CAN THERE BE A MORE PATIENT-CENTERED APPROACH TO DETERMINING CLINICALLY IMPORTANT EFFECT SIZES FOR RANDOMIZED TREATMENT TRIALS

Sample sizes for treatment trials with categorical outcomes are conven tionally derived by balancing three elements: a difference between alt ernative treatments in the event rates for the outcomes of interest (c ommonly termed the clinically important difference), the alpha error t olerance (false positive risk) and the beta error tolerance (false neg ative risk). Clinically important differences used to plan trials are chosen in part based on earlier experience with similar interventions (i.e. biological or clinical plausibility). Methodological conventions and clinicians' perceptions will also affect choices. Lastly, practic al concerns about the feasibility of accruing large numbers of subject s may drive trialists to specify bigger differences as clinically impo rtant, with a view to containing sample size requirements. We suggest that patients or other members of the public be given an active role i n determining the magnitude of the clinically important treatment effe ct for trial planning. Probability trade-offs could be constructed to enable patients and/or healthy volunteers to indicate the degree of be nefit they would want from a ''new'' treatment, given the potential si de-effects of the same treatment. This method has the advantage of res pecting patient autonomy and principles of informed consent. It provid es an additional consideration when plausible effect sizes and error t olerances on hypothesis tests are balanced against feasibility of accr uing various sample sizes. Its primary disadvantage is inconvenience, as it adds another step to trial design. On the other hand, if patient -based clinically important differences are generated for a variety of disease states and types of treatments, specific trade-off exercises may be needed only for unusual trials. Another disadvantage is that pa tients' perspectives may differ markedly from clinicians' or from soci ety at large, leading to conflicts of perspective that could prove dif ficult to resolve. However, we believe that raising and addressing suc h conflicts of perspective is itself a useful part of the evaluative p rocess.