Michele L. RobinsonWashington Editor

WASHINGTON _ In the ongoing saga of FDA reform, agencycontrol of companies' communications materials on unapproved usesof drugs is the latest bone of contention for industry and regulators.

At the last House Commerce Oversight Subcommittee hearing onFDA reform, industry and FDA officials indicated agreement onseveral areas to streamline regulation of biotech drugs, but this issuehas polarized biotech companies and the agency.

Rep. Ron Wyden (D-Ore.), member of the House CommerceCommittee and a proponent of FDA reform legislation, said at theMay 25 hearing that "we need to make sure that scientificallycredible information is being disseminated. But the agency is actinglike a censor," Wyden added.

He wants to sustain FDA's authority to limit what companies sayabout unapproved uses of a drug but he questioned whether theagency's current policy violates the First Amendment and isimpractical.

Instead, Wyden wants the FDA to take action against companies thatdisplay a clear pattern of abuse.

Wyden is planning to introduce legislation that would restrict theFDA's jurisdiction over company promotional materials andexplicitly permit drug firms to distribute scientific journals tophysicians, third-party insurers and drug formulary committees, saidStephan Lawton, an attorney for Hogan & Hartson, a Washington lawfirm. Lawton has been closely involved in drafting FDA reform bills.Wyden has not indicated when the legislation will be ready forreview.

The FDA associate commissioner for policy, Bill Schultz, whoformerly served as Commerce Committee counsel and was a key aideto then Health Subcommittee Chairman Henry Waxman (D-Calif.)vigorously defended FDA's review policy.

"FDA has no business being involved in the exchange of informationwhen a pharmaceutical company is not involved. But we do act whena promotion involves the use of a drug not approved by FDA,"Schultz told the subcommittee on May 25.

"FDA believes that it is fine for drug makers to fund continuingeducation as long as the people involved are independent of themanufacturer and the manufacturer has no control over the content ofthe meeting," he said.

"However, the issue of whether manufacturers can distribute journalarticles goes to the heart of the efficacy standard," Schultz said.

The FDA is concerned about the unintended consequences of thedissemination of information about the off-label use of drugs andmedical devices as well as company claims to managed care insurersabout the cost effectiveness of their products. As a result,manufacturers are canceling continuing medical educationconferences and firms are stopping distributing peer reviewed journalarticles to physicians, said the Washington Legal Foundation chiefcounsel, Richard Samp.

The foundation mounted a First Amendment legal challenge to theFDA's policy to review all company promotional materials involvedwith off-label use. Motions were filed in 1994 and a ruling isexpected late in 1995, Samp said.

Interestingly, the Foundation's lawsuit was developed by AlanSlobodin, then head of its legal research department and now counselto the House Commerce Oversight and Investigations Subcommittee.

The division between the agency and biotech industry has become sowide that communications between the two are breaking down.

"FDA is paralyzed by the issue," Steve Push, Genzyme's vicepresident for corporate communications, said in an interview withBioWorld Today. FDA officials withdrew from a recent seminarPush had organized to discuss the issue.

FDA officials declined requests by BioWorld Today to beinterviewed on this issue.

Data Must Back Up Claims

The agency's long reach into a company's communications hasrestricted what drug firms say to managed care insurers. Push saidthat FDA's policy has meant that if companies want to make anyclaims to a managed care firm, they must be careful to make sure theyhave completed cost-effectiveness analyses.

Russell Herndon, Genzyme's vice president for regulatory affairs saidCenter for Biologics Evaluation and Research's (CBER) policy toregulate promotional materials is more strict for biotech drugs andbiologics than synthetic drugs. "While the Center for DrugEvaluation and Research [CDER] limits its reviews of companymaterials to the `pre-launch stage' of a synthetic drug, the CBERreviews all company materials associated with a product, includingpress releases and video presentations."

"CBER has defined labeling broadly to include any printed materialsor advertisements and promotion materials," Herndon said.

"They are nebulously interpreting whether a company's claim tomanaged care insurers about a product cost-effectiveness violates theproduct's labeling," he said.

"If a manufacturer says its product reduces hospitalization, themanaged care firm may force a firm to `prove' that claim bycontacting FDA for documentation to support the company'sassertions. FDA then may come back to the manufacturer and ask thatit support these claims with treatment outcomes studies and quality oflife analyses," he said.

Herndon attributes these differences to the Centers' differentauthorization legislation. CDER was authorized under the Food,Drug and Cosmetic Act while CBER operates under authority of thePublic Health Service Act.

Genzyme and other manufacturer's are prohibited from distributingpeer-reviewed journal articles that evaluate its products. "FDA hastaken the position that the journal article constitutes promotionalmaterials and that we must be able to substantiate any claims. But ofcourse we can't do that," Herndon said.

"The agency does let us get around this by permitting a company todistribute a journal article if a physician calls with a specificquestion," he said.

Genentech Forbids Claims Not Approved By FDA

At Genentech, sales people are strictly precluded from making anyclaims that are have not been cleared by FDA, David MacFarlane,vice president for regulatory affairs, told BioWorld Today.

"If a physician wants information about an off-label use of a drugbeyond the scope of Genentech's promotional materials, theirquestions are directed to the medical information group which reportsdirectly to clinical affairs, not marketing," MacFarlane said.

MacFarlane said that because managed care firms are making most ofthe decisions about whether a new drug or procedure should beadopted, the FDA's attempts to control claims about a drug havebeen eclipsed by these new economic incentives.

"Managed care insurers have formulary committees made up ofpharmacologists, physicians, nurses and pharmacists who decidewhether to reimburse for a new drug based on the scientific literatureand their own experience. They don't make their decisions based onwhat the company says," he said.

To illustrate his point, MacFarlane said that "FDA a few months agohad a meeting with representatives of the drug industry and managedcare firms where it was told by the managed care officials that `wehave our own mechanism for deciding about a drug.'"

"But we still err on the side of safety and voluntarily submit allmaterials to FDA," he said. "For example, when GUSTO waslaunched, we submitted letters to physicians, press releases, B-rolls,and videos to the agency for clearance." (GUSTO stands for GlobalUtilization of streptokinase and tPA in Occluded Coronary Arteries,the largest clinical trial involving 41,000 patients.)

"Several years ago we distributed an article that we thought only hada vague reference to GUSTO, but the agency called us and told us thedrug had not been approved and to stop distribution of the journalarticle," MacFarlane told BioWorld Today.

"The bottom line is that FDA assumes that physicians and providerscannot make educated choices so they intend to do it for them,"Herndon said. n

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