Trial emulation to assess the effect of surgery on survival when there are competing risks, with application to patients with thoracic aortic aneurysms.

Abstract

Objective: This study extends methods to estimate average causal effect of aneurysm repair surgery on (i) overall survival and (ii) aneurysm-related mortality, accounting for competing risks using data from the Effective Treatments for Thoracic Aortic Aneurysms (ETTAA) cohort.

Study design and setting: ETTAA, a prospective cohort study, recruited 886 patients between 2014 and 2018. Patients were linked to UK national hospital and mortality databases by NHS digital and followed-up for later surgeries and deaths. We compared a strategy of open or endovascular surgery (whichever appropriate) within 12 months of enrolment to ETTAA with no surgery within 12 months using the trial emulation framework, and cloning-censoring-weighting analysis. Key confounders at baseline were controlled for using inverse probability weighting methods.

Results: In complete case analysis, estimated 7-year survival probability if everyone received surgery within a 12-month grace period was 57.4% (95% CI: 47.3%, 67.4%) versus 49.9% (44.0%, 55.0%) if no one received surgery. This benefit was primarily attributable to reduction in aneurysm-related deaths (difference -8.7%, 95% CI: -14.0%, -3.9%), with no significant effect on deaths from other causes. Findings were consistent under sensitivity analyses, including multiple imputation of missing confounders. Our cloning-censoring-weighting approach addressed selection-for-treatment, allowed for surgery to be received within a grace period and used appropriate methods to separate aneurysm-related mortality from competing risks.

Conclusion: The study demonstrates the utility of trial emulation and counterfactual methods in estimation of causal effects on competing risks using observational data. Findings suggest a benefit for aneurysm-related survival up to 7 years after enrolment.