Guidelines for Avoiding Conflicts
of Interest in Multicenter Clinical Trials
National Heart, Lung, and Blood
Institute National Institutes of Health
Updated: September 6, 2000
In 1995, the Department released its final rule on
"Objectivity in Research" (Federal Register, July 11, 1995). Under this rule,
an investigator must disclose to an official in his or her institution "any
Significant Financial Interests (and those of his/her spouse and dependent
children) that would reasonably appear to be affected by the research proposed
for funding by the PHS. The institutional official(s) will review those
disclosures and determine whether any of the reported financial interests could
directly and significantly affect the design, conduct, or reporting of the
research and, if so, the institution must, prior to any expenditure of awarded
funds, report the existence of such conflicting interests to the PHS Awarding
Component and act to protect PHS-funded research from bias due to the conflict
of interest." These are minimum requirements. Individual institutions
may interpret them and implement them somewhat differently, and investigators
may decide to go beyond them. Also, in certain circumstances, these rules may
need to be adapted to the specific research program. For example, it would be
reasonable for investigators in multicenter clinical trials to come up with a
study-wide policy on conflict of interest, as different interpretations of the
guidelines by different investigators and their institutions may be
inappropriate. Certainly, the credibility of the study might depend on all of
the investigators having stronger policies for conflict than are mandated by
the PHS. Even if one or two of the investigators have financial interests in a
drug or device being evaluated in the trial, or in a competitor of the drug or
device, questions may arise as to the validity and interpretation of the trial
results. An example of this is TIMI-1, where some of the investigators had
considerable financial interest in tPA, leading to Congressional investigation.
Most, but not all, clinical trial investigator groups have since
developed conflict of interest guidelines. These have ranged from disclosure of
interests to prohibition against buying or selling stock in a company
manufacturing one of the interventions, to having any equity. In some cases,
consulting or giving paid talks for the manufacturers has been discouraged.
Any clinical trial assessing an intervention for which there is or might
be an IND (for drugs) or an IDE (for devices) has additional requirements.
Details about these requirements may be obtained from
www.fda.gov/oc/guidance/financialdis.html.
In summary, the integrity of the study must not be compromised by
financial interests. To assure that, investigators cannot have financial
arrangements that reward a particular study outcome, proprietary interest in
the intervention being tested, significant equity in the manufacturer of the
intervention, or significant payments of other sorts. Specified financial
arrangements must be disclosed. The sponsor of the IND or IDE is responsible
for collecting information about financial interests. The NHLBI, even if it is
not the sponsor of the IND or IDE, will take an active role in ensuring that
these requirements are followed. It is in the Institute's interest to
strongly advise the investigative group to develop guidelines that avoid any
perception that the study design, conduct, and data analysis and interpretation
might have been biased by investigator conflict. To help investigators comply
with the PHS regulations, the Institute Project Officer or Program Scientist
and the Principal Investigator(s) must discuss the conflict of interest policy
for the study at an early stage in the protocol development process. Although
the Institute does not specify exactly what policy a given study should
develop, it needs to remind the investigative group that study credibility
depends on reasonably strict guidelines. These policies should be clearly
spelled out in the protocol. In addition, the Project Officer or Program
Scientist should be apprised of conflicts that arise and the corrective actions
by the investigator's local institution. As noted in regulations, the Institute
"may at any time inquire into the Institutional procedures and actions
regarding conflicting financial interests in PHS-funded research, including a
requirement for submission of, or review on site, all records pertinent to
compliance with this subpart."
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