Review of pain measurement strategies to support product labeling in US regulated clinical trials

Abstract

Researchers are limited in their ability to substantiate treatment benefit hypotheses for new pain products as it is unclear whether existing instruments meet current US regulatory requirements. The goal of this poster is to evaluate pain product labels approved by the FDA over the past 5 years and describe the measurement strategies that have proved successful in demonstrating treatment efficacy and withstanding regulatory review. A search of the PROLabels database was conducted to identify pain treatments approved in the US since 2006. The measurement strategies used in each are summarized with respect to aspect of pain measured, name of instrument, type of scale used, recall period, frequency of assessment, outcome period, quantitative endpoint, and the data analytic procedure used to guide the interpretation of observed change. Since 2006, the FDA has approved labeling for pain or analgesia indications in n=24 labels. Pain intensity was the most frequent pain-related outcome (n=11) though others were used (eg, pain, pain relief). Single item scales were the most frequently used but others such as the BPI and WOMAC were also employed. With respect to scale type, numeric rating scales, verbal response scales, and visual analogue scales were all observed and both paper and electronic methods were employed. As indication dependent variables, frequency of assessment and outcome period were variable across trials and, therefore, so were the specific quantitative endpoints for pain. Researchers primarily relied upon average difference in pain scores and specifying a priori responder definitions to guide the interpretation of trial results. To meet US regulatory expectations, researchers must substantiate their measurement strategy decisions within the context of FDA guidance. By summarizing salient aspects of successfully employed pain measurement strategies, researchers may better understand how to develop their own measurement strategies that can both evaluate treatment efficacy and withstand regulatory review.