Controlled clinical trials
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Control Clin Trials · Dec 2003
Randomized Controlled Trial Clinical TrialAn international multicenter protocol to assess the single and combined benefits of antiemetic interventions in a controlled clinical trial of a 2x2x2x2x2x2 factorial design (IMPACT).
For various diseases clinicians have to combine different drugs or interventions when a single drug or intervention does not lead to satisfactory results. However, quantifying the relative benefit of certain drugs or interventions when given alone and in combination under controlled conditions requires a complex factorial design. This paper describes such a method applied to a large multicenter trial for the prevention of postoperative nausea and vomiting (PONV), which may be of great interest for other specialties. ⋯ Eligible patients are adults scheduled for elective surgery under general anesthesia with an increased risk for PONV so that the expected incidence in the control group (with none of the six antiemetic interventions) is approximately 60%. In order to allow analyses for up to three factor interactions, a sample size was estimated to be in the range of approximately 5000 patients. To the best of our knowledge this is the first randomized controlled trial of a six-way factorial design that may serve as an example for numerous other medical specialties.
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The Digitalis Investigation Group (DIG) trial was the first large simple trial conducted by the National Heart, Lung, and Blood Institute in conjunction with the Department of Veterans Affairs. A large simple trial is a major undertaking. Simplification at the sites requires careful planning and discipline. Lessons learned from the DIG trial were: (1) keep a large simple trial very simple and keep all study procedures very simple; (2) ancillary studies are important and can complement a large simple trial but require careful advanced planning; (3) anticipate special needs when shipping study drugs internationally; (4) regional coordinating centers can be very useful; (5) recruit as many capable sites as possible; (6) provide research-inexperienced sites/investigators with extra help to obtain federalwide assurance statements from the Office for Human Research Protections and institutional review board approvals; (7) adequately reimburse sites for the work completed; (8) maintain investigator enthusiasm; (9) monitor the slow performers and sites with numerous personnel changes; (10) choose an endpoint that is easy to ascertain; (11) keep the trial simple for participants; and (12) plan early for closeout and for activities between the end of the trial and publication of results.