Two new studies, published in JAMA and The Millbank Quarterly, blame the accelerated drug approval process for harmful drugs entering the marketplace. The accelerated approval of drugs created by the FDA in 1992 during the HIV/AIDS crisis, is designed for quicker approval of drugs that treat serious conditions and fill an unmet medical need. However, what seemed like a good idea has had unintended consequences and repercussions for patients.
“Only about a third of the clinical studies that are done on these medications are so-called randomized trials, which are the gold standard of evidence where we can find out if the drug works or if it is better than another,” said Dr. Huseyin Naci of the London School of Economics and Political Science, who co-authored the recent studies. “The key implications of this research is that patients, doctors and the wider healthcare community are very much being shortchanged. The majority of the evidence that exists on these medications are flawed, and they are not actually sufficient to address the information needs of patients and doctors.”
This new approval process bypasses this “gold standard” and relies on what the industry calls a “surrogate endpoint” which is expected to predict clinical benefit or harm based on some other scientific evidence. The FDA says that the use of surrogate endpoints can considerably shorten the time required to receive FDA approval because these are things that happen much sooner. “This approval pathway is especially useful when the drug is meant to treat a disease whose course is long, and an extended period of time is needed to measure its effect,” the FDA says. “After the drug enters the market, the drug maker is required to conduct post-marketing clinical trials to verify and describe the drug’s benefit. If further trials fail to verify the predicted clinical benefit, FDA may withdraw approval.”
The problem occurs when patients are harmed during the intervening time period between market approval and the post-marketing clinical trials. The other major issue concerns the fact that the drug manufacturer is in charge of these post-clinical trials. Such a relationship creates an inherent conflict of interest and if the drug is popular and profitable, the drug manufacturer is inclined to do everything in its power to keep the drug on the market and expand its profit margin.
Currently, about 10 percent of new drugs are approved through the accelerated process. It is one of several expedited approval programs created in the last 30 years, including another called “fast track,” which was created in 1988 to permit approval after a single study of drugs to treat severely debilitating diseases. More than half of new drugs are allowed onto the U.S. market through one of the expedited pathways.
In some instances, the results of clinical trials conducted to follow-up accelerated approval has prompted the FDA to withdraw approval.
One example is Avastin (bevacizumab), which was cleared through the accelerated process for treatment of breast cancer. But later trials showed no increase in overall survival of breast cancer patients, and raised some significant safety issues, including severe high blood pressure, bleeding, heart attack or heart failure, as well as injury to the nose, stomach and intestines. Avastin is still allowed to be marketed for other cancers.
Clearly, the accelerated drug approval process is flawed and requires FDA re-evaluation. The benefits promised by accelerated approval are few relative to the harm done by bad drugs that would have never been approved under traditional testing methods.