Controlled Clinical Trials 24 (2003) 736–751 Design paper An International Multicenter Protocol to Assess the single and combined benefits of antiemetic interventions in a Controlled clinical Trial of a 2 × 2 × 2 × 2 × 2 × 2 factorial design (IMPACT) Christian C. Apfel, M.D. a,b, *, Kari Korttila, F.R.C.A., Ph.D. c , Mona Abdalla, Ph.D. d , Andreas Biedler, M.D. e , Peter Kranke, M.D. a , Stuart J. Pocock, Ph.D. d , N. Roewer, M.D. a a Department of Anesthesiology, University of Wuerzburg, Wuerzburg, Germany b Outcomes Research Institute and Department of Anesthesiology, University of Louisville, Kentucky, USA c Department of Anesthesiology and Intensive Care, University of Helsinki, Helsinki, Finland d Statistics Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom e Department of Anesthesiology and Intensive Care, University Hospital of Saarland, Homburg, Germany Manuscript received October 10, 2002; manuscript accepted June 23, 2003 Abstract 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. Approximately 28 million operations are performed annually in the United States, mainly under general anesthesia with volatile anesthetics. Unfortunately, one-third of these patients suffer from PONV. This prompted extensive research of antiemetic and anesthetic drugs, but none of the interventions appeared to satisfactorily prevent PONV. Scuderi et al. were the first to almost eliminate PONV by combining various antiemetic interventions; however, the relative benefit of each intervention remained unclear. Accordingly, we have designed a large randomized controlled trial studying six different antiemetic interventions—three involving use of various antiemetic drugs and three involving choice of anesthetic drugs—to answer the following main questions: (1) What is the relative benefit of each of the antiemetic intervention? (2) Are certain combinations of antiemetic * Corresponding author: Dr. Christian C. Apfel, Department of Anesthesiology and Outcomes Research Institute, University of Louisville, 501 E Broadway, Suite 210, Louisville, KY 40202. Tel.: 502-852-4055; mobile: 502-298-8932; fax: 502-852-2610. E-mail address: apfel@ponv.org and christian.apfel@louisville.edu 0197-2456/03/$—see front matter  2003 Elsevier Inc. All rights reserved. doi:10.1016/S0197-2456(03)00107-7