WASHINGTON _ Several witnesses at an FDA publichearing Thursday questioned the premise for a plannedrule that seeks to ensure clinical investigators are notswayed by financial incentives.

John Siegfried, associate vice president of thePharmaceutical Research and Manufacturers of America(PhRMA), faulted the agency for failing to establish whythe rule is needed and for failing to substantiate that aregulation would diminish a perceived problem.

He disputed the FDA's claim that "there has been agrowing concern for some time both at FDA and withinthe academic and scientific communities, that somefinancial arrangements between clinical investigators andproduct sponsors, as well as the personal financial interestof clinical investigators, are a potential source of bias inclinical trials."

The FDA currently has no procedures for gatheringinformation about the financial interests of its clinicalinvestigators.

The agency proposed the conflict of interest regulationson Sept. 22, 1994 and received 47 comments, some ofwhich questioned the basis of the planned rule. The FDAsaid it convened Thursday's public hearing to get furthercomments, particularly on the issue of where to establishthe threshold to define financial conflict of interest.

The proposed regulations state that a manufacturerseeking market approval would have to certify that thecompany has not entered into any financial arrangementwith clinical investigators that might color the outcome ofthe study and that the clinical investigator has notreceived significant payments from the drug company andhas no proprietary interests in the product.

In lieu of certification, the drug firm must disclose thespecific financial arrangements with the clinicalinvestigators, any payments made, and steps taken tominimize the potential for bias in the data submitted.

Failure to either certify or disclose financial arrangementswith clinical investigators would prompt the FDA not tofile the drug application.

Siegfried told the hearing that he doubted that "FDAcould construct a threshold which would create a bias freeenvironment.

"Make no mistake. PhRMA supports the intent of theproposed rule," said Siegfried. "Our member firms makea significant investment of time and money to ensure thevalidity of clinical data . . . and are acutely aware thatsubmission of data of questionable or limited validity willultimately destroy their product."

He said that perhaps the FDA should propose conflict ofinterest regulations for statisticians "because they havemore access to data than the clinical investigators."

Jeffrey Gibbs, a Washington attorney with Hyman,Phelps and McNamara, said that the FDA hasunderestimated the reporting burden on small biotechfirms and medical device companies. Gibbs estimatedthat each firm will have to develop new managementreporting systems to track financial relationships withclinical investigators. Gibbs said each company will haveto check its financial records carefully to determinedisclosable interests, mindful that knowingly signing afalse statement is potentially a felony. "This cannot bedone in the 30 minutes as FDA says, even in smallcompanies, let alone multinational corporations," Gibbssaid.

Siegfried urged the FDA officials to differentiate betweenfraud and bias. He noted "most recent illustrations ofscientific fraud that have come to public attention havenot been related to the FDA and pharmaceuticalcompanies but rather have involved academic centers andother government agencies."

The FDA does not have a documented case ofinappropriate financial interest held by a clinicalinvestigator that affected the outcome of clinical trials ofa product later approved by FDA, said agencyspokeswoman Betsy Adams.

Dealing with bias is a far more subtle exercise, Siegfriedsaid. "Bias in the scientific community comes frommultiple sources _ job security, the need to `public orperish,' professional jealousy, the desire of academicadvancement, and others. Financial influence is only onetype of bias and the attempt to single out one source ofbias without dealing with other has limited value." n

-- Michele L. Robinson Washington Editor

(c) 1997 American Health Consultants. All rights reserved.

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