Optimal healthcare decision making under multiple mathematical models: application in prostate cancer screening

Important decisions related to human health, such as screening strategies for cancer, need to be made without a satisfactory understanding of the underlying biological and other processes. Rather, they are often informed by mathematical models that approximate reality. Often multiple models have been made to study the same phenomenon, which may lead to conflicting decisions. It is natural to seek a decision making process that identifies decisions that all models find to be effective, and we propose such a framework in this work. We apply the framework in prostate cancer screening to identify prostate-specific antigen (PSA)-based strategies that perform well under all considered models. We use heuristic search to identify strategies that trade off between optimizing the average across all models' assessments and being conservative by optimizing the most pessimistic model assessment. We identified three recently published mathematical models that can estimate quality-adjusted life expectancy (QALE) of PSA-based screening strategies and identified 64 strategies that trade off between maximizing the average and the most pessimistic model assessments. All prescribe PSA thresholds that increase with age, and 57 involve biennial screening. Strategies with higher assessments with the pessimistic model start screening later, stop screening earlier, and use higher PSA thresholds at earlier ages. The 64 strategies outperform 22 previously published expert-generated strategies. The 41 most conservative ones remained better than no screening with all models in extensive sensitivity analyses. We augment current comparative modeling approaches by identifying strategies that perform well under all models, for various degrees of decision makers' conservativeness.