NIH TO UNVEIL SECOND VERSION OF CONFLICT-OF-INTEREST GUIDES AT UPCOMING MEETING, POSSIBLY BY YEAR’s END; FINANCIAL INTERESTS MAY BE PERMITTED

The National Institute's of Health second try at conflict-of-interest guidelines for clinical investigators working on government-funded trials will rely on institutions to set and police the rules on financial interests.

According to a draft of the second version of conflict-of-interest guidelines from NIH, institutions involved in Public Health Service clinical studies for a commercial product would be required to "solicit and review disclosures of financial interests of investigators...and where necessary, take action to eliminate or prevent inappropriate financial interests."

NIH has floated the second set of guidelines in some research circles in preparation for a public proposal in 1991. NIH issued a first version of conflict-of-interest guidelines in September 1989. Those guidances, based on a premise of "full disclosure of all financial interests and outside professional activities," elicited more than 700 responses.

Before publishing the second draft of guidelines, NIH is likely to hold a large open meeting to address some of the questions raised by the first proposal. That meeting tentatively has been scheduled for December but may occur after the start of the new year. In a draft notice for the upcoming meeting, NIH said that the purpose of the meeting will be "to discuss the approaches to the development of a policy, which may be published as a regulation, to protect against inappropriate financial interest in commercial products under study in clinical trials."

The schedule for NIH's guidelines development was discussed at a recent meeting on the conflict-of-interest question in Boston. Speaking at an Oct. 15-16 symposium sponsored by Public Responsibility in Medicine and Research, Ronald Lamont-Havers of the Massachusetts General-Harvard Cutaneous Biology Research Center predicted a Federal Register notice regarding conflict-of-interest in clinical trials will be published "within a very short period of time." Lamont-Havers, a former deputy director of NIH, said he expects "reg restriction to come probably by the end of 1991 or the beginning of 1992."

The previous guidelines had asked for financial disclosures from all people in positions to make decisions about NIH-supported research. The current draft narrows the focus to clinical trial investigators. NIH is considering allowing clinical investigators to maintain "a financial interest in the product under study," if the institution judges that the financial stake "is unlikely to compromise the design, conduct, or reporting of the study."

NIH would also recommend that the institution "impose requirements to minimize even perceived conflict, for example, by requiring disclosure of interests in resulting publications." The draft proposal would also require investigators and institutions "to disclose to the PHS all sources of support (before and after award [and] when changes occur)."

News of NIH's new proposal met with mixed reactions from participants at the conflict-of-interest conference in Boston. New England Journal of Medicine Executive Editor Marcia Angell, MD, advocated more restrictive federal regulations. She espoused a position that all clinical investigators involved in government-sponsored research of any kind should be prohibited from owning stock in any health care company so as to prevent conflicts-of-interest.

"There is no particular reason why the investigator has to have stock in the health care field at all, not just stock in the company whose product he is investigating," Angell declared. "Why should researchers lose their objectivity by having stock in the health care field? There are millions of Americans who don't." Angell noted that The New England Journal of Medicine prohibits its editors from owning stock in health companies.

Angell's suggestion for a blanket prohibition on investment in health care companies was criticized by several other panel members. Lita Nelsen, associate director of the Technology Licensing Office at MIT, questioned, for example, whether such a policy would not quell "entrepreneurial fervor," as well as eliminate uniquely qualified researchers from certain clinical trials.

Louis Lasagna, MD, dean of the Sackler School at Tufts University, called the proposal "draconian" and predicted that its implementation would "significantly thin the ranks of researchers in the scientific community."

Lasagna and several other conference panelists, most notably Joseph Allen, director of the office of Technology Commercialization at the U.S. Department of Commerce, and Kenneth Yale, DDS, chief of staff at the White House Office of Science and Technology, suggested that federal intervention and regulation of conflict-of-interest be kept to a minimum.

"Conflict-of-interest is a management problem, not a government one," Allen said. Conceding that some form of federal intervention is inevitable for researchers in NIH-funded clinical trials, Allen maintained that NIH enforcement of sweeping regulations in other areas of research would be problematic. For example, he noted the difficulties in forcing disclosure or prohibiting stock ownership when spouses or relatives are factored into the conflict-of-interest equation.

"We are dealing with a political phenomenon, a media phenomenon, and a question of public perception...the semblance of unseemliness...and not any evidence that data is invalid," declared Lasagna.

In lieu of wide-scale federal regulations, Allen, Yale and Lasagna advocated institutionally-administered conflict-of-interest policies that would allow universities and public laboratories to address their own specific needs. Several such institutional programs for controlling conflicts-of-interest were showcased at the two-day conference.

Harvard University recently has introduced a policy calling for complete disclosure by all researchers of financial assets. Johns Hopkins has designed a policy which forbids all medical faculty from owning stock in any company whose product they are researching.

Louis Sherwood, MD, exec VP worldwide development for Merck, encouraged institutions to keep in mind two basic principles while designing their policies. "First, we believe that no rewards of compensation for a university or government scientist should be contigent upon the success of the research effort, whether it be in basic research or in the clinical evaluation of drugs or medical devices...That is we do not grant and don't believe that individuals should be granted equity or management positions in companies."

Conflict-of-interest guidelines must require transparency, Sherwood said. "To put it simply," the Merck exec said, "universities and government laboratories should establish their own rules, suiting their own individual needs...but these rules should be designed to assure themselves and the public that they know exactly what their faculties and scientists are doing."

Genentech Senior Director of Government Affairs Martin Rose, MD, reported that in the last year Genentech has altered its conflict-of-interest policies so that all clinical investigators are now required to sign written agreements stating that "they will not buy or sell any Genentech stock during the period that they are clinical investigators [for Genentech], nor will they hold Genentech stock, if they already bought it on the open market, during the time that they are clinical investigators unless they get written permission from Genentech." Written permission, he noted, is granted only after an ad hoc meeting of clinical investigators and the company's legal staff.

Rose cautioned institutions against attempting to extend conflict-of-interest policies to address "non-evaluative trials" or consultancy and honoraria arrangements because he feared that such restrictions might impede industry's ability to recruit top scientists. "If we make it really difficult for our best scientists to appear in the trials, then we may be shooting ourselves in the foot," Rose said.