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Wednesday, August 2, 2017

NIH’s Efforts to Reduce the Opioid Epidemic - Dr. Nora Volkow, NIDA

Dr. Volkow provided background on the opioid epidemic highlighting the staggering increase in overdose death rates from 1999 to 2015. Over this time period, opioid prescriptions increased and peaked around 2011. Opioid fatalities are increasing and there has been a sharp increase in synthetic opioids such as fentanyl.  Despite the increase in opioid prescriptions, the chronic pain crisis has not gotten better and pain treatment has not improved. 

The NIH has launched an initiative focused on 3 major areas: Pain management, opioid addiction treatment and overdose reversal.  Pharmaceutical companies and key scientists in pain research and other fields were invited to attend a series of workshops focused on combating the overlapping crises of chronic pain treatment and opioid misuse.

The first workshop held on June 5th, 2017 focused on medications and assisted therapies for opioid use disorder.  There is evidence that medication assisted treatments can decrease opioid use, opioid-related overdose deaths, criminal activity and infectious disease transmission.  It can also increase social functioning, retention in treatment. Currently, medication assisted therapies are being highly underutilized due to infrastructure and certain requirements.  Workshop participants were asked to consider main challenges and opportunities. 

The following key themes were identified:

  • Lack of treatment infrastructure for medications is a significant challenge, including reimbursement for medications for opioid use disorders.
  • Incentives are needed to encourage pharmaceutical and biotechnology company investment.
  • There is a need for better surveillance on overdoses and the use of naloxone to reverse them.
  • Technology can help to treat disorders and prevent overdose but more funding needed.

In the next steps, public-private partnerships will be initiated to develop: new formulations of existing medications; engage CMS to address reimbursement challenges for medications as well as medical devices that may dis-incentivize industry from investing in this area; and explore mechanisms to expedite NIH review of quality grant proposals.

The second workshop held on June 16th, 2017 focused on accelerating the development of pain medications.  Research in this area shows a significant number of potential targets with therapeutic potential.   For example, chemokine antagonists and drugs that affect neuronal transmission sensitivity.  Workshop participants were asked to provide information on challenges and opportunities for analgesic drug development.

The following key themes were identified:

  • There has been significant progress in target identification and structure based drug development; there are many therapeutics in the pipeline.
  • There is a need to reset expectations of what is achievable with pain treatment.
  • Heterogeneity among patients with chronic pain poses significant challenges; objective biomarkers are needed to improve the speed and efficiency of clinical trials.
  • Need for basic research on diverse pain conditions, including better animal models.
  • Advances in neuroscience technologies are poised to accelerate development of treatments for pain.
  • There is significant potential value in coordinating across both pharmaceutical and academic research.

The next steps are: Developing a data sharing cooperative; Establishing a clinical trials network with cohorts of patients with severe unmet treatment needs; Initiating an effort to develop objective measures of pain (e.g. a “pain-meter(s)” grand challenge); and Accelerating development of therapeutics including: disease modifying drugs, compounds in late stage development, repurposed compounds, and validation of current and new targets.

The third workshop held on July 7th, 2017 focused on understanding the neurobiology of pain.  There was an emphasis on understanding the transition from acute to chronic pain so that chronic pain could be prevented in the first place.  Workshop participants were asked to identify key themes. 

The following key themes were identified:

  • More neuroscientists needed in the field of pain research.
  • Pain processing is complex with diffuse mechanisms throughout the brain and periphery.Multidisciplinary needed to understand pain at the molecular, cellular, and system levels.
  • Standardized, objective measures of pain and treatment response are needed for animal models with translational validity in humans.
  • Extensive patient phenotyping needed to develop objective biomarkers of pain and treatment response and enable precision medicine.
  • Objective screens, based on the neurobiology of pain, are needed to validate targets and accelerate the drug development process.
  • Important research gaps include: the prolonged effects of chronic pain, long term impacts of treatment, and the transition from acute to chronic pain.


The next steps are to: Promote cross-sector data and expertise sharing to facilitate more efficient use of resources; Develop biomarkers of pain with predictive validity for treatment response; Develop biologically based objective measures of pain; Develop a standardized platform for the validation of drug targets; Develop a composite set of clinically relevant outcome measures to enhance clinical research; and Facilitate a research collaboratory to explore: Mechanisms of pain in the peripheral nervous system, spinal cord, and brain; The long-term impact of chronic opioid treatment; The transition from acute to chronic pain; Stratification of patients who do/do not respond to treatment, and to placebo; The impact of co-morbidities on clinical trajectory, treatment response, and long-term outcomes; and Mechanisms underlying placebo response.

Members briefly discussed details of the public-private partnership.  Drs. Volkow and Koroshetz commented that the 3 workshops are industry-focused and thus limited to efforts that are within the interests of pharmaceutical companies. At this stage, resources are not available to deploy all of the action items identified above. Dr. Collins has asked for a rough budget and plans to present it to industry and government officials.


The Comprehensive and Recovery Addiction Act (CARA) Advisory committee - Dr. Linda Porter, NINDS

The Comprehensive and Recovery Addiction Act (CARA) was signed into law in 2016.  It establishes a comprehensive, coordinated, balanced strategy through enhanced grant programs that would expand prevention and education efforts while also promoting treatment and recovery. The CARA leadership is asking for suggestions for committee members.  A Federal Register Notice will be released to solicit nominations for people willing to serve from public organizations as well as Federal agencies.  One of the mandates is to review clinical best practice guidelines already in place at the state and federal levels and come up with a guideline that integrates the most valuable components. The guideline should incorporate high-risk populations, the private sector, state and local resources for pain management. They are planning for a first draft to be released in 2018.  NIH and other Federal agencies are being asked to contribute to the costs of the committee.  The NIH Pain Consortium has been asked to distribute the nominations notice widely.


SAMUELI FUND - Dr. Linda Porter, NINDS

The Samueli Fund is interested in supporting objectives from the National Pain Strategy.  They are considering funding a workshop related to best practices for models of pain care.   They are most interested in the education focused objectives, both public and provider education.  More information to follow.



A common fund proposal for ‘Acute-to-Chronic Pain Transition Signatures’ is currently being considered. Dr. Collins is supportive of a pain-related proposal that can contribute to combating the opioid epidemic. The goal of the common fund projects is to have results within 5 years that would have a significant impact on the field. The 3rd opioid workshop recommendations seem to fit best with a potential proposal.  The proposal would focus on identifying a signature to better understand the transition from acute to chronic pain.  Patients with a clear starting point or pain condition that are at high risk to develop chronic pain would be followed for about 12 weeks.  The primary deliverable would be a robust dataset for analysis to identify a signature that may be predictive.  Multi-site clinical projects would be established and go through a process to optimize the study parameters and consider key questions such as ‘how many patients per pain type should we expect?’.   There is a quick turn-around time for concept clearance, by September 1st.   Recommendations from the Federal Pain Research Strategy will be useful.

Additional recommendations were made regarding the proposal including: considering the physical activity common fund project as a model; the potential for a prospective study to look at opioid dependence, opioid-induced hyperalgesia and addiction as outcome measures; considering various levels from which to extract information (for example, VA healthcare model); creating a platform to ensure standardized measures; prospective trials chronic pain patients to confirm pain signatures from naïve pain patients; consideration of psychosocial elements and the heterogeneity of transition to chronic pain;


NCCIH DOD/VA Initiative - Dr. Josie Briggs, NCCIH

NCCIH in collaboration with the Department of Defense and the U.S. Department of Veterans Affairs launched an initiative on pragmatic approaches to pain management.  The goal of the initiative is to develop the capacity to implement cost-effective large-scale clinical research in military and veteran health care delivery organizations focusing on non-pharmacological approaches to pain management and other comorbid conditions. The structure is similar to the NIH collaboratory. There will be a coordinating center and individual projects will be phased.  At the date of the meeting there were 40 applicants, 20 of which were reviewed.  The VA and DoD anticipate funding about 5-6 projects, with NCCIH being a primary contributor.  Dr. Briggs asked the pain consortium reps to consider contributing.

RFA-AT-17-002: NIH-DoD-VA Pain Management Collaboratory - Coordinating Center (U24)
RFA-AT-17-001: NIH-DoD-VA Pain Management Collaboratory - Pragmatic Clinical Trials Demonstration Projects (UG3/UH3)


National Institute of Nursing Research Initiative - Dr. Martha Matocha, NINR

Dr. Matocha provided background on current pain-related funding opportunity announcements. As of the date of this meeting, there were 7 unique announcements that were related to chronic pain including the “Mechanisms, Models, Measurement & Management” funding initiative which is led by NINR.  Although this FOA is broad, it is not framed to include non-pharmacological approaches. Dr. Matocha along with her colleague Dr. Becky Roof are proposing several initiatives that focus on non-pharmacological approaches.

Initiative #1 - Self-management for chronic pain: a biopsychosocial approach

  • Addresses biological, psychological, and social aspects to improve one’s ability to self-manage chronic pain
  • Considers more than pathophysiology; addresses pain at multiple levels of the person
  • Develop interventions that address the physical, psychological and social factors underpinning chronic pain and disability
  • Identify barriers, facilitators, and mediators to optimal self-management behaviors in individuals with chronic pain

Initiative #2 – Symptom Science: Biobehavioral approaches to chronic pain

  • Applies a disease agnostic lens
  • Aimed at characterizing pain phenotype (biological and clinical data) and using tools such as ‘omics’ to identify biomarkers and provide rational targets for biobehavioral interventions
  • Integrate data (clinical, imaging, genomics, patient self-report) to develop predictive models of chronic pain relief/exacerbation
  • Examine associations between phenotype and ‘omic’ profiles as a means to stratify patient groups and tailor chronic pain interventions

Dr. Matocha stated that she was interested in partnering and hearing from other ICs about their interest.  A timeline has not been set yet.  Dr. Porter mentioned that the American Pain Society received funds from Pfizer for two grants in self-management strategies (one in adults and one in children). There are also two projects from the collaboratory that are likely to be funded that are related to self-care.  One representative suggested using common data measures.