The object of this article was to systematically review available methods to measure comorbidity and to assess their validity and reliability. A search was made in Medline and Embase, with the keywords comorbidity and multi-morbidity, to identify articles in which a method to measure comorbidity was described. The references of these articles were also checked, and using a standardized checklist the relevant data were extracted from these articles. An assessment was made of the content, concurrent, predictive and construct validity, and the reliability. Thirteen different methods to measure comorbidity were identified: one disease count and 12 indexes. Data on content and predictive validity were available for all measures, while data on construct validity were available for nine methods, data on concurrent validity, and interrater reliability for eight methods, and data on intrarater reliability for three methods. The Charlson Index is the most extensively studied comorbidity index for predicting mortality. The Cumulative Illness Rating Scale (CIRS) addresses all relevant body systems without using specific diagnoses. The Index of Coexisting Disease (ICED) has a two-dimensional structure, measuring disease severity and disability, which can be useful when mortality and disability are the outcomes of interest. The Kaplan Index was specifically developed for use in diabetes research. The Charlson Index, the CIRS, the ICED and the Kaplan Index are valid and reliable methods to measure comorbidity that can be used in clinical research. For the other indexes, insufficient data on the clinimetric properties are available.
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