When working with certain governmental entities, there are additional steps and protections that PIs and IRBs must be aware of and execute, or risk complications with their funding.
In addition to the Federalwide Assurance (FWA) agreement approved by the Department of Health and Human Services (DHHS), the University of Wisconsin-Madison (UW) has signed an addendum with the United States Air Force that adds special requirements to conducting any human subjects research for DOD-supported studies. Researchers and their staff must be aware of these additional requirements when planning a study, as they may add a significant amount of time to the regulatory review and approval process.
These additional requirements are summarized in this guidance. It is highly recommended researchers work with the granting agency/DOD component to verify compliance with these requirements, as well as to determine if there are any agency-specific requirements not noted here that will affect their study.
Human subject research is 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 about whom identifiable private information is obtained. For purposes of DOD-supported research, this individual is known as an experimental subject, meaning “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.” (3216.02, 2. Applicability (2); 32 CFR 219; 10 USC 980).
Human subject research involves the DOD when any of the following apply:
DoD Components include but are not limited to:
Exemptions: listed 32 CFR 219.101 (b)
Components of the Navy (including Marine Corps) and the Army may require independent scientific review and approval prior to IRB review of new applications and substantive modifications.
The scientific review conducted by a funding agency (including DOD) or by an established internal review mechanism in the researcher’s school or department will satisfy this requirement.
UW IRBs do not offer any additional guidance or checklists for DOD sponsored studies, however they will refer to many of the documents listed in “Other Resources: Department of Defense”, found below, when reviewing and approving these studies. Of note, an IRB initial review must contain:
Evidence of scientific review: While this is done before the IRB would initially review a DOD sponsored study at UW, the results of this review must be included in the IRB report.
Level of risk: The level of risk to potential subjects participating in the study must be clearly established in the IRB’s minutes. If a study is determined to contain more than minimal risk (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), additional safeguards will be required to conduct the trial, such as continuous review by an independent Research Monitor. (See: 32 CFR 219.102(i), reference (c).)
Necessity of Research Monitor: If warranted by the level of risk, a research monitor will be appointed to the study. This person will be mentioned by name in the IRB application, will be independent of the study team, and will possess sufficient education and professional experience to serve as the subject/patient advocate. This means if the monitor would require specific medical knowledge to perform their duties, then this person should be a physician, psychologist, dentist, nurse, or other appropriate healthcare professional.
As described in DOD Instruction 3216.02 section 8(2), the research monitor shall have 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. Research monitors shall have the responsibility to promptly report their observations and findings to the IRB or other designated official. The duties, authority, and responsibilities for the research monitor will be approved by the IRB in a written summary.
The Institutional Official of the DOD Component may waive the requirement for the monitor.
Assurance that protocols involving exposure to ionizing radiation, radiopharmaceuticals, or biologically hazardous materials are approved by the appropriate committee prior to IRB approval.
If the non-DOD institution determines the activity is non-exempt research involving human subjects, the granting agency must perform an administrative review of the research before the activities that involve human subjects can begin.
Results of the Continuing Review must be reported to the funding agency.
Modifications that significantly change the original protocol (i.e., new primary or secondary aim(s), elimination of safety procedures or addition of new procedures, the addition or removal of protected subject populations) will require that a new scientific review be performed and filed with the IRB before the study can be reapproved.
A DOD-supported trial does not alter the criteria UW IRB will use in determining the type of review they will perform (i.e., full vs. expedited) at any of the given time points.
As referenced in section B.3 above, for research involving more than minimal risk to subjects, an independent medical monitor shall be appointed by name. Medical monitors shall 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. Medical monitors shall be independent of the investigative team and shall possess sufficient educational and professional experience to serve as the subject/patient advocate.
Depending on the nature of the study, the medical monitor may be assigned to oversee and/or assess one or more of the following phases of a research project: subject recruitment, subject enrollment, data collection, or data storage and analysis.
At the discretion of the IRB, the medical monitor may be assigned to discuss research progress with the principal investigator, interview subjects, consult on individual cases, or evaluate adverse event reports. Medical monitors shall promptly report discrepancies or problems to the IRB. They shall have the authority to stop a research study in progress, remove individual subjects from a study, and take whatever steps are necessary to protect the safety and well-being of research subjects until the IRB can assess the medical monitor's report.
Research involving the administration of surveys to, or interviews of, DOD personnel (military or civilian) may require DOD approval as well as IRB approval.
Captured or detained personnel: any persons deemed to be civilian internees, retained persons, or lawful/unlawful enemy combatants are prohibited from participating in DOD research, except research with investigational new drugs or devices where such treatment would also be offered to US military service members at the same location and with the same medical condition consistent with established medical practice.
Military personnel: Command approval may be required for military personnel to participate in human subjects research as some types of research could impact a soldier’s readiness in the field. Investigators may be asked to provide documentation of Command approval. DOD requires the following protections for military personnel being recruited for research that involves greater-than-minimal risk.
Compensation for US military personnel: On-duty federal personnel including military members may receive up to $50 for blood draws, but no compensation for general research participation. Off-duty federal personnel including military members may receive up to $50 for blood draws and compensation for general research participation. Stipends cannot be paid directly from a federal source (payment from a federal contractor or non-federal source is permissible). Non-federal personnel may receive up to $50 for blood draws and compensation for general research participation. Stipend funds may come from a federal or non-federal source.
Additional DOD protections do not apply when DOD personnel incidentally participate as subjects in research that is not supported by DOD, and DOD personnel are not an intended population of the research.
International populations: studies conducted outside of the United States that involve subjects that are not US citizens or DOD personnel must be conducted in compliance with local laws, regulations, customs, and practices and provide documentation indicating the following.
Pregnant women, prisoners, and children: the typical exemptions granted to research being done on pregnant women, prisoners, and children under DHHS 45 CFR 46 are not recognized for DOD-supported research, except for research involving observations of public behavior when the investigator(s) do not participate in the activities being observed.
Consent form language related to injury and adverse events: the IRB will ensure any specific DOD component language concerning research-related injury will be disclosed in the consent form.
Waiver of consent: the IRB is not allowed to approve a waiver of informed consent for any DOD-supported trial that meets the definition of human subjects research without prior approval from the Secretary of Defense, with the following exceptions:
This places limitations on research involving deception, decisionally-impaired individuals, or research being conducted under emergency conditions where the subject may not be able to provide consent. This rule does not apply to screening of records to identify possible subjects, and does not apply to retrospective research involving analysis of data or specimens, observational studies, blood draws, or tissue collection. The IRB may grant a waiver of consent for such activities.
Research in which legally-authorized representatives (LARs) provide consent: per military law and DOD directive, informed consent may be provided by a legally-authorized representatives of subjects if:
It should be noted that any additional costs associated with the use of a Research Monitor should be budgeted into and covered by your study’s indirect overhead.
There are no additional funding requirements for DOD studies. Refer to the UW department of Research and Sponsored Programs website for finding guidance: https://www.rsp.wisc.edu/
There are no additional human subjects training requirements for study staff engaged in DOD-supported research. (Study staff are expected to take human subjects research training as required by the UW, and maintain this certification while participating on a DOD trial.) However, agency-specific training, such as the Department of the Navy’s DON-Supported Extramural Performers (available through the CITI program) might be required. Investigators are strongly urged to contact their funding agency to determine if component specific training is necessary.
UW researchers are responsible for notifying their granting agency within 30 days of the following:
The institutional official is responsible for notifying the granting agency within 30 days of the following:
Researchers and their study staff are expected to follow UW policy on reporting adverse events, continuing reviews, etc.
Original copies of DOD-supported research documents may be required to be stored with the DOD component rather than kept on site or archived by the UW researcher.
Records maintained that document compliance or non-compliance with DOD regulations 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.
Refer to UW IRB for recordkeeping guidance here:
DOD Component Requirements: DOD Components may require that other research, not specifically identified by 32 CFR 219, also comply with the terms of this Addendum (32 CFR 219.101(d)).