How trial designs impact on guidelines

Evidence-based treatment guidelines and practice parameters have been developed in most areas of medicine. They are important because insurance companies, formulary managers, and health maintenance organizations rely on guidelines for formulary and coverage decisions. The methodology for practice parameter development by the AAN is described as it was applied to evaluating AEDs. Systematic criteria are used to classify the evidence as class I, II, III or IV. There is value in designing clinical trials so they will be considered to provide a high level of evidence. The major variables that will be assessed include presence of randomization, use of a control group, use of masked outcome assessment, and in an active-controlled trial, use of an adequate comparator and adequate enrollment to detect a difference if one exists. Minor variables also must be addressed, including a priori definition of the primary outcome variable, clearly defined Inclusion/exclusion criteria, presence of equivalent treatment groups at baseline, adequate duration of assessment to answer the clinical question, and appropriate management and statistical handling of drop-outs. Understanding of the variables that will be considered for treatment guidelines can improve the methodological strength of studies and lead to recommendations for practice.