EVALUATION OF EVIDENCE SOURCE AND ANALYSES TYPE PRESENTED IN RARE DISEASE NICE SUBMISSIONS AS INCLUSION IN JCA APPROACHES
Author(s)
Regina Leadley, BSc1, Janine Ross, MSc1, Megan Brodie-Farmer, MSc2, Judith Peatman, MSc3.
1Petauri, York, United Kingdom, 2Petauri, Bicester, United Kingdom, 3Petauri, Manchester, United Kingdom.
1Petauri, York, United Kingdom, 2Petauri, Bicester, United Kingdom, 3Petauri, Manchester, United Kingdom.
OBJECTIVES: From 2028, the Joint Clinical Assessment (JCA) will expand to include rare diseases (RDs). Challenges exist around small patient numbers, disease heterogeneity, and ethical considerations of RD trials. This research aims to explore sources of evidence and types of analyses presented in recent RD National Institute for Health and Care Excellence (NICE) submissions.
METHODS: NICE technology appraisals published from May 2025 to 2026 were downloaded, screened to identify submissions for RD, and RD status verified using Orphanet. Appraisals were scrutinised to determine what type of evidence (e.g. randomised controlled trials [RCTs], single-arm studies [SAS], real-world evidence [RWE]) was used; analyses (e.g network meta-analyses [NMAs], indirect treatment comparisons [ITCs], matching-adjusted indirect comparisons [MAICs], simulated treatment comparison [STCs]) presented, and response from evidence assessment groups (EAGs) and NICE. Steps were conducted by one reviewer and checked by a second.
RESULTS: Of the 96 submissions identified, 23 were in RD. 8 were terminated due to inadequate evidence, no submission, or company withdrawal, leaving 15 submissions. Preliminary findings showed RCTs provided the primary evidence for most submissions (93.3%), often supplemented by SAS. SAS were the main source in 1 (6.7%). Key analyses included MAICs (n=4), ITCs (n=3), STC (n=1) and NMA (n=1). No analyses were conducted in 7 submissions indicating they were either not required (n=5) or not feasible (n=2). Where MAICs were used, the control arm was primarily sourced from comparator trials, not RWE. Concerns raised included generalisability of evidence to UK practice, trial selection, short follow-up, and small sample sizes. Some EAGs endorsed MAICs, some advised caution, while others suggested comparison with a STC.
CONCLUSIONS: RCT evidence featured heavily in submissions, often with no further analyses required. MAICs were the primary analyses providing alternative comparator arms for RCT evidence. RCT evidence was criticised for limited generalisability, and RWE was recommended to contextualise results.
METHODS: NICE technology appraisals published from May 2025 to 2026 were downloaded, screened to identify submissions for RD, and RD status verified using Orphanet. Appraisals were scrutinised to determine what type of evidence (e.g. randomised controlled trials [RCTs], single-arm studies [SAS], real-world evidence [RWE]) was used; analyses (e.g network meta-analyses [NMAs], indirect treatment comparisons [ITCs], matching-adjusted indirect comparisons [MAICs], simulated treatment comparison [STCs]) presented, and response from evidence assessment groups (EAGs) and NICE. Steps were conducted by one reviewer and checked by a second.
RESULTS: Of the 96 submissions identified, 23 were in RD. 8 were terminated due to inadequate evidence, no submission, or company withdrawal, leaving 15 submissions. Preliminary findings showed RCTs provided the primary evidence for most submissions (93.3%), often supplemented by SAS. SAS were the main source in 1 (6.7%). Key analyses included MAICs (n=4), ITCs (n=3), STC (n=1) and NMA (n=1). No analyses were conducted in 7 submissions indicating they were either not required (n=5) or not feasible (n=2). Where MAICs were used, the control arm was primarily sourced from comparator trials, not RWE. Concerns raised included generalisability of evidence to UK practice, trial selection, short follow-up, and small sample sizes. Some EAGs endorsed MAICs, some advised caution, while others suggested comparison with a STC.
CONCLUSIONS: RCT evidence featured heavily in submissions, often with no further analyses required. MAICs were the primary analyses providing alternative comparator arms for RCT evidence. RCT evidence was criticised for limited generalisability, and RWE was recommended to contextualise results.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA283
Topic
Health Technology Assessment, Methodological & Statistical Research, Study Approaches
Topic Subcategory
Decision & Deliberative Processes, Systems & Structure
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Rare & Orphan Diseases