ACCEPTABILITY OF INDIRECT TREATMENT COMPARISONS IN ORPHAN VERSUS NON-ORPHAN NICE TECHNOLOGY APPRAISALS
Author(s)
Xin Zhang, MPhil, MSc, Zheyuan Yang, MSc, Dominic Muston, BSc, MSc, Jasim Uddin, PhD.
LCP Health, Lane Clark & Peacock LLP (LCP), London, United Kingdom.
LCP Health, Lane Clark & Peacock LLP (LCP), London, United Kingdom.
OBJECTIVES: This study aims to assess how the National Institute for Health and Care Excellence (NICE) evaluates indirect treatment comparisons (ITCs) in technology appraisals (TAs), and to compare ITC acceptability between orphan and non-orphan appraisals.
METHODS: NICE TAs published from April 2023 to May 2026 were extracted and reviewed by two independent reviewers. TAs were categorised by disease context (orphan/rare vs. non-orphan), ITC method used, and ITC acceptance outcome. The analysis focused on appraisals that applied at least one ITC method and compared overall acceptance rates and committee concerns between orphan/rare and non-orphan appraisals. ITC acceptance was evaluated using four categories: accepted with no caveats, accepted with standard caveats, accepted with major caveats, or not accepted.
RESULTS: Among the 272 NICE TAs reviewed, 143 used at least one ITC method. Of these, 45 (31.5%) were categorised as orphan/rare appraisals. Overall, 80.0% of orphan/rare ITCs were accepted, compared to 80.6% of non-orphan ITCs. However, accepted orphan/rare ITCs were more frequently accepted with major caveats or high uncertainty than non-orphan ITCs (63.9% vs. 29.1%). Among TAs using an ITC, network meta-analysis (NMA) was the most commonly used method (45.5%), followed by matching-adjusted indirect comparison (MAIC; 30.8%). In orphan/rare appraisals, major committee concerns included single-arm evidence, limited adjustment for prognostic factors, small sample sizes, residual confounding, and immature survival data.
CONCLUSIONS: ITCs were commonly included in NICE appraisals, with over half of reviewed TAs using at least one ITC method. NICE appeared willing to accept ITCs in orphan/rare appraisals, with no substantial difference in overall acceptance rates compared with non-orphan appraisals. However, accepted orphan/rare ITCs were substantially more likely to be associated with major caveats or high uncertainty. These findings indicate that limited evidence in rare diseases may not diminish ITC acceptance, but it may lead to a more scrutinised decision-making process by health technology assessment bodies.
METHODS: NICE TAs published from April 2023 to May 2026 were extracted and reviewed by two independent reviewers. TAs were categorised by disease context (orphan/rare vs. non-orphan), ITC method used, and ITC acceptance outcome. The analysis focused on appraisals that applied at least one ITC method and compared overall acceptance rates and committee concerns between orphan/rare and non-orphan appraisals. ITC acceptance was evaluated using four categories: accepted with no caveats, accepted with standard caveats, accepted with major caveats, or not accepted.
RESULTS: Among the 272 NICE TAs reviewed, 143 used at least one ITC method. Of these, 45 (31.5%) were categorised as orphan/rare appraisals. Overall, 80.0% of orphan/rare ITCs were accepted, compared to 80.6% of non-orphan ITCs. However, accepted orphan/rare ITCs were more frequently accepted with major caveats or high uncertainty than non-orphan ITCs (63.9% vs. 29.1%). Among TAs using an ITC, network meta-analysis (NMA) was the most commonly used method (45.5%), followed by matching-adjusted indirect comparison (MAIC; 30.8%). In orphan/rare appraisals, major committee concerns included single-arm evidence, limited adjustment for prognostic factors, small sample sizes, residual confounding, and immature survival data.
CONCLUSIONS: ITCs were commonly included in NICE appraisals, with over half of reviewed TAs using at least one ITC method. NICE appeared willing to accept ITCs in orphan/rare appraisals, with no substantial difference in overall acceptance rates compared with non-orphan appraisals. However, accepted orphan/rare ITCs were substantially more likely to be associated with major caveats or high uncertainty. These findings indicate that limited evidence in rare diseases may not diminish ITC acceptance, but it may lead to a more scrutinised decision-making process by health technology assessment bodies.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA284
Topic
Clinical Outcomes, Health Technology Assessment, Study Approaches
Topic Subcategory
Decision & Deliberative Processes
Disease
Rare & Orphan Diseases