Improving Clinical Trial Design in Low Back Pain: Insights from Studies of Gabapentinoids.
TL;DR
Key methodological and clinical factors, such as the accurate use of terminology, appropriate patient selection, effective application of screening tools, and mechanism-based selection of medicines at therapeutic doses are discussed.
Abstract
Low back pain (LBP) is one of the leading causes of disability worldwide, affecting hundreds of millions of people globally. Scientific literature continues to highlight key issues in managing these patients, including accuracy of diagnostic terminology, identification of the specific pain mechanisms, and lack of effective licensed treatment options. Using published clinical trials of gabapentinoids to provide insights, we discuss key methodological and clinical factors, such as the accurate use of terminology, appropriate patient selection, effective application of screening tools, and mechanism-based selection of medicines at therapeutic doses. It is important to select a patient population appropriately for the specific pain mechanism treated by the medicine under assessment. Current evidence suggests that identification of a neuropathic component in clinical trials is often inadequate, with many studies either failing to use available validated screening tools or applying them without sufficient methodological rigor. Alongside this, spontaneous resolution of acute pain in low back patients remains an important confounder that is often not thoroughly accounted for. Patients with LBP represent a highly heterogeneous group, and the potential disconnect between diagnosis and mechanism is not helped by older nonspecific terminology. The clinical community continues to improve the terminology, such as the recent International Association for the Study of Pain (IASP) definition of "spine-related leg pain" updating the older diagnosis of "sciatica." Defining or further stratifying a patient population (for example, using neuropathic screening tool scores) and then evaluating multiple treatments effective for nociceptive or neuropathic pain may improve a study's discriminatory power while reducing the number of patients required. Once initial drug efficacy has been established in randomized, placebo-controlled trials, additional study designs targeting specific patient populations can still provide valuable insight into key clinical questions, often requiring substantially fewer resources.