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Often, post-approval marketing studies don't materialize because drug companies question their value. Independent review of the need for such studies would address pharma's concern that they may be warranted.
Following the sudden resignation of FDA commissioner Lester Crawford, acting commissioner Andrew von Eschenbach has an unequaled opportunity to set the record straight on the agency's role in drug safety. A good start would be to state clearly that, contrary to popular belief, it is not the job of FDA to approve drugs that are safe and effective.
Kenneth I. Kaitin
Instead, von Eschenbach should affirm that FDA will vigorously adhere to its mandate to approve drugs for which the overall expected benefits outweigh the known risks of using those drugs. Most significantly, it's the public that largely determines where that risk-benefit balance is set.
Why should the acting commissioner be so bold? Because better public understanding of the risk-benefit relationship would help set realistic expectations surrounding drug safety, and even help curtail the rising cost of new-drug development. It also would go a long way toward restoring public confidence in FDA.
Critics of FDA and the research-based drug industry claim that there has been an alarming rise in the number of drugs that have been withdrawn from the market for safety reasons in recent years. They also contend that faster approval times of new drugs, one of the achievements of the Prescription Drug User Fee Act of 1992, have come at the expense of rigorous standards for drug approval and have led to more safety problems.
While both assertions seem plausible, they are based on faulty foundations. Recent research by the Tufts Center for the Study of Drug Development shows that:
Perhaps most importantly, longer approval times do not assure greater drug safety. Average approval time for drugs withdrawn since 1980 was actually longer than for all drug approvals during that time: 2.14 vs. 2.08 years.
The foregoing is not meant to suggest that drug safety isn't an important public health concern, or that FDA shouldn't address inefficiencies in the processes of risk assessment and post-marketing surveillance. Much can be done to improve drug safety, and the following steps will help.
Adequately fund FDA's Office of Drug Safety This three-year-old department needs continued strong support and funding. For example, coordination and communication channels between the Office of Drug Safety and the rest of FDA (especially the Office of New Drugs) should be enhanced without compromising its integrity. Calls, by some, for an independent drug-safety review board are misguided and send the wrong message. Drug safety cannot be looked at in a vacuum; one must consider a drug's risks in relation to its benefits.
Leverage existing clinical data FDA possesses an enormous quantity of preclinical and clinical data on drugs that have been approved or are in various stages of regulatory review. While current law forbids FDA from revealing proprietary clinical data, the agency could analyze these data to make general findings, such as which specific enzymes or biomarkers are associated with particular drug toxicities. This would cut development costs and speed development time by helping drug companies avoid re-discovering lessons learned from past drug-development programs. It would also likely reduce future safety withdrawals.
Foster exchange of early research findings While it may appear counter-intuitive, companies have a strong incentive to share preclinical and clinical data, to avoid engaging in dead-end research. Sharing this information will help firms identify unsuccessful drugs early on, lower R&D costs, and reduce potential withdrawals. FDA, or a third party, could publish findings that provide useful information without identifying specific companies.
Hold pharma to post-approval commitments In some cases, FDA agrees to approve a new drug on condition that the company conducts post-approval marketing studies—for example, to provide additional data on the drug's safety and efficacy in specific patient groups. Often, these studies don't materialize, in part, because drug companies question their value or because FDA doesn't have the resources to follow up. Independent review of the need for such studies would address industry's concern that requested studies may be unwarranted. FDA should devote adequate resources for ensuring that requested studies are conducted, that submitted data receive quick and thoughtful review, and that any necessary action regarding a drug's fate is taken expeditiously.
Renew focus on Critical Path FDA's Critical Path initiative seeks to improve pharma R&D by reducing late-stage research failures and speeding new, safe, and effective drugs to market. This program, which has elevated the level of interaction between FDA and drug developers, had a promising start. This should not be allowed to get sidetracked. (See "What Ever Happened to Critical Path?")
Launch proactive risk-assessment programs Today, the United States relies on private physicians to identify potential drug-safety problems and report those problems to FDA. This passive approach to post-marketing drug surveillance should be supplemented with a proactive system, similar to the direction taken by FDA's European counterpart, the European Medicines Agency. FDA should work with industry to develop risk-assessment programs, which could become part of a company's application for a new-drug approval. For example, random patient surveys by a third party could help create profiles of patient outcomes on specific drugs and safety problems associated with the use of those drugs.
Ensure that DTC ads communicate drug risks While these ads typically provide information on the benefits and risks of specific drugs, they can also play an important role in educating consumers on the benefit-risk balance inherent in the use of all prescription medicine. Consumers should understand that no drug comes without a certain degree of risk, and the level of risk one is willing to assume should be balanced against the benefit that the drug provides. That decision is typically in the hands of the patient and their physician.
As long as there are new drugs approved, there will be some that are withdrawn due to unforeseeable safety problems. Although the benefits of the vast majority of prescription drugs in the United States far outweigh the associated risks, drug companies and the public have an equally strong incentive to understand those benefits and risks to the greatest extent possible. Doing so will lower development costs and improve patient outcomes, to the advantage of all.
Kenneth I. Kaitin is director of the Tufts Center for the Study of Drug Development. He can be reached at firstname.lastname@example.org