking and lung cancer. (U.S. Dept. Health, Education, Welfare, 1964; Hill, 1965).
  2. The criteria for general causation as outlined by Hill are:
    1. The consistency of the association;
    2. The specificity of the association;
    3. Temporality (Do biologically realistic temporal relationships exist?);
    4. Biological gradient (i.e., the principle of dose---response where within some range of doses the incidence of the response increases with increasing dose);
    5. Biological plausibility (the response in humans is likely to be consistent with the observed response in animal tests, or would be predicted from the known animal toxicity and mechanism of action for that toxicity);
    6. Coherence (there is an internal and external consistency to all of the evidence);
    7. Experiment (the response decreases or increases with corresponding decreases or increases in exposure); and
    8. Analogy (structure activity relationships with other chemicals suggest the
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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DASG-PPM-NC

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

chemical should be capable of producing the toxicity of interest).

  1. In order to determine proximate cause, or a “significantly strong causal link” between the test agent and the health outcome, it is necessary to evaluate the strength of the link (the evidence). This approach of grading or qualitatively assessing evidence is referred to as a “level of evidence” or “weight of evidence” approach. There are a variety of frameworks which evaluate the quality of evidence. Many of these are utilized in identifying “evidence-based medicine” recommendations for treatments or screening procedures. The framework may categorize or grade the amount and quality of the evidence or the grade based on the type of study or whether the finding is an expert opinion. Other frameworks were created to evaluate the evidence for carcinogenicity and consider animal testing as well as epidemiological evidence (International Agency for research on Cancer (IARC), EPA). It is well recognized within the scientific/medical community that the above criteria form the scientifically accepted method for establishing general causation. These or very similar criteria have been adopted by the World Health Organization (WHO, 1987), the IARC (2006), the United States Environmental Protection Agency (USE PA) (2005), and the American Council of Governmental Industrial Hygienists (ACGIH) (2014).
  2. The fundamental issues of general causation are generally answered in the scientific literature. Following a review of the available evidence by the members of the BAP, the evidence will be graded, or given weight, based on the quality and/or quantity of the evidence in totality. While there are numerous approaches to weight of evidence, the BAP will utilize the strength of evidence framework used by the Institute of Medicine of the National Academies in the report “Adverse Effects of Vaccines: Evidence and Causality” (IOM, 2012). This approach considers both epidemiologic evidence and a mechanistic assessment to reach a causality conclusion. The first assessment applies to the weight of evidence from the epidemiological literature while the second applies to the weight of evidence from the mechanistic literature, as available. The specific grading described for the epidemiological and mechanistic evidence for vaccines is partially related to the type of information available from vaccine trials, as well as the collection of vaccine adverse events, and so will be modified for to suit the information available to the BAP. As such, the epidemiological literature will be evaluated for its strengths and weaknesses, as well as the type of information or study (case report, cross sectional study, case-control study, or cohort study), size of the population in the study or report, and potential power of the study, and then this information synthesized into a body of evidence and assigned a weight of evidence. Mechanistic information is considered by looking at the mechanism of action of the agent, known target organs of effect, whether the effect is a localized or systemic effect, analogy to other similar
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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DASG-PPM-NC

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

  1. agents, etc. These two assessments evaluate both the quality and the quantity of evidence. These contribute to the third assessment about the causal relationship. The causality conclusions are 1) convincingly supports, 2) favors acceptance, 3) favors rejection, or 4) inadequate to accept or reject. (See flow diagram, “Strength of Evidence that Determined the Causality Conclusions”, IOM, 2012).

  2. Specific causation (i.e., whether the exposure incident in question caused a particular person’s specific health effect) cannot be answered by the scientific literature alone. The mere fact that a chemical may be capable of producing various health effects does not mean that a particular person’s specific adverse health effect is a direct result of the exposure incident. Specific causation is a scientific determination as to whether a known or alleged chemical exposure an individual may have received was the most likely cause of the injuries or diseases of the individual. Assuming that general causation has been established for a given chemical or agent(s) and disease(s), the following additional steps are considered to establish specific causation in an individual person:
    1. The exposure was of sufficient magnitude (concentration and duration) to produce the alleged medical condition (satisfying the principle of dose-response).
    2. The chemical exposure was temporally related to the onset of the alleged medical condition (satisfying the principle of temporality).
    3. Potential alternate causes of the medical condition (confounders) can be adequately ruled out (eliminating alternative possible etiologies for the condition).
    4. There is coherence and consistency in the evidence evaluated in this specific case (establishing that the evidence is consistent with all scientific facts and beliefs).
    5. The BAP will consider this information to the degree that it is available; for example, for the most part, the BAP will likely not have complete information on confounding variables and thus will not be able to rule out alternative etiologies.
  3. In making its determination, the Panel, in its discretion, may also equitably weigh the following factors:
    1. The research program occurred over 40 years ago;
    2. Records concerning the research program may be limited or incomplete;
Page 16 Cite Bookmark
Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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DASG-PPM-NC

SUBJECT: Memorandum of Instruction, Benefits Application Panel Review and Adjudication of Applications for Medical Care

    1. Scientific studies on the long-term health effects of certain chemical or biological substances may be limited or incomplete; and
    2. Evidence related to the precise proximate cause of a particular diagnosed medical condition may not be definitive.
  2. Documentation.
    1. The BAP review will be recorded in memorandum format, and BAP votes and decision rationale will be documented.
    2. After the results are submitted to the MEDCOM CoS, BAP members may not discuss panel proceedings, unless authorized to do so by the CoS/DSG or TSG. If there is a request for specific details regarding the BAP findings, the request should be forwarded to the Staff Judge Advocate (SJA) for legal review regarding what information can be disclosed.
    3. Even though the Project Manager (PM) has determined an application is complete, the BAP may return an application to the PM with a specific request for any additional information if needed by the BAP. The PM will notify the applicant. The applicant will also be notified that the 120 day suspense was paused when the application was returned to the PM.
  3. Decisions to recommend approval or disapproval will be provided to the Program Manager who will coordinate the Secretarial Designee status approval and communicate with the applicant regarding the Board’s decision.
  4. Point of contact for this memorandum is Dr. Coleen Baird. She may be reached at coleen.p.baird.civ@mail.mil, or 410-436-2714.

JOHN J. RESTA

Acting Deputy Chief of Staff for Public Health

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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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Suggested Citation: "Attachment 2." National Academies of Sciences, Engineering, and Medicine. 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press. doi: 10.17226/25025.
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