Author Insights: Rapid Drug Approvals Leave Many Safety Questions Unanswered

An analysis by Thomas J. Moore, AB (above), a senior scientist at the Institute for Safe Medication Practices, and Curt Furberg, MD, PhD, of the Wake Forest School of Medicine in Winston-Salem, North Carolina, found that studies used for expedited drug approvals are so small they may be unable to answer key safety questions.

An analysis by Thomas J. Moore, AB (above), a senior scientist at the Institute for Safe Medication Practices, and Curt Furberg, MD, PhD, of the Wake Forest School of Medicine in Winston-Salem, North Carolina, found that studies used for expedited drug approvals are so small they may be unable to answer key safety questions.

The US Food and Drug Administration (FDA) has created fast-track approval processes to speed certain drugs to market, but an analysis of these expedited approvals finds they often leave important safety questions unanswered. The analysis was published today in JAMA Internal Medicine.

To help expedite approval of drugs, the FDA has created processes that waive some of the requirements that are part of a standard drug approval. These expedited reviews, popular with industry and patient groups, are used for drugs that the FDA determines represent “a significant therapeutic advance” or that fill unmet needs. The Obama administration has also proposed additional ways to speed the pace of drug approval.

But an analysis of the differences between standard and fast-track reviews by Thomas J. Moore, AB, a senior scientist at the Institute for Safe Medication Practices (ISMP) in Alexandria, Virginia, and Curt Furberg, MD, PhD, of the Wake Forest School of Medicine in Winston-Salem, North Carolina, found that although fast-track approvals may shave about 2½ years off approval time, they also provide less information about the safety and efficacy of the drugs.

Moore and Furberg examined 20 drugs approved by the FDA in 2008, including 8 that received expedited reviews and 12 that received standard reviews, finding that the expedited drugs took a median of 5.1 years of clinical development to reach approval compared with 7.5 years for the drugs undergoing standard approval. But the expedited drugs were tested on far fewer patients—a median of 104 patients, compared with a median of 580 patients for the standard review drugs. Safety problems emerged after approval for drugs in both categories, but many safety questions that might have been resolved by postmarketing studies by the FDA remain unanswered, as less than one-third of 85 such studies had been completed by 2013.

Moore discussed the implications of the study’s findings with news@JAMA.

news@JAMA: Why did you decide to do this study?

Thomas Moore: The question this study was trying to address is: are novel drugs today tested enough? We found that many questions are left unanswered.

news@JAMA: What kinds of questions are going unanswered with the expedited reviews?

Thomas Moore: As trials get smaller or shorter, you know less about critical issues, like whether there is target organ toxicity, whether certain subpopulations develop adverse events, what the contraindications are, and how the response differs between women and men. The more you look, the more problems you identify.

news@JAMA: How long does it take to get these answers after approval?

Thomas Moore: For novel treatments, the drugs are developed and approved very quickly, in about 5 years. But answers to unanswered safety questions come slowly after approval. Two studies, one by ISMP and one by the FDA, have found that significant safety warnings emerge at a median of 11 years after approval. We are approving drugs quickly, but we are taking a very long time to address the questions we left on the table.

news@JAMA: What implications do your findings have for proposals to further speed the approval process?

Thomas Moore: The FDA is advancing several proposals that would further reduce the amount of preapproval testing. Is this movement in the wrong direction? This is an issue for the medical community to debate and think about. Physicians and patients need to think about whether we want drugs quicker or whether we want more study so we know how to use them wisely.

news@JAMA: What do you think physicians and patients should know about drugs that have undergone expedited approval?

Thomas Moore: Physicians need to be aware when they use novel drugs approved under expedited review the safety information available is much more limited than for other drugs they use. That means they should use these drugs with more caution and extra vigilance.

What patients need to realize is that even experienced physicians can’t always tell if a drug is working. We have one really good tool to assess drug effectiveness and safety: randomized controlled clinical trials. The sad story we have witnessed is that often patients want new drugs and are willing to take risks to get them, but then hundreds of thousands of dollars may be spent on the drug before we realize it doesn’t work or patients [are harmed]. Patients need to be aware of the importance of clinical testing so they can benefit from drugs and reduce their chance of getting hurt.

The wise and safe use of drugs requires clinical testing.



Categories: Health Policy, Medical Ethics, Public Health, Statistics and Research Methods

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