Integration of pain score and morphine consumption in analgesic clinical studies.

UNLABELLED: In pain clinical trials, the rescue analgesic medication such as patient-controlled analgesia morphine is often made available for patients for breakthrough pain. The patient-controlled analgesia morphine usage decreases the study agent's effect on pain relative to placebo and introduces greater variability in attainment of pain scores. For assessment of analgesic efficacy, the isolated statistical analysis of pain score or morphine consumption as a surrogate marker for pain not only loses statistical efficiency but also may incur increased false-positive findings because of multiple testing. The aim of this article is to review the research to date for choices of statistical tests for pain or morphine consumption outcome, with a focus on systematically evaluating a means for collective analgesic assessment of pain and morphine consumption using an integrated outcome. A case example is illustrated for data visualization, statistical comparison, and effect size estimation using the new endpoint. Some implications for clinical practice and further research are discussed. PERSPECTIVE: This article provides statistical evidence to conclude that an integrated outcome of pain score and morphine consumption provides an efficient means for integrated analgesic assessment.