	Background

FDA’s four expedited programs—accelerated approval, breakthrough  therapy designation, fast track designation, and priority review—are  intended to facilitate and expedite development and review of new drugs  to address unmet medical needs in the treatment of a serious condition. There are two different ways that drug applications are selected for  review using an expedited program. For accelerated approval and priority  review, sponsors do not submit formal requests. After FDA approves a drug for marketing, the agency continues to  monitor the drug’s safety and is required by law to publicly report on  certain aspects of its postmarket safety efforts. FDA Granted More than Half of Requests for Fast Track Designation and Denied Most Requests for Breakthrough Therapy Designation

		FDA Granted Two-Thirds of Requests for Fast Track Designation and Denied Most Requests for 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. 1.) In contrast to granting most of the requests for fast track designation,  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. FDA  granted 71 requests for breakthrough therapy designation since the  program was established, including 31 requests granted in each of fiscal  years 2013 and 2014. One in Four Drug Applications Approved by FDA Used at Least One Expedited Program, and the Most Frequent Category Was Oncology Drugs

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. Drug applications may use multiple expedited  programs, although most used one program. Of 444 approved drug  applications that used one or more expedited programs, 344 (77 percent)  used one expedited program, 78 used 2 programs, 20 used 3 programs,  and 2 used all four programs. FDA Lacks Reliable Information for Postmarket Safety Reporting and Oversight

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. CDER’s internal  evaluations of data in its DARRTS database revealed problems with the  completeness, timeliness, and accuracy of the data. These problems, as  well as problems with the way data are recorded that impair their  accessibility, have prevented FDA from publishing some required  postmarket safety reports in a timely manner, and have restricted its  ability to perform systematic oversight. Although FDA has taken some steps to  address the problems with its data, it lacks comprehensive plans for doing  so. Additionally, FDA  officials said they do not have plans to analyze tracked safety issue  and postmarket study data to inform the agency’s oversight of its  expedited programs, such as determining if drugs that used an  expedited program were subsequently associated with tracked safety  issues at rates or of types that differed from drugs that used FDA’s  standard process. FDA officials said that they do not subject  applications that used an expedited program to greater postmarket  safety monitoring and they do not have plans to do so because, to  obtain approval for marketing, these applications are required to meet  the same standard of evidence for safety and effectiveness as are  applications that used FDA’s standard process. However, we found  problems with the agency’s efforts to oversee and track potential safety  issues and postmarket studies once those drugs are on the market. While  internal control standards for the federal government specify that  information should be recorded in a form and within a time frame that  enables staff to carry out their responsibilities and that relevant, reliable,  and timely information should be available for external reporting  purposes, FDA’s data on postmarket safety issues and studies were  found to be incomplete, outdated, to contain inaccuracies, and to be  stored in a manner that made routine, systematic analysis difficult. Recommendations for Executive Action

To improve the data on tracked safety issues and postmarket studies that  are needed for required reporting and for systematic oversight of  postmarket drug safety, we recommend that the Secretary of HHS direct  the Commissioner of FDA to take the following two actions: 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. HHS also pointed out the differences between the standards for  granting breakthrough therapy designation or fast track designation—that  is, the ability for a drug sponsor to use one of these two expedited  programs—and FDA approval of the drugs for marketing; these  distinctions are also noted in our report.
Why GAO Did This Study

FDA oversees the safety and effectiveness of drugs sold on the U.S. market. When there is an unmet need for the treatment of a serious condition, FDA may use one or more of its expedited programs, such as fast track and breakthrough therapy designation, which are intended to bring drugs to market more quickly. FDA is also responsible for monitoring the safety of drugs and reporting on those efforts.
GAO was asked to provide information about FDA's expedited programs and its postmarket monitoring of expedited and nonexpedited drugs. This report examines (1) the number and types of requests for fast track or breakthrough therapy designation, (2) the number and types of FDA-approved drug applications that used an expedited program, and (3) the extent to which FDA's data on tracked safety issues and postmarket studies allowed the agency to meet its reporting and oversight responsibilities. GAO analyzed FDA data on requests for fast track or breakthrough therapy designation and approved drug applications that used an expedited program from October 1, 2006, to December 31, 2014 (the most recent available). GAO reviewed FDA information on tracked safety issues and postmarket studies, including FDA internal evaluations and guidance, and interviewed FDA officials.

What GAO Found

From October 1, 2006, to December 31, 2014, the Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER) received about 1,000 requests for fast track designation and breakthrough therapy designation—two of the agency's four expedited programs to facilitate and expedite the development and review of new drugs. 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. Regardless of whether sponsors submit a request for an expedited program, they are required to submit a marketing application prior to offering a drug for sale in the United States; using an expedited program does not ensure FDA approval of the marketing application. Sponsors submitted more than 770 requests for fast track designation since fiscal year 2007, and 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.
About a quarter of the drug applications CDER approved for the U.S. market from October 1, 2006, to December 31, 2014, used at least one expedited program, according to FDA data. Included among these applications were new drug applications, biologic license applications, and efficacy supplements, which allow for revisions to the original application, such as changes in the drug's indicated use. Although most of these applications used one program, some applications used two or more, including two oncology drug applications that used all four expedited programs (accelerated approval, breakthrough therapy designation, fast track designation, and priority review). The most common product area among these applications was oncology (19 percent).
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. Tracked safety issues are potential safety issues that FDA determines are significant and that it tracks using an internal database. Internal control standards for federal agencies specify that information should be recorded in a form and within a time frame that enables staff to carry out their responsibilities and that relevant, reliable, and timely information should be available for external reporting purposes. However, evaluations conducted by CDER of data in its database revealed problems with the completeness, timeliness, and accuracy of the data. These problems, as well as problems with the way data are recorded that impair their accessibility, have prevented FDA from publishing statutorily required reports on certain potential safety issues and postmarket studies in a timely manner, and have restricted the agency's ability to perform systematic oversight of postmarket drug safety. Although FDA has taken some steps to address the problems with its data, the agency lacks plans that comprehensively outline its efforts and establish related goals and time frames. Additionally, FDA does not have plans to use these data to inform its oversight of its expedited programs, such as determining if drugs that used an expedited program were subsequently associated with tracked safety issues at rates or of types that differed from drugs that used FDA's standard process.

What GAO Recommends

FDA should develop plans to correct problems with its postmarket safety data and ensure that these data can be easily used for oversight. HHS agreed with GAO's recommendations and provided additional information on FDA's postmarket safety efforts.