A methodological review of population-adjusted indirect comparisons reveals inconsistent reporting and suggests publication bias

J Clin Epidemiol. 2023 Nov:163:1-10. doi: 10.1016/j.jclinepi.2023.09.004. Epub 2023 Sep 16.


Objectives: Population-adjusted indirect comparisons (PAICs) were developed in the 2010s to allow for comparisons between two treatments evaluated in different trials while accounting for differences in patient characteristics if individual patient data (IPD) are available for only one trial. Such comparisons are increasingly used in market access applications when a pharmaceutical company compares its new treatment (with IPD available) to another treatment developed by a competitor (with only aggregated data available). This study aimed to describe the characteristics of these PAICs, assess their methodology, and describe the reported results.

Study design and setting: Original articles reporting the use of at least one PAIC were searched on PubMed between January 1, 2010 and April 2, 2022. Two reviewers independently selected articles and extracted data.

Results: We included 133 publications reporting the results of 288 PAICs. Half of the articles were published on or after May 7, 2020, and 71 (53%) pertained to onco-hematology. The pharmaceutical industry was involved in 130 (98%) articles. Key methodological aspects were reported inconsistently, with only three articles adequately reporting all aspects. A total of 161 (56%) articles reported a statistically significant benefit for the treatment evaluated on IPD. Conversely, only one PAIC significantly favored the treatment evaluated on aggregated data.

Conclusion: Although the number of published PAICs is increasing, the methodology and transparency need to be improved. Moreover, our study strongly suggests a reporting bias. This situation calls for strengthening guidelines to improve trust in PAIC results and thus their reliability in market access applications.

Keywords: Clinical research; Health technology assessment; Matching-adjusted indirect comparisons; Methodological review; Population-adjusted indirect comparisons; Simulated treatment comparisons.

MeSH terms

  • Humans
  • Publication Bias*
  • Reproducibility of Results