The FDA lacks reliable, readily accessible data on potential safety issues needed to meet postmarket safety responsibilities and to conduct systematic oversight of new drugs.

This was the conclusion of a recent report issued by the U.S. Government Accountability Office (GAO). The GOA found that the FDA’s Center for Drug Evaluation and Research’s (CDER) internal data evaluations have problems with completeness and accuracy. These problems prevent the timely publication of legally required postmarket studies and reports on tracked safety issues—potential safety concerns the FDA determined to be significant, and which the FDA monitors using an internal database.

Internal control standards for federal agencies specify that postmarket drug information should be recorded within a timeframe that will enable staff to carry out their responsibilities. The standards also require that relevant, reliable and timely information be available for external reporting purposes.

The GAO report found a number of issues with the FDA’s compliance to these standards. The findings indicate that the FDA’s data on tracked safety issues is incomplete; the FDA’s postmarket study data is outdated and contains inaccuracies; tracked safety issues and postmarket study data is not readily accessible to FDA staff for analysis; the FDA lacks complete and accurate data that prevents timely publication of required reports; the FDA lacks reliable and accessible data, restricting the organization’s ability to conduct systematic oversight of postmarket safety; and the FDA lacks a comprehensive plan to address its problems with tracked safety and postmarket study data.

Of particular concern is the FDA’s lax oversight of drugs approved through the agency’s expedited programs to accelerate review of new drugs. One in four drug applications CDER approved for the U.S. market from October 1, 2006, to December 31, 2014—the time period examined by  the GAO—used at least one expedited program.

During this time, CDER received about 1,000 requests for Fast Track designation and Breakthrough Therapy designation, two of the agency’s four expedited programs. Drug sponsors are required to submit formal requests to use these two programs. For the other two expedited programs—Accelerated Approval and Priority Review—sponsors are not required to submit formal requests.

 According to the GAO study, sponsors submitted more than 770 requests for Fast Track designation since fiscal year 2007, and the FDA granted about two-thirds of these requests. Sponsors submitted more than 220 requests for Breakthrough Therapy designation since it was established in July 2012, and the agency denied more than half of these requests. Antiviral and oncology drugs were the most common categories among applications granted Fast Track and Breakthrough Therapy designation.   

 The FDA has acknowledged that expedited drug approvals can pose risks for patients, according to the GAO report. The agency also stated that expedited programs do not change the standard of evidence required for approval. The FDA contends 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.

Nevertheless, “this new GAO report clearly highlights that the FDA is not doing its due diligence when tracking drug safety issues and postmarket studies that are critical to ensuring patient safety,” said Connecticut Congresswoman Rosa DeLauro, who commissioned the GAO study.

“This is not a new problem,” said Marcia Crosse, Ph.D., director for the Health Care Team at the GAO. Reports dating back to 2006 have produced similar findings. Because the GAO only examined only two of the FDA’s four expedited pathways, the findings are likely an underestimate. “Our concern is that the increasing use of the expedited review process means that more risk is being pushed into the postmarket sphere,” said Crosse.

 One of the underlying problems with postmarket surveillance is that the FDA’s data systems are outdated. “The FDA has had an ongoing struggle to have current technologies that meet their needs,” said Crosse.

“In the U.S., we depend solely on physicians to report problems,” said Harold Glass, Ph.D., Dean’s professor in the department of Health Policy at the University of the Sciences in Philadelphia. “Reporting is voluntary, and my sense is that the FDA doesn’t have enough data.”

Another problem is that many of the same FDA staffers who handle premarket reviews of drugs are also responsible for processing postmarket data, according to Crosse. When resources are limited, the premarket analysis takes top priority, and postmarket surveillance falls behind.

Another complication is the FDA’s heavy reliance on industry to cover the cost of drug review. The upfront fees drug companies pay for the review of new drugs fund about 70% of CDER’s drug review operations, according to Crosse. “Throughout the past decade, a larger and larger portion of the FDA’s budget for premarket approval is coming from the pharmaceutical industry,” echoes Glass.

 “The FDA is faster than Europe in terms of premarket review,” Glass said. “But of the industrialized countries, the U.S. has one of the less demanding systems for postmarket surveillance.” Many other countries require more frequent postmarket safety reports than the U.S., according to Glass, and the consequences of noncompliance tend to be more severe.

Going forward, the GAO recommended that the Secretary of the Department of Health and Human Services (HHS) direct the Commissioner of the FDA to initiate development of comprehensive plans, with goals and time frames, to help ensure that identified problems with the completeness, timeliness, and accuracy of information in its database are corrected.
Additionally, the GAO advised the FDA identify potential improvements to their current database or future information technology investments. The goal would be to capture information in a form that can be easily, systematically used by staff for oversight purposes.

 In response, the HHS stated that conducting rigorous oversight of postmarket safety is a priority. Crosse said that during the next five years the GAO will continue to monitor the FDA’s progress as it pertains to meeting the report recommendations.

“Today, if the FDA wants to know if there are problems with a drug, there is no reliable or readily accessible data for them to conduct a comprehensive overview and make informed decisions,” said Congresswoman DeLauro. “This system is a severe safety risk for consumers.”

This article was reprinted from Volume 20, Issue 14, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »