ObjeCtivesTo describe the content of non-public complete response letters issued by the US Food and Drug Administration (FDA) when they do not approve marketing applications from sponsors (drug companies) and to compare them with the content any subsequent press releases issued by those sponsors Design Cross sectional study.

ImportanceThe US Food and Drug Administration (FDA) has 4 programs that can be used alone or in combination to expedite drug availability: Accelerated Approval, Breakthrough Therapy, Fast Track, and Priority Review. Drugs using these programs can include novel drugs, which do not contain a previously FDA-approved active moiety, and orphan drugs, intended for diseases or conditions affecting fewer than 200 000 people; to date, no comprehensive evaluation of how these programs have been used in combination has been published.ObjectiveTo assess how often and in what combinations expedited programs are used in the development and review of approved novel biologics and small-molecule drugs, stratified by orphan drug status and indication.Design, Setting, and ParticipantsThis cross-sectional study evaluated all novel drugs that were FDA approved between January 1, 2008, and December 31, 2021.Main Outcomes and MeasuresThe main outcome was the frequency with which expedited programs were used and in what combinations, stratified by orphan drug status and drug type (small molecule vs therapeutic biologic). The unit of analysis was the novel drug–indication pair because a drug can be approved for multiple indications, each of which may use a different expedited program or differ in orphan drug status.ResultsThe study included 581 novel drug–indication pairs approved during the 14-year study period; 252 (43.4%) were orphan drugs, 139 (23.9%) were therapeutic biologics, and 442 (76.1%) were small-molecule drugs. Use of at least 1 expedited program increased from 11 of 26 drug-indication pairs (42.3%) in 2008 to 41 of 55 (74.5%) in 2021. Of the 363 approved drug-indication pairs using at least 1 expedited program, 225 (62.0%) were orphan drugs; at least 1 expedited program was used by 97 of the 139 approved biologic drugs (69.8%) and by 266 of the 442 approved small-molecule drugs (60.2%). Eighty-two of the 581 novel drug–indication pairs (14.1%) used the Accelerated Approval Program; of those, 65 (79.3%) were oncology drugs and 70 (85.4%) had an orphan designation.Conclusions and RelevanceThe study showed that use of the FDA’s expedited programs to bring novel drugs to market in the US increased from 2008 to 2021. The findings suggest that this trend is likely to continue.

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IMPORTANCE Before reviewing drug applications, the US Food and Drug Administration (FDA) conducts "filing reviews" to assess whether they are complete enough for full review. If the applications are incomplete, the FDA issues refuse-to-file (RTF) letters identifying deficiencies. The FDA does not make these RTF letters public at the time of issuance. Why the FDA issues RTF letters and how often the letters and their contents are made publicly available are unknown. OBJECTIVES To quantitatively analyze the FDA's reasons for issuing RTF letters and assess the public transparency of RTF letters and their contents. DESIGN AND SETTING This cross-sectional study analyzes RTF letters issued in response to new drug applications and efficacy supplements (applications for new indications or patient populations for already approved drugs)

Discussion | This analysis confirms the findings of previous studies that have identified severe health and HRQOL disparities affecting the transgender population. 4,5 These disparities require informed attention from clinicians and policy makers and further investigation by researchers. Until all states and territories field the BRFSS Sexual Orientation and Gender Module, however, the generalizability of the findings in this study remains limited. Given ongoing nationwide debates about public accommodations access, nondiscrimination protections, and other issues that influence transgender health, 6 all states and territories should field the module to facilitate research that draws on fully representative samples of the US transgender population. Furthermore, future analyses should investigate differences within the transgender population by factors such as gender, race/ethnicity, and sexual orientation.