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

from Value in Health at on October 30, 2020 at 01:30PM

Available online 29 October 2020

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


There is a growing need for including patient preferences in benefit–risk assessment in general, and for noninferiority clinical trials specifically.

Preference elicitation can be done as ancillary study during a noninferiority trial.

Using the multiple-imputation approach, preferences could be restored for all trial participants, and thus provide a transparent evaluation of the overall benefit-risk.



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.


multicriteria decision analysis

multiple imputation


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© 2020 ISPOR-The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc.