There are other essential goals in clinical trial design as well. For instance, a well-designed trial will have a sample size that provides adequate statistical power to detect a clinically meaningful effect. An antidepressant trial, for example, must be designed to detect an effect of about .40 standard deviation units (ie, Cohen’s d=.40) and that requires about 100 participants per

treatment group for 80% statistical power for a t-est with a two-tailed alpha-level of .05. However, there is a tradeoff between power and feasibility. Recruitment of 100 per group is only feasible if compatible with both the budget and Inhibitors,research,lifescience,medical the study site patient flow. Furthermore, a trial must be designed such that the false-positive rate (ie, Type I error) is acceptable; the convention is 0.05. This is because false-positive treatments, of course, do not reduce suffering in patients. Finally, the design must be applicable. That is, Inhibitors,research,lifescience,medical the recruited sample should yield results Inhibitors,research,lifescience,medical that generalize to the target patient population; ie, that for which the indication is sought. A well-designed and well-implemented RCT is the gold standard for treatment evaluation. This is because the groups tend to be well-balanced at baseline,

and therefore subsequent group différences can be attributed to treatment effects, providing strong internal validity. However, there are limitations of results from RCTs for psychiatric Inhibitors,research,lifescience,medical disorders. For example, trials for mood disorder interventions typically involve short-term treatment (4 to 12 weeks) despite the chronic nature of the disorders. Furthermore,

Inhibitors,research,lifescience,medical the samples tend to be highly- selected and that restricts the generalizability (ie, external validity) of the results. For instance, it has been shown that RCTs for major depression evaluate treatment in rarefied samples, excluding as many as 85% of those who are PD184352 (CI-1040) screened.3 The exclusions are, for example, based on illness severity (too severe or not severe enough) and safety risk (eg, suicidality, concomitant medication, or psychosis). Therefore the results do not inform the treatment of patients who have such features. Finally, the attrition poses a serious threat to the internal validity of a clinical trial. The attrition rates in antidepressant trials range from 30% to 40% and they are higher for antipsychotics, ranging from 50% to 60%:’ Self-selection of this type (ie, attrition) and of this magnitude severely compromises MI-773 mw randomization. Features of design and analysis that reduce the impact of attrition on RCTs of psychotropics have been discussed in detail elsewhere.