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.