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. According to FDA, these programs are intended to help ensure that drugs for serious conditions are approved and available to patients as soon as it can be concluded that the benefits of the drugs justify their risks. Depending on the specific expedited program, sponsors of new drugs may receive a variety of benefits, such as additional opportunities to meet with and obtain advice from FDA officials during drug development; a rolling review—that is, when FDA reviews portions of the application as they come in instead of waiting for the complete application; the ability to use certain surrogate endpoints or an intermediate clinical endpoint that is reasonably likely to predict clinical benefit; or a shorter goal for review time for the drug application. According to FDA, its expedited programs have the potential to shorten the amount of time necessary for a drug to get to market and to reduce development costs for drug sponsors. There are two different ways that drug applications are selected for review using an expedited program. For breakthrough therapy designation and fast track designation, the sponsor requests and then FDA determines whether to grant or to deny the request, generally during the drug development process before the sponsor submits the application for approval to market the drug. For accelerated approval and priority review, sponsors do not submit formal requests. Instead, discussions between drug sponsors and FDA of the appropriateness of accelerated approval generally begin during the drug development process. For priority review designation, FDA assesses each new drug application when it is submitted to determine if it should undergo priority review. Additionally, drug applications can use multiple expedited programs. For example, in December 2014, FDA granted accelerated approval for Lynparza, a drug to treat advanced ovarian cancer—and this drug application also received priority review. See table 1 for a summary of FDA’s expedited programs. FDA has acknowledged that expediting drug application approvals can pose risks for patients. For example, for accelerated approval, FDA guidance states that there is a risk that patients may be exposed to a drug that ultimately will not be shown to provide an actual clinical benefit. FDA’s guidance also states that with fewer, smaller, or shorter clinical trials, there may be less information about rare or delayed adverse events. 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. 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. For example, FDA tracks information about certain potential safety issues, such as serious adverse events and medication errors, in its internal database, the Document Archiving, Reporting, and Regulatory Tracking System (DARRTS). DARRTS is used, among other things, to generate a work plan and assign responsibilities for managing these tracked safety issues, as well as to provide updates on their status. Only those potential safety issues that FDA determines are significant—that is, have the potential to result in FDA taking one or more actions, such as requiring labeling changes—are tracked in DARRTS. FDA is required to publish a quarterly report listing certain potential safety issues that it has identified using its adverse event reporting system; FDA identifies those potential safety issues from among the tracked safety issues in DARRTS. Another important aspect of FDA’s postmarket safety oversight is monitoring the progress of postmarket studies—conducted after a drug has been approved—that FDA can request or require. Under certain circumstances, FDA can require sponsors to conduct a postmarket study as a condition of approval, such as for drugs granted accelerated approval. The results of postmarket studies provide further information about a drug’s safety, efficacy, or optimal use that FDA can use to take one or more actions, such as approving a drug for new uses. Under the accelerated approval program, if sponsors do not conduct the required postmarket study, called a confirmatory trial, with due diligence, or the results of the trial do not confirm the drug’s clinical benefit, FDA has the authority to begin procedures for withdrawing the drug’s approval for marketing. For example, in 2012, FDA withdrew approval for the NDA for the cancer drug Iressa after the results of its confirmatory trial failed to show an improvement in survival for patients who took it compared with patients who received a placebo. FDA tracks information about postmarket studies, such as their status and projected completion date, in DARRTS. FDA is required to publish an annual report in the Federal Register on the status of certain postmarket studies. In its past reports, FDA has summarized the number of postmarket studies and the extent to which they were proceeding according to established time frames for completion. Although FDA is responsible for overseeing postmarket studies and ensuring they are completed in a timely manner, we and others have found that, in the past, FDA has not adequately done so. HHS’s Office of Inspector General concluded in a 2006 report that FDA could not readily identify whether or how timely postmarket study commitments were progressing toward completion. In 2009, we found that FDA had not been routinely monitoring the status of postmarket studies, primarily because oversight of these studies was not considered a priority. Both reports note that FDA’s inadequate oversight was due, in part, to staff not meeting timeliness goals for the review of submissions from sponsors, such as annual status reports that contain information on the progress of postmarket studies and final reports that include results of completed studies. In 2008, FDA hired a contractor to help meet requirements under the Food and Drug Administration Amendments Act of 2007 (FDAAA) that FDA annually review and report on the “backlog” of postmarket studies, which FDA defined as studies that were open (i.e., not fulfilled or released) as of the date of enactment of FDAAA (September 27, 2007). The contractor found that this backlog contained more than 500 postmarket studies where a final report had been submitted that FDA had not yet reviewed, including reports for confirmatory trials that were required for drugs granted accelerated approval. 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. By receiving fast track designation, sponsors may have increased communication with and guidance from FDA officials and may have a rolling review of their drug application. FDA denied about one- fourth (or 207) of the requests for fast track designation; according to FDA officials, requests are generally denied because the drug application does not meet the criteria for fast track designation. For example, requests for fast track designation in which the drug is not intended to treat a serious medical condition will be denied. The 40 remaining requests were either withdrawn by the sponsor or categorized as other by FDA. Since fiscal year 2011, the number of requests FDA has granted fast track designation has increased, from 54 requests granted in fiscal year 2011, to 89 granted in fiscal year 2014. (See fig. 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. According to FDA officials, most requests for this designation are denied because of poor study design associated with the request. 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. (See fig. 2.) According to FDA data, 34 requests for breakthrough therapy designation were withdrawn by the sponsor during the period. 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 category (with 112 requests granted) was for antiviral drugs. For example, Isentress—an antiviral drug to treat human immunodeficiency virus that was approved by FDA in 2007—used fast track designation. This product category was followed by oncology (81 requests granted), neurology (74 requests granted), anti-infectives (55 requests granted), gastroenterology and inborn errors (46 request granted), hematology (34 requests granted), and cardiovascular and renal (32 requests granted). The remaining requests that FDA granted for fast track designation (91 requests) were for drugs in other product categories. (See fig. 3.) Appendix I has more information on requests for fast track designation that FDA granted, by product category. 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 (15 requests granted), antiviral (14 requests granted), and hematology (14 requests granted). For example, FDA granted breakthrough therapy designation for the oncology drug Keytruda (a drug to treat patients with advanced melanoma who are no longer responding to other drugs) because, according to FDA, the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over other therapies. The rest of the requests for breakthrough therapy designation FDA granted were for drugs in the FDA product categories of pulmonology, allergy, and rheumatology (7 requests granted); gastroenterology and inborn errors (5 requests granted); psychiatry (4 requests granted), and other (12 requests granted). (See fig. 4.) Appendix II has more information on requests for breakthrough designation that FDA granted, by product category. 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.