• R N Harden and S Bruehl.
• Center for Pain Studies, Rehabilitation Institute of Chicago, Department of Physical Medicine and Rehabilitation, Northwestern University Medical School, Illinois 60610, USA.
• Am J Phys Med Rehabil. 2001 Jul 1; 80 (7): 547-57.

AbstractDesign of clinical trials to establish drug efficacy in chronic pain is a complicated issue, and numerous factors must be considered in identifying an optimal study design. Investigators should begin by identifying a focused and testable research question, with the outcome variables operationalized in a way that allows appropriate quantitative analysis. The prospective, randomized, placebo-controlled, doubled-blind study using validated quantitative measures is considered the optimal clinical trial design. Within this general study type, the between-subjects design has less statistical power than does the crossover design, in which the patient serves as his or her own control. However, potential problems with the drug effects from the first condition carrying over into, and confounding, the second drug condition present a noteworthy limitation that must be addressed through adequate washout periods and statistical control if crossover designs are used. Retrospective designs may be useful primarily to take advantage of samples of convenience for development of pilot data that provide the basis for conducting better-controlled prospective studies. Sample selection issues must be considered during study design, including the sample size required (based on statistical power analysis), appropriate inclusion and exclusion criteria, and likely availability of qualifying patients. There are numerous statistical options for analyzing data that must be selected based on whether data are parametric or nonparametric, whether within-subject (crossover) or between-subject comparisons are used, and whether baseline values of outcome measures affect the degree of change in these measures over the course of the study. Involvement of a biostatistical consultant is recommended during all phases of clinical trials.

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