Leveraging Real-World Data Versus External Trials to Inform Comparative Efficacy within Single-Arm Trial-Based NICE Submissions
Author(s)
Sherry Wu, MPH, Eileen Zhang, MS, Denise Zou, MA.
Thermo Fisher Scientific, Wilmington, NC, USA.
Thermo Fisher Scientific, Wilmington, NC, USA.
Presentation Documents
OBJECTIVES: Randomized controlled trials with anchored matching-adjusted indirect comparison (MAIC) are commonly used to provide comparative efficacy for external comparators. However, this approach is not feasible for single-arm trials (SATs), making real-world data (RWD) with appropriate statistical methods a pragmatic option. Currently, there are no explicit health technology assessment (HTA) guidelines for generating comparative evidence for SAT-based submissions. This study reviews the acceptance of RWD versus external trials to inform comparative efficacy in SAT-based HTA submissions.
METHODS: Oncology SAT-based appraisals from the National Institute for Health and Care Excellence (NICE) between May 2017 and May 2022 were reviewed. Full-text screening of committee papers and guidance was conducted to identify the approach used to derive comparative efficacy and committee commentaries.
RESULTS: Of the 31 submissions reviewed, 58% used external trials only to derive comparative efficacy, 29% used RWD only, and 13% used both, with the variance driven by external data availability, limitations, and relevance. Half of these sources were deemed fit-for-purpose by the committee. Among the 13 submissions leveraging RWD, over 60% were accepted as valid evidence, benefiting from the ability to mitigate uncertainty due to lack of direct comparison by allowing precise matching and covariate adjustment. Overall, the committee emphasized that unanchored MAIC does not effectively reduce uncertainty or bias, often favoring supplementation with naïve analyses as benchmarks (52%). Criticisms of SAT-based submissions focused on data limitations (42%) and insufficient comparability (35%). Other concerns included limited generalizability of the results (23%), inadequate covariate adjustments (23%), and inappropriate statistical methods (16%).
CONCLUSIONS: RWD has been increasingly used as an alternative to suboptimal trials for external control in SAT-based HTA submissions, offering more granularity and flexibility. However, HTA consensus on its appropriateness for external control remains low, with key discussions on whether the data are fit-for-purpose and the adequacy of covariate adjustments.
METHODS: Oncology SAT-based appraisals from the National Institute for Health and Care Excellence (NICE) between May 2017 and May 2022 were reviewed. Full-text screening of committee papers and guidance was conducted to identify the approach used to derive comparative efficacy and committee commentaries.
RESULTS: Of the 31 submissions reviewed, 58% used external trials only to derive comparative efficacy, 29% used RWD only, and 13% used both, with the variance driven by external data availability, limitations, and relevance. Half of these sources were deemed fit-for-purpose by the committee. Among the 13 submissions leveraging RWD, over 60% were accepted as valid evidence, benefiting from the ability to mitigate uncertainty due to lack of direct comparison by allowing precise matching and covariate adjustment. Overall, the committee emphasized that unanchored MAIC does not effectively reduce uncertainty or bias, often favoring supplementation with naïve analyses as benchmarks (52%). Criticisms of SAT-based submissions focused on data limitations (42%) and insufficient comparability (35%). Other concerns included limited generalizability of the results (23%), inadequate covariate adjustments (23%), and inappropriate statistical methods (16%).
CONCLUSIONS: RWD has been increasingly used as an alternative to suboptimal trials for external control in SAT-based HTA submissions, offering more granularity and flexibility. However, HTA consensus on its appropriateness for external control remains low, with key discussions on whether the data are fit-for-purpose and the adequacy of covariate adjustments.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
EE26
Topic
Economic Evaluation
Disease
SDC: Oncology