FDA Fails to Track Postmarket Drug Studies Sufficiently: GAO

Ken Terry

January 20, 2016

The US Food and Drug Administration (FDA) is not doing a good job of tracking the clinical effectiveness or the safety of drugs with expedited approval after they have been released to the market, according to a new report from the General Accountability Office (GAO).

Previous government reports in 2006 and 2009 found that the FDA was not meeting its responsibilities in tracking postmarket studies of approved drugs. Similarly, the new GAO report states, "FDA lacks reliable, readily accessible data on tracked safety issues and postmarket studies needed to meet certain postmarket safety reporting responsibilities and to conduct systematic oversight."

The FDA's Center for Drug Evaluation and Research (CDER) has four programs for expediting the approval of new drug applications. These include accelerated approval, priority review, fast-track designation, and breakthrough therapy designation. Only the latter two categories require formal requests to CDER, which grants expedited approvals to important new medications for treating serious conditions.

Expediting drug application approvals can pose risks for patients, the FDA has acknowledged. Because these products do not have to go through the standard review process, there is less information available about their clinical benefits and any rare or delayed adverse events associated with the use of those drugs.

"FDA has stated, however, that its expedited programs do not change the standard of evidence required for approval and that some additional risk may be acceptable because patients and physicians are generally willing to accept greater risk when treating life-threatening and severely debilitating diseases," the GAO notes.

From 2006 to 2014, the GAO found, the FDA granted about two thirds (525) of 772 requests for fast-track designation. The number of approved requests increased from 54 in 2011 to 89 in 2014, the most in any year since 2007.

In contrast, the FDA denied 120 of 225 requests for breakthrough therapy designation from July 2012, when the category was established, through the end of 2014. The agency granted 71 requests, and the rest were withdrawn.

Antiviral and oncology drugs were the most common types of products granted fast-track or breakthrough therapy designation.

The FDA may request or require postmarket studies from drug companies; in some cases, it can require these studies as a condition of approval. When a new drug application receives accelerated approval, for example, its clinical effectiveness must be studied after it goes on the market.

If a drug's sponsor does not do a required postmarket study, or the trial does not confirm the product's benefit, the FDA can withdraw the drug's approval. That is what the agency did with the cancer drug Iressa (AstraZeneca) in 2012, after confirmatory trials failed to show improvement in survival for the patients who took it (Iressa has since been approved again in the United States for some case of lung cancer).

Outdated and Inaccurate

The FDA is required to publish an annual report in the Federal Register on the status of certain postmarket studies. In addition, the FDA maintains a database on potential safety issues, such as serious adverse events and medication errors, in an internal database known as the Document Archiving, Reporting, and Regulatory Tracking System (DARRTS). CDER uses this database to generate work plans and assign responsibility for managing tracked safety issues. The FDA also is required to publish a quarterly report listing potential safety concerns, which are identified in DARRTS.

The GAO found that postmarket study data in CDER's database was outdated and contained inaccuracies, partly as a result of delays in in staff review submissions. More than half of sponsors' submissions on 1400 postmarket studies from 2008 to 2013 were delayed or overdue.

The GAO suggests that the problems with the completeness, timeliness, and accuracy of data in DARRTS might stem from the challenges of data entry and the requirements for conducting structured reviews of postmarket studies.

The agency's tracking software was also deemed inadequate. All of the tracking data must be entered manually, GAO notes, and the database cannot be queried to determine characteristics of tracked safety issues, such as therapeutic area, the population affected, or past regulatory actions.

The GAO recommends that the Department of Health and Human Services order the FDA commissioner to develop a comprehensive plan to address the identified problems and that the FDA upgrade its information technology system.

In response to the GAO report, the Department of Health and Human Services said it does not see any reason to submit expedited drugs to more scrutiny on safety issues than nonexpedited products receive after they go on the market. The same standards for effectiveness and safety are applied to both categories of drugs, the department noted.

The GAO responded that the FDA's lack of analysis on tracked safety issues and postmarket studies in expedited drugs indicates the agency lacks information on whether these drugs "pose additional safety risks to patients once they are on the market."

There was no information in the report on whether drug companies always conduct postmarket trials on expedited medications in response to FDA requests. The GAO also did not offer an opinion on whether CDER has sufficient staff to process data on all the postmarket trials as the number of expedited new drug applications rises.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.