Millions of American experience acute and chronic pain. Despite considerable progress identifying pathophysiologic mechanisms of acute and chronic pain, available treatments remain inadequate. Consequently, there is a compelling public health need for the development of treatments with improved efficacy, safety, and tolerability. Unfortunately, numerous analgesic treatments examined in recent randomized clinical trials have failed to show efficacy. The explanations for these negative results are unknown, raising questions about the ability of clinical trials in chronic pain to distinguish efficacious treatments from placebo or less efficacious treatments (i.e., assay sensitivity). Patient characteristics, clinical trial research designs and methods, outcome measures, approaches to data analysis, and statistical power may all play a role in accounting for difficulties in demonstrating the benefits of efficacious analgesic treatments vs. placebo. The identification of specific clinical trial characteristics associated with assay sensitivity in existing data has the potential to establish an evidence-based approach to the design of analgesic clinical trials. The U.S. Food and Drug Administration recently launched Analgesic Clinical Trial Innovations, Opportunities, and Networks (ACTION), a public-private partnership intended to facilitate the discovery and development of analgesics with improved efficacy, safety, and tolerability for acute and chronic pain. ACTION will establish a collaborative initiative to prioritize research objectives, develop a standardized analgesic database platform, and conduct methodologically-focused studies to increase the assay sensitivity and efficiency of analgesic clinical trials. The results of these studies and other activities have the potential to inform and accelerate the development of improved pain management interventions of all types, not just pharmacologic treatments.

Public Health Relevance

Millions of American suffer from acute and chronic pain and the available treatments are inadequate. The primary objective of the Analgesic Clinical Trial Innovations, Opportunities, and Networks (ACTION) public-private partnership is to identify, prioritize, sponsor, coordinate, and promote innovative activities that will expedite the discovery and development of improved analgesic treatments for the benefit of the public health. The research projects conducted by ACTION will focus on optimizing the methods used in clinical trials, and the knowledge to be gained from these studies and ACTION's other activities has the potential to make novel medications and other interventions available that are more effective, safer, and have fewer side effects than existing pain treatments.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZFD1-SRC (99))
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University of Rochester
Schools of Dentistry
United States
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Smith, Shannon M; Dworkin, Robert H; Turk, Dennis C et al. (2017) The Potential Role of Sensory Testing, Skin Biopsy, and Functional Brain Imaging as Biomarkers in Chronic Pain Clinical Trials: IMMPACT Considerations. J Pain 18:757-777
Gewandter, Jennifer S; McKeown, Andrew; McDermott, Michael P et al. (2015) Data interpretation in analgesic clinical trials with statistically nonsignificant primary analyses: an ACTTION systematic review. J Pain 16:3-10
McKeown, Andrew; Gewandter, Jennifer S; McDermott, Michael P et al. (2015) Reporting of sample size calculations in analgesic clinical trials: ACTTION systematic review. J Pain 16:199-206.e1-7
Smith, Shannon M; Paillard, Florence; McKeown, Andrew et al. (2015) Instruments to Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: An ACTTION Systematic Review. J Pain 16:389-411
Smith, Shannon M; Dart, Richard C; Katz, Nathaniel P et al. (2013) Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations. Pain 154:2287-96