How similar is similar enough? Assessment of indirect treatment comparisons to support similarity for NICE's cost comparison route.

Objectives: Health technology assessment bodies are increasingly using cost comparison (cost-minimisation) analysis to manage rising demand. Such an approach requires demonstration of clinical similarity. While head-to-head comparisons from equivalence or non-inferiority studies are usually accepted as evidence of similarity, guidance is lacking on when equivalence may be assumed from indirect treatment comparison (ITC), either quantitative or qualitative.

Methods: We reviewed methods papers and previous NICE appraisals to assess methods for determining equivalence when no head-to-head trial exists, identify how NICE and their committees decide if a cost-comparison route is suitable, and explore how best to present evidence of similarity to aid decision-making.

Results: We identified 5 methods papers, 41 case studies, and 33 appraisals that used cost comparison based on ITC. All 33 appraisals were recommended, though none applied any of the formal methods identified from the literature. Instead, companies used narrative summaries to assert similarity, often based on a lack of significant differences, leading to committee uncertainty that was typically resolved through clinical expert input. The most promising methods we reviewed were the estimation of non-inferiority ITCs in a Bayesian framework followed by a straightforward, probabilistic comparison of the indirectly estimated treatment effect against a pre-specified non-inferiority margin.

Conclusions: Formal methods to assess equivalence in ITC-based cost comparison are emerging but have not yet been applied in practice. We provide recommendations for how these methods and qualitative methods, such as evaluation of the plausibility of class effects and clinical expert input, could help address uncertainties in assuming equivalence.