Statistical Evaluation of Relationships between Analgesic Dose and Ordered Ratings of Pain Relief over an Eight-Hour Period
SA Gansky, GG
Koch, and J.Wilson
1994 Journal
of Biopharmaceutical Statistics,
4(2), 233-265
Keywords:
Longitudinal design; relative potency; weighted least squares;
ordinal response; multivariate analysis; marginal models.
Abstract
Statistical considerations are discussed for the application of
alternative methods to a clinical trial involving repeated ordinal
ratings and multiple dosage levels of active drugs. Analyses included
summary measures traditionally employed in studies of acute pain: sum
of pain intensity differences from baseline, total pain relief, and
total pain half gone. Estimators and confidence intervals of relative
potency are developed for univariate and multivariate situations,
using weighted least squares analysis with mean response and
variances from Taylor series linearizations. The estimates from these
methods are compared to those from traditional methods, such as
ordinary least squares regression and Fieller's method for confidence
intervals, as well as those from more recent developments, such as
generalized estimating equations and sample survey data regression. A
double- blind, two-center, randomized clinical trial of acute pain
relief comparing placebo with two analgesics, each at two dosage
levels, over an 8-hour period serves as an illustrative example for
these techniques and comparisons.