December 2020

Who is a “prisoner” according to DHHS regulations and when are investigators “engaged” in prisoner research?

For the purposes of human subjects research, a prisoner is defined in 45 CFR 46.303(c) as “any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.”

It is the policy of the Organization that a Hopkins investigator and the Organization are "engaged" in research involving prisoners when both of the following circumstances apply:

1. The investigator obtains data through intervention or interaction with a prisoner, or identifiable private information about a prisoner; AND
2. The investigator knows that one or more of the data subjects includes a person whose circumstances meet the regulatory definition of "prisoner" under 45 CFR 46.303(c).

The Organization takes the position that for the research to "involve" prisoners, the investigator must have actual knowledge of circumstances that would cause a subject to fall under the regulatory definition. The Organization does not require investigators to determine prospectively whether each potential subject is or may become a prisoner.

For example, if an investigator proposes to perform a chart review of patients who have been treated for a particular disease, it is unlikely that the investigator will know or discover as a result of reviewing charts that one or more of the patients in the cohort is a prisoner. The investigator is not required to seek information about subjects' prisoner status if such information is not necessary to answer the research question. If, however, the investigator should happen to learn that one or more subjects is actually a prisoner, the protections and requirements of 45 CFR 46 Subpart C will then apply to the research if that individual is to be enrolled in the study.

It is the policy of the Organization that the responsibilities for IRB review of prisoner research under Subpart C must be fulfilled for all research involving prisoners, regardless of funding source.

IRB Review of Research Involving Prisoners:

For all research involving prisoners, an IRB member who qualifies as a prisoner representative must be present at the convened meeting of the IRB and during the presentation, discussion, and vote of any study which involves prisoners. A majority of the IRB members (exclusive of prisoner members) must have no association with the prison involved, apart from their membership on the IRBs.

The prisoner representative:

• Must be a voting member of the IRB. (This individual may be listed as an alternative member who becomes a voting member when needed).
• Must review research involving prisoners, focusing on the requirements in Subpart C or equivalent protections. The prisoner representative must receive all review materials pertaining to the research (same as primary reviewer).
• Must be present at a convened meeting when the research involving prisoners is reviewed. If the prisoner representative is not present, research involving prisoners cannot be reviewed or approved. Attendance may be by phone, video-conference, or webinar, as long as the representative is able to participate in the meeting as if they were present in person at the meeting.
• Must present his/her review either orally or in writing at the convened meeting of the IRB when the research involving prisoners is reviewed.

The JHM IRBs must make the required determinations when reviewing an application involving prisoner research and will use a checklist to document the determinations required by the regulations noted below along with protocol specific findings justifying those determinations:

1. Whether the research under review represents one of the categories of research permissible under 45 CFR 46.306(a)(2);
2. Whether the advantages of participating in this research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such magnitude to impair the participant's ability to weigh the risks of the research against the value of such advantages in the limited choice environment;
3. Whether the risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;
4. Whether the procedures for the selection of participants within the prison (or other institution) are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners;
5. Whether the information is presented in language that is understandable to the participant population;
6. Whether the JHM IRB has adequate assurance that parole boards will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and
7. If the IRB finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners' sentences, and for informing participants of this fact.

Continuing review must occur using the same procedures for initial review, including the responsibility of the prisoner representative to review the continuing review materials and participate in the meeting (as described above). (If no subjects have been enrolled, the research may receive continuing review using the expedited procedure under expedited category #8).

Modifications involving more than a minor change reviewed by the convened IRB must use the same procedures for initial review including the responsibility of the prisoner representative to review the modification and participate in the meeting (as described above).

Minor modifications to research involving prisoners may be reviewed using the expedited procedures described below, based on the type of modification.

Research involving prisoners may not receive exempt review.

Expedited IRB Review Procedures for Research Involving Prisoners

For research involving interaction with prisoners:

• Research involving interaction with prisoners may be reviewed by the expedited procedure if a determination is made that the research involves no greater than minimal risk for the prison population being studied. (“Minimal risk is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.” [45 CFR 46.303(d)].
  • The prisoner representative must concur with the determination that the research involves no greater than minimal risk.
• The prisoner representative must review the research as a reviewer or consultant, designated by the IRB Chair. This may be as the sole reviewer or in addition to another reviewer, as appropriate.
• Review of modifications and continuing review must use the same procedures for initial review using this expedited procedure including the responsibility of the prisoner representative.

For research that does not involve interaction with prisoners (e.g. existing data, record review) reviewed by the expedited procedure:

• Research that does not involve interaction with prisoners may be reviewed by the expedited procedure, if a determination is made that the research involves no greater than minimal risk for the prison population being studied.
• Review by a prisoner representative is not required.
• The prisoner representative may review the research as a reviewer or consultant if designated by the IRB Chair.

Review of modifications and continuing review must use the same procedures as initial review.

When a Participant Becomes a Prisoner While Enrolled in a Study:

PI’s Responsibilities:

For studies originally reviewed and approved by the IRB without prisoners as participants, if the PI learns that a participant has become a prisoner during the study, the PI must submit a Further Study Action (Problem Event Report) to inform the JHM IRB of the individual’s change in status. In this report, the PI must indicate whether the individual’s incarceration is expected to be temporary and, if not, whether the PI intends for the subjects to continue as a participant while incarcerated. If so, the PI must also submit a Further Study Action (Change in Research), requesting IRB approval for prisoners as a study population under Subpart C and indicating the following:

• If it is in the subject’s best interests to continue on the study as a prisoner, and whether the subject’s status as prisoner affects the risks of participation in the study or the potential benefits that might accrue from continued participation;
• If the subject wishes to continue as a study participant, and what the re-consent process will be;
• If there are practical complications of subject continuation in the study,
• If there is any other factor that is important for the JHM IRB to consider when determining whether the subject should continue as a participant in the study.

IRB Review:

The JHM IRB must make the final determination whether the subject may continue as a participant. If a subject becomes a prisoner while enrolled in a research study that was not previously reviewed by the IRB according to Subpart C:

• When Subpart C applies the IRB will:
  • Confirm that the incarcerated subject meets the definition of a prisoner.
  • Terminate enrollment of the incarcerated subject or review the research study under Subpart C if it is feasible for the incarcerated subject to remain in the study.
  • Before terminating the enrollment of the incarcerated subject the IRB should consider the risks associated with terminating participation in the study.
  • If the incarcerated subject cannot be terminated for health or safety reasons
    • Keep the subject enrolled in the study and review the research under Subpart C.
      • If some of the requirements of Subpart C cannot be met, but it is in the best interests of the subject to remain in the study, keep the subject enrolled and inform OHRP of the decision along with the justification for doing so.
    • Remove the subject from the study and keep the subject on the study intervention under an alternate mechanism such as compassionate use, off-label use, etc.

• When Subpart C does not apply, the IRB will provide equivalent protections by:
  • Confirming that the subject meets the definition of a prisoner.
  • Deciding whether it is in the best interests of the incarcerated subject to remain in the study or to terminate enrollment.
  • Also deciding whether it is feasible for the subject to remain in the study.
  • If it is in the best interests of the subject to remain in the study, keep the subject in the study and review the research at next meeting of the convened IRB.

Note: If a subject is incarcerated temporarily while enrolled in a study, the IRB will determine the following:

• If the temporary incarceration has no effect on the study, keep the subject enrolled.
• If the temporary incarceration has an effect on the study, the IRB will review the involvement of the prisoner under the above criteria for an individual who becomes a prisoner while enrolled in a research study.

Additional Requirements for Department of Defense-Funded Research

• When a previously enrolled human participant becomes a prisoner, and the protocol has not been reviewed and approved by the IRB in accordance with Subpart C, the investigator must promptly notify the IRB and the DoD HRPO (and other federal agencies where required).
• Research involving detainees or prisoners of war[1] is prohibited, except where:
  • It is conducted under FDA investigational new drug or investigational device regulations when the purpose is for diagnosis or treatment of a medical condition in a patient;
  • The informed consent of the detainees or prisoners of war is obtained; and,
  • Only when the same product may be available to DoD-affiliated personnel consistent with established medical practices.
• In addition to the research on prisoners permissible under Subpart C, two additional categories are permissible[2]:
  • Epidemiological research is permitted under the following conditions:
    • Where the sole purpose of the research is to describe the prevalence or incidence of a disease by identifying all cases, or study potential risk factor associations for a disease.
    • The research presents no more than minimal risk.
    • The research involves no more than inconvenience to the prisoner-participants.
    • Prisoners are not a particular focus of the research.
  • Human participant research involving prisoners that would otherwise meet exemption criteria may be conducted, but must first be approved by an IRB.

DHHS Reporting Requirements for Prisoner Research

From OHRP Guidance on the Involvement of Prisoners in Research (2020):

“An institution that intends to conduct HHS-supported research involving prisoners as subjects must certify to the Secretary (through OHRP) that the IRB has made the seven findings required under 45 CFR 46.305(a), including the finding that the proposed research represents one of the permissible categories of research under 45 CFR 46.306(a)(2). The institution must send OHRP a completed Subpart C Certification Form, which includes the name and address of the institution and the relevant grant number. OHRP encourages the electronic submission of Subpart C certifications requests. Requests should be sent to [email protected].

Under its authority at 45 CFR 46.115(b), OHRP requires the responsible institution to also submit to OHRP a copy of the research proposal so OHRP can determine whether the proposed research involves one of the categories of research permissible under 45 CFR 46.306(a)(2), and if so, which one. The term "research proposal" includes:

• the IRB-approved protocol;
• any relevant HHS grant application or proposal;
• any IRB application forms required by the IRB; and
• any other information requested or required by the IRB to be considered during initial IRB review

The Organization has determined that for studies where JHM IRB is the Reviewing IRB for multisite research, the JHM IRB will file the necessary prisoner certification for all research sites.

[1] See Article 4, Geneva Convention Relative to the Treatment of Prisoners of War.

[2] The JHM IRBs will consider these additional categories, but will make all determinations concerning this population in accordance with institutional policy and state law.