OBJECTIVES: In recent years, immuno-oncology (I-O) therapies have emerged as effective treatment options for cancer. Their efficacy has been compared to chemotherapy and other treatments in Health Technology Assessment submissions, using indirect treatment comparisons (ITCs) when head-to-head trials were not available. We evaluated the appraisal of I-O ITCs by the National Institute for Health and Care Excellence (NICE) in the UK and summarised the different approaches and main critiques to their implementation.

METHODS: I-O appraisals published between 2011-2022 were identified from the NICE website based on the Cancer Research Institute classification (excluding terminated appraisals). ITC methods and Evidence Review Groups (ERGs) and NICE committees’ critiques were extracted from Final Appraisal Documents.

RESULTS: Of the 92 I-O appraisals identified, 64.1% (59/92) included an ITC, most commonly a network meta-analysis (NMA; 50.8%, 30/59). Matching-adjusted indirect comparisons (MAICs) were frequently included in I-O submissions (30.5%, 18/59), while naïve comparisons were also conducted (28.8%, 17/59), mostly alongside MAICs. Simulated treatment comparisons were rarely performed (5.1%, 3/59). Approximately half of the ITCs (49.2%, 29/59) were considered acceptable for decision-making by NICE; most of these treatments were then recommended for reimbursement (82.8%, 24/29). Substantially fewer treatments were reimbursed when an ITC was considered unsuitable for decision-making (43.3%, 13/30). The main criticism highlighted by the ERGs and NICE committees concerned the choice of ITC method (e.g. naïve comparison instead of MAIC), the comparator study selection (e.g. study design heterogeneity, patient cohort differences), the statistical analyses performed (e.g. choice of NMA model, insufficient matching of effect modifiers in MAICs), and the poor face validity of the results.

CONCLUSIONS: Only half of the I-O ITCs were considered acceptable by NICE for reimbursement decision-making, with NMA being the most widely used and acknowledged method. Manufacturers should ensure methodological validity and clinical plausibility to increase their chances of I-O treatment approval.