If you had a debilitating or terminal disease, you would cheer FDA fast-track approval of a drug that showed promise for your disease, wouldn't you? But suppose that drug was not really effective. Then you would have lost the opportunity for treatment with other regimens or drugs. Or worse, the drug did something bad.
The FDA's How Drugs are Developed and Approved tells that the Center for Drug Evaluation and Research (CDER) is responsible for ensuring that drugs are safe and effective. As you probably know, the FDA does not conduct the clinical studies that will permit the product to be marketed. The submitting company is responsible for performing the clinical data and analysis. The FDA monitors the studies that demonstrate the safety and effectiveness. The FDA also monitors the studies to ensure that volunteers in the study are protected. Following the completion of the studied, a team of physicians, statisticians, chemists, pharmacologists, and others review the data and the proposed treatment regimen. If the drug is effective and its benefits outweigh the risks, then the FDA will approve if for sale.
For priority reviews, the FDA will review the product in six months, and for standard reviews, the product will be evaluated in ten months. Accelerated approval is for serious or life threatening diseases that can be evaluated with a surrogate end point. This replaces the effectiveness metric. As an example, a medicine for prevention of strokes might simply demonstrate reduced blood pressure since there is a plausible correlation between high blood pressure and strokes. For a cancer drug, the surrogate endpoint might be reduction in tumor size. In neither of these examples, is there clinical data that demonstrates effectiveness in curing the disease.
Obviously clinical trials cannot last forever, so the FDA assesses continuing studies during the post-marketing life of a drug. They evaluate the medical risks including: product quality defects, known side effects, avoidable side effects, unavoidable side effects, medication errors, and rare events (1 in 10,000 patients). From this post-marketing surveillance, they identify adverse effects not previously submitted in the clinical testing. Then they can require new labeling, education, or even product cancellation.
Today, the General Accounting Office (GAO) released the report, FDA Needs to Enhance its Oversight of Drugs Approved on the Basis of Surrogate Endpoints. In the past 16 years, the FDA has approved 90 applications using surrogate endpoints. 79 of these were for cancer, HIV, and inhalation anthrax. (All good candidates.) An additional 69 drugs were approved as new molecular entities (ingredients never before approved in the U.S.) with surrogate endpoints. The primary criticism of the GAO is that the FDA is not diligent in post-marketing analysis of these accelerated approval drugs. The FDA has never withdrawn approval of a medicine when the pharmaceutical company had delayed post-marketing data.
Appendix I of the GAO's report contains a list of the drugs approved under the accelerated approval process. Two antibiotics that I posted recently - Cipro and Levaquin were approved under this process. (See Caution About Levaquin. This specific approval was for anthrax, not the general antibiotic use, indicating the yin and yang of FDA approval. There are not very many drugs effective against anthrax.) The surrogate endpoints were "Serum CIPRO concentrations" and "Drug exposure in surviving Rhesus monkeys compared to human plasma concentrations", respectively. The approved indication was treatment of inhalation anthrax.
Mmm. These are hard decisions. Engineers are used to computing one failure in a billion. Medical researchers - one in a thousand. The FDA's comments to the GAO's findings defend the accelerated approval program. It has significantly improved the quality of life and survival of HIV and cancer patients. The FDA agrees that improved post-marketing surveillance is needed. Congress has recently provided additional funding for this activity and more oversight/tracking is being implemented. In the end, the FDA must choose for the greater good.
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