Evaluation of Comparative Treatment Trials

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HE EVALUATION OF THE COMPARATIVE EFFECTIVENESS of treatments should not depend on the statistical effect of treatments on individual measures of outcome (benefits or harms), but rather on the clinical effects of treatments (both benefits and harms) on individual patients who experience both benefits and harms. Such evaluation requires both statistical assessment of the rates of cooccurrence of such benefits and harms and clinical assessment of their combined clinical effects on patients. Randomized clinical trials (RCTs), carried out appropriately, have the potential to move research rapidly toward personalized medicine. 1 However, to do this, RCT methodology must be updated. Several such updates already exist, some to promote optimal use of existing RCT methods (RCT registration, 2 CONSORT guidelines 3 ) and others to modify and extend their clinical significance (effect sizes) rather than statistical significance (P values) 4 or moderators of treatment choice. 5 However, all of these advances depend crucially on the quality of the RCT outcomes. RCTs should consider outcomes at the patient level, taking into account the simultaneous benefits and harms experienced by each patient, much as a physician does when deciding between 2 treatment options. Information on benefit alone is useful only if potential harms are of no clinical importance and vice versa. For instance, there is concern that use of selective serotonin reuptake inhibitor antidepressants in adolescents may increase the risk of suicidal ideation and suicidality. 6 If only benefits are considered, a small subgroup of young patients may be exposed to serious harm; however, if only harms are considered, other patients may be denied a potentially lifesaving treatment. Methods for assessing clinical effects of interventions on patients rather than on measures are already available, and better methods can be developed, but this type of information must be demanded of RCTs.