Assigning disease clusters to people: A cohort study of the implications for understanding health outcomes in people with multiple long-term conditions.

Background: Identifying clusters of co-occurring diseases may help characterise distinct phenotypes of Multiple Long-Term Conditions (MLTC). Understanding the associations of disease clusters with health-related outcomes requires a strategy to assign clusters to people, but it is unclear how the performance of strategies compare. Aims: First, to compare the performance of methods of assigning disease clusters to people at explaining mortality, emergency department attendances and hospital admissions over one year. Second, to identify the extent of variation in the associations with each outcome between and within clusters. Methods: We conducted a cohort study of primary care electronic health records in England, including adults with MLTC. Seven strategies were tested to assign patients to fifteen disease clusters representing 212 LTCs, identified from our previous work. We tested the performance of each strategy at explaining associations with the three outcomes over 1 year using logistic regression and compared to a strategy using the individual LTCs. Results: 6,286,233 patients with MLTC were included. Of the seven strategies tested, a strategy assigning the count of conditions within each cluster performed best at explaining all three outcomes but was inferior to using information on the individual LTCs. There was a larger range of effect sizes for the individual LTCs within the same cluster than there was between the clusters. Conclusion: Strategies of assigning clusters of co-occurring diseases to people were less effective at explaining health-related outcomes than a person's individual diseases. Furthermore, clusters did not represent consistent relationships of the LTCs within them, which might limit their application in clinical research.