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Objectives Real-world evidence (RWE) has gained increased attention in recent years as a complement to traditional clinical trials. The use of RWE to establish the efficacy of oncology drugs for Food and Drug Administration (FDA) approval has not been described. In this paper, we review 5 recent examples where RWE was submitted in support of the FDA approvals of original or supplementary indications for oncology drugs. Methods To identify cases where RWE was used, we reviewed drug approval packages available at Drugs@FDA for oncology drugs approved between 2017 and 2019. Five cases were selected to present a broad overview of different types of RWE, different circumstances under which RWE has been used for regulatory approvals, and how FDA evaluated the data in each case. The type of RWE submitted, the indication, limitations identified by FDA reviewers, and the outcome of the submission are discussed. Results RWE, particularly historical controls for rare or orphan indications, has been used to support both original and supplementary oncology drug approvals. Types of RWE included data from electronic health records, claims, post-marketing safety reports, retrospective medical record reviews, and expanded access studies. Small sample sizes, data quality, and methodological issues were among concerns cited by FDA reviewers. Conclusion By bridging the gap between the constraints of the trial setting and the realities of clinical practice, RWE can add value to a regulatory submission. These early examples provide insight into how regulators evaluated RWE submitted as evidence of efficacy for oncology drugs.

Objectives: COVID-19 diagnostic testing has been a critical element of managing risk during the pandemic. Point-of-care rapid antigen tests have been authorized by the Food and Drug Administration (FDA) for use among symptomatic individuals, as an alternative to the gold standard PCR-based tests (which have a much longer turnaround time). Inaccurate test results can detrimentally affect the spread of infection. In this study, we assessed false positives and false negatives reported for COVID-19 rapid antigen tests with Emergency Use Authorizations (EUAs), using FDA’s Manufacturer and User Facility Device Experience (MAUDE) database (a repository of deidentified reports of issues associated with authorized medical devices). Methods: The MAUDE database was queried for reports of false positives or false negatives associated with COVID-19 rapid antigen tests, from the date of the first EUA (05/08/2020) through 12/31/2020. When noted in the MAUDE report, off-label use of the test was recorded. Results: Five of the 11 authorized rapid antigen tests had false positive or false negative reports in the MAUDE database. Of the total 1816 reports, 1725 (95.0%) were false positives and 91 (5.0%) were false negatives. Off-label use in asymptomatic individuals was noted in 1024 (56.4%) reports. Conclusions: Our study found that nearly all erroneous results with rapid antigen tests reported to MAUDE were false positives, and half involved samples from asymptomatic individuals. These findings suggest that false negatives, which are more consequential for virus transmission, occur infrequently with rapid antigen tests. Limitations of this study include potential under-reporting to MAUDE, the unknown denominator of COVID-19 tests, and the inability to establish device malfunction in relation to aberrant results. This analysis provides important new insights into real-world use of COVID-19 rapid antigen tests and the potential negative ramifications of off-label use.