E8-25177. Final Guidance on Engagement of Institutions in Human Subjects Research

AGENCY:

Office for Human Research Protections, Office of Public Health and Science, Office of the Secretary, HHS.

ACTION:

Notice.

SUMMARY:

The Office for Human Research Protections (OHRP), Office of Public Health and Science, is announcing the availability of a guidance document entitled, “OHRP Guidance on Engagement of Institutions in Human Subjects Research.” The guidance document describes: (1) Scenarios that, in general, would result in an institution being considered engaged in a human subjects research project; (2) scenarios that would result in an institution being considered not engaged in a human subjects research project; and (3) IRB review considerations for cooperative research in which multiple institutions are engaged in the same non-exempt human subjects research project. The guidance document is intended primarily for institutional review boards (IRBs), research administrators and other relevant institutional officials, investigators, and funding agencies that may be responsible for the conduct, review and oversight of human subject research that is conducted or supported by the Department of Health and Human Services (HHS).

The guidance document announced in this notice finalizes the draft guidance with the same title that was made available for public comment in the Federal Register on December 8, 2006 (71 FR 71169). OHRP received twenty-four comments on the draft guidance document, and those comments were considered as the guidance was finalized. The final guidance document replaces two existing OHRP guidance documents on the engagement of institutions in human subjects research: (1) The January 26, 1999, document on “Engagement of Institutions in Research,” and (2) the December 23, 1999, document on “Engagement of Pharmaceutical Companies in HHS Supported Research.”

DATES:

Comments on OHRP guidance documents are welcome at any time.

ADDRESSES:

Submit written requests for single copies of the guidance document entitled, “OHRP Guidance on Engagement of Institutions in Human Subjects Research,” to the Division of Policy and Assurances, Office for Human Research Protections, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852. Send one self-addressed adhesive label to assist that office in processing your request, or fax your request to 240-453-6909. See the SUPPLEMENTARY INFORMATION section for information on electronic access to the guidance document. Submit written comments to ENGAGEMENT GUIDANCE COMMENTS, Office for Human Research Protections, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852. Comments also may be sent via e-mail to [e-mail] or via facsimile at 240-453-6909.

FOR FURTHER INFORMATION CONTACT:

Ms. Julie Kaneshiro, Office for Human Research Protections, Department of Health and Human Services, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852; 240-453-6900; e-mail [e-mail].

SUPPLEMENTARY INFORMATION:

I. Background

OHRP, Office of Public Health and Science, is announcing the availability of a guidance document entitled, “OHRP Guidance on Engagement of Institutions in Human Subjects Research.” HHS, through OHRP, regulates research involving human subjects conducted or supported by HHS in regulations codified at 45 CFR part 46. The HHS human subject protection regulations stipulate substantive and procedural requirements for the conduct of HHS-conducted or -supported research, including requirements for review and approval by an IRB before research involving human subjects may begin, criteria for IRB approval of research, and requirements for informed consent or the waiver of informed consent.

The HHS protection of human subjects regulations at 45 CFR 46.103(a) and (b) require that each institution “engaged” in human subjects research that is conducted or supported by HHS (1) provide OHRP with a satisfactory assurance that the institution will comply with the regulations, and (2) certify to the HHS agency conducting or supporting the research that the research has been reviewed and approved by an IRB designated in the assurance and will be subject to continuing review by an IRB, unless all the research meets one or more of the categories for exemption from the regulatory requirements under 45 CFR 46.101(b). The Federalwide Assurance (FWA) is the only type of assurance currently accepted by OHRP. The FWA generally identifies required policies and procedures for the institution and describes the activities to which the regulations apply.

On January 26, 1999, the Office for Protection from Research Risks (OPRR), OHRP's predecessor office, issued guidance on “Engagement of Institutions in Research.” OPRR later issued guidance on “Engagement of Pharmaceutical Companies in HHS Supported Research,” dated December 23, 1999.

In the Federal Register of December 8, 2006 (71 FR 71169), OHRP announced the availability of a draft guidance document entitled, “OHRP Guidance on Engagement of Institutions in Human Subjects Research,” dated October 27, 2006, which OHRP proposed would replace the two guidance documents that had been issued in 1999. OHRP received twenty-four comments on the draft guidance and those comments were considered as the guidance was finalized. See section II. Discussion of Public Comments for a summary of the main comments received and OHRP's responses.

This guidance is only applicable to HHS-conducted or -supported research projects that have been determined to involve human subjects and that are not exempt under the HHS regulations at 45 CFR 46.101(b). Once an activity is determined to involve non-exempt human subjects research, this guidance can be used to determine whether an institution involved in some aspect of the research would be considered “engaged” in human subjects research, and would thus need to (1) hold or obtain an applicable OHRP-approved FWA, and (2) certify to the HHS agency conducting or supporting the research that the research has been reviewed and approved by an IRB designated in the assurance and will be subject to continuing review by an IRB.

II. Discussion of Public Comments

Most of the comments expressed general support for OHRP's draft guidance document. Some comments suggested clarifying changes and others recommended more substantive changes to the scenarios described in the draft guidance. All of the comments received were considered as the guidance was finalized. A discussion of the main comments follows.

Institutions Engaged in Human Subjects Research

Awardee Institutions

OHRP's draft guidance document proposed that institutions that receive an award through a grant, contract, or cooperative agreement directly from HHS for non-exempt human subjects research (i.e., awardee institutions) would generally be considered engaged in human subjects research, even where all activities involving human subjects are carried out by agents of another institution. A few of the commenters urged OHRP to reconsider its view that such awardee institutions should generally be considered engaged in human subjects research when all activities involving human subjects are carried out by agents of another institution. The commenters noted that considering such awardee institutions to be engaged in human subjects research often results in duplicative review by IRBs and administrative burden for awardee institutions that choose to modify their FWAs to rely on another institution's IRB to satisfy the regulatory requirements under 45 CFR part 46. These commenters questioned whether human subjects were offered greater protections by considering such awardee institutions to be engaged in human subjects research.

OHRP believes that institutions that receive an award directly from HHS for non-exempt human subjects research should generally be considered engaged in human subjects research. However, the office understands these commenters' concerns and agrees that in some circumstances, institutions that receive an award for non-exempt human subjects research, but that do not carry out any of the activities involving human subjects, should not be considered engaged in the human subjects research. OHRP will continue to consider this issue in consultation with the HHS funding agencies.

Institutions Not Engaged in Human Subjects Research

Release of Identifiable Private Information or Biological Specimens

In the Federal Register of December 8, 2006 (71 FR 71169), OHRP noted that the office was particularly interested in the public's comments on the proposal that institutions whose employees or agents release to investigators at another institution identifiable private information or identifiable biological specimens pertaining to the subjects of the research, not be considered engaged in human subjects research.

The public comments supported this proposed scenario. OHRP retained this scenario in the final guidance document, with only minor clarifying changes (see scenario B.(6) in the final guidance).

Administration of Clinical Trial-Related Medical Services

In the Federal Register of December 8, 2006 (71 FR 71169), OHRP also noted that the office was particularly interested in the public's comments on the proposal that institutions (including private practices) not selected as research sites whose employees or agents administer clinical trial-related medical services, not be considered engaged in human subjects research provided that specified conditions were met. One of the proposed conditions was that the institution's employees or agents do not administer the primary study interventions being tested under the protocol.

The public comments on this proposed scenario were generally supportive, but several commenters sought clarifications on some of the proposed conditions. In addition, a few of the commenters recommended that OHRP expand the scenario to permit the employees or agents of an institution not selected as a research site to administer the study intervention being tested or evaluated under the protocol, and still not consider such an institution to be engaged in human subjects research.

In the final guidance, OHRP retained the proposed scenario, with minor changes in response to the public comments (see scenario B.(2) in the final guidance). However, OHRP also has included another scenario in the final guidance that would allow employees or agents of an institution not initially selected as a research site to administer the study interventions being tested or evaluated under the protocol, provided that this occurs on a one-time or short-term basis, and specified conditions are met (see scenario B.(3) in the final guidance). OHRP believes this is responsive to the concern raised in a public comment that research subjects are sometimes unexpectedly hospitalized or otherwise unexpectedly unable to receive a study intervention being tested or evaluated in a protocol from an institution that had previously been designated as a research site.

III. Comments

Interested persons may submit comments regarding this guidance document to OHRP at any time. Please see the ADDRESSES section for information on where to submit written comments.

IV. Electronic Access

Persons with access to the Internet may obtain the guidance document on OHRP's Web site at http://www.hhs.gov/​ohrp/​humansubjects/​guidance/​engage08.htm.

Dated: October 16, 2008.

Ivor A. Pritchard,

Acting Director, Office for Human Research Protections.