Office of Human Research Ethics SOP 2001: Research Supported by the Department of Defense (DoD)

Title

Office of Human Research Ethics SOP 2001: Research Supported by the Department of Defense (DoD)

1. Purpose

The purpose of this SOP is to ensure compliance with Department of Defense (DoD) requirements regarding the conduct of human subjects research.  Research supported by the DoD is reviewed and conducted in compliance with 32 CFR 219, 10 USC 980, applicable parts of 21 CFR (50, 56, 312, 600, 812), DoD Instruction 3216.02, DoD Instruction 3210.07, and applicable additional requirements from respective DoD component(s).

2. Responsibilities

It is the responsibility of the principal investigator to ensure compliance with all additional Department of Defense (DoD) requirements for human subject protection. It also is the responsibility of the IRB to ensure that all additional requirements by Department of Defense components for human subject protection have been met before IRB approval of the research project.

3. Definitions

The following definitions apply to human subjects research supported by the DoD or one of its components:

Research means any systematic investigation, including research, development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.

Research involving a human being as an experimental subject means an activity, for research purposes, where there is an intervention or interaction with a human being for the primary purpose of obtaining data regarding the effect of the intervention or interaction. If consent is to be obtained from the subject’s legal representative, the intention of the key investigator must be for the research to be beneficial to the subject.

Minimal risk means that 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. The phrase “ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or test”" must 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 populations should not be evaluated against the inherent occupational risks that certain subjects face in their everyday life (e.g., those encountered by Service members, law enforcement, or first responders while on duty; risks resulting from or associated with high-risk behaviors or pursuits; risks experienced by individuals whose medical conditions involve frequent tests or constant pain).

4. Procedures

The following additional requirements apply to all biomedical and social/behavioral research involving human research participants conducted under the jurisdiction of the University of North Carolina at Chapel Hill (UNC-Chapel Hill) when it:

1. Conducts, reviews, approves, oversees, supports manages otherwise is contractually subject to regulation by the DoD; and/or
2. Human subject research performed under the jurisdiction of UNC-Chapel Hill using DoD property, facilities, or assets.

In most cases, protocols covered by these requirements also will have review, approval and oversight by the DoD Human Research Protections Program. For clarity, the DoD requires Component Level Administrative Review (CLAR) of all non-exempt human subjects research when any of the following conditions occur:

• Research is conducted in a foreign country, unless it is conducted by a DoD overseas institution, or involves subjects who are DoD-affiliated personnel that are U.S. citizens;
• The research requires a waiver of informed consent pursuant to Title 10 U.S.C. Section 980, Paragraph (b);
• The research is fetal research as described in Sections 289g-289g-2 of Title 42, U.S.C.;
• Large scale genomic data is collected from DoD-affiliated personnel;
• Research is required to be approved by the DoD Directorate of Human Research Protections (DOHRP).

UNC-Chapel Hill assures that DoD supported research complies with all relevant DoD human subjects protection requirements, including but not limited to:

1. The Belmont Report;
2. Title 32 Code of Federal Regulations Part 219 (32 CFR 219), Department of Defense Regulations, “Protection of Human Subjects” (DoD adoption of the “Common Rule”);
3. 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 DoD Instruction (DoDI) 3216.02;
4. Title 21 Code of Federal Regulations 50, 56, 312, and 812, Food and Drug Administration (FDA) Regulations;
5. DoDI 3216.02, “Protection of Human Subjects and Adherence to Ethical Standards in DoD-supported Research;"
6. Title 10 United States Code Section 980 (10 USC 980), “Limitation on Use of Humans as Experimental Subjects;"
7. DoDI 3210.7, “Research Integrity and Misconduct;" and
8. DoDI 6200.2, “Application of Food and Drug Administration (FDA) Rules to Department of Defense Force Health Protection Programs."

4.1 - Key Additional Requirements Not Covered by 45 CFR 46, Subparts B, C and D or 21 CFR 50, 56, 312, and 812

Research Involving Testing of Chemical or Biological Agents

UNC-Chapel Hill permits research involving chemical or biological agents under the exceptions set forth in Section 1520a of Title 50 U.S.C. Such research is subject to review as specified in UNC-Chapel Hill Office of Human Research Ethics (OHRE) policies and other applicable University policies and standard operating procedures.

Scientific Merit 

The IRB must consider the scientific merit of the study. The IRB may rely on outside experts to provide an evaluation of the scientific merit of the research. Scientific review conducted by another site in a multi-site study may be sufficient.

Education and Training 

Individual DoD components may have stricter or specific educational requirements and may require re-certification more frequently than currently mandated by the UNC-Chapel Hill OHRE. Accordingly, UNC-Chapel Hill researchers conducting DoD-supported research may be required to complete training beyond that required by the UNC-Chapel Hill OHRE.  Researchers should contact their DoD Program Officer or DoD Component Human Research Protections Officer (HRPO) to inquire about any unique requirements. UNC-Chapel Hill Principal Investigators are responsible for ensuring that all study team members engaged in conducting DoD-supported research complete required training.

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. UNC-Chapel Hill may conduct research involving experimental subjects.

4.2 - Additional Protections for Pregnant Women, Prisoners, and Children (Subparts B, C and D) of 45 CFR 46)

Research Involving Pregnant Women, Fetuses or Neonates as Human Subjects

Research involving pregnant women, fetuses or neonates as human subjects is subject to the following:

• For purposes of applying Subpart B, the phrase “generalizable knowledge" replaces the phrase “biomedical knowledge."
• The applicability of Subpart B is limited to research involving 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 involving fetuses or neonates as participants.
• Fetal tissue research must comply with the US Code Title 42, Chapter 6A, Subchapter III, Part H, 289g-289g-2.

Research Involving Prisoners as Human Subjects

• In addition to the categories of permissible human subjects research involving prisoners identified in 45 CFR 46, Subpart C, two additional categories are permissible:
  • Epidemiological research that meets the waiver criteria in accordance with Pages 36929-36931 of Volume 69, Federal Register, may be approved in accordance with the applicable requirements of Subpart C, DoDI 3216.02, and other applicable requirements.
  • Human subjects research that would otherwise meet exemption criteria may be conducted, but must first be approved by an IRB and must meet the requirements in 45 CFR 46, Subpart C, DoDI 3216.02, and other applicable requirements.

Research Involving Children as Human Subjects

Human subjects research involving children as subjects must comply with 45 CFR 46, Subpart D. 

Research Involving a Detainee or Prisoner of War as a Human Subject

Research involving a detainee or prisoner of war as a human subject is prohibited.

• However, this prohibition does not apply to activities covered by investigational new drug or investigational device provisions of Title 21 CFR, when the purpose is for diagnosis or treatment of a medical condition in a patient.
• Such treatment may be offered to detainees or prisoners of war with their informed consent when the medical products are subject to Title 21 CFR, and only when the same product may be available to DoD-affiliated personnel consistent with established medical practices.

4.3 - DoD-Affiliated Personnel as Subjects in DoD-Conducted or -Supported Human Subjects Research

If the human subjects research involves DoD-affiliated personnel as subjects and if the human subjects research includes any risks to their fitness for duty (e.g. health, availability to perform job, data breach), the informed consent document must inform DoD-affiliated personnel about these risks and that they should seek command or Component guidance before participating.

If the human subjects research involves DoD-affiliated personnel, the key investigator must receive command or Component approval to execute the research.

Military and civilian supervisors, officers, and others in the chain of command are prohibited from influencing their subordinates to participate in human subjects research and must not be present at any human subjects research participant recruitment sessions or during the consent process for DoD-affiliated personnel. Excluded supervisors or those in the chain of command may participate in separate recruitment sessions, if applicable.

In order to approve research involving DoD-affiliated personnel as human subjects, the IRB or HRPO must determine whether the following requirements have been satisfied:

• The consent documentation must include, if applicable, potential risks for the revocation of clearance, credentials, or other privileged access or duty.

For greater than minimal risk research, and when recruitment occurs in a group setting, the IRB must appoint an ombudsperson. The ombudsperson:

1. must not have a conflict of interest with the research or be part of the research team;
2. must be present during the recruitment, monitoring that the recruitment and informed consent explain that participation is voluntary and that the information provided about the research is consistent with the IRB-approved script and materials, including digitally-provided materials; and
3. should be available to address DoD-affiliated personnel’s concerns about participation.

As specified elsewhere in this SOP, compensation to DoD-affiliate personnel for participation in research while on duty is prohibited, with some exceptions for purposes consistent with Section 30 of Title 24 U.S.C.

4.4 Research Involving Large-Scale Genomic Data (LSGD) on DoD-Affiliated Personnel

All research involving LSGD collected from DoD-affiliated personnel will apply an HHS Certificate of Confidentiality pursuant to Title 42 U.S.C. and Public Law 114-255.

Research involving LSGD collected from DoD-affiliated personnel is subject to DoD Component security review to ensure the adequacy of the proposed administrative, technical, and physical safeguards, including the secondary use or sharing of de-identified data or specimens.

4.5 Limitation of Waivers and Exceptions from Informed Consent

If the research participant meets the definition of “experimental subject,” policies and procedures prohibit a waiver of the consent process unless a waiver is obtained from the DOHRP or its delegate. The DOHRP or its delegate may waive the requirements for consent when all of the following are met:

• The research is to advance the development of a medical product necessary to the DoD;
• The research may directly benefit the individual experimental subject; and
• The research is conducted in compliance with all other applicable laws and regulations.

4.6 Limitations on Compensation for U.S. Military Personnel - [Dual Compensation Act and 24 U.S.C. 30]

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 if not applicable to enlisted off-duty military personnel in relation to their military duty.

When research involves U.S. military personnel, limitations on dual compensation include:

• Federal employees while on duty and non-Federal persons may be compensated for blood draws for research up to $50 for each blood draw.
• 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.
• Prohibit an individual from receiving pay of compensation for research during duty hours.
• U.S. military personnel may be compensated for research if the participant is involved in the research when not on duty.

4.7 Protecting Human Subjects from Medical Expenses if Injured

DoD-supported research involving human subjects: All non-exempt human subjects research must meet the requirement in Section 219.116 of Title 32 CFR.

DoD-conducted research involving human subjects:  All human subjects research that is determined to be greater than minimal risk must meet the requirement of Section 219.116 of Title 32 CFR, to provide subjects with an explanation as to whether any compensation and any medical treatments are available for research-related injuries.

Explanations must include a statement that subjects may, for the duration of the study, be eligible for health care services for research-related injuries at a military treatment facility, in accordance with Part 108 of Title 32 CFR. This eligibility for health care services extends beyond subjects’ participation in the study to such time after the study has ended, in accordance with Section 219.108 of Title 32 CFR.

Institutional HRPPs must document how institutions will care for subjects with research-related injuries, including injuries that are the direct result of activities performed by DoD-affiliated personnel in studies that are collaborative with a non-DoD institution.

Subjects injured in DoD-conducted research may obtain care for such injuries at a DoD medical treatment facility on a space-available basis during the pendency of the research study in accordance with DoDI 6025.23.

4.8 Requirements for Reporting

The Institution must promptly (no longer than within 30 days) notify the HRPO of the following:

• Significant changes to the research protocol approved by the IRB;
• Transfer of oversight to a different IRB;
• Notification by any federal body, State agency, official governing body of a Native American or Alaskan native tribe, other entity, or foreign government that the non-DoD institution’s DoD-supported human subjects research is under investigation;
• Any problems involving risks to subjects or others, suspension or termination of IRB approval, or any serious or continuing noncompliance pertaining to DoD-supported human subjects research;
• The results of the IRB’s continuing review, if required;
• Change in status when a previously enrolled human subject becomes pregnant, or when the researcher learns that a previously enrolled human subjects is pregnant, and the protocol was not reviewed and approved by the IRB in accordance with 45 CFR 46, Subpart B;
• Change in status when a previously enrolled participant becomes a prisoner, and the protocol was not reviewed and approved by the IRB in accordance with 45 CFR 46, Subpart C; and
• Study closure.

4.9 Recordkeeping Requirements

32 CFR 219 requires all institutions engaged in DoD-conducted or DoD-supported human subjects research to retain records for at least three (3) years after the completion of the research, or longer if required by DoD Manual 6025.18, the Privacy Act, FDA regulations, or other applicable requirements. Records maintained that document compliance or non-compliance with DoD requirements must 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.

4.10 Addressing and Reporting Allegations of Non-Compliance with Human Research Protections

Allegations of non-compliance shall be investigated in accordance with applicable agreements, and shall be furnished to the supporting DoD organization via the HRPO.

4.11 Prohibition of Research with Prisoners of War (POW) and Detainees

Research involving any person captured, detained, held or otherwise under the control of DoD personnel (military and civilian, or contractor employee) is prohibited.

4.12 Survey Research

Research involving surveys of Department of Navy personnel typically requires Navy Survey Review and Approval, as specified in OPNAVINST 5300.8B.

4.13 Classified research

Classified Research is not reviewed or conducted under the auspices of UNC-Chapel Hill.