What Have We Learned about Trial Design From NIMH-Funded Pragmatic Trials?

Abstract

At the 2008 annual meeting of the American College of Neuropsychopharmacology (ACNP), a symposium was devoted to the following question: 'what have we learned about the design of pragmatic clinical trials (PCTs) from the recent costly long-term, large-scale trials of psychiatric treatments?' in order to inform the design of future trials. In all, 10 recommendations were generated placing emphasis on (1) appropriate conduct of pragmatic trials; (2) clinical, rather than, merely statistical significance; (3) sampling from the population clinicians are called upon to treat; (4) clinical outcomes of patients, rather than, on outcome measures; (5) use of stratification, controlling, or adjusting when necessary and not otherwise; (6) appropriate consideration of site differences in multisite studies; (7) encouragement of 'post hoc' exploration to generate (not test) hypotheses; (8) precise articulation of the treatment strategy to be tested and use of the corresponding appropriate design; (9) expanded opportunity for training of researchers and reviewers in RCT principles; and (10) greater emphasis on data sharing.

Update on Typical and Atypical Antipsychotic Drugs

“…The highly publicized primary endpoint finding was difference in time to discontinuation, which favored olanzapine, with improvement in psychopathology a secondary endpoint, which also slightly favored olanzapine (9). However, subsequent independent scrutiny of the design and data analysis of this study revealed serious flaws, leading to the conclusion that it was impossible to draw conclusions about the relative merits of the drugs from CATIE's findings (1,(68)(69)(70)(71). These flaws included allowing patients to remain on the same drug they had been receiving prior to randomization, which affected many of those randomized to risperidone or olanzapine (9), and olanzapine dosage up to 30 mg/day (9), three times the dose found to be effective for non-TRS (72).…”

Policy and service development implications of the second Australian National Survey of High Impact Psychosis (SHIP)

“…Greater understanding of the influence of factors such as patient characteristics on treatment response may assist the development of more systematic, tailored treatment guidelines (Kane andCorrell, 2010, Weiden et al, 2007). There is thus enormous scope for conducting pragmatic clinical trials to improve the evidence base for optimal prescribing by clinicians and to improve patient outcomes, especially the risk to benefit ratio (March et al, 2010;Tunis et al, 2003).…”

Pharmacotherapy of cognition in schizophrenia

“…The flaws in design and execution of the CATIE study have been documented by experts in effectiveness research in schizophrenia, and some of these apply to its cognitive results as well, for example, prolonged treatment with atypical APDs prior to randomization, which was often the same drug received during prior treatment [18]. A special issue in the cognition study was the failure to appreciate the effect of tardive dyskinesia (TD) on the cognitive response to AAPDs, now shown to inhibit the improvement with these agents [17 ].…”