OBJECTIVES : Although randomized controlled trials are the ‘gold-standard’ for health technology assessments (HTAs), single-arm trials are increasingly submitted when comparative trials are infeasible or unethical to conduct. Real-world evidence (RWE) is often used to support these submissions by addressing uncertainties. This systematic review assessed the extent of RWE used to support oncology appraisals containing pivotal single-arm trials (PSATs), across six HTA agencies.

METHODS : Single technology assessments (STAs) evaluating pharmacological interventions published by NICE were searched in accordance with Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify oncology appraisals with PSATs published between January 2016 and search date (20/11/2020). RWE use to fulfill comparative effectiveness requirements was evaluated, and reception of RWE by NICE was extracted. Ten NICE STAs containing PSATs with extensive RWE use were identified as case studies, and submissions of the same product and indication were compared across five additional HTA agencies: SMC (Scotland), CADTH (Canada), INESSS (Quebec), HAS (France) and IQWiG (Germany).

RESULTS : Among 284 NICE STAs screened, 145 STAs in oncology were identified, of which 32 (22%) contained PSATs. Matching-adjusted (N=15), or naïve indirect comparisons (N=13) were frequently used to demonstrate comparative effectiveness, followed by simulated treatment comparisons (N=3), and pooled data (N=1). Twenty-two (66%) STAs with PSATs used RWE in their comparator arms, most with a retrospective cohort design (81%). The number of supporting RWE references in ten STA case studies varied across submissions: CADTH (N=22), NICE (N=17), INESSS (N=15), SMC (N=11), IQWiG (N=10), and HAS (N=8). Acceptance rate of RWE was highest within SMC (72%), followed by NICE (71%), HAS (63%), INESSS (60%), CADTH (59%), and IQWiG (30%).

CONCLUSIONS : RWE is often used within HTAs with PSATs in oncology to support comparative effectiveness assessments. RWE use was well-received by respective committees within the UK, Canada, and France, with the lowest acceptance rate in Germany.