Comprehensive Benefit-Risk Assessment of Noninferior Treatments Using Multicriteria Decision Analysis

To develop a simple approach for evaluating the overall benefit-risk of a new noninferiority treatment compared with a standard of care.

We propose using multicriteria decision analysis that accounts for uncertainty associated with both clinical outcomes and patient preference data. Because patients' preferences are likely to be influenced by their baseline characteristics, we suggest carrying out a preference study at the beginning of a trial. To reduce the burden of an additional study questionnaire, preference elicitation could be done on a small sample of trial participants. To restore preferences for all trial participants, we propose using multiple imputation (MI). Using simulations, we examine whether 3 different MI procedures lead to the same benefit-risk assessment conclusion, as if all trial participant preferences were obtained. We also compare MI results to complete case analysis, where only preferences of the small sample of trial participants are considered.

We show that the MI procedure successfully restores patients' preferences for the trial participants using different outcome criteria and preferences. For example, using 3 outcome criteria with only 10% of the trial participants providing their preferences, complete case analysis demonstrated a new noninferior treatment as favorable only 5.1% of the time, whereas MI procedures did so between 16.2% and 17.9% of the time. Given that 17.6% correspond to the fully observed weights, the MI methods demonstrate favorable results.

The MI procedure can help facilitate a simple comprehensive benefit-risk assessment for new noninferior treatments.