[Federal Register Volume 71, Number 236 (Friday, December 8, 2006)]
[Notices]
[Pages 71169-71172]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-20849]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Draft Guidance on Engagement of Institutions in Human Subjects 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.

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SUMMARY: The Office for Human Research Protections (OHRP), Office of 
Public Health and Science, is announcing the availability of a draft 
guidance document entitled, ``OHRP Guidance on Engagement of 
Institutions in Human Subjects Research.'' The draft guidance document 
would revise and replace 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.'' To facilitate public review of 
the draft guidance document, OHRP has developed a table presenting a 
side-by-side comparison of OHRP's draft revised guidance document and 
the current guidance documents on the engagement of institution in 
human subjects research, which is available on the OHRP Web site at 
http://www.hhs.gov/ohrp/requests/.
    OHRP's current engagement guidance documents and the proposed draft 
guidance document provide examples of when institutions generally would 
be considered to be engaged or not engaged in human subjects research. 
The draft document is intended primarily for institutional review 
boards (IRB), research administrators and other relevant institutional 
officials, investigators, and funding agencies that may be responsible 
for the conduct, review and oversight of human subject

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research that is conducted or supported by HHS. OHRP will consider 
comments received before issuing the final guidance document.

DATES: Submit written comments by February 6, 2007.

ADDRESSES: Submit written requests for single copies of the draft 
guidance document entitled, ``OHRP Guidance on Engagement of 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, The Tower 
Building, 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 301-402-2071. See the 
SUPPLEMENTARY INFORMATION section for information on electronic access 
to the guidance. Submit written comments to ENGAGEMENT GUIDANCE 
COMMENTS, Office for Human Research Protections, The Tower Building, 
1101 Wootton Parkway, Suite 200, Rockville, MD 20852. Comments also may 
be sent via e-mail to [email protected]. or via facsimile at 301-
402-2071.

FOR FURTHER INFORMATION CONTACT: Mr. Glen Drew, Office for Human 
Research Protections, Department of Health and Human Services, The 
Tower Building, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852; 
301-496-7005; e-mail [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    The Department of Health and Human Services (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) require that each institution ``engaged'' in human subjects 
research that is conducted or supported by HHS provide OHRP with a 
satisfactory assurance that the institution will comply with the 
regulations, 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.
    OHRP is proposing to replace these two documents with a single 
document, ``OHRP Guidance on Engagement of Institutions in Human 
Subjects Research,'' draft dated October 27, 2006. This guidance is 
only applicable to 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 submit an FWA to OHRP. Like OHRP's existing 
guidance documents on engagement, this draft document provides: (1) 
Examples of activities that, in general, would result in an institution 
being considered engaged in a human subjects research project; and (2) 
examples of activities that, in general, would result in an institution 
being considered not engaged in a human subjects research project. The 
draft guidance document proposes modifications to the set of examples 
of when an institution generally would be considered engaged or not 
engaged in human subjects research. The proposed modifications include 
combining, clarifying, and changing existing examples, as well as 
adding further examples and explanation.
    To facilitate public review and comments, OHRP has created a 
comparison table presenting a side-by-side display of the text from 
OHRP's draft guidance document matched with the comparable text from 
the 1999 guidance documents. This table is available on the OHRP Web 
site at http://www.hhs.gov/ohrp/requests/. The table is not part of the 
draft guidance document.

II. Electronic Access

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

III. Request for Comments

    OHRP is making its draft guidance document available for public 
comment. OHRP's revised guidance document on the engagement of 
institutions in human subjects research will be finalized and issued 
after the public comments have been considered.
    OHRP is particularly interested in the public's comments on two 
examples of activities which would not result in the institution being 
considered engaged in a human subjects research project under OHRP's 
current draft guidance document:
    1 Example B(1): Institutions whose employees or agents release to 
the investigators at another institution identifiable private 
information or identifiable biological specimens pertaining to the 
subjects of the research; and,
    2 Example B(7): Institutions (including private practices) not 
selected as research sites whose employees or agents administer 
clinical trial-related medical services if all of the following 
conditions are met:
    (a) The institution's employees or agents do not enroll subjects, 
or obtain the informed consent of any subject for research 
participation;
    (b) The institution's employees or agents do not administer the 
primary study interventions being tested under the protocol;
    (c) The institution's employees or agents provide only services 
that either are clinically indicated, or are dictated by the protocol 
but not clinically indicated, and would typically be performed as part 
of routine clinical monitoring and/or follow-up of subjects enrolled at 
a study site by clinical trial investigators, such as a blood test, 
chest X-ray, CT scan, medical history and physical examination, or an 
assessment and reporting of an adverse event;
    (d) The investigator(s) from an institution engaged in the research 
retain responsibility for oversight of all protocol-related activities 
and assure that appropriate arrangements are made for any safety 
monitoring and adverse event reporting required under the IRB-approved 
protocol;
    (e) When appropriate, the informed consent document states that 
follow-up data are to be provided to the investigators by the 
institution's employees or agents; and,
    (f) When providing follow-up data to the investigators, the 
institution's employees or agents provide such data to the 
investigators in accord with the procedures described in the informed 
consent.
    Proposed example (B)(1) would represent a modification in OHRP

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policy. OHRP's current guidance document issued in 1999 states that an 
institution whose employees or agents release individually identifiable 
private information about subjects, for research purposes, without the 
subjects' explicit written permission is considered to be engaged in 
human subjects research. The proposed modification in guidance is based 
on the definition of human subject at 45 CFR 46.102(f), which states in 
part, ``human subject means a living individual about whom an 
investigator * * * conducting research obtains * * * identifiable 
private information.'' (emphasis added). OHRP has concluded that 
releasing identifiable private information for research purposes is not 
equivalent to obtaining identifiable private information; thus, an 
institution releasing such identifiable private information is not 
involved in an activity including a ``human subject'' as defined by the 
HHS protection of human subjects regulations. Therefore, the revised 
example would clarify that an institution, whose employees or agents 
release to the investigators at another institution identifiable 
private information about living individuals or identifiable biological 
specimens that came from living individuals, is not considered engaged 
in human subjects research.
    Proposed example (B)(7) would represent another modification in 
OHRP policy. OHRP's current guidance document states that an 
institution (or private practitioner) whose clinical staff provide 
protocol-related care and/or follow-up to subjects enrolled at distant 
sites by clinical trial investigators in OHRP-recognized Cooperative 
Protocol Research Programs (CPRPs) (e.g., the oncology group clinical 
trials sponsored by the National Cancer Institute) is not considered to 
be engaged in human subjects research provided certain specified 
conditions are met. OHRP is proposing two key modifications to this 
current example: (1) That the example not be limited to scenarios 
involving human subjects research at OHRP-recognized CPRPs; and (2) 
that the example exclude an institution whose employees or agents 
administer the primary study intervention being tested in the research. 
OHRP is proposing to broaden the example beyond OHRP-recognized CPRPs 
because OHRP does not believe that the conditions specified in example 
(B)(7) of the current draft guidance document are unique to clinical 
trials conducted under CPRPs. In addition, to better protect human 
subjects involved in research, OHRP believes that an institution whose 
employees or agents administer the primary study intervention being 
tested in the study should be required: (1) To obtain an OHRP-approved 
FWA, and (2) to certify to the HHS agency conducting or supporting the 
research that the application of proposal for research has been 
reviewed and approved by an IRB designated in the FWA, and will be 
subject to continuing review by an IRB. Therefore, through example 
(B)(7) in the current draft engagement guidance document, OHRP is 
proposing to clarify that institutions whose employees or agents 
administer the primary study intervention being tested in the study 
would be engaged in human subjects research. OHRP does not believe the 
requirement for an FWA will be unduly burdensome for such institutions 
since OHRP has simplified the assurance process with the implementation 
of the FWA, and now permits an institution holding an OHRP-approved FWA 
to extend the applicability of its FWA to cover collaborating 
independent investigators and collaborating institutional investigators 
through an Individual Investigator Agreement (IIA) (see http://www.hhs.gov/ohrp/humansubjects/assurance/guidanceonalternativetofwa.htm).
    In addition, OHRP wants to highlight three other proposed changes 
in the current draft guidance document:
    1. The draft guidance document does not include examples regarding 
when ``statistical centers,'' ``operations centers,'' or ``coordinating 
centers'' for multi-site research would be engaged in human subjects 
research. The existing January 26, 1999 guidance document includes 
examples of when such entities would be engaged in human subjects 
research (see the January 26, 1999 document on ``Engagement of 
Institutions in Research, examples (A)(6) and (A)(7)). OHRP is 
proposing to delete these examples in the new engagement guidance 
document since OHRP believes that these entities' activities are 
subsumed under example (A)(5) in the draft engagement guidance 
document, which states that an institution would be engaged in human 
subjects research if the institution's employees or agents ``* * * 
obtain for research purposes identifiable private information or 
identifiable biological specimens from any source * * * .'' In 
addition, the January 26, 1999 document provided guidance on what 
component(s) of the study would require review by the IRB for the 
statistical, operations, or coordinating centers. Because this issue of 
IRB review could apply to any institution engaged in a component of a 
cooperative research project, OHRP's draft guidance document addressed 
this general issue separately at the end of the section III. A.
    2. OHRP is proposing that an institution be considered not engaged 
in human subjects research in the event the institution's employees or 
agents consult or collaborate on the human subjects research by 
obtaining coded private information or human biological specimens from 
an institution engaged in the research that retains a link to 
individually identifying information (such as name or social security 
number), if one of several specified conditions is met (see example 
(B)(2) in the draft engagement guidance document). OHRP believes this 
additional example helps to clarify the distinction and relationship 
between: (1) Determining when a research study involving coded private 
information or human biological specimens involves human subjects (see 
OHRP's August 10, 2004, Guidance on Research Involving Coded Private 
Information or Biological Specimens at http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf), and (2) determining whether an 
institution is engaged in human subjects research if it receives coded 
private information or human biological specimens for a research study 
that already has been determined to involve human subjects.
    3. OHRP is proposing that an institution be considered not engaged 
in human subjects research if the institution's employees or agents 
author a paper, journal article, or presentation describing a human 
subjects research study (see example (B)(8) in the current draft 
engagement guidance document). This is in contrast to the January 26, 
1999 guidance document, which suggests that such authorship would make 
an institution engaged in human subjects research (see example (B)(2) 
in the January 26, 1999 guidance document). OHRP is proposing this 
clarification because OHRP believes that for an institution to be 
engaged in human subjects research, an institution's employees or 
agents must obtain: (1) Data about the subjects of the research through 
intervention or interaction with them; or (2) identifiable private 
information about the subjects of the research. If the institution's 
employees or agents do not obtain such information, the portion of the 
activity conducted by the institution does not involve human subjects, 
as defined by 45 CFR 46.102(f). Because authorship does not always 
involve obtaining such data or information about the subjects of the 
research, OHRP does not believe that it is helpful to consider 
authorship as a factor in determining whether an

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institution is engaged in human subjects research.
    All of the modifications and clarifications proposed in OHRP's 
draft guidance document, including those discussed above, are reflected 
in the comparison table of the previous guidance documents and the new 
draft guidance document on OHRP's Web site at http://www.hhs.gov/ohrp/requests/. OHRP welcomes comments on its draft guidance.

    Dated: December 1, 2006.
Melody Lin,
Deputy Director, Office for Human Research Protections.
[FR Doc. E6-20849 Filed 12-7-06; 8:45 am]
BILLING CODE 4150-36-P