REAL-WORLD EVIDENCE EXTERNAL CONTROL ARMS IN HTA SUBMISSIONS OF NEW ONCOLOGY AND RARE DISEASE THERAPIES: COVERAGE OUTCOMES AND APPRAISAL TIMELINES ACROSS NICE, CDA-AMC, AND PBAC (2020-2025)
Author(s)
Ahmad Hecham Alani, PharmD1, Diana Rebeca Acosta Focil, MD1, David Thompson, PhD2, Mackenzie Mills, PhD1.
1HTA-Hive (Hive Health Optimum Ltd.), London, United Kingdom, 2Rubidoux Research LLC, Manchester, MA, USA.
1HTA-Hive (Hive Health Optimum Ltd.), London, United Kingdom, 2Rubidoux Research LLC, Manchester, MA, USA.
OBJECTIVES: The increasing use of single-arm trials (SATs) in oncology and rare diseases has intensified reliance on real-world evidence (RWE)-based external control arms (ECAs) to support comparative effectiveness in HTA submissions. This study compared population-level coverage outcomes and appraisal timelines between SAT submissions supported by RWE-based ECAs and submissions supported by randomised controlled trials (RCTs) across three jurisdictions.
METHODS: A retrospective cross-sectional analysis was conducted using HTA-Hive, a proprietary database of HTA reports, covering initial drug launches appraised by NICE (England & Wales), CDA-AMC (Canada), and PBAC (Australia) between 2020 and 2025. Analyses were restricted to oncology and rare disease submissions. SAT submissions supported by RWE-based ECAs were compared with RCT-based submissions on: (i) population-coverage outcomes (full coverage, partial coverage, or rejection); and (ii) time from marketing authorisation (MA) to first positive HTA recommendation. Associations were assessed using χ² and t-tests (α=0.05).
RESULTS: Of 321 appraisals, 35 were SAT submissions with RWE-based ECAs and 222 were RCT-based; the remaining 64 comprised SATs with interventional-study ECAs (n=32), other ECA configurations (n=21), and other or multi-design studies (n=11), and were excluded from the primary contrast. For RCT-based versus RWE-ECA-based submissions, rates of full coverage, partial coverage, and rejection were 24.3%, 57.7%, and 18.0% versus 31.5%, 37.0%, and 31.5%, respectively (χ²=5.66; p=0.0589). RWE-ECA-based submissions showed higher rejection and lower partial-coverage rates. Mean time from MA to positive HTA decision was 343 days (~10 months) for RCT-based (n=181) and 389 days (~12 months) for RWE-ECA-based submissions (n=24) (p=0.4914).
CONCLUSIONS: SAT submissions supported by RWE-based ECAs appeared to face a less favourable population-coverage profile than RCT-based submissions, with higher rejection and lower partial-coverage rates, although differences did not reach conventional statistical significance. Mean appraisal timelines were numerically longer for RWE-ECA-based submissions. These benchmarks contextualise RWE-based ECA strategies in oncology and rare disease SAT-led development.
METHODS: A retrospective cross-sectional analysis was conducted using HTA-Hive, a proprietary database of HTA reports, covering initial drug launches appraised by NICE (England & Wales), CDA-AMC (Canada), and PBAC (Australia) between 2020 and 2025. Analyses were restricted to oncology and rare disease submissions. SAT submissions supported by RWE-based ECAs were compared with RCT-based submissions on: (i) population-coverage outcomes (full coverage, partial coverage, or rejection); and (ii) time from marketing authorisation (MA) to first positive HTA recommendation. Associations were assessed using χ² and t-tests (α=0.05).
RESULTS: Of 321 appraisals, 35 were SAT submissions with RWE-based ECAs and 222 were RCT-based; the remaining 64 comprised SATs with interventional-study ECAs (n=32), other ECA configurations (n=21), and other or multi-design studies (n=11), and were excluded from the primary contrast. For RCT-based versus RWE-ECA-based submissions, rates of full coverage, partial coverage, and rejection were 24.3%, 57.7%, and 18.0% versus 31.5%, 37.0%, and 31.5%, respectively (χ²=5.66; p=0.0589). RWE-ECA-based submissions showed higher rejection and lower partial-coverage rates. Mean time from MA to positive HTA decision was 343 days (~10 months) for RCT-based (n=181) and 389 days (~12 months) for RWE-ECA-based submissions (n=24) (p=0.4914).
CONCLUSIONS: SAT submissions supported by RWE-based ECAs appeared to face a less favourable population-coverage profile than RCT-based submissions, with higher rejection and lower partial-coverage rates, although differences did not reach conventional statistical significance. Mean appraisal timelines were numerically longer for RWE-ECA-based submissions. These benchmarks contextualise RWE-based ECA strategies in oncology and rare disease SAT-led development.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
RWD52
Topic
Health Technology Assessment, Real World Data & Information Systems, Study Approaches
Disease
Oncology, Rare & Orphan Diseases