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.
This narrative review describes and evaluates clinical trial phases, specific POC pain trials, and approaches to patient profiling.
We describe common POC trial designs and their value and challenges, a mechanism-based approach, and statistical issues for consideration.
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.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
aDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA
bDepartments of Anesthesiology & Perioperative Medicine and Biomedical & Molecular Sciences, Queen's University, Kingston, ON, Canada
cDivision of Pain Medicine, Johns Hopkins University, Department of Anesthesiology and Critical Care Medicine, Baltimore, MD, USA
Corresponding Author. Address: Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Dr, Suite 100 Baltimore, MD 21224. Tel.: (410) 510-7989; fax: (410) 510-0117. E-mail address: firstname.lastname@example.org (C.M. Campbell).
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Received March 13, 2018
Received in revised form September 24, 2018
Accepted September 26, 2018