Section XVII:

Special Requirements and Guidance for Investigators

WPP #: XVII-12

Title 12:

Additional Department of Defense (DoD)-Department of the Navy (DoN) Requirements for Human Subject Protection

Effective Date:

7-30-14

Revision History:

2-15-09; 5-27-14

Policy Statement

All non-exempt research involving human participants supported by the Department of Defense (DoD) must comply with additional requirements established by the DoD in order to be approved by the IRB. DoD-supported research must be reviewed by the VCU IRB (not an external IRB), regardless of funding source (direct or indirect).

Definitions

Classified Research: Research involving the use or access to information that has been classified as top secret, secret, or confidential as determined by the U.S. Government to prevent unauthorized disclosure for the protection of U.S. citizens, U.S. democratic institutions, homeland security, and U.S. interactions with foreign nations.

DoD-supported research involving human subjects: Research involving human subjects for which the Department of Defense is providing at least some of the resources. Resources may include but are not limited to funding through any DoD operation, facilities, equipment, personnel (investigators or other personnel performing tasks identified in the research protocol), providing access to or information about DoD personnel for recruitment, or identifiable data or specimens from living individuals. It includes both DoD-conducted research involving human subjects (intramural research) and research conducted by a non-DoD institution.

DoD personnel: DoD civilian employees and members of the military services.

  • DoD civilian employee: An individual meeting the definition of “employee”. It includes DoD civilian employees filling full-time, part-time, intermittent, or on-call positions; and individuals serving under personal service contracts. It excludes employees of contractors (other than personal services contractors) and foreign nationals of host countries.
  • DoD service members: Individuals appointed, enlisted, or inducted for military service under the authority of the Department of Defense. The Military Services are the Army, Navy, Air Force, Marine Corps, Coast Guard, and the Reserve Components, which includes the Army and the Air National Guards of the United States. Members of the Reserve Components are included when in a duty status.

Research involving human subjects: Activities that include both a systematic investigation designed to develop or contribute to generalizable knowledge AND involve a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or identifiable information.

Research involving a human being as an experimental subject: An activity, for research purposes, where there is an intervention or interaction with a living individual for the primary purpose of obtaining data regarding the effect of the intervention or interaction. Research involving a human being as an experimental subject is a subset of research involving human subjects. This definition does not include activities that are not considered research involving human subjects, activities that meet the exemption criteria, and research involving the collection or study of existing data, documents, records, or specimens from living individuals.

Research monitor: Individuals with expertise consonant with the nature of risk(s) identified within the research protocol, whose role is to protect the safety and well-being of human subjects.

Minimal risk: The definition of minimal risk is based on the phrase “ordinarily encountered in daily life or during the performance of routine physical or physiological examination or tests.” This shall not be interpreted to include the inherent risks certain categories of human subjects face in their everyday life. For example, the risks imposed in research involving human subjects focused on a special population should not be evaluated against the inherent risks encountered in their work environment (e.g., emergency responder, pilot, soldier in a combat zone) or having a medical condition (e.g., frequent medical tests or constant pain.)

Procedures and Guidance

  1. Regulatory Requirements: DoD supported research must comply with the following regulatory requirements:
    • The Belmont Report
    • Title 32 Code of Federal Regulations Part 219 (32 CFR 219), Department of Defense Regulations, “Protection of Human Subjects” (DoD adoption of the “Common Role”)
    • Title 45 Code of Federal Regulations Part 46, (45 CFR 46) Department of Health and Human Services Regulations, “Protection of Human Subjects,” Subparts B, C, and D as made applicable by DODD 3216.02
    • Title 21 Code of Federal Regulations 50, 56, 312, and 812, Food and Drug Administration (FDA) Regulations
    • DoD Instruction (DoDI) 3216.02, “Protection of Human Subjects and Adherence to Ethical Standards in DoD-supported Research”
    • Title 10 United States Code Section 980 (10 USC 980), “Limitation on Use of Humans as Experimental Subjects”
    • DoD Instruction 3210.7, “Research Integrity and Misconduct”
    • DoD Instruction 6200.2, “Use of Investigational New Drugs in Force Health Protection”
    • Department of the Navy
      • SECNAVINST 3900.39D of 6 November 2006
      • SECNAVINST 5720.44B of 1 November 2005
      • SECNAV M-5210.1 of 1 December 2005
      • OPNAVINST 5300.8C of 24 April 2008
  2. Specific Additional Requirements for IRB Review not covered by Title 45 CFR 46, Subparts B, C and D; 21 CFR 50, 56, 312, and 812; and other VCU IRB Written Policies and Procedures (WPP):

    ORSP will ensure principal investigators and research staff are made aware of this WPP and the additional requirements through written communications when research is funded or supported by the DoD. The IRB and ORSP staff will utilize this WPP when conducting reviews of DoD supported research to ensure all DoD specific requirements are met prior to approving research.

    1. Scientific Merit Review

      The IRB must consider the scientific merit of the DoD supported research activity during the IRB review process. The IRB may rely on outside experts to provide an evaluation of scientific merit, such as the Departmental Reviewer or by calling upon an outside consultant.

    2. Appointment of a Research Monitor

      For research involving more than minimal risk to subjects, an independent research monitor must be appointed by name. Research monitors may be physicians, dentists, psychologists, nurses, or other healthcare providers capable of overseeing the progress of research protocols, especially issues of individual subject/patient management and safety. When research involves a research monitor, the following apply:

      • The IRB must approve a written summary of the monitor’s duties, authorities, and responsibilities. The IRB shall communicate with research monitors to confirm their duties, authorities, and responsibilities. The duties of the research monitor should be determined on the basis or specific risks or concern about the research. The monitor may perform oversight functions (e.g., observe recruitment, enrollment procedures, and the consent process for individuals, groups or units; oversee study interventions and interactions; review monitoring plans and unanticipated problem reports; and oversee data matching, data collection, and analysis) and report their observations and findings to the IRB or a designated official.
      • Research monitors must be independent of the investigative team.
      • The research monitor should possess sufficient educational and professional experience to serve as the subject/patient advocate. There may be more than one research monitor if different skills or experiences are necessary. The monitor may be an ombudsman or a member of the data safety monitoring board.
      • The research monitor may discuss the research protocol with investigators, interview human subjects, and consult with others outside of the study about the research.
      • The research monitor has the authority to stop a research protocol in progress, remove individual human subjects from a research protocol, and take whatever steps are necessary to protect the safety and well-being of human subjects until the IRB can assess the monitor’s report.
      • The research monitor must promptly report observations and findings to the IRB or other designated official.
      • The research monitor is appointed by name.
      • There may be more than one research monitor if different skills or experience are needed.
      • The monitor may be an ombudsman or a member of the data and safety monitoring board.
    3. Additional protections for pregnant women, prisoners, and children (Subparts B, C and D) of 45 CFR 46)

      Research supported by the Department of Defense must apply 45 CFR Subparts B, C, and D with the following additional stipulations:

      • Subpart B – Pregnant Women, Fetuses and Neonates
        • When applying Subpart B, the phrase “biomedical knowledge” is replaced with “generalizable knowledge”.
        • The applicability of the subpart is limited to research involving 1) pregnant women as participants in research that is more than minimal risk and includes interventions or invasive procedures to the woman or the fetus; or 2) involving fetuses or neonates as participants
        • No research on nonviable living human fetuses ex utero or a living human fetus ex utero for whom viability has not been ascertained may be conducted unless the research
          • May enhance the well-being or meet the health needs of the fetus or enhance the probability of its survival to viability; or
          • Will pose no added risk of suffering, injury, or death to the fetus and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means.
          • Fetal research must comply with the US Code Title 42, Chapter 6A, Subchapter III, Part H, 289g.
          • If consent is to be obtained from the experimental subjects’ legal representative, the research must intend to benefit the individual participant.
          • The determination that research is intended to be beneficial to the individual experimental subject must be made by an IRB.
      • Subpart C - Prisoners
        • Research involving prisoners must be reviewed by the convened IRB. The prisoner representative must be present in order to obtain quorum.
        • In addition to the categories of allowable research under Subpart C, epidemiological research is allowable when:
          • The research describes the prevalence or incidence of a disease by identifying all cases or studies potential risk factor association for a disease;
          • The research presents no more than minimal risk; and
          • The research presents no more than an inconvenience to the participant
        • When a participant becomes a prisoner:
          • The PI may assert that it is in the best interest of the prisoner-participant to continue in the research. The IRB chair may determine that the prisoner-participant may continue until the convened IRB can review a request to change the research protocol and until the organizational official and DoD Component office review the IRB’s approval to change the research protocol. Otherwise, the IRB chair shall require that all research interactions and interventions with the prisoner-subject (including obtaining identifiable private information) cease until the convened IRB can review this request to approve a change in the research protocol.
          • The convened IRB must re-review the research protocol to ensure the rights and well being of the prisoner-participant are not in jeopardy. The prisoner representative must be involved in this evaluation. The panel may approve the addition of the prisoner-participant when:
            • The prisoner-participant can continue to consent and is capable of meeting the research protocol requirements;
            • The terms of the confinement does not inhibit the ethical conduct of the research; and
            • There are no other significant issues preventing the research involving the prisoner-participant from continuing as approved.
          • The approval of the convened IRB is limited to the individual prisoner-participant.
        • Research involving any person captured, detained, held or otherwise under the control of DoD personnel (military and civilian, or contractor employee) is prohibited. This prohibition does not apply to research involving investigational drugs and devises when the same products would be offered to US military personnel in the same location for the same condition.
        • Research involving prisoners of war is prohibited.
        • The IRB is aware of the definition of “prisoner of war” for the DoD component granting the addendum.

        For purposes of this paragraph, actions authorizing or requiring any action by an official of the Department of Health and Human Services (HHS) shall be under the authority of the Director, Defense Research and Engineering.

      • Subpart D – Children
        • Research involving children cannot be exempt
    4. Additional safeguards for research conducted with international populations

      Research involving human subjects who are not U.S. citizens or DoD personnel, conducted outside the United States, and its territories and possessions, requires permission of the host country. The laws, customs, and practices of the host country and those required by this instruction will be followed. An ethics review by the host country, or local Naval IRB with host country representation, is required.

    5. Limitation of waivers and exceptions from informed consent

      When research involves human beings as experimental subjects (an intervention or interaction with a living individual for the primary purpose of obtaining data regarding the effect of the intervention or interaction), the IRB may not waive the requirement for informed consent. The Secretary of Defense may waive the prohibition in this section with respect to a specific project to advance the development of a medical project necessary to the armed forces if the research project may directly benefit the subject and is carried out in accordance with all other applicable laws.

      Note: The IRB cannot waive the requirement for informed consent or grant an exception from informed consent for emergency research unless it has documentation that the Secretary of Defense has approved it.

    6. Use of a legally authorized representative to obtain informed consent

      A legally authorized representative may provide informed consent on a subject’s behalf only when the research is intended to benefit the individual subject.

    7. Research-related Injury

      When collaborating with a DoD component on greater than minimal risk research, the disclosure for research-related injury should follow the requirements of the collaborating DoD component.

    8. Requirements for Involving DoD Personnel (Service and Civilian) as Subjects
      • Superiors are prohibited from influencing the decisions of their subordinates regarding participation as subjects in research.
      • Superiors may not be present at any human subject recruitment sessions or during the consent process in which members of units under their command are afforded the opportunity to participate as human subjects.
      • Ombudsman - When greater than minimal risk research involves Service members as human subjects and when recruitment occurs in a group setting, the IRB must appoint an ombudsman. The ombudsman should not be associated in any way to the research and will be present during the recruitment in order to monitor that the voluntary involvement or recruitment of the Service members is clearly and adequately stressed and that information provided about the research is clear, adequate and accurate. The ombudsman may also be the research monitor.

      For research involving Service members, determined to be no greater than minimal risk, and when recruitment is occurring in a group setting, the IRB will determine when it is appropriate to appoint an ombudsman for the same purposes. For research involving civilians as human subjects and when recruitment occurs in a group setting, the IRB will discuss appointing an ombudsman for the purposes described above. The decision to require the appointment of an ombudsman should be based in part on the human subject population, the consent process, and the recruitment strategy.

      Officers and senior non-commissioned officers will have a separate opportunity to participate.

    9. Limitations on compensation for U.S. military personnel
      • The Dual Compensation Act prohibits an individual from receiving pay from more than one position for more than an aggregate of 40 hours of work in one calendar week. This prohibition applies to employees paid from either appropriated or non-appropriated funds, or a combination thereof, and includes temporary, part-time and intermittent appointments. This law is not applicable to enlisted off-duty military personnel in relation to their military duty.
      • Human subjects involved in DoD supported research involving human subjects may be compensated for blood draws in the following ways:
        1. On-Duty Federal Personnel and non-Federal Personnel: may be compensated for blood draws for research up to $50 for each blood draw.
        2. Non-Federal Personnel: when the research is not federally funded, may be compensated for research participation other than blood draws in a reasonable way as determined appropriate by the IRB according to local prevailing rates and the nature of the research.
        3. Note: DoD3126.02 stipulates that on-duty federal personnel may be compensated in limited circumstances. It is the policy of the VCU IRB, however, to restrict all compensation for on-duty personnel.
    10. Survey research requires additional review

      Surveys of DoD military members and their families and DoD civilian personnel must be approved through the appropriate DoD authority prior to implementation to ensure surveys provide maximum benefits. Surveys must be administered according to the requirements outlined in OPNAVINST 5300.8C

      A Privacy Act Statement must be displayed prominently on all Navy personnel surveys without exception regardless of whether personal identifiers are requested. The statement will identify the authority for survey administration (including OPNAV RCS and expiration date), advise respondents of the purpose and routine uses of the survey, indicate that the survey is voluntary, explain the intended use(s) of the data, and describe measures used to safeguard confidentiality. The IRB may choose to combine the privacy statement with an informed consent document.

    11. Provisions for research with human subjects using investigational test articles (drugs, device and biologics)

      Principal investigators may not be sponsors for INDs and IDEs.

    12. Multi-Site research

      When conducting multi-site research, a formal agreement between organizations is required to specify the roles and responsibilities of each party.

    13. Classified research

      When the research activity involves classified information, the following must apply:

      • Prior approval from the Secretary of Defense must be obtained.
      • The IRB review must be conducted by the convened panel. Expedited review is not permissible.
      • Informed consent may not be waived.
      • Informed consent procedures must include:
        • Identification of the DoD as the supporting institution of the research, unless the research involves no more than minimal risk. The Secretary of Defense may waive this requirement.
        • A statement that the research involving human subjects is classified and an explanation of the impact of the classification.
      • The IRB must determine whether potential human subjects need access to classified information to make a valid, informed consent decision.
      • Disclosure or use of classified information complies with the federal requirements for access to and protection of classified information.
      • Any IRB member who disagrees with a majority decision to approve a research activity may appeal the decision to the Secretary of Defense.
    14. Educational Requirements
      • All research personnel engaged in the conduct of research supported by the Department of Defense must complete initial and continuing research ethics education. The VCU CITI training program fulfills this basic requirement. The DoD component supporting the research may require additional specific education or certification, which research personnel must complete.
      • The DoD component supporting the research may evaluate the VCU education policies and programs to ensure research personnel are qualified to perform the research, based on the complexity and risk of the research.
  3. Reporting Requirements
    1. Principal Investigator Reporting Requirements

      The Principal Investigator is responsible for notifying the Human Research Protection Office of the DoD, within 30 days, of all of the following:

      • Initial approval has been granted by the VCU IRB
      • When significant changes to the research protocol are approved by the IRB
      • The results of the IRB continuing review
      • A change of reviewing IRB
    2. Office of Research Subject Protection Reporting Requirements

      The ORSP is responsible for notifying, within 30 days of identifying a reportable event, the Human Research Protection Office of the DoD, the DoN Human Research Protections Program (HRPP) Office, and supporting DoD component of the following:

      • All suspensions or terminations of previously approved research protocols.
      • The initiation and results of investigations of alleged non-compliance with human subject protections.
      • Unanticipated problems involving risks to subjects or others.
      • Any for-cause investigations of DoD-supported research conducted by any Federal department of agency or national organization.
      • All restrictions, suspensions, or terminations of institutions’ assurances.
    3. Office of Research Integrity and Ethics Reporting Requirements

      When research misconduct is investigated, the following, as applicable, must be reported to the Administrative Contracting Officer, Grants Office, Agreement Officer, or other designated official:

      • If public health or safety is at risk.
      • The research institution’s resources or interests are threatened or at risk.
      • Research activities are to be suspended because of the inquiry into or investigation of a research misconduct allegation.
      • There is a possible violation of civil or criminal law.
      • Action to protect the interests of those involved in the inquiry into or investigation of the allegation is required from the DoD Component.
      • A premature public disclosure of the inquiry into or investigation of the allegation may compromise the process.
      • The broader research community or public should be informed.
      • Following completion of the investigation, provide a copy of the evidentiary record, the report of the investigation, recommendations made to the institution’s adjudicating official, and the written response of the individual that is the subject of the allegation to any recommendations.
      • All findings of research misconduct shall be reported to the Director, Defense Research and Engineering.

Records maintained that document compliance or non-compliance with DoD requirements shall be made accessible for inspection and copying by representatives of the DoD at reasonable times and in a reasonable manner as determined by the supporting DoD component.

References

See body of WPP