Population Adjusted-Indirect Comparisons in Health Technology Assessment: A Methodological Systematic Review

OBJECTIVES: In health technology assessment (HTA), population-adjusted indirect comparisons (PAICs) are increasingly considered to adjust for the difference in the target population between studies. We aim to assess the conduct and reporting of PAICs in recent HTA practice.

METHODS: We conducted a methodological systematic review of studies implementing PAICs. We systematically searched for eligible articles using the following keywords: ‘transportability’, ‘direct standardization’, ‘population adjustment’, ‘external control’, ‘simulated treatment comparison(s)’, ‘population-adjusted indirect comparison(s)’, and ‘matching-adjusted indirect comparison(s)’ from PubMed, EMBASE Classic, Embase/Ovid Medline All, and Cochrane databases from January 1, 2010 to Feb 13, 2023. Four independent researchers screened the titles, abstracts, and full-texts of the identified records, then extracted data on methodological and reporting characteristics of 162 eligible articles.

RESULTS: Most PAIC analyses (96.9%, n=157) were conducted by (or received funding from) pharmaceutical companies. Prior to adjustment, 44.5% of analyses (n=72) (partially) aligned the eligibility criteria of different studies to enhance the similarity of their target populations. In 37.0% of analyses (n=60), the clinical and methodological heterogeneity across studies were extensively assessed. In 9.3% of analyses (n=15), the quality (or bias) of individual studies was evaluated. In 47.5% of the records (n=77), sensitivity analysis was not implemented to assess the robustness of the findings. Among eligible records, 67.3% (n=109) adequately described the covariate distribution before population adjustment, and 63.3% of the MAIC records (n=95) adequately described the covariate distribution after population adjustment. Among 18 analyses using methods that required an outcome model, results of the model fitting procedure were adequately reported in three analyses (16.7%).

CONCLUSIONS: The conduct and reporting of PAICs are remarkably heterogeneous and suboptimal in current practice. More recommendations and guidelines on the conduct and reporting of PAICs are warranted to enhance the quality of these analyses in the future.

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