Perils of Speedy Drug Approval

   I was invited to speak at a November FDA meeting about the upcoming 2007 re-authorization of the Prescription Drug User Fee Act. Initially passed in 1992, PDUFA allows the FDA to collect a user fee from any  drug company that submits a New Drug Application. In exchange, the FDA agrees to complete its review of the drug company’s clinical trials proving safety and efficacy within six months for priority drugs. And within a year for all others. What follows is a summary of my remarks.

  - In 2004, most of the money for new drug reviews came from industry. Its growing role as the major source of funds for FDA reviews creates a potential conflict of interest that is likely to erode, if it hasn’t already, the public’s trust in both the FDA’s independence and the safety of new drugs.   

  - PDUFA has clearly enabled the FDA to complete the review of new drug applications more quickly. Almost all reviews are completed within the specified time limits. And the agency reports that more than 1,000 new drugs have been approved since PDUFA. But there is no evidence that either faster review times or access to the 1,000 new drugs, many of which offer no advantage over older drugs, have benefited the public.

  - There has been concern that faster review times may be causing harm by exposing millions of people to new products that are subsequently found unsafe. Vioxx and Bextra are perhaps the best known examples. And 14 other drugs, approved since 1992, have been withdrawn because of serious harm.

  -  The FDA asked all the people who addressed the meeting to comment on the successes and failures of PDUFA since 1992 and what should be improved or changed in 2007. But since there is little or no research evidence on which to base such an assessment, that leaves only anecdotes, which is a poor substitute for science when making public policy. 

- Despite the paucity of evidence about the consequences of continuing the user fees, the realities of a strained federal budget and chronic underfunding of the FDA by Congress, mean that user fees are likely to be a necessary evil for the foreseeable future.

   - The FDA’s voluntary MedWatch program that collects reports of adverse drug reactions from doctors and the public is of limited value, even if it were provided with more resources. If PDUFA is reauthorized, it should fund the FDA’s ability to monitor drug safety using 21st century technologies. This includes proactive monitoring of data derived from such large electronic databases as those of the Veteran’s Administration and health plans like Kaiser-Permanente. This would allow the FDA staff to link prescription drug use with medical histories—a critical tool for both uncovering unexpected adverse drug reactions and having enough information to establish cause.

- If PDUFA is reauthorized, user fees must be increased to a level permitting FDA to hire a sufficient number of trained staffers to monitor adverse reactions after the drugs become available. Money is also needed to beef up FDA’s computer capacity and to enable its top officials to share safety information with other federal health agencies, specifically the National Institutes of Health, Centers for Disease Control and Prevention, and the Agency for Healthcare Quality and Research.

- Unfortunately, industry funding of drug safety surveillance creates a potential conflict of interest. For that reason, reliance on user fees to pay for enhanced FDA drug safety efforts must be contingent on erecting a firewall between industry and the agency so he who pays the piper cannot call the tune.

- Congress should mandate the creation of a new Office of Drug Safety that operates independently of the FDA   drug approval staff. The new office should be given the authority to order a drug off the market if safety concerns warrant. It must also have the power to take other actions to limit harm such as ordering a drug maker to put warnings about adverse reactions in the product information given to professionals and patients. At present FDA can only negotiate such critical changes in labeling with the maker. In the case of Vioxx, it took almost two years for Merck to agree to include even a mild caution about an increased risk of heart attack and stroke.

Arthur A. Levin, MPH, Center for Medical Consumers © December 2005