NOTE: THIS GUIDANCE DOCUMENT HAS BEEN REPLACED BY THE FOLLOWING OHRP GUIDANCE: “OHRP Guidance on the Involvement of Prisoners in Research”. THE NEW GUIDANCE HAS BEEN UPDATED FOR FORMAT AND TO PROVIDE ADDITIONAL GUIDANCE ON RESPONSIBILITIES OF IRBs AND INSTITUTIONS REQUIRED UNDER SUBPART C. May 19, 2000 TO: OPRR Staff FROM: Director of Regulatory Affairs, OPRR Director, Division of Human Subject Protections SUBJECT: OPRR Guidance on Approving Research Involving Prisoners 1. General Regulatory Background Subpart C of Part 46 of the Department of Health and Human Services (DHHS) Regulations on Protection of Human Subjects (45 CFR Part 46.301 et.seq) provides additional protections for biomedical and behavioral research involving prisoners as subjects. The regulations are applicable to all biomedical and behavioral research conducted or supported by DHHS involving prisoners as subjects. 45 CFR 46.301. It is important to note that the regulations provide that Abiomedical or behavioral research conducted or supported by DHHS shall not involve prisoners as subjects@unless the research is specifically authorized within the Subpart. See 45 CFR 46.306(b). In the preamble to the final Subpart C rule, the drafters noted: AIn fact, most testimony before the Commission opposed the use of prisoners in any form of medical research not intended to benefit the individual prisoner.@ 43 Fed. Reg. 53652,53653 (November 16, 1978). DHHS did determine that some limited research would be permissible but not Auntil additional and more stringent review procedures are conducted.@ Id. at page 53652. A. Subpart C applies where any subject is or becomes a prisoner. The provisions of Subpart C apply to any research funded by the Department of Health and Human Services (DHHS) in which prisoners are subjects. This includes situations where a human subject becomes a prisoner after the research has commenced. As the Purpose section of the regulation notes: AInasmuch as prisoners may be under constraints because of their incarceration which could affect their ability to make a truly voluntary and uncoerced decision whether or not to participate as subjects in research, it is the purpose of this subpart to provide additional safeguards for the protection of prisoners involved in activities to which this subpart is applicable.@ 45 CFR 46.302. These concerns apply whether the research involves prisoners or a person who at a later date becomes a prisoner. In the latter situation, it is unlikely that review of the research and the consent document contemplated the constraints imposed by incarceration. B. The definition of prisoner. The word prisoner is defined in 45 CFR 46.303(c) as follows: A Prisoner means 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. C. Special Composition of IRB. When an Institutional Review Board (IRB or Board) reviews a protocol in which a prisoner is a subject, the composition of the IRB might well require a change. 45 CFR 46.304 requires that: (a) A majority of the Board (exclusive of prisoner members) shall have no association with the prison(s) involved, apart from their membership on the Board. (b) At least one member of the Board shall be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one Board only one Board need satisfy this requirement. Thus, the overall composition of the IRB might need to change if a number of individuals are associated with the prison. In addition, the IRB must include a prisoner or a prisoner representative. In the absence of choosing someone who is a prisoner or has been a prisoner, the IRB should choose a person who has a close working knowledge of prison conditions and the life of a prisoner. Suitable individuals could include present or former prisoners; prison chaplains; prison psychologists, prison social workers, or other prison service providers; persons who have conducted advocacy for the rights of prisoners; or any individuals who are qualified to represent the rights and welfare of prisoners by virtue of appropriate background and experience. In addition, the IRB must notify OPRR of any change in the IRB roster occasioned by the addition of a prisoner or a prisoner representative. IRBs should be alert to the impact of roster changes on quorum requirements (46.108(b)). If a protocol involves more than one IRB, only one reviewing IRB must meet this requirement. The IRB must meet the special composition requirements for all types of review of the protocolBinitial review, continuing review, protocol amendments, and reports of unanticipated problems involving risks to subjects. D. Additional duties of the IRB where prisoners are involved. When an IRB is reviewing a protocol in which a prisoner is a subject, the IRB must make seven additional findings under 45 CFR 46.305 as follows: (1) the research under review represents one of the categories of research permissible under Section 46.306(a)(2); (2) any possible advantages accruing to the prisoner through his or her participation in the 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 a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired; (3) the risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers; (4) procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the Board justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project; (5) the information is presented in language which is understandable to the subject population; (6) adequate assurance exists 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) where the Board 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. (B) the Board shall carry out such other duties as may be assigned by the Secretary. (C) The institution shall certify to the Secretary, in such form and manner as the Secretary may require, that the duties of the Board under this section have been fulfilled. E. Permitted research involving prisoners. For research conducted or supported by DHHS to involve prisoners, two actions must occur: (1) the IRB must certify to the Secretary (OPRR) that it has reviewed and approved the research under 45 CFR 46.305; and (2) the Secretary (OPRR) must determine that the proposed research falls within one of the categories of permissible research specified in 45 CFR 46.306(a)(2). Where an institution holding an OPRR-approved Multiple Project Assurance (MPA) wishes to involve prisoners in non-HHS-supported research, certification is not required. However, OPRR recommends that the IRB apply the standards of Subpart C in reviewing the research. Should the research (i) involve conditions particularly affecting prisoners as a class[45 CFR 46.306(a)(2)(C)], or (ii) not satisfy the stipulations at 45 CFR 46306(A)(2)(A)(B)(D), OPRR recommends that the research proceed only after the IRB has consulted with appropriate experts, as determined by the IRB. The categories of permissible research are as follows: 1. The research in categories= (A) and (B) must be minimal risk research (note that the definition of minimal risk for prisoner research at 45 CFR 46.303(d) differs from the definition of minimal risk for other research which is subject to the definition at 45 CFR 46.102(i)): (A) study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects; (B) study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects; 2. The research in categories= (C) and (D) may require OPRR to have the research reviewed by appropriate experts and may require a notice of intent to approve the research published in the Federal Register. (C) research on conditions particularly affecting prisoners as a class ( for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addition, and sexual assaults) provided that the study may proceed only after the Secretary has consulted with appropriate experts including experts in penology, medicine, and ethics, and published notice, in the FederalRegister, of his intent to approve such research; (D) research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the subject. In cases, in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to control groups which may not benefit from the research, the study may proceed only after the Secretary has consulted with appropriate experts, including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of the intent to approve such research. Note that paragraph (D) requires OPRR to consult with appropriate experts if the research involves a control group. F. Documentation of IRB Findings. The DHHS regulations at Subpart C require the IRB to make specific findings when approving research involving prisoners. OPRR strongly recommends that these findings be fully documented, including protocol-specific information justifying each IRB finding. 2. Responsibilities of Institutions The institution should: Notify OPRR of the name and qualifications of the prisoner representative, if the approved IRB roster does not currently reflect this information. Maintain the CV of the prisoner representative serving on the IRB. Have a record of the determination of the IRB regarding the seven additional findings under 45 CFR 46.305 and the specific category which authorizes the research under 45 CFR 46.306. Send to OPRR a certification letter pursuant to 45 CFR 46.305(c) and 45 CFR 46.306(a)(1) stating that (i) the IRB has been constituted according to the regulation; (ii) that the IRB considered and made the required 7 findings set forth in 46.305; and (iii) that the IRB finds that category ___ of 46.306 permits this research to go forward with prisoners as human subjects. The certification letter should also provide a brief description of the research sufficient to allow OPRR to determine whether or not to concur with the IRB; and, whether OPRR needs to consult with appropriate experts and publish a Federal Register Notice. The institution should retain a copy of this letter. 3. Responsibilities of OPRR Following receipt of sufficient information from the IRB in the form of the certification letter, OPRR will determine whether it concurs with the decision of the IRB that research involving prisoners may occur. OPRR will consult with appropriate experts with respect to certain research that falls under paragraphs (C) and (D) of 45 CFR 46.306(a)(2). When applicable, OPRR will also publish in the Federal Register a notice of intent to approve such research. Covered research involving prisoners may not proceed until OPRR issues its determination on behalf of the Secretary under 45 CFR 46.306(a)(2). 4. Frequently Asked Questions 1. Does Subpart C apply only where the research targets prisoners as subjects? Answer: No. Subpart C applies whenever any human subject in a research protocol subject to 45 CFR Part 46 becomes a prisoner at any time during the protocol. 2.What should an investigator do if a subject becomes a prisoner after enrollment in research? Answer: The investigator should report this situation to the IRB immediately. 3.What does the IRB do when a human subject becomes a prisoner after enrollment? Answer: At the earliest opportunity, the IRB should review the protocol again with a prisoner representative on the IRB and an eye to the special conditions of being a prisoner. The IRB can either (a) approve the involvement of the prisoner-subject in the research in accordance with Subpart C or (b) determine that this subject must be withdrawn from the research. Note that 46.116 requires, when appropriate, that the informed consent process include information on Aanticipated circumstances under which the subject=s participation may be terminated by the investigator without regard to the subject=s consent. 4. Is an adolescent (e.g., age 14) detained in a juvenile detention facility a prisoner? Answer: Yes. In addition to Subpart C, most likely Subpart D would also apply. 5. Can research involving prisoners be expedited? Answer: OPRR recommends that the full IRB review research involving prisoners as human subjects. 6. Do the exemptions apply to research involving prisoners? Answer: The exemptions at 45 CFR 46.101(b) do not apply to research involving prisoners. See 45 CFR 46.101(i). 7. What is the definition of minimal risk for prisoner research? Answer: The definition of minimal risk for research involving prisoners can be found at 45 CFR 46.303(d). This definition, promulgated in 1978, differs from the definition of minimal risk in the Common Rule, or Subpart A of the DHHS regulations. See 45 CFR 46. 102(i). For research involving prisoners, the definition of minimal risk requires reference to physical or psychological harm, as opposed to harm or discomfort, to risks normally encountered in the daily lives, or routine medical, dental or psychological examination of healthy persons. Definition of Minimal Risk in Prisoner Subpart 45 CFR 46.303(d)(1978) 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. Definition of Minimal Risk in Common Rule (Subpart A, 45 CFR Part 46) 45 CFR 46.102(i) (1991) A 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.