Author Insights: More Companies Following Through on Postmarketing Safety Studies But More Improvement Is Needed

Kevin Fain, JD, MPH, a fellow at Johns Hopkins School of Public Health, and colleagues found more companies are completing postmarketing safety studies.

Kevin Fain, JD, MPH, a fellow at Johns Hopkins School of Public Health, and colleagues found more companies are completing postmarketing safety studies.

Although more companies are completing postmarketing safety studies requested by the US Food and Drug Administration (FDA) than in the past, a growing number of delays in such studies remains a concern, according to an analysis published in JAMA today.

When many drugs are first approved by the FDA, the information about their safety profile is often limited. In some cases, serious drug safety problems have been identified only after millions of US patients have been exposed to a problematic medication. To help better understand the safety of new drugs, the FDA has long requested that companies perform postmarketing safety studies to provide more information after drug approval.

But the FDA could do little to force companies to follow through, and historically, companies failed to conduct many such studies and some postmarketing studies have dragged on for years without completion. To remedy these problems, the 2007 Food and Drug Administration Amendments Act (FDAAA) granted the FDA new authority to require postmarketing studies and ensure that they are completed.

The researchers analyzed data published by the FDA in the Federal Register to see how things have changed since the law was passed. The percentage of studies the FDA requested (before FDAAA went into effect) that had not been initiated decreased from 56.7% to 43.5% between 2007 and 2011, and the percentage of completed studies that had been requested before FDAAA has increased from 6.6% to 12.6% over the same period. However, the proportion of studies that the FDA requested after FDAAA went into effect in 2008 that have not yet started has increased each year, reaching 15.2% in 2011. No studies requested since FDAAA went into effect had been completed at the time of the analysis.

Kevin Fain, JD, MPH, a fellow at Johns Hopkins School of Public Health, discussed the findings with news@JAMA.

news@JAMA: Why did you and your colleagues decide to conduct this study?

Kevin Fain: About 7 years ago, a lot of attention was focused on postmarketing safety after reports from the Institute of Medicine [IOM] and the Office of Inspector General [OIG] were published. The reports found the majority of postmarketing studies were not initiated and many were not completed. The IOM and OIG expressed concern that the FDA didn’t have much legal authority to require studies or keep them on track. This led to the passage of FDAAA in 2007, which gave the FDA much more legal authority to require studies and keep them on track. We had not seen any analyses that looked at the status of postmarketing studies since then.

news@JAMA: What has changed?

Kevin Fain: Since the IOM and OIG reports and the new law, there has been more research on postmarketing safety and more public recognition of its importance. More studies are being initiated and more are being fulfilled. It is still too early to make a determination about the studies required under the new law, but at least our study can provide a foundation for future research. We do know that more studies each year are being required under the new law.

news@JAMA: What distinguishes postmarketing studies required under FDAAA from earlier ones?

Kevin Fain: Prior to FDAAA, the FDA’s authority to require postmarketing studies was limited to certain areas in pediatrics and for drugs that received accelerated approval. But now the new law covers a much broader area. If FDA thinks there are potential safety issues it wants to monitor, the law allows it to require postmarketing studies. It’s very helpful because the law’s requirements can be applied to many types of drugs.

news@JAMA: What kinds of enforcement tools did the FDA gain under FDAAA?

Kevin Fain: One is to issue a warning letter, which can be seen on the FDA’s website. If the FDA sees a study that is seriously delayed, it can issue a warning letter. If it finds other significant problems with the study or with the company’s compliance, the FDA can go to court and order a seizure of the drug or an injunction against the production of the drug. The warning letters are the starting point. They get the attention of the company and the public.

news@JAMA: Why has the number of uncompleted FDAAA studies increased?

Kevin Fain: I think the number of uncompleted studies under FDAAA has increased because it is relatively new and studies can take several months to years to go from protocol development through recruitment, completion, and submission for FDA review. For a clinical trial, that can be a long process. Because FDAAA only became effective in 2008 and some studies weren’t requested until 2009 or 2011, it will be important over the next 5 years to keep monitoring the FDAAA studies and the pace of their completion.

news@JAMA: What do you think can be done to ensure that postmarketing studies are completed?

Kevin Fain: I think putting focus on these studies and encouraging companies to make them a priority is always important. With the new law, the FDA can put focus on them and there is an enforcement tool. FDAAA is a great first step; you can already see the numbers shifting. But we all need to continue to look to make sure the studies are being completed.

news@JAMA: What would you hope to see over the next 5 years?

Kevin Fain: For the pre-FDAAA studies that are pending, I would hope companies continue to push to prioritize and put resources into completion. We do see the delays in study initiation increasing from 6% to 12%. Companies definitely need to focus on those delayed studies. For post-FDAAA, the FDA needs to keep monitoring study progress and use enforcement when needed. For these studies, the FDA has more power and can step in if something goes wrong.