Drug Safety: FDA Expedites Many Applications, But Data for Postapproval Oversight Need Improvement
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.
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.
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.
Recommendations for Executive Action
|Department of Health and Human Services||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, the Secretary of HHS should direct the Commissioner of FDA to 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.||
FDA has developed, and is in the process of implementing, plans with associated goals and time frames for correcting problems with its data on tracked safety issues and postmarket studies. In February 2018, FDA created new policies and procedures to evaluate and address tracked safety issues that require centralized tracking and provide for greater management oversight; the agency piloted them beginning in April 2018. Using information gained from the pilot, as of August 2019, FDA was in the process making additional refinements to its policies and procedures and developing an IT system to support safety issue tracking. FDA plans to complete the IT system in spring of 2020 and issue a report that will evaluate its new process by September 30, 2022, as required under the Prescription Drug User Fee Act VI. For postmarket study data oversight, FDA began creating annual project plans with goals and time frames starting in fiscal year 2017. As specified in the 2017 project plan, FDA implemented a quality management plan starting in 2018 that includes monthly checks of postmarket study data for timeliness and accuracy. According to FDA, in September 2018 the agency also added staff dedicated to quality checks on, and timely entry of, postmarket data.
|Department of Health and Human Services||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, the Secretary of HHS should direct the Commissioner of FDA to 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.||
FDA has taken steps intended to improve its processes for overseeing tracked safety issues, and postmarket study data. For tracked safety issues, on April 8, 2019, FDA held a one-day workshop to solicit input from staff on changes to its tracked safety issue process and collect user requirements for a new IT system to support tracking safety issues. In April 2020, FDA finalized new policies and procedures and implemented a new IT system for tracking safety issues. The new IT system allows anyone within FDA's Center for Drug Evaluation and Research to enter new safety signals and has integrated product and adverse event dictionaries. FDA stated that integrating standardized data will support consistent regulatory decisions and improve the quality of analysis. For postmarket studies, in February 2021, FDA created a project team involving stakeholders from FDA's Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to address specific concerns related to postmarket study data. As of June 2022, FDA indicated that the project team had worked to identify and diagram the key processes involved in developing, monitoring, and tracking postmarket studies, and had recommended that these processes be prioritized for initial development in FDA's new IT system. GAO is keeping this recommendation open until FDA has implemented its new IT system.