Target trial emulation using new comorbidity indices provided risk estimates comparable to a randomized trial.

Objectives: To quantify the ability of two new comorbidity indices to adjust for confounding, by benchmarking a target trial emulation against the randomized controlled trial (RCT) result.

Study Design And Setting: Observational study including 18,316 men from Prostate Cancer data Base Sweden 5.0, diagnosed with prostate cancer between 2008 and 2019 and treated with primary radical prostatectomy (RP, n = 14,379) or radiotherapy (RT, n = 3,937). The effect on adjusted risk of death from any cause after adjustment for comorbidity by use of two new comorbidity indices, the multidimensional diagnosis-based comorbidity index and the drug comorbidity index, were compared to adjustment for the Charlson comorbidity index (CCI).

Results: Risk of death was higher after RT than RP (hazard ratio [HR] = 1.94; 95% confidence interval [CI]: 1.70-2.21). The difference decreased when adjusting for age, cancer characteristics, and CCI (HR = 1.32, 95% CI: 1.06-1.66). Adjustment for the two new comorbidity indices further attenuated the difference (HR 1.14, 95% CI 0.91-1.44). Emulation of a hypothetical pragmatic trial where also older men with any type of baseline comorbidity were included, largely confirmed these results (HR 1.10; 95% CI 0.95-1.26).

Conclusion: Adjustment for comorbidity using two new indices provided comparable risk of death from any cause in line with results of a RCT. Similar results were seen in a broader study population, more representative of clinical practice.