PROJECT SUMMARY / ABSTRACT Chronic pain impacts 20-30% of U.S. adults. Unfortunately, currently available pain treatments tend to be only moderately effective and there are many individuals for whom treatments do not provide any relief or who cannot tolerate their adverse side effects. Attempts to treat chronic pain with opioid analgesics contributed, at least in part, to the current opioid crisis, affecting both individuals with pain and their family members and friends, highlighting the need for the development of novel, non-addictive analgesics. The NIH responded to this need by emphasizing the importance of high-quality analgesic clinical trials that incorporate novel biomarkers and endpoints in order to promote the development of effective analgesics. To drive this effort, the NIH established the Early Phase Pain Investigation Clinical Network (EPPIC-Net) to provide a robust and readily accessible infrastructure for rapid design and performance of phase II clinical trials. The PI of this application is the MPI of the University of Rochester EPPIC-Net, specialized clinical research center (UR-EPPIC-Net), providing a unique opportunity to train mentees in the conduct of multisite analgesic clinical trials. Further, the PI’s ongoing program of research addresses the need for novel outcome measures in analgesic clinical trials and synergizes with EPPIC-Net efforts to (1) make valuable contributions to the field of clinical pain research and (2) offer a range of opportunities for mentees to participate in clinical pain research. The overall goal of this administrative supplement is to provide mentoring and research opportunities for Dr. Sonia Sharma to contribute to the goal of increasing the number of skilled clinical pain researchers who can design, conduct, analyze, and transparently disseminate results of high-quality pain clinical trials, and in turn accelerate the development of novel therapies for chronic pain. Aim 1 will leverage the UR-EPPIC-Net clinical trials to train Dr. Sharma on the necessary skills to conduct high-quality clinical trials for chronic pain therapies. Aim 2 is a research project focused on developing novel outcomes for use in clinical trials of neurogenic intermittent claudication (NIC), a phenotypically-distinct chronic low back pain syndrome. Specifically, aim 2 will evaluate the content and construct validity of clinically- relevant, accelerometry-based outcomes for NIC. The proposed research activities will provide Dr. Sharma with the practical experiences necessary to conduct high-quality randomized clinical trials of chronic pain treatments, conduct analyses related to novel outcome development, and obtain preliminary data and publications to support applications for independent research funding.

PROJECT NARRATIVE Chronic pain affects 20-30% of U.S. adults, but unfortunately, available pain treatments are not effective for everyone and can have unwanted side effects, including the risk of addiction in the case of opioid analgesics. To address the need for safer and more effective treatments for chronic pain, the NIH established the Early Phase Pain Investigation Clinical Network (EPPIC-Net), comprised of a network of academic centers and pain experts working together to quickly design and perform high-quality studies of new pain treatments. The goal of supplement is to use the University of Rochester’s (UR) EPPIC-Net specialized clinical research center and the UR-EPPIC-Net investigator’s ongoing program of research focused on developing better methods for testing new pain treatments in order to provide a robust educational environment to train Dr. Sharma on the proper design, conduct, analyses, and dissemination of pain clinical trials in order to increase the number of highly- trained researchers focused on improving the treatment of pain.