[Federal Register Volume 74, Number 88 (Friday, May 8, 2009)]
[Proposed Rules]
[Pages 21610-21613]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-10666]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
42 CFR Part 50
45 CFR Part 94
[Docket No. NIH-2008-0002]
RIN 0925-AA53
Responsibility of Applicants for Promoting Objectivity in
Research for Which Public Health Service Funding Is Sought and
Responsible Prospective Contractors; Request for Comments
AGENCY: Department of Health and Human Services.
ACTION: Advance notice of proposed rulemaking.
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SUMMARY: On behalf of the Department of Health and Human Services (HHS)
and the Public Health Service (PHS), a component of the HHS, the
National Institutes of Health (NIH) seeks comments from the public on
whether the HHS should amend its regulations on the responsibility of
applicants for promoting objectivity in research for which phs funding
is sought and on responsible prospective. We are interested
particularly in receiving comments on the issues presented below from
the general public, individual Investigators, scientific societies and
associations, Members of Congress, other Federal agencies that support
or conduct research, and institutions that receive PHS funds to conduct
or support biomedical or behavioral research.
DATES: To assure consideration, comments must be received by July 7,
2009.
ADDRESSES: Individuals and organizations interested in submitting
comments, identified by RIN 0925-AA53 and Docket Number NIH-2008-0002,
may do so by any of the following methods:
Electronic Submissions
You may submit electronic comments in the following way:
The Regulations.gov portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
To ensure timelier processing of comments, NIH is no longer
accepting comments submitted to the agency by e-mail. The NIH
encourages you to continue to submit electronic comments by using the
Regulations.gov portal: http://www.regulations.gov.
Written Submissions
You may send written submissions in the following ways:
Fax: 301-402-0169.
Mail: Attention: Jerry Moore, NIH Regulations Officer,
NIH, Office of Management Assessment, 6011 Executive Boulevard, Suite
601, MSC 7669, Rockville, MD 20852-7669.
Hand Delivery/Courier (for paper, disk, or CD-ROM
submissions): Attention: Jerry Moore, 6011 Executive Boulevard, Suite
601, Rockville, MD 20852-7669.
Docket
For access to the docket to read background documents or comments
received, go to the Regulations.gov portal and insert the docket number
provided in brackets in the heading on page one of this document into
the ``Search'' box and follow the prompts.
FOR FURTHER INFORMATION CONTACT: Jerry Moore at the address above, or
telephone 301-496-4607 (not a toll-free number) concerning questions
about the rulemaking process; and Sally J. Rockey, PhD, Deputy
Director, Office of Extramural Research, One Center Drive, Building 1,
Room 142, Bethesda, MD 20892, e-mail [email protected] concerning
programmatic questions.
SUPPLEMENTARY INFORMATION: Proper stewardship of Federal funds includes
ensuring objectivity of results by protecting federally funded research
from compromise by financial conflicts of interest (FCOI).
In 1995, the PHS and the Office of the Secretary of Health and
Human Services published the regulations at 42 CFR Part 50 Subpart F
and 45 CFR Part 94, designed to promote objectivity in PHS-funded
research.\1\ The regulations are applicable to Institutions \2\ that
apply for PHS funding for research (except for Small Business
Innovation Research (SBIR)/Small Business Technology Transfer Research
(STTR) Phase I applications/proposals) and, through implementation of
the regulations by these Institutions, to each Investigator \3\
participating in the research. Generally, under the regulations:
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\1\ 48 CFR Subpart 9.1, ``Responsible Prospective Contractors,''
and 48 CFR Subpart 9.5, ``Organizational and Consultant Conflicts of
Interest,'' also address conflicts of interest in Federally-funded
projects. These provisions apply only to acquisitions, not to grants
or cooperative agreements.
\2\ An ``Institution'' is defined under 42 CFR Part 50, Subpart
F, as any domestic or foreign, public or private, entity or
organization (excluding a Federal agency), and under 45 CFR Part 94
as any public or private entity or organization (excluding a Federal
agency) that (1) submits a proposal for a research contract whether
in response to a solicitation from the PHS or otherwise, or (2) that
assumes the legal obligation to carry out the research required
under the contract. See 42 CFR 50.603; 45 CFR 94.3.
\3\ An ``Investigator'' is defined under the regulations as the
principal investigator and any other person who is responsible for
the design, conduct, or reporting of research funded by PHS, or
proposed for such funding. For purposes of the regulatory
requirements relating to financial interests, the term
``Investigator'' includes the Investigator's spouse and dependent
children. See 42 CFR 50.603; 45 CFR 94.3.
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The Institution is responsible for complying with the
regulations, including developing and maintaining a written and
enforced policy; managing, reducing, or eliminating identified
conflicts; and reporting identified conflicts to the PHS funding
component. The reports denote the existence of a conflict and assure
that it has been managed, reduced, or eliminated.
The participating Investigators are responsible for
complying with their Institution's written Financial Conflict of
Interest (FCOI) policy and for disclosing their Significant Financial
Interests \4\ (SFI) to their Institution.
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\4\ A ``Significant Financial Interest'' is defined under the
regulation as anything of monetary value, including but not limited
to (1) Salary or other payments for services (e.g., consulting fees
or honoraria); (2) equity interests (e.g., stocks, stock options or
other ownership interests); and (3) intellectual property rights
(e.g., patents, copyrights and royalties from such rights). The term
does not include (1) Salary, royalties, or other remuneration from
the institution; (2) any ownership interests in the institution, if
the institution is an applicant under the SBIR program; (3) income
from seminars, lectures, or teaching engagements sponsored by public
or nonprofit entities; (4) income from service on advisory
committees or review panels for public or nonprofit entities; (5) an
equity interest that, when aggregated for the investigator and the
investigator's spouse and dependent children, does not exceed
$10,000 in value as determined through reference to public prices or
other reasonable measures of fair market value, and does not
represent more than a five percent ownership interest in any single
entity; and (6) salary, royalties, or other payments that when
aggregated for the investigator and the investigator's spouse and
dependent children over the next twelve months are not expected to
exceed $10,000. 42 CFR 50.603; 45 CFR 94.3.
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[[Page 21611]]
The PHS funding components are responsible for overseeing
Institutional compliance with the regulations.
Ensuring objectivity in research requires a commitment from
Institutions and their Investigators to complete disclosure,
appropriate review, and robust management of identified conflicts
consistent with the level of risk presented. The existing regulations
were designed to provide standards to ensure that the design, conduct,
or and reporting of PHS-funded research is not biased by any FCOI.
In the intervening years since the publication of these
regulations, the pace of translation of new discoveries from the
research bench into effective treatment of patients has significantly
accelerated. As a result, the biomedical research enterprise in the
United States is extensive and growing in size and complexity.
Researchers frequently work in multidisciplinary teams to develop new
strategies and approaches for translating basic research into clinical
application. In addition, these newer translational strategies often
involve complex collaborations between investigators and the private
sector. Together, these factors may generate an increased potential of
investigators to hold financial interests in multiple sources which, if
not reported and appropriately managed, reduced, or eliminated, could
introduce bias into the conduct of their research. Recognition of the
growing complexity of biomedical research, the increased interaction
between Government and the private sector in meeting common public
health goals, and recent public scrutiny have raised the question of
whether a more rigorous approach to Investigator disclosure, management
of conflicts, and Federal oversight is required.
Ensuring the objectivity of research results requires a commitment
to uphold the following principles:
1. Research must be conducted with transparency and the highest
scientific and ethical standards in a manner that promotes and respects
the rights, safety, and welfare of all human research participants.
2. Appropriate interactions and relationships between government,
academia, and industry, which do not compromise objectivity in
research, frequently have beneficial outcomes and should be encouraged.
3. The integrity of the scientific record is critical to the
conduct of science.
4. Risk management is essential in evaluating and managing conflict
of interest; risk management should be commensurate with the level of
risk of the research.
5. Complete and timely disclosure of financial interests and
effective management of conflicts of interest are essential to ensuring
objectivity in research.
For the reasons cited above, we are considering whether to revise
the current regulations to provide Institutions with a more
comprehensive set of guidelines based on these five principles. The
complex and controversial issues surrounding FCOI warrant a carefully
considered, open dialogue with all affected parties. Consequently, we
invite public comments on all aspects of potential regulation in this
area, and particularly on the following issues:
I. Expanding the Scope of the Regulation & Disclosure of Interests
The regulations are applicable to Institutions that apply for PHS
funding for research and, through implementation of the regulations by
each Institution, to each Investigator participating in such research.
However, the regulations do not apply to Phase I SBIR/STTR applications
(42 CFR 50.602, 45 CFR 94.2).
The regulations require that Investigators disclose to the
Institution only those Significant Financial Interests (SFI) (1) that
would reasonably appear to be affected by the research for which
funding is sought from the PHS; and (2) in entities whose financial
interests would reasonably appear to be affected by the research (42CFR
50.604(c)(1); 45 CFR 94.4(c)(1)).
a. Should the regulations be expanded so that they also apply to
Phase I SBIR/STTR research applications/proposals for PHS funding?
b. In May 2004, HHS issued a guidance document entitled,
``Financial Relationships and Interests in Research Involving Human
Subjects: Guidance for Human Subject Protection'' that raises points to
consider in determining whether specific financial interests, including
Institutional financial interests, in research affect the rights and
welfare of human subjects and if so, what actions could be considered
to protect those subjects. In February 2008, the Association of
American Medical Colleges (AAMC) and the Association of American
Universities (AAU) Advisory Committee on Financial Conflicts of
Interest in Human Subjects Research issued a report, ``Protecting
Patients, Preserving Integrity, Advancing Health: Accelerating the
Implementation of COI Policies in Human Subjects Research,'' which
offered a number of recommendations designed to enhance Institutional
conflict of interest policies. One recommendation was that
investigators conducting human subjects research should be required to
report all of their outside financial interests directly or indirectly
related to their professional responsibilities to their Institution,
regardless of dollar amount and regardless of whether or not the
investigator believes that the reported financial interests might
reasonably appear to be affected by his or her current or anticipated
research. In light of the above, should Investigators be required to
disclose to their Institutions all Significant Financial Interests that
are related to their Institutional responsibilities? Would this
expanded disclosure allow the Institution to better determine which of
these Significant Financial Interests constitute a FCOI?
II. Definition of ``Significant Financial Interest''
A ``Significant Financial Interest'' is defined by the current
regulations as anything of monetary value, including but not limited
to:
Salary or other payments for services (e.g., consulting
fees or honoraria);
Equity interests (e.g., stocks, stock options or other
ownership interests);
Intellectual property rights (e.g., patents, copyrights
and royalties from such rights).
The term does not include the following types of financial
interests:
Salary, royalties, or other remuneration from the
Institution;
Any ownership interests in the Institution, if the
Institution is an applicant under the SBIR/STTR program;
Income from seminars, lectures, or teaching engagements
sponsored by public or nonprofit entities;
Income from service on advisory committees or review
panels for public or nonprofit entities;
An equity interest that, when aggregated for the
Investigator and the Investigator's spouse and dependent children, does
not exceed $10,000 in value as determined through reference to public
prices or other reasonable measures of fair market value, and does not
represent more than a five percent ownership interest in any single
entity;
Salary, royalties or other payments that when aggregated
for the Investigator and the Investigator's spouse and dependent
children over the next twelve
[[Page 21612]]
months, are not expected to exceed $10,000. (42 CFR 50.603; 45 CFR
94.3).
a. Should the current exemptions be maintained?
If so, are the current de minimis thresholds ($10,000 and
5 percent ownership interest in any single entity) reasonable? If not,
how should the de minimis thresholds be changed? Should these
thresholds be the same for all types of research?
If not, which exemptions should be reconsidered, and why?
b. Should certain Significant Financial Interests (i.e.,
Significant Financial Interests received from specific sources or
related to certain types of research) automatically be considered a
FCOI under the regulations? If so, what types of Significant Financial
Interests?
III. Identification and Management of Conflicts by Institutions
The regulations require that an official(s) designated by the
Institution review all financial disclosures; determine whether a
financial conflict of interest exists; and, if so, determine what
actions the Institution should take to manage, reduce, or eliminate the
conflict of interest (42 CFR. 50.605; 45 CFR 94.5). The regulations
provide that a conflict of interest exists when the designated
official(s) reasonably determines that a Significant Financial Interest
could directly and significantly affect the design, conduct, or
reporting of the research funded by the PHS (42 CFR 50.605; 45 CFR
94.5). The regulations currently do not define the term ``designated
Institutional official(s)'', or mandate specific actions that
Institutions must take to manage, reduce or eliminate particular types
of FCOIs.
a. Should large Institutions (defined as greater than 50 employees)
be required to establish an independent committee to review financial
disclosures, and require that committee to report to an organizational
level within the Institution that is not conflicted by the short-term
financial interests of the Investigator or Institution? Would a 50
employee threshold reasonably balance the risk of a more relaxed
requirement for smaller Institutions against the burden imposed by
requiring an independent panel for these evaluations?
b. For certain types of research, should the Institution be
required to develop a conflict management plan when the Institution
decides to manage or reduce, rather than eliminate, the conflict? If
so, for which types of research? Should there be prescribed standards
for the conflict management plans? Should the Institution be required
to submit this plan to the PHS funding component when it reports the
existence of a conflict to the component?
c. Should Investigators who are involved in participant selection,
the informed consent process, and clinical management of a trial, be
prohibited from having a Significant Financial Interest in any company
whose interests could be affected by their research or clinical trial?
If so, what special circumstances would justify waiving this condition,
if any?
d. Should the regulations prescribe specific approaches for the
management, reduction, or elimination of particular types of FCOI? If
so, for which types of FCOI? Which approaches?
e. Should specific requirements related to the identification,
management, and reporting of FCOI be established for subrecipients
(i.e., subgrantees, contractors, subcontractors, collaborators)?
f. Should amounts received by Investigators from certain kinds of
organizations be limited to certain maximum thresholds if an
Investigator is supported with PHS research funds? If so, which kinds
of organizations? At what thresholds?
IV. Assuring Institutional Compliance
Under the current regulations, the PHS funding component may at any
time inquire into the Institutional procedures and actions regarding
conflicting financial interests in PHS-funded research, including a
requirement for submission, or review on site, of all records pertinent
to compliance with the regulation (42 CFR 50.606; 45 CFR 94.6). On the
basis of its review of records and/or other information that may be
available, the PHS funding component may decide that a particular
conflict of interest will bias the objectivity of the research it funds
to such an extent that further corrective action is needed or that the
Institution has not managed, reduced, or eliminated the conflict of
interest in accordance with the regulation(s) (42 CFR 50.606; 45 CFR
94.6). The PHS funding component may determine that suspension of
funding/the issuance of a Stop Work order is necessary until the matter
is resolved(42 CFR 50.606; 45 CFR 94.6).
a. Should the regulations enhance existing enforcement options in
the event of noncompliance?
b. Should Investigators be required under the regulations to
complete routine FCOI training?
c. Should independent confirmation of an Institution's compliance
with the regulation be required? If so, what should this confirmation
look like (e.g., accreditation by an outside body, an independent
audit)?
V. Requiring Institutions to Provide Additional Information to the PHS
Under the current regulations, prior to spending any funds under an
award, the Institution must report to the PHS funding component the
existence of any conflicting financial interest found by the
Institution and assure that the interest has been managed, reduced, or
eliminated in accordance with the regulation(s) (42 CFR 50.604(g)(2),
45 CFR 94.4(g)(2)). The regulations do not require the Institution to
report to PHS officials the nature of the interest or other details (42
CFR 50.604(g)(2), 45 CFR 94.4(g)(2)).
a. Should Institutions be required to submit to the PHS funding
component additional information on any identified conflict? If they
should not be required to submit additional information for all
identified conflicts, should they be required to submit additional
information for identified conflicts involving certain types of
research? If so, for which types of research? What kind of information
would provide valuable data to the PHS funding component in evaluating
these reports and the potential risk of bias in conduct of research?
VI. Institutional Conflict of Interest
Institutional conflict of interest is currently not addressed by
the regulations, although there has been movement in the research
community toward incorporating Institutional standards in conflict of
interest policies (see, for example, the February 2008 AAMC/AAU report,
``Protecting Patients, Preserving Integrity, Advancing Health:
Accelerating the Implementation of COI Policies in Human Subjects
Research''), and some Institutions have adopted such standards. This is
an area of increasing concern. If the regulation were to be amended to
address Institutional conflict of interest, how should it address the
following issues?
a. How would Institutional conflict of interest be defined?
b. What would an Institutional conflict of Interest policy address
in order to assure the PHS of objectivity in research?
[[Page 21613]]
Dated: February 2, 2009.
Raynard S. Kington,
Acting Director, National Institutes of Health.
Approved: April 9, 2009.
Charles E. Johnson,
Acting Secretary.
[FR Doc. E9-10666 Filed 5-7-09; 8:45 am]
BILLING CODE 4140-01-P