Real-World Evidence in Support of Oncology Product Registration: A Systematic Review of New Drug Application and Biologics License Application Approvals from 2015-2020.

Real-world evidence (RWE) has garnered great interest to support registration of new therapies and label expansions by the United States Food and Drug Administration (FDA). Currently, practical insights on the design and analysis of regulatory-grade RWE are lacking. This study aimed to analyze attributes of real-world studies in FDA's decision-making and characteristics of full versus accelerated approvals through a systematic review of oncology product approvals. Oncology approvals from 2015 to 2020 were reviewed from FDA.gov. Applications were screened for inclusion of RWE, and variables related to regulatory designations of the application, pivotal clinical trial, and real-world studies were extracted. FDA feedback was reviewed to identify takeaways and best practices for adequate RWE. Among 133 original and 573 supplemental approvals for oncology, 11 and 2, respectively, included RWE; none predated 2017. All real-world studies were retrospective in nature; the most common data source was chart review, and the most common primary endpoint was overall response rate, as in the pivotal trial. The FDA critiqued the lack of the following: a prespecified study protocol, inclusion/exclusion criteria matching to the trial, comparability of endpoint definitions, methods to minimize confounding and address unmeasured confounding, and plans to handle missing data. All full (versus accelerated) approvals shared the following characteristics: high magnitude of efficacy in the pivotal trial; designations of orphan disease, breakthrough therapy, and priority review; and no advisory committee meeting held. This study found that findings from external control real-world studies complemented efficacy data from single-arm trials in successful oncology product approvals.

Health disparities in time to aneurysm clipping/coiling among aneurysmal subarachnoid hemorrhage patients: a national study.

OBJECTIVE: Previous studies have suggested disparities in quality of health care and time to treatment across socioeconomic groups. Such differences can be of greatest consequence in the setting of emergent medical conditions. Surgical or endovascular treatment of ruptured cerebral aneurysms within the first 3 days of aneurysmal subarachnoid hemorrhage (aSAH) is associated with improved outcome. We hypothesize that race and payer status disparities effect the time to treatment for ruptured aneurysms. METHODS: Discharge data were collected from the Nationwide Inpatient Sample during the years 2002-2010. International Classification of Diseases, 9th Edition; Clinical Modification codes were used to identify patients with aSAH who were treated by either surgical clipping or endovascular coil embolization. Time to procedure was dichotomized into 1) treatment in 3 days or less or 2) treatment in greater than 3 days. Time to treatment was evaluated according to demographic factors, including race, payer status, and median zip code income via multivariable analysis. RESULTS: A total of 78,070 aSAH admissions were treated by either aneurysm clip ligation or coil embolization. Hispanic race and Medicaid payer status were associated with increased time to treatment (P < 0.05). CONCLUSION: Racial and socioeconomic factors are associated with delayed time to treatment in aSAH. Identification of factors underlying these delays and standardization of care may allow for more uniform treatment protocols and improved patient care.