Washington Editor

WASHINGTON - Last week's Government Accountability Office (GAO) report on drug safety came as no surprise to many FDA critics who have charged that the agency lacks teeth when it comes to enforcement on pharmaceutical products after they're on the market, while others said the findings shed light on issues that the FDA already is working to improve.

The GAO was frank in its analysis at times, claiming that the FDA "lacks clear and effective processes" on post-approval safety issues, but the government's investigational division also commended the regulatory agency for some recent organizational and policy changes, such as its new Drug Safety Oversight Board. However, the report added that "more could be done" in its oversight of post-approval safety issues to improve the dispute resolution process and to strengthen collaboration between the FDA's Office of New Drugs and its Office of Drug Safety. Both are housed within the agency's Center for Drug Evaluation and Research.

"My sense," said Michael Werner, president of the Werner Group, a Washington-based life sciences consulting firm, "is that it was a good analysis."

Noting that the findings could be interpreted two ways - favoring reformers who have called for drastic changes, but also supporting others who believe a bit of tweaking could go a long way - he expects that the GAO report will not have a major impact on Capitol Hill. "The system is not broken," he told BioWorld Today. But to be certain, safety issues have returned front and center in recent days, and expect more this summer when the Institute of Medicine issues another analysis on the FDA.

"I think [the GAO report] stirs the pot a little," Werner added, "and puts drug safety back on the front burners for policy-makers."

FDA critics warmed to the GAO's recommendation that Congress should consider giving the agency the authority to require post-approval drug safety studies, which also are referred to as Phase IV commitments or post-marketing studies. But that would require legislative change, because under current law, only accelerated approvals come with mandated Phase IV requirements. Other post-approval commitments are seen as points of negotiation between the FDA and drug companies and essentially become de facto requirements.

Some regard the GAO's suggestion to better empower the agency when it comes to Phase IV requirements as a boost to those in Congress who have been pushing safety-related legislation.

Leading the charge is Sen. Charles Grassley (R-Iowa), who a year ago introduced a bill that would give the FDA's safety office independence from CDER. Last week, Grassley, who also is the Finance Committee chairman, said the GAO report highlights cultural problems within the agency. His measure would establish the Center for Postmarket Drug Evaluation and Research, a separate entity from CDER, at the FDA. Grassley's proposed bill is labeled S. 930, and its companion House bill is H.R. 4429.

Other lawmakers pushing for change include Sens. Mike Enzi (R-Wyo.) and Edward Kennedy (D-Mass.), who are working on legislation to address "shortcomings" associated with post-approval drug safety. Enzi, who chairs the Senate's Health, Education, Labor and Pensions Committee, which has FDA oversight authority, called the GAO report "extremely helpful" in evaluating the agency's post-approval monitoring procedures. Kennedy, the committee's ranking member, said the report "underscores the urgency of our efforts." Both said they would soon introduce "comprehensive drug safety legislation."

However, not everyone favors new laws, and there are many opponents of an independent safety division within the FDA. Notably, the GAO made no such recommendation. As the appropriations process moves forward, speculation continues that money could be directed toward improving the agency's existing infrastructure for pharmaco-vigilance, better funding for health care information technology that would prove useful in developing adverse event databases and matters related to the Critical Path Initiative.

"I don't think that you can look at safety in a vacuum," Werner said.

Others see change coming through a new iteration of the Prescription Drug User Fee Act, which is up for reauthorization next year. One possibility would apply some drug industry-generated user fees to better fund post-approval oversight. It's likely that the industry would balk at that, though, in addition to resisting an independent safety office.

In a response to the GAO report, the FDA called the findings "reasonable and consistent with" actions already under way or planned - namely additional efforts examining internal post-approval procedures. Among them is an ongoing analysis by the Institute of Medicine, and the agency recently enlisted the consulting firm Booz Allen Hamilton Inc. to further investigate the Phase IV process.

That latter report, expected in about a year, might provide explanations on a lack of adherence to post-approval study commitments. According to recently published numbers in the Federal Register by the FDA, of the nearly 1,550 post-approval study commitments on record as of Sept. 30, more than half (915) had not yet begun. About 325 were ongoing, nearly 225 had been submitted for review and 80 were behind schedule. Per current regulations, once a Phase IV commitment has been made, a drug company must report progress on the anniversary of the product's approval until the commitment is completed or terminated. The FDA determines when that has been fulfilled, or whether it is either no longer feasible or not providing useful information.

The FDA took issue with the GAO's characterization that the safety office takes a backseat to the new drugs office. Instead, the FDA called both groups "co-equal partners" in identifying and resolving safety issues.

The GAO's findings were reported to Grassley and Rep. Joe Barton (R-Texas), the chairman of the House Committee on Energy and Commerce. The report was requested in late 2004 after Merck & Co. Inc., of Whitehouse Station, N.J., recalled Vioxx (rofecoxib) following its link to cardiovascular problems after several years on the market.

In addition to recommending more power to enforce Phase IV studies, the GAO report also recommended that the FDA "systematically track" post-approval drug safety issues, revise and implement its draft policy on "major post-market safety decisions," and clarify the Office of Drug Safety's role in scientific advisory committees. The GAO also said the FDA should continue its efforts to develop observational studies and access additional health care databases.