OBJECTIVES: Indirect treatment comparisons (ITC) are needed to perform comparisons of therapies when head-to-head comparison trials are lacking. This study aims to review and critique methodologies used in ITC of advanced therapies in ulcerative colitis (UC) submitted to NICE.

METHODS: NICE single technology appraisals (STAs) published for UC till date were reviewed. Information on approaches and methodology of ITC, and key issues were extracted from company submissions and evidence review group (ERG) reports by one reviewer and quality checked by the second reviewer to ensure accuracy.

RESULTS: Nine STAs of UC therapies published between December-2008 and January-2023 were found. Two were excluded (one terminated appraisal; one different population). Seven were included, comprising upadacitinib, ozanimod, filgotinib, ustekinumab, tofacitinib, vedolizumab, and anti-TNF agents. In all STAs, network meta-analysis (NMA) approach was considered for ITC. Multiple NMAs were conducted in each submission, covering both induction and maintenance phase and biologic-naïve and biologic-pretreated patients. All NMAs explored both fixed-effect and random-effect models for estimation. For the continuous outcomes, generalized linear model framework using Bayesian Markov Chain Monte Carlo simulations was utilized (n=2). For binary outcomes, multinomial probit model (n=4) and binomial logit model (n=5) were mainly considered. The most cited modeling critiques include concerns about sources of heterogeneity in included trials, inability to test the inconsistency assumption, maintenance phase NMA results less reliable, lack of transparency in calculations, unclear source of data for NMAs, lack of subgroups data for safety, and unclear direction of effect.

CONCLUSIONS: The study highlights the predominant use of NMA in ITC for UC therapies in NICE submissions. The use of novel approaches such as matching-adjusted indirect comparison and simulated treatment comparisons was lacking. The highlighted critiques emphasize the need for adherence to the existing methods and guidelines to ensure robust and reliable ITC assessment in the evaluation of UC therapies.