Medical Device Daily Washington Editor

Increasing public concern and scrutiny from Capitol Hill may not have had anything to do with it, but the deputy commissioner of the FDA said Monday that drug makers should be ready to pay more in user fees to pay for the agency’s post-market surveillance of drugs.

The FDA’s Scott Gottlieb offered no firm figures for user fees to fund surveillance, but whatever the number, industry is sure to resent the lack of appropriate funding of the FDA. Since 1992, drug makers have seen their share of the review budget at the Center for Drug Evaluation and Review soar from 7% to 53%. User fees for this industry may total $86 million for fiscal year 2007.

In remarks to the Manhattan Institute (New York) this past Monday, Gottlieb said he sees no reason to believe that “safety and innovation ... are in conflict,” but he opined that improved safety hinges on “innovation in the way that we develop drugs.” However, he cautioned against “creating costly and inefficient obstacles to the development of new technology,” a prospect that he argued “has been given short shrift in Washington policy circles.”

To improve safety, the FDA has awarded four contracts to obtain access to databases that “contain pharmaco-epidemiologic information, which will be used to study the association of various medicines with serious adverse effects,” Gottlieb said. He also reminded the audience that the agency and the Centers for Medicare & Medicaid Services are working on a project that would allow the FDA to tap CMS data on Part D claims matched with data on hospitalizations and visits to doctors’ offices to track adverse events.

The FDAer said the agency “plans to develop a series of new guidance documents” that will “lay out approaches to making the most efficient and effective use of epidemiology data” to alert authorities more quickly as to post-market reactions to drugs.

The FDA announcement precedes by several days a hearing in the Senate titled “Building a 21st Century FDA: Proposals to Improve Drug Safety and Innovation” by the Senate’s Health, Education, Labor and Pensions (HELP) committee. The HELP committee will review S. 3807, a bill titled “Enhancing Drug Safety and Innovation Act,” which the current committee chair, Mike Enzi (R-Wyoming), and the current ranking member, Ted Kennedy (D-Massachusetts), forged over the duration of the 109th Congress. In a prepared statement, Enzi said that S. 3807 would mandate that “drug makers ... engage in better planning before a drug is approved and by helping patients and healthcare providers make better informed decisions” by more quickly publishing the results of clinical trials.

Introduced to the committee this past August, S. 3807 would require makers of drugs and biologics to include a strategy for risk evaluation and minimization with each application. The bill would also establish a clinical trial database registry and allow the establishment of other offices at the FDA to advance Critical Path science.

Study: PCI no help after three days

As medical science avails itself of greater volumes of data, old standards occasionally fall by the wayside. An article in the current edition of the New England Journal of Medicine keeps that trend alive with the results of a study of the efficacy of balloon angioplasty in patients whose cardiac events took place at least three days prior to medical intervention.

Judith Hochman, MD, et al put together a randomized prospective trial of almost 2,200 patients who had waited three days to see a doctor (the delay was an inclusion criterion, not part of the study protocol) over four years. Roughly half the participants went through angioplasty, stenting and medical therapy and the balance only medical therapy.

The authors write that “the four-year cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group,” an outcome that flies in the face of conventional thinking on the subject. Rates of non-fatal reinfarction were similarly tilted away from expectation, at 7% for the PCI group and 5.3% for those who had nothing but drugs to deal with the blockage.

The authors concluded that “PCI did not reduce the occurrence of death, reinfarction or heart failure.” Hochman, who is a professor of cardiology at New York University Medical Center , announced the results at the annual meeting of the American Heart Association (Dallas) and admitted that the rates of heart attack might represent a statistical aberration, as suggested by the high P score. On balance, however, the paper had a lot of credibility.

Elizabeth Nabel, MD, the director of the National Heart, Lung and Blood Institute (NHLBI), said that the findings “were really a surprise,” and that “for a long time, we thought that opening up the artery at any time after a heart attack was better than leaving it closed.” NHLBI was the primary funder of the study.

In an editorial in the Nov. 15 edition of NEJM, David Hillis, MD, and Richard Lange, MD, said that the results obtained by Hochman and her colleagues may run counter to previous studies because “almost all the [other] studies ... were retrospective and not randomized” and that as a consequence, those studies may have suffered from selection bias or unnoticed confounders.

The drug treatment in the current trial included beta adrenergic blockers as well as ACE and platelet inhibitors. Hillis and Lange state that in previous studies, “beta adrenergic blockers were as effective as mechanical restoration of antegrade flow in improving survival,” but they complained that the Hochman study did not include follow-up on the approximately 263 subjects (controls and study subjects) who got no beta adrenergic blockers, presumably due to problems with tolerance. The editors noted that those who do not tolerate this class of drugs might do well to undergo PCI even after the duration described in the study.

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