Generalized Pairwise Comparisons to Support Shared Decision-Making in the CODA Trial

Abstract

Importance Shared decision-making (SDM) can be made difficult by the multifaceted nature of outcome assessment. A rigorous method for analyzing results from multiple outcomes is called generalized pairwise comparisons (GPC), which could assist in SDM. Objective To examine whether GPC can be useful in SDM by using individual-patient data from the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants This comparative effectiveness study used data from participants in the multicenter US CODA trial (conducted between May 2016 and March 2020). All possible pairs of patients (one from each arm) were formed to analyze each of 7 outcomes of interest sequentially. Data were analyzed between February 2020 and early 2024. Exposures Three scenarios of priorities related to a different order of outcomes were considered. The first scenario came from a consensus exercise with patients that favored antibiotics, whereas the other 2 were arbitrarily chosen to illustrate the range of possible outcomes depending on prioritizations. Scenario 2 favored neither treatment, and scenario 3 favored appendectomy. Main Outcomes and Measures The primary outcome was the net treatment benefit (NTB), a formal measure of benefit-risk, which is the net probability that a randomly selected patient from the antibiotic-assigned arm would have a more favorable outcome than a randomly selected patient from the appendectomy-assigned arm. Results A total of 1552 patients were included in the CODA trial, with 776 (mean [SD] age, 38.3 [13.4] years; 286 [37%] female) in the antibiotic arm and 776 (mean [SD] age, 37.8 [13.7] years; 290 [37%] female) in the appendectomy arm. The NTB of antibiotic treatment was 12.8% (95% CI, 7.1% to 18.3%; P < .001) for the first scenario, 3.2% (95% CI -2.4% to 8.7%; P = .27) for the second, and -14.5% (95% CI. -20.2% to -8.8%; P < .001) for the third. These results respectively favored antibiotics, neither treatment, or appendectomy, thus illustrating that benefit-risk varies considerably according to individual priorities. Conclusions and Relevance This comparative effectiveness study of antibiotics and appendectomy illustrates that the GPC method is a flexible yet mathematically rigorous quantitative analysis of benefit-risk balance. This method provides a more exhaustive and nuanced quantitative assessment of the differences between 2 treatment modalities in terms of prioritized outcomes. Furthermore, GPC could support SDM by considering individual prioritizations of the multiple outcomes.