GAO Report on the Safety of Drugs Approved Using Expedited Programs Finds Shortcomings in FDA’s Postmarket Oversight, Reviews Use of Expedited Programs Instead

February 16, 2016

By James E. Valentine

Last month, the U.S. Government Accountability Office (GAO), the independent, nonpartisan agency that provides auditing, evaluation, and investigative services to Congress, publicly released the findings of a report on FDA’s handling of drug postmarket safety oversight.  As reflected in the title of the report, “FDA Expedites Many Applications, But Data for Postapproval Oversight Need Improvement,” the focus was on the safety of drugs brought to the market more quickly through use of FDA’s expedited programs (breakthrough therapy, accelerated approval, fast track, and priority review).  The GAO report was commissioned by Congresswoman Rosa DeLaura, D-Conn., following the release of another GAO report in October 2015 that implicated the safety oversight of medical devices approved by FDA. 

The report sought to examine the status of postmarket safety oversight of drugs approved using one or more of FDA’s expedited programs, which are programs to facilitate and expedite the development and review of new drugs.  This would have allowed GAO to determine the validity of Congresswoman DeLaura and consumer advocates’ concern that the use of expedited programs increases the risk of unforeseen safety issues once marketed (e.g., because there is less information due to fewer, smaller, or shorter clinical trials).  However, because “FDA lacks reliable, readily accessible data on tracked safety issues and postmarket studies needed to…conduct systematic oversight,” there was not reliable data to allow GAO to test this hypothesis.

In the absence of information on postmarket safety reporting and oversight, the GAO report instead independently examined the use of certain expedited programs. Here are some highlights of GAO’s findings:

Expedited Program Requests: Fast Track and Breakthrough Therapy Designation

  • Of the 772 requests for fast track designation FDA received from October 1, 2006, through December 31, 2014, FDA granted about two-thirds (or 525) of them.
  • FDA denied one-fourth (or 207) of the request for fast track designation, and the remaining 40 requests were either withdrawn by the sponsor or the drug application was inactivated, terminated, or cancelled before FDA could make a decision on the request.
  • Since fiscal year 2011, the number of requests FDA has granted fast track designation has increased, from 54 requested granted in fiscal year 2011, to 89 granted in fiscal year 2014.
  • In contrast, FDA denied more than half (or 120) of the 225 requests for breakthrough therapy designation that the agency received since that expedited program was established in July 2012 through the end of December 2014.

Expedited Program Requests: By Product Category

  • Of the 525 requests for fast track designation that FDA granted from fiscal year 2007 through the first quarter of fiscal year 2015, the most common product categories to be granted fast track were:
    • Antiviral with 112;
    • Oncology with 81;
    • Neurology with 74;
    • Anti-infectives with 55;
    • Gastroenterology and inborn errors with 46;
    • Hematology with 34; and
    • Cardiovascular disease and renal with 32.
  • The most common product categories among the 71 requests for which FDA granted breakthrough therapy designation from July 9, 2012, through December 31, 2014, were:
    • Oncology with 15;
    • Antiviral with 14; and
    • Hematology with 14.

Approvals Using Expedited Programs

  • About a quarter of the 1,717 drug applications that FDA approved from October 1, 2006, through December 31, 2014, used at least one expedited program.
  • Of 444 approved drug applications that used one or more expedited programs, 344 (77%) used one expedited program, 78 used 2 programs, 20 used 3 programs, and 2 used all four programs.
  • Priority review was the most used program, with 408 of the 444 drug applications (92%) receiving priority review.
  • FDA review time was an average of 8.6 months for marketing applications for drugs that used at least one expedited program compared with 12.1 months for marketing applications for drugs that did not.
  • The most common product category for drug applications approved by FDA from October 1, 2006, through December 31, 2014, that used at least one expedited program was:
    • Oncology with 19% of applications;
    • Antivirals with 17% of applications; and
    • Hematology with 12 % of applications.

GAO Recommendations

While GAO confirmed that expedited programs play a significant role in the development and review of drugs (as demonstrated by the findings described above), GAO made two recommendations to FDA that would facilitate the future assessment of whether these programs pose additional postmarket safety risks to patients once they are on the market:

  • Develop comprehensive plans, with goals and time frames, to help ensure that identified problems with the completeness, timeliness, and accuracy of information in its database on tracked safety issues and postmarket studies are corrected, and
  • Work with stakeholders within FDA to identify additional improvements that could be made to FDA’s current database or future information technology investments to capture information in a form that can be easily and systematically used by staff for oversight purposes.

While, in FDA’s comments to the GAO recommendations, the Agency concurred with these recommendations, FDA clarified that FDA-approved drugs that used an expedited program do not necessarily require different postmarket safety monitoring than other drugs, noting that tracked safety issues and postmarket studies are utilized to monitor all drugs after they are approved by FDA. Therefore, it is unclear, even once it has implemented these recommendations, whether FDA will increase scrutiny of postmarket safety risks for those drugs approved using an expedited program.