Clinical Trials

❘❙❚■ Chapter 11 | Factorial Designcombinations. It is then possible to test the independent effect of eachintervention on the expected outcome, in addition to the combined effect of bothinterventions. Such trials allow investigators a golden opportunity to testcommercially profitable and nonprofitable therapies together.In the analysis and reporting of a factorial design trial, it should be stated that thepotential interaction effect between treatments has been tested for and excluded.The economical advantage and simplicity of these studies usually outweigh thecomplications that arise due to unexpected treatment interactions, and thesestudies should be used more frequently in clinical practice where appropriate.References1. Fawzi W, Msamanga G, Spiegelman D, et al. Randomised trial of effects of vitamin supplementson pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet1998;351:1477–82.2. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: A randomisedfactorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphatein 58,050 patients with suspected acute myocardial infarction. Lancet 1995;345:669–85.3. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular eventsin high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.N Engl J Med 2000;342:154–60.4. The Canadian Cooperative Study Group. A randomized trial of aspirin and sulfinpyrazonein threatened stroke. N Engl J Med 1978;299:53–9.5. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico. Dietarysupplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction:results of the GISSI-Prevenzione trial. Lancet 1999;354:447–55.6. Robbins G, De Gruttola V, Shafer RW, et al. Comparison of sequential three-drug regimensas initial therapy for HIV-1 infection. N Engl J Med 2003;349:2293–303.7. Pocock SJ. Clinical Trials: A Practical Approach. New York: John Wiley & Sons, 1983.8. Cera KR, Mahan DC. Effect of dietary calcium and phosphorus level sequences onperformance, structural soundness and bone characteristics of growing-finishing swine.J Anim Sci 1988;66:1598–605.9. Hung HM. Evaluation of a combination drug with multiple doses in unbalanced factorial designclinical trials. Stat Med 2000;19:2079–87.10. Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the preventionof postoperative nausea and vomiting. N Engl J Med 2004;350:2441–51.11. Montgomery AA, Peters TJ, Little P. Design, analysis and presentation of factorial randomisedcontrolled trials. BMC Med Res Methodol 2003;3:26.12. Green S, Liu PY, O’Sullivan J. Factorial design considerations. J Clin Oncol 2002;20:3424–30.112