Adjusting for comorbidity in observational cancer studies: A systematic review to assess alignment between index and study.

Epidemiological and retrospective clinical studies on cancer outcomes frequently adjust for patients' comorbid conditions. Despite the existence of multiple comorbidity indices, the Charlson comorbidity index (CCI) is the most frequently applied. Indices are developed in specific settings and the extent of alignment between the development setting and subsequent study is unclear. The present study provides a contemporaneous snapshot of comorbidity indices used in retrospective observational cancer studies and the extent to which cancer type(s), data source(s) and outcome(s) matched the studies in which the indices were developed. A systematic literature search in PubMed identified retrospective, observational studies on outcomes in patients with cancer published between March 2015 and March 2020. Information including the cancer type, data source and outcome were extracted and compared to those used in the validation study of the comorbidity index used. Of 158 papers reviewed, 79 used the CCI, either alone or in combination with other indices. The cancer type matched to that used in the validation study of the comorbidity index in 16 of the 115 studies using an established index, whilst the data source matched in 27 studies and outcome in only two. Justification was rarely provided for index choice (15 of the 115 studies). It may be concluded that, while the CCI remains the dominant comorbidity index, it may not always align to key elements of the study design in terms of cancer type, data source and outcome. A range of indices exists and identification of the most appropriate measure has the potential to improve adjustment for comorbidity. The present study provided information about the indices used in included studies and encourages future studies to consider which comorbidity index offers the best alignment with the study population, data source and question addressed.