60. Department of Defense (DoD) Regulations for Human Subject Research
Human research that is supported or conducted by the Department of Defense (DoD), or that involves of DoD personnel must comply with the Common Rule, Subparts B, C, and D (32 CFR 219); the DoD Instruction, Number 3216.02, November 8, 2011; Dual Compensation Act; DoD Directive 3216.2, SECNAVINST 3900.39D; OPNAVINST 5300.8C; 10 U.S.C. 980: Limitation on use of humans as experimental subjects; and other regulations as applicable, including those specific to the separate DoD components: Army, Navy, Air Force and Marine Corps.
A DoD researcher form and review worksheet are used to assess DoD-supported research projects for the additional DoD regulations. In presenting the protocol to the IRB, the primary reviewer will address the additional DoD regulatory requirements.
Additional DoD Requirements for Ethics Training and Risk Assessment
Each DoD component has educational requirements in the conduct of human research for personnel involved in the conduct, review, or approval of research sponsored by DoD. The type and extent of training depend upon the duties and responsibilities of the persons involved in the research.
University and affiliate PIs are advised to consult with the DoD component sponsoring or involved in the research to identify the specific or additional educational or certification requirements.
University and affiliate PIs are responsible for
- Conveying additional DoD training requirements to the IRB
- Providing the DoD Component and the IRB with verification that the additional training requirements have been met. IRB approval is contingent on this verification
The DoD component may evaluate the University's HRPP training policies to determine that, based on the complexity and risk of the research, personnel are qualified to perform the research.
Assessing Risk in DoD-supported Research
Federal regulations at 45CFR46.102, item (i) and 32CFR219.102, item (i) state that "minimal risk means the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests." However, additional constraints apply to the definition of minimal risk under DoD requirements (DoD Instruction 3215.02 11/09/2011 ver, p 19). For DoD research, when making minimal risk determinations, PIs may NOT consider the inherent risks certain categories of human subjects face in their everyday lives. Specifically, when research involves a special population, the risks imposed by the research must not be evaluated against
- the inherent risks encountered in the populations' work environment (e.g., emergency responder, pilot, soldier in a combat zone); or
- the inherent risks of having a medical condition (e.g., frequent medical tests or constant pain).
Additional DoD Review Requirements
Requirements for Review of Non-exempt DoD Classified Research
- The involvement of classified information must be limited to information needed for IRB approval and oversight of the research, and to inform the human subjects during the consent process; and information provided by the human subjects during the course of the research.
- Classified non-exempt human subject research must be approved by the Secretary of Defense; the research is submitted by the Head of the OSD or the DoD Component conducting the research.
- Waivers of informed consent are prohibited for DoD Classified Research.
- Informed consent procedures for greater than minimal risk research must identify the DoD as the supporting institution unless the requirement is waived by the Secretary of Defense.
- Informed consent procedures must identify the research as classified and explain the impact of the classification.
- All classified DoD Research will be reviewed by the convened IRB.
- During the review, at least one voting IRB member must be a non-Federal employee.
- Any IRB member who disagrees with the Board's determination may appeal the determination to the Secretary of Defense.
- The IRB must determine whether prospective participants need access to classified material to make a valid, informed consent decision.
- Disclosure or use of classified information must comply with the requirements for access to and protection of classified information (see Executive Order 13526, "Classified National Security Information," December 29, 2009).
Requirements for Non-DoD Institutional Review
- As with all research, the University IRB will consider the scientific merit of DoD research and may rely on outside experts to provide an evaluation of same.
- Substantive changes to approved DoD-sponsored research, including modifications to research reviewed by expedited procedures, must undergo scientific review prior to IRB review.
Requirements for Concurrence or Administrative Review by DoD HRPO or Component Representative
HRPO or DoD Component Concurrence/Administrative Review
The DoD HRPO (Human Research Protection Official) must concur with all RI or IRB determinations of "not human subject research" or "exempt research" before project activities may be initiated.
If the University IRB determines an activity is non-exempt research involving human participants, the DoD HRPO must administratively review and approve the research, including substantive revisions requested by the IRB, as specified in DoDI 3216.02 Enclosure 3, 4.c.(2)(a)-(3) before the activities that involve human participants can begin. The purpose of this approval is to confirm the research is compliant with DoD regulations and directives; and all applicable laws and requirements, and cultural sensitivities for DoD research conducted in a foreign country.
The DoD HRPO must administratively review and approve surveys developed for administration to DoD personnel, after IRB review and approval and before activities involving human participants may commence.
The following conditions require administrative review and approval by the DoD component:
- Collaborative research in which a DoD institution will rely on a University IRB.
NOTE: Requires a written agreement specifying the responsibilities and authorities of both organizations, use of the University's FWA, and that the involvement of DoD personnel is secondary to that of the University.
- DoD-supported research permitting a waiver of informed consent.
NOTE: University and affiliate investigators have never and are not expected to engage in DoD-supported fetal research, making requirements for DoD administrative review of fetal research moot.
Also see the section "Additional DoD Reporting Requirements" at the end of this policy.
IRB Notification of DoD HRPO or Component Concurrence/Administrative Review
In all cases when DoD HRPO or Component concurrence or administrative review is required, the PI must provide documentation of the required concurrence/review in a subsequent package. The IRB will acknowledge the documentation and confirm that research activities involving human participants may commence.
Additional DoD Requirements for Research Monitors
A medical monitor must be appointed for research involving more than minimal risk. The IRB may require a research monitor for a portion of and for all aspects of studies involving no more than minimal risk.
- The medical monitor is appointed by name.
- University and affiliate PIs must name the medical monitor in the application.
- The monitor may be an ombudsman or a member of the data safety monitoring board.
- The medical monitor must be independent of the team conducting the research.
- There may be more than one research monitor if different skills or experiences are needed.
The IRB must approve a written summary from the Principle Investigator regarding the monitors' duties, authorities, and responsibilities. The duties of the research monitor are determined on the basis of specific risks or concerns about the research and may include the following:
- Observing recruitment, enrollment, and consent processes;
- Overseeing study interventions and interactions;
- Reviewing monitoring plans and unanticipated problems involving risks to participants or others;
- Overseeing data collection and analysis;
- Discussing the research protocol with investigators;
- Interviewing human participants;
- Consulting with others outside of the study; and
- Reporting observations and findings to the IRB or a designated official.
The research monitor may take any steps necessary to protect the safety and well-being of participants until the IRB can assess the situation or incident including
- Stopping a research study in progress, or
- Removing individuals from the study.
Additional DoD Requirements for Command Permission, Recruitment, and Informed Consent
Requirements for Command Permission for Service Members to Participate in Human Subject Research
Service members must follow their command policies regarding the requirement to obtain command permission to participate in research involving human subjects while on-duty. Additionally a Service member's ability to perform his or her military duties may be affected by participating in research during off-duty time (i.e., on leave or during non-duty hours). Therefore, Service members shall follow their Component and command's policies for approving off-duty employment or activities. The University IRB requires the PI to indicate if command permission is required and if so, to describe how the PI will confirm each Service member's commander supports that member's participation in DoD-supported human research.
Requirements for Recruitment
- Officers are not permitted to influence the decision of their subordinates.
- Officers and senior non-commissioned officers cannot be present at the time of recruitment.
- Officers and senior non-commissioned officers must be given a separate opportunity to participate (when applicable).
When research involves service members and recruitment will take place in a group setting, an independent ombudsman must be present when risk is greater than minimal. Under similar conditions when research risk is no greater than minimal, the IRB may require that an ombudsman be appointed. In the latter case, The IRB will base its decision to require an ombudsman on the sample population, and recruitment and consent processes.
Requirements for Informed Consent
- For individuals with impaired consent capacity when consent is to be obtained from participants' legal representative
o the intent of the research must be to benefit the individual participant, and
o an IRB must make the determination that the intent of the research is to benefit the individual experimental subject.
- Waivers of informed consent are prohibited for classified research.
- Waivers of informed consent are prohibited for non-exempt research involving a human being as an experimental subject (see Policy Manual Definitions) unless a waiver is obtained from the Assistant Secretary of Defense for Research and Engineering. The waiver may only be obtained when the research
o is necessary to advance the development of a medical product for the Military Services,
o may directly benefit the individual experimental subject, and
o is conducted in compliance with all other applicable laws and regulations.
- Research-related injury language in consent documents must follow the requirements of the DoD component. University and affiliate PIs conducting DoD research are advised to contact the DoD component for details about component-specific language.
o Stricter requirements for disclosure of research-related injury language may apply: See item 10.b. in the DoD Directive 3216.02: Protection of Human Subjects and Adherence to Ethical Standards in DoD-Supported Research
NOTE: Neither University nor Affiliate investigators conduct planned emergency research. Therefore the DoD prohibition against waiving informed consent for planned emergency research does not apply.
Additional DoD Requirements for Special or Vulnerable Populations
See informed consent (above) for DoD requirements for obtaining consent for individuals with impaired consent capacity.
DoD Prohibitions on Research Involving Prisoners of War or Detainees
- Research with prisoners of war is prohibited. Investigators should refer to the definition of "prisoner of war" for the particular DoD component supporting the research.
- Research involving a detainee is prohibited unless
o an investigational new drug or investigational device is offered to detainees with the detainees' informed consent, and
o the same product would be offered to members of the U.S. Military Services in the same location for the same medical condition.
Additional DoD Requirements for Research Involving Prisoners
- DoD research involving prisoners cannot be reviewed by the expedited procedure and the IRB prisoner representative must be present for the quorum.
- DoD allows epidemiological research involving prisoners when the following are true:
o The research describes the prevalence or incidence of a disease by identifying all cases, or studies potential risk-factor associations for a disease.
o The research presents no more than minimal risk and presents no more than an inconvenience to the participant.
- When a research participant becomes a prisoner while enrolled in DoD research, the PI must notify the IRB of the change in the participant's status to prisoner.
o If the PI asserts it is in the incarcerated participant's best interest to continue in the research, the IRB chair may determine that she/he may continue to participate until both of the following occur:
(1) The convened IRB reviews and approves a change in the research protocol to allow the participant to continue in the study while a prisoner. (See below for the role of the prisoner representative for the review.)
(2) The University or affiliate IO, and the DoD component review and agree with the IRB's decision.
o If the PI cannot assert it is in the prisoner-participant's best interest to continue in the research, the IRB chair shall require that all research interactions and interventions with the prisoner-participant cease until the convened IRB can review the change in the research protocol.
o Upon receipt of notification that a previously enrolled human participant has become a prisoner, the prisoner representative at a convened IRB meeting
(1) shall re-review the research protocol to ensure that the rights and wellbeing of the human participant, now a prisoner, are not in jeopardy;
(2) shall review the request to modify the protocol; and
(3) may recommend approval of the modification if all of the following conditions are met:
§ The prisoner-participant can continue to participate voluntarily and fully-informed.
§ The prisoner participant is capable of meeting the research protocol requirements.
§ The terms of the prisoner-participant's confinement does not inhibit the ethical conduct of the research.
§ There are no other significant issues preventing the research involving human participants from continuing as approved.
NOTE: This review and approval is limited to the continued participation of the individual prisoner-participant and does not allow recruitment of prisoners as participants.
Additional DoD Requirements for Research Involving Pregnant Women, Human Fetuses and Neonates
- For purposes of these requirements, the phrase "biomedical knowledge" shall be replaced with "generalizable knowledge" and be interpreted to have the same meaning.
- The applicability of 45 CFR 46 subpart B is limited to research
o that is more than minimal risk and
o includes interventions or invasive procedures to the woman or the fetus, or fetuses or neonates (i.e., newborns as defined in §46 subpart B).
- Fetal research must comply with US Code Title 42, Chapter 6A, Subchapter III, Part H, 289g.
Additional DoD Requirements for Compensation in Research
- US military personnel are prohibited from receiving compensation for research participation during duty hours but may be compensated when participation occurs when personnel are involved in the research when not on duty.
- Federal employees while on duty and non-Federal persons may be compensated for up to $50 for each blood draw for research.
- Non-Federal persons may be compensated for research participation other than blood draws in a reasonable amount as approved by the IRB according to local prevailing rates and the nature of the research.
DoD Requirements for Multi-site or Transnational Research
For multi-site DoD-sponsored research, the participating organizations must have a formal agreement that specifies the roles and responsibilities of each party.
University and affiliate investigators proposing to conduct transnational DoD-research must complete and submit an application for international research. This form requests information about the foreign government's standards of review, identification of the host site and local mentor, and the name of the local IRB or ethics board with contact person.
- The investigator must have permission to conduct research in that country by certification of local ethics review and provide the IRB with documentation of that approval.
- Documentation of local ethics review must address specific local requirements for human participant research and identify any legal issues that bear consideration.
- If local review is not required, the PI must verify to the IRB that local review is not required.
- If local review is not possible, the PI must submit a letter to the IRB explaining why local review is not possible.
- The investigator must agree to abide by all applicable local laws regulations, customs, and practices, and all requirements of the local IRB or ethics board reviewing the research.
Periodically, but no less than annually, the RI QA/QI Officer, qualified designee, or local entity must conduct a systematic and independent examination to assess whether the research activities were implemented; and the data were recorded, analyzed and accurately reported according to the IRB protocol.
- The examination may involve a review of materials and documents provided by the investigator.
- The assessment may include interviews with the local mentor, monitoring body (if present) or research participants; or a site visit.
DoD Prohibition on Human Subject Research Involving Chemical or Biological Agents
DoD research involving use of humans for testing of chemical or biological agents is generally prohibited.
Additional DoD Reporting Requirements
University and affiliate principal investigators are responsible for informing the DOD-component human research protection officer within 30 days of any of the following:
- significant changes to the research protocol that are approved by a University IRB (including amendments approved by expedited procedures);
- results of IRB continuing review (including continuing review by expedited procedures);
- change of reviewing IRB;
- IRB determinations of unanticipated problems involving risks to subjects or others, or serious or continuing noncompliance;
- suspension or termination DoD research; and
- notification that any part of the University HRPP is under for-cause investigation by any Federal department, agency or national organization for a DoD research protocol.
The University IRB will ensure records documenting compliance and noncompliance with DoD regulations are accessible for inspection and copying by representatives of the DoD at reasonable times and in a reasonable manner as determined by the relevant DoD component.