Competing events and costs of clinical trials: Analysis of a randomized XXXX .

@entity1 @entity263 @entity3
BACKGROUND: Clinical trial costs may be reduced by identifying enriched subpopulations of @entity1 with favorable risk profiles for the events of interest. However, increased selectivity affects accrual rates, with uncertain impact on clinical trial cost. METHODS: We conducted a secondary analysis of Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy for high-risk @entity263 . The primary endpoint was @entity3 ( @entity3 ), defined as time to @entity3 or death from any cause (competing mortality). We used competing risks regression models to identify an enriched subgroup at high risk for @entity3 and low risk for competing mortality. We applied a cost model to estimate the impact of enrichment on trial cost and duration. RESULTS: The treatment effect on @entity3 was similar in the enriched subgroup (HR, 0.42; 95% CI, 0.23-0.76) compared to the whole cohort (HR, 0.50; 95% CI, 0.30-0.81) while the effect on competing mortality was not significant in the subgroup or the whole cohort (HR 0.70; 95% CI 0.39-1.23, vs. HR 0.94; 95% CI, 0.68-1.31). Due to the higher incidence of @entity3 relative to competing mortality in the enriched subgroup, the treatment effect on @entity3 was greater in the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36-0.82, vs. HR 0.77; 95% CI, 0.58-1.01). Trial cost was 75% less in the subgroup compared to the whole cohort ( 1.7million vs.  6.8million), and the trial duration was 30% shorter (8.4 vs. 12.0years). CONCLUSION: Competing event enrichment can reduce clinical trial cost and duration, without sacrificing generalizability.
