Measuring Clinical Uncertainty and Equipoise by Applying the Agreement Study Methodology to Patient Management Decisions

Background: Clinical uncertainty and equipoise are vague notions that play important roles in contemporary problems of medical care and research, including the design and conduct of pragmatic clinical trials. Our goal was to show how the reliability study methods normally used to assess diagnostic tests can be applied to particular management decisions to measure the degree of clinical uncertainty and equipoise regarding the use of rival management options prior to the conduct of randomized trials. Methods: We first illustrate how we have used the reliability study methodology to measure uncertainty in clinical decision-making regarding mechanical thrombectomy in acute stroke. We then follow the layout provided by standard guidelines to review how the various design elements of diagnostic reliability studies can be adapted to assess the repeatability of management decisions and measure clinical uncertainty. Results: The example shows how this methodology can be used to show disagreement in decisions for thrombectomy, and justify that sufficient clinical uncertainty exists to warrant the conduct of additional randomized trials. The general method we propose is that a sufficient number of diverse individual cases sharing a similar clinical problem and covering a wide spectrum of clinical presentations be assembled into a portfolio that is submitted to a variety of clinicians who routinely manage patients with the clinical problem. Clinicians are asked to independently choose one of the predefined management options, which are selected from those that would be compared within a randomized trial that would address the clinical dilemma. Intra-rater agreement can be assessed at a later time with a second evaluation. Various professional judgments concerning individual patients can then be compared and analyzed using kappa statistics or similar methods. Interpretation of results can be facilitated by providing examples or by translating the results into clinically meaningful summary sentences. Conclusions: Measuring the uncertainty regarding management options for clinical problems may reveal substantial disagreements, provide an empirical foundation for the notions of clinical uncertainty and equipoise, and inform or facilitate the design/conduct of clinical trials to address the clinical dilemma.