Factorial design clinical trials

Factorial randomised trials allow investigators to evaluate more than one intervention in a single experiment, whether (1) testing the treatment effects independently or (2) when the treatments are thought to be complementary and a specific aim is to investigate the treatment interactions.  In the simplest case, a 2×2 design is a study when two treatment factors are involved each with two levels.  For example, in a cardiovascular disease prevention trial, patients are being randomised to receive aspirin vs matching placebo and then beta-carotene vs matching placebo.

Analysis of factorial trials requires more attention than simple parallel studies.  Specifically, choice of statistical methods and how to handle treatment interactions.

Resources:

• Montgomery AA, Peters TJ, Little P.  Design, analysis and presentation of factorial randomised controlled trials.  BMC Med Res Methodol. 2003 Nov 24;3:26.
• Green S, Liu PY, O’Sullivan J.  Factorial design considerations.  J Clin Oncol. 2002;20:3424-30.

Examples of published studies

• Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, Van Someren EJ.  Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial.  JAMA. 2008 11;299:2642-55.
• Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N; IMPACT Investigators.  A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350:2441-51.