ObjectiveChallenges can exist when framing the decision question in a cost-effectiveness analysis, particularly when there is disagreement among experts on relevant comparators. Using prostate cancer screening and recent developments in risk-stratification, early-detection biomarkers, and diagnostic technologies as a case study, we report a modified-Delphi approach to handle decision question uncertainty.Methods The study involved two rounds of anonymous online questionnaires to identify the prostate cancer screening strategies that international researchers, clinicians and decision-makers felt important to consider in a cost-effectiveness model. Both purposive and snowball sampling were used to recruit experts. The questionnaire was based on a review of the literature and was piloted for language, comprehension and ease of use prior to dissemination. In round 1, respondents indicated their preferred screening strategy (including no screening) through a series of multiple-choice questions. The responses informed a set of 13 consensus statements which respondents ranked their agreement with on a 9-point Likert scale (round 2). Consensus was considered reached if >70% of participants indicated agreement and <15% indicated disagreement.ResultsTwenty participants completed round 1 and 17 completed round 2. Consensus was shown towards comparing no formal screening, age-based, and risk-based strategies. The risk-based approaches included screening only higher-risk men, using shorter screening intervals for higher-risk men, screening higher-risk men at an earlier age, and tailoring screening intervals based on Prostate Specific Antigen (PSA) level at a previous test. There was agreement that inclusion of MRI in the pathway should be considered, but disagreement on the inclusion of new biomarkers.ConclusionIn disease areas where technologies are rapidly evolving, a modified-Delphi provides a useful tool to identify relevant comparators in an economic evaluation.