Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions
The Research Need
Pain is a major factor in many acute and chronic conditions. Yet only 2 percent of new therapeutics for pain — compared to 10 percent of new therapeutics for other conditions — advance from Phase 1 clinical trials to approval.
Carefully selecting participants based on specific, measurable characteristics can improve the success of clinical trials. These characteristics, called “biomarkers,” may be indicators of a normal or abnormal process, a condition or disease, or a response to an intervention. Some biomarkers can help predict which patients are more likely to respond to treatment. Using patient selection biomarkers improves the chance that a trial will advance from Phase 1 to approval by 17.5 percent.
Identifying biomarkers for pain conditions could help accelerate the development of therapeutics for pain by improving patient selection for therapeutic clinical trials.
About the Program
The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, will support biomarker discovery and rigorous validation to advance the clinical development of non-addictive pain treatments toward Phase 2 trials and beyond.
The research will address the assessment and management of pain within the context of both injuries and chronic health conditions. Researchers plan to use biomarkers to assess individuals’ pain levels and responses to various treatment regimens and to predict the development of chronic pain after injury. Using objective methods to analyze pain and the efficacy of pain treatments will facilitate the development of new individualized therapies for pain management. In the long term, this research will provide translational tools that can help prevent chronic pain and reduce opioid use in patients who do not respond to opioids.
Promising biomarkers identified through this program may advance to clinical validation through program-funded prospective clinical studies or through the Early Phase Pain Investigation Clinical Network (EPPIC-Net).
To date, through the NIH HEAL Initiative, NIH has awarded approximately $31.7 million through nine grants that address the discovery of biomarkers, biomarker signatures, and endpoints for pain. Numerous institutes and centers across NIH support these grants. The awarded institutions will undertake preclinical research and development as well as initial clinical validation of biomarkers and signatures that could help reduce the extensive and long-term use of opioids in pain management.
Researchers will develop objective measures to identify and grade pain as well as new methods to analyze the effectiveness of pain treatments.
Examples of research and development that awardees will undertake include:
- Identifying biomarkers to predict which patients will develop persistent headaches after a concussion or nerve pain after a spinal cord injury
- Using brain signals as signatures to predict the severity and duration of pain
- Developing biomarkers to diagnose eye pain
- Developing the use of biomarkers from a patient’s immune response to determine the type and level of pain in people who have sickle cell disease
- Identifying biomarkers to diagnose and monitor treatments for musculoskeletal pain in adolescents and adults
- Discovering a novel bio-signature of human pain that is translatable to prevention and treatment of post-operative pain
- Cleveland Clinic Lerner College of Medicine, Case Western Reserve University – Ohio
- Mayo Clinic Arizona – Arizona
- Medical College of Wisconsin – Wisconsin
- Stanford University – California
- Tufts Medical Center – Massachusetts
- University of Maryland, Baltimore – Maryland
- The University of Texas Health Science Center at Houston – Texas
Participating NIH Institutes, Centers, and Offices
- National Cancer Institute (NCI)
- National Center for Complementary and Integrative Health (NCCIH)
- National Institute on Aging (NIA)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- National Institute of Dental and Craniofacial Research (NIDCR)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute on Drug Abuse (NIDA)
- National Institute of Neurological Disorders and Stroke (NINDS)
- BEST Resource: Harmonizing Biomarker Terminology
- Biomarker Qualification: Evidentiary Framework: Guidance for Industry and U.S. Food and Drug Administration (FDA) Staff
- NIH HEAL Initiative Pain Biomarker Workshop, Nov 14-15, 2018, videocast