Designing and conducting proof-of-concept chronic pain analgesic clinical trials. (May 2019)

• Record Type: Journal Article
• Authors: Campbell, Claudia M.; Gilron, Ian; Doshi, Tina; Raja, Srinivasa
• Is Part Of: Pain reports. Volume 4:Number 3(2019)
• Publication Date: 2019-05
• Subjects: Pain -- Proof-of-concept -- Clinical trial -- ACTTION -- Quantitative sensory testing, Pain testing, Personalized medicine
• DOI: 10.1097/PR9.0000000000000697
• Languages: English
• ISSNs: 2471-2531

Abstract

Abstract: Introduction: The evolution of pain treatment is dependent on successful development and testing of interventions. Proof-of-concept (POC) studies bridge the gap between identification of a novel target and evaluation of the candidate intervention's efficacy within a pain model or the intended clinical pain population. Methods: This narrative review describes and evaluates clinical trial phases, specific POC pain trials, and approaches to patient profiling. Results: We describe common POC trial designs and their value and challenges, a mechanism-based approach, and statistical issues for consideration. Conclusion: Proof-of-concept trials provide initial evidence for target use in a specific population, the most appropriate dosing strategy, and duration of treatment. A significant goal in designing an informative and efficient POC study is to ensure that the study is safe and sufficiently sensitive to detect a preliminary efficacy signal (ie, a potentially valuable therapy). Proof-of-concept studies help avoid resources wasted on targets/molecules that are not likely to succeed. As such, the design of a successful POC trial requires careful consideration of the research objective, patient population, the particular intervention, and outcome(s) of interest. These trials provide the basis for future, larger-scale studies confirming efficacy, tolerability, side effects, and other associated risks.