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."