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.

Increased Health Care Resource Utilization and Costs Associated with Herpes Zoster Among Patients Aged ≥50 Years with Chronic Obstructive Pulmonary Disease in the United States.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are potentially at increased risk of herpes zoster (HZ). Little is known about the impact of an HZ episode on health care resource utilization (HRU) and costs among patients with COPD. METHODS: This retrospective cohort study of individuals aged ≥50 years in the United States (US) used administrative claims data from Optum's de-identified Clinformatics Data Mart Database for commercially insured and Medicare Advantage members (2013-2018). Two cohorts of patients with COPD, with HZ (COPD+/HZ+) and without HZ (COPD+/HZ-), were identified. All-cause and COPD-related HRU rates and costs (2018 US dollars) were compared between cohorts for up to 12 months of follow-up. Comparisons were controlled for baseline differences through propensity score adjustment. RESULTS: A total of 3415 COPD+/HZ+ and 35,360 COPD+/HZ- patients (mean ages 73.2 ± 9.0 and 72.4 ± 9.4 years, respectively) were identified. Patients in the COPD+/HZ+ versus COPD+/HZ- cohort had increased use of all-cause (adjusted incidence rate ratio [aIRR] 1.17; 95% confidence interval [CI] 1.14, 1.21) and COPD-related (aIRR 1.27; 95% CI 1.21, 1.34) medical services (both P<0.001) and higher mean total all-cause ($4140 versus $3749 per person per month [PPPM]; adjusted cost difference +$313 PPPM) and COPD-related ($1541 versus $1231 PPPM; +$152 PPPM) costs (both P<0.004) in the year after HZ. CONCLUSIONS: HRU and cost burden is higher in patients with COPD with vs without HZ. These results could help to estimate the potential cost benefits of HZ vaccination among patients with COPD.