COUNCIL ON GOVERNMENTAL RELATIONS

1200 New York Avenue, N.W., Suite 320, Washington, D.C. 20005

\(202\) 289-6655/(202) 289-6698 (FAX)

November 25, 2002

Margaret M. Dotzel

Associate Commissioner for Policy

Dockets Management Branch (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Rm 1061

Rockville MD 20852

# SUBJECT: Docket No. 02D-0320

Draft Guidance for Industry and Clinical Investigators on the Use of
Clinical Holds Following Clinical Investigator Misconduct (67 FR 55025)

Dear Ms. Dotzel:

The Council on Governmental Relations (COGR) is an association of 150
research intensive universities in the United States that works with
federal agencies to develop a common understanding of the impact that
policies, regulations and practices may have on the research conducted
by its membership. The use of clinical holds on investigators will
affect members of our faculty and staff and we welcome the opportunity
to comment on the draft guidance.

We share the Food and Drug Administration's (FDA) goal of protecting
human subjects from risk and harm that might result from the unethical
treatment of human subjects by a clinical investigator. We believe that
a modification to the proposed Guidance will more efficiently achieve
this goal. Therefore, we ask that in the case of university-affiliated
investigators, the university should be notified first of any
allegations of misconduct and/or unethical treatment of subjects prior
to notification of the investigator and sponsor. Making this change will
result in two advantages: it assures the immediate intervention to
protect the health of human research participants, and secondly, the
university can address the FDA's additional concern of research
misconduct.

In an academic setting, there are two mechanisms designed to deal
directly with the unethical treatment of human subjects and alleged
research misconduct: suspension of the research by the Institutional
Review Board (IRB) and intervention by university-appointed officials
under research misconduct procedures. Because these procedures operate
at the institution-level, they offer the most appropriate way to respond
promptly to any FDA concerns in these academic settings.

It is important to recognize this delegation of authority within
universities. Notification of an external sponsor about a
university-affiliated investigator's misconduct may not ensure that the
appropriate institutional official and offices are alerted to the
problem. In the case of human subjects, the federal regulations
governing the protection of human subjects give the IRB the
responsibility to suspend or terminate a previously approved research
protocol (21 CFR 56.113 and 45 CFR 46.113). The IRB, working in
cooperation with the university, can act to stop on-going investigations
and continuing work by an investigator. In addition to the regulations
governing the protection of human subjects, universities must comply
with the Federal Policy on Research Misconduct as implemented by the
various departments and agencies. These agency policies, including the
HHS /PHS policy (42CFR50 SubpartA) require an investigation of any
allegation of research misconduct brought forward concerning one of its'
investigators, including allegations made by the FDA. As with the
protection of human subjects, the university is in the best position to
conduct an investigation of allegations of misconduct concerning one of
its employees.

In the current proposal, the first step for the FDA would be "contact
with the sponsor to attempt to resolve the matter." This approach
assumes that a company sponsor and the independent
physician-investigator are the principal parties in the conduct of a
clinical trial and will work well for these paradigms. However, it will
not be efficient for the organizational structures that govern
university- based clinical trials.

We recommend therefore that the FDA consider two models or paths to deal
with clinical investigator misconduct -- one that addresses independent
investigators; and another for university-affiliated investigators that
begins with immediate notification of the research organization's
institutional official. The institution is responsible for the research
conducted under its auspices and can work to ensure the immediate
protection of human research participants.

Thank you for the opportunity to comment.

Sincerely,

Katharina Phillips

President