Introduction

On June 16, 2020 at 1:30 p.m., a meeting of the Interagency Pain Research Coordinating Committee (IPRCC) convened by WebEx Teleconference. In accordance with Public Law 92-463, the meeting was open to the public. Walter Koroshetz, MD, Director of the National Institute of Neurological Disorder and Stroke (NINDS), presided.

The following members of the IPRCC were in attendance:

Federal Members: David Clark, MD, PhD; Charles G. Helmick, II, MD; Elizabeth Kato, MD
Scientific Members: Daniel B. Carr, MD; Beth Darnall, PhD; Christine Goertz; Robert D. Kerns, PhD; Jose Maron-Concepcion, PhD; Christine Sang, MD; David Williams, PhD
Public Members: George Carter; Katherine Hammitt; Gwenn Herman; Sue Pinkham; Irma Rodriguez
Ex-Officio Members: Helene M. Langevin, MD, CM 
Designated Federal Official: Linda L. Porter, PhD

Call to Order, Welcome and Introductions
Dr. Walter Koroshetz, Chair IPRCC

Dr. Koroshetz welcomed everyone to the meeting and apologized that we could not meet in person. A few people are still going through the approval process and we hope to have a full slate by the next meeting. New members were introduced and gave a brief description of themselves. 

Beth Darnall, PhD is from Standford University with a background in clinical psychology and her research focuses on prescription opioid tapering and behavioral medicine treatments.
Dr. Jose Maron-Concepcion is a professor at Washington University and his laboratory studies the mechanisms underlying addiction and the intersection with pain.
Sue Pinkham is the president of the Coalition Against Pediatric Pain and volunteers with children who have chronic pain issues and their families.
Jim Broatch is a clinical social worker and has been with the Sympathetic Dystrophy Association for over twenty years.
Dr. Christine Goertz is a Professor and Director of System Development and Coordination for Spine Health at the at Duke University. She is also a chairperson on the board of governors of the Patient Centered Outcomes Research Institute (PCORI) and her area of specialty is health services research and pragmatic trials of non-pharmacological approaches for pain management. 
Dr. Elizabeth Kato works for the Agency for Healthcare Research and Quality and works with Arlene Bierman to coordinate substance abuse related activities across the agency.
Dr. Dave Williams is a Clinical Psychologist and co-directs the Chronic Pain and Fatigue Research Center at the University of Michigan. 
Dr. Christine Sang is an adult and child anesthesiologist and acute and chronic post-surgical pain specialist at Brigham and Women’s hospital in Boston, MA.
Irma Rodriquez is a board member of the Interstitial Cystitis Association. 

A group of IPRCC members are officially rotating off in July of 2020, but we may be asking some people to stay on until we get the new slate officially appointed. Returning members were also invited to give a brief introduction.

Dr. Chad Helmick is a medical epidemiologist at the Centers for Disease Control and Prevention in Atlanta where he works on arthritis, lupus and pain issues.
Gwenn Herman is the Clinical Director of Pain Connection programs for the US Pain Foundation. She is a licensed clinical social worker and works with people in pain and has an extensive background working with people with addictions. 
Katherine Hammitt is Vice President of Medical and Scientific affairs for the Sjögren's Foundation. The name was changed from the Sjögren's Syndrome Foundation as Sjögren's can affect any body or organ system and can involve pain in many areas. Neurological pain from peripheral neuropathy or migraine from CNS involvement. It can also include ocular and oral pain because it damages the moisture producing glands in the body. 
Dr. Bob Kerns is a Clinical Psychologist by training and has been a member of the IPRCC for several years. He is a professor at Yale in the Departments of Psychiatry, Neurology and Psychology and his interests are pain and more specifically the psychosocial aspects of pain.
Dr. Dan Carr is from the Tufts University School of Medicine. He has a background in internal medicine, anesthesiology and pain studies. He has been involved in a variety of evidence based guidelines and policy panels.
Dr. David Clark is a Professor of Anesthesiology at Stanford where he has interests in laboratory, translational and some clinical pain research. He is present on the IPRCC as a Federal Member representing the VA where he has been a career employee and investigator. 
Mr. George Carter represents Sickle Cell Virginia that advocates for around 4,000 sickle cell patients in Virginia. 

Dr. Koroshetz introduced the IC Directors and their representatives.
Dr. Helene Langevin is the Director of the National Center for Complementary and Integrative Health. 
To represent Dr. Nora Volkow is Dr. Will Aklin from the National Institute on Drug Abuse. Dr. Aklin directs the behavior, therapies and development program in the division of Therapeutics at NIDA and is the NIDA representative to the NIH Pain Consortium. 
Dr. Jonathan Horsford is the Acting Deputy Director of the National Institute for Dental and Craniofacial Research.

Dr. Koroshetz presented an overview of the Meeting Agenda covering updates on pain activities from IPRCC members, pain initiatives and the NIH and new activity and the challenges that the research community is facing during the COVID-19 pandemic. 

The NIH Pain Consortium Symposium was held virtually and the Videocast is archived on the NIH Pain Consortium website. Dr. Sean Mackey gave a Keynote presentation about technology for improved understanding of pain. The Mitchell Max Award was presented to Dr. Ana Moreno, a young investigator in pain from Novega Therapeutics in San Diego who presented work on using gene editing to suppress sodium channels in the treatment of neuropathic pain.

Dr. Korshetz presented a science advance by Dr. Hua and colleagues using anesthetics to dampen reception then finding which neurons are dampened. It is a nice example of identifying a set of neurons in the brain with the ability to turn the gain up or down on one’s perception of pain. If this could be done in humans, it would be a very powerful way to take away the suffering of people with chronic pain. He also noted that the Kavli Prize went to David Julius, for work on the structure of pain and sense receptors, so the science of pain is moving forward and hopefully therapeutics will follow.

Brief Updates on ongoing and planned programs
Chad Helmick CDC, Elizabeth Kato, AHRQ, David Clark VA; IPRCC Federal Members

Dr. Helmick provided a brief update on Healthy People (HP) 2030.

As a reminder, we had four pain objectives for HP2020 and are down to three, for HP2030, but this is only a 25% reduction compared to the almost 60% reduction of total questions. One of the questions is a core question, and the other two are developmental with ways to measure them so they will become core eventually. He also reminded everyone that there was a big change in how much information is collected on the National Health Interview Survey, which is a survey of the non-institutionalized populations in the United States. The 2019 NHIS added questions about the location and impact of pain, including two questions that are used on HP2020 and questions about pain management, and pain has its own topic area These data will be available in September of 2020. 

Discussion:

The question was asked why the education question was taken out of HP2030. It was decided that the question was not an appropriate objective, because they could not determine a way to measure it. 
A discussion was ensued about the importance of developing a research approach for measuring public awareness of pain. If we can change how people think about pain, we could change a lot of other aspects of pain management.
A question was asked about how the question of how much pain affected activity in the last three months was measured. That particular question was developed by the IPRCC many years ago. The question gets at the idea of High Impact Chronic pain.
The group expressed their appreciation for Dr. Helmicks work.

Dr. David Clark presented an overview of the pain research that goes on in the VA.

The diversity of work is not often appreciated. VA-pain related research is separated into specific areas.

Biomedical Laboratory Research and Development (BLR&D)

• Pain related to neurological disorders such as neuropathy with a focus on pain conditions that are relevant to the types of injuries that are more common with soldiers.

Clinical Science Research and Development (CSR&D)

• Clinical and translational studies in which the VA is involved.

Cooperative Studies Program (CSP)

•  A cooperative studies program that bands together many institutions into large multi-center studies. One example is SCEPTER study, a larg

Health Services Research and Development (HSR&D)

• Evaluation of health services delivery
• Development and testing implementation of evidence-based, non-opioid therapies for acute and chronic pain management.
• Evaluating health services delivery approaches to expand OUD therapies.

Rehabilitation Research and Development (RR&D)

• Focused on rehabilitation form injury and pain is one of the factors that might impact rehabilitation.
• Cover everything from animal to clinical studies on ways to manage pain.

The VA has a very broad set of research interests in pain, from molecule to management.

Discussion:

The group discussed the NIH-VA-DoD collaboratory. It has been funding studies on non pharmacological approaches to chronic pain management. They are phased trials that start with two planning years. So far, all of the studies have transitioned or are close to transitioning, so it has so far been a successful project.
It was discussed that embedding research within a healthcare system such as the VA demonstrates the feasibility of adopting practices within the healthcare system. Several studies look at models of care, and integrating these in the delivery of care is an extension of this research. An implementation science workgroup has been added to the collaboratory to help advance the field. There is also a very strong external board that includes the partners and outside organizations. It is hoped that this will optimize the likelihood that what is learned from the collaboratory will make in into other healthcare settings. The website for the collaboratory can be found at : https://painmanagementcollaboratory.org/ 

Dr. Elizabeth Kato presented an update on AHRQ’s systematic reviews.

Recently completed and available reviews

• Opioid treatments for chronic pain
• Nonopioid pharmacologic treatments for chronic pain
• Noninvasive Nonpharmacologic treatments for chronic pain

 In preparation and should be available for comment later in the summer

• Treatments for Acute Pain
• Treatment of Acute Episodic Migraine

Upcoming reviews -IPRCC members may be contacted for expertise

• Plant-based treatments
• Integrated Pain Management and multidisciplinary multi-modal treatment models.

The digital health division has been working on an electronic system to allow patients and their providers to share information and make pain management decisions. Prototypes should be ready for testing in Spring 2021. These will be apps, but will also be integrated with Electronic Health Records.

HEAL Initiative Update 
Dr. Rebecca Baker, Director NIH HEAL Initiative

Dr. Baker provided an update on the NIH HEAL Initiative. The NIH HEAL Initiative provides an opportunity to improve pain management and reduce the chances of addiction. HEAL stands for Helping to End Addiction Long-term and it is the NIH’s cross-cutting response to the opioid crisis with a major emphasis on pain. The Mission of HEAL is to provide scientific solutions to the opioid crisis. The NIH was given the sustained investment of $500M/year. Dr. Baker provided an overview of the research areas covered by HEAL. Improving treatments for opioid misuse and addiction includes; novel opioid medications, enhanced outcomes for affected newborns, new prevention and treatment strategies and translating research into practice. Pain management includes; pre-clinical and translational research in pain management and clinical research in pain management.
In the preclinical space, the aim is to quickly increase the number of viable programs that have the potential to bring about new therapeutic options. This includes discovery and validation of novel targets, translating discoveries into treatments, preclinical screening platforms and biomarkers, signatures and endpoints for pain. The clinical programs include a number of networks and consortia focused on evaluating treatments and improving pain management.
The HEAL initiative focuses on distributing projects across NIH institutes, and across the United States to provide better solutions for the millions of Americans experiencing pain.
In January, the NIH had the first HEAL Investigators meeting to bring researchers together to enhance collaboration and consider cross-cutting challenges related to pain researchers. The researchers also discussed data sharing and harmonization. The NIH HEAL initiative is working on increasing investigator involvement and connection. The HEAL initiative will be an ongoing effort. Some of the future funding has been set aside for new HEAL projects in future years. 
The HEAL Initiative 2020 funding was focused on addressing gaps in the first rounds of funding. These include understanding the relationship between pain and addiction; addressing opioid use disorder and pain co-occurring with mental health conditions; reducing the stigma of addiction and pain; understanding diversity in care and research; and increasing diversity in the workforce.
There are a series of upcoming HEAL workshops, though they may be changing because of COVID-19.
The priority areas for FY21 include facilitating early therapeutic development for pain, overlapping pain conditions and managing co-morbid chronic pain and opioid use disorder. 
More information, including funding opportunities can be found on the HEAL website.

Discussion:

It was discussed that patient representatives were included in the panel sessions in the meeting. This will be an ongoing priority for the NIH HEAL initiative.  
It was discussed that reducing stigma, requires a measure of the change in public awareness. For example, AIDS and Breast Cancer campaigns must have measured public awareness. This is a focus for HEAL moving forward.
It was discussed that the HEAL initiative is a long-term research initiative. The OUD side of the HEAL initiative includes implementation science including the HEALing Communities studies. In the pain space, we have collaborated with CMS to look at acupuncture. It is an ongoing effort to get the research that comes out of the HEAL initiative into the hands of researchers and policy makers. One of the goals of the PRISM trial includes implementation research. Many non-pharmacological interventions have been in the clinical guidelines, but it is important to do implementation research to help with reimbursement and access. 
It was suggested that the IPRCC is in a good position to encourage inter-agency collaboration and help to emphasize and promote implementation research and improving access. 
Mr. George Carter made the comment that we currently have a lot of people in pain now. This has been dramatized by the fact that many people who require opioids to manage their pain cannot get them. The future is now. What are we doing for these people now? What needs to be done is to advocate for the proper use of what we have now. The CDC guidelines published in 2016 has unfortunately scared a lot of practitioners. We need to work for the proper prescription of opioids until the promised replacements are available. Mr. Carter noted that he has been with the same physician for 30 years and even he has stopped prescribing opioids
The CDC guidelines are being rewritten, and will be coming out in 2021. It is reasonable to advocate to those that are making the recommendations. They are including patients and physicians in the process and are sensitive about how the 2016 guidelines were misinterpreted. 

HEAL Pain Research Priorities
Dr. Walter Koroshetz

Dr. Korshetz presented cross-cutting priorities for future HEAL projects. 

Preclinical priorities

• New Drug targets are addressed by target discovery and validation networks.
• Late stage pipeline platforms have been established for optimizing non-addictive therapies. This is very similar to what a drug company would do but many companies have gotten out the pain field so the NIH felt that it was appropriate to provide assistance.
• To advance translational science, platforms have been set up to establish human cell-based screening platforms. A network of animal models of pain to aid in preclinical screening allowed academics and industries to test compounds and devices.
• The HEAL group is developing a data management center.
• Several studies are working to develop biomarkers for pain.
• BACPAC is an ambitious project to perform deep phenotyping to understand which treatments work for backpain, which is a very prevalent pain condition in this country.
• The BRAIN Initiative and the NINDS portfolio fund a lot of basic science to examine the circuits and mechanisms of pain.

Clinical Priorities

• The common fund Acute to Chronic Pain Signatures program is trying to understand the risk factors for developing chronic pain.
•  A number of clinical trial networks have been established.  A large number of non-pharmacological treatments are being tested.
• Treating pain in people with an opioid use disorder is a gap that will be addressed in the future.
• A number of programs are working to develop biomarkers and clinical endpoints.
• Studying common co-morbidities with pain is a gap to be addressed in the future.

A HEAL Analgesic Development Program is being proposed as part of the pre-clinical pain program.

Goal: Accelerate development of novel, non-addictive analgesics.
Refocusing pre-clinical work to drive towards fining promising new targets that can get FDA approval. Two stages.
Early: Bringing in at least 5 promising therapeutics with the mission to move them to the next stage of development.
Late: Bringing in at least 3 novel analgesics to get to an IND and first stage human testing that are ready for clinical efficacy studies within 5 years.

This program will have an external panel of consultants and there will be advanced coordination. The HEAL initiative has a great deal of expertise that can aid in therapeutic development. The idea is to de-risk new therapy development so that pharmaceutical companies will take on pain projects.
Small molecules and biologics could come into the early stage and promising compounds would move to late stage project where they would prepare it to move to the FDA.
The projects would be fed with planning awards, before moving them to team projects. The teams have access to the expertise of networks to help with success. 
Biomarker work will be done in the project specifically to enable these late-stage projects to move forward and to evaluate them in human trials.

COVID19 effects on pain research 
Dr. Walter Koroshetz

COVID-19 has had a tremendous effect on research across the country. Most laboratories have been shut down since March and the NIH is just preparing to re-open. Much of the clinical work has been shifted to COVID-19 research to look at vaccines and therapeutics. Most non-COVID trials are on hold, but a few are in the planning phases and have been able to continue work preparing to open once possible. The NIH has been given money for COVID-19 research, but to this point nothing has been allocated for helping to get laboratories up and running post-COVID. 
A silver lining that may come from this is that it may help advance telemedicine for both medical visits and clinical trials.  The NIH and others have had success shifting meetings into the virtual space. 
Currently, the NIH is allowing a lot of flexibility in rules and timelines.
Across NIH, there have been extensions for early stage investigator eligibility.
NINDS is extending some training grants and transition awards. 

Discussion:

Is there a potential to gather data on the treatment of COVID, such as intubation as risk factors for the development of chronic pain. It was discussed that a longitudinal study of COVID patients should be done.  The literature shows that some people with acute respiratory distress syndrome have been shown to develop fatigue and chronic pain. Researchers who have received funding are currently dealing with the acute phase, but hopefully we’ll be able to push for the collection of prospective data. NCCIH is especially interested in strategies to mitigate chronic psycological stress and we know that this can worsen long-term pain. Strategies such as telehealth mindfulness interventions may be useful, and there are calls for applications to look at that. NINDS has called for applications to look at neurologic complications. Now is the time to develop a very carefully designed prospective study to look at consequences of COVID.
Pain management collaboratory trials have been disrupted or have been nimble including delivery of virtual care. Developed a measure for participents to asses their experience with COVID. This is being made available for other investigators.

HEAL Pain and OUD Intersection: Workshop Overview
Dr. Leslie Derr, Lead on NIH HEAL BACPAC program, NIAMS

Dr. Derr provided an update on a HEAL workshop Managing Chronic Pain in Individuals with Co-occuring OUD and other Psychiatric conditions. The HEAL Multi Disciplinary Working Group realized that there was not much research on the intersection of the two main areas of focus for HEAL, improving treatment for and prevention of addiction, and improving pain management. This workshop was developed to address this gap as well as the co-occurrence of pain with other psychiatric conditions.

The goals of the workshop were to:

• Understand the current state of the science. 
• Discuss what is needed to optimize or transform treatment approaches.
• Discuss what changes can be implemented within five years.

The workshop included 4 sessions.

1. Setting the stage, discussing topics such as the physical nature of dependence, the biopsychosocial aspects of pain, stigma and healthcare disparities and the patient perspectives.
2. Physical dependence and opioid tapering.
3. Co-morbid chronic pain and OUD
4. Comorbid Alcohol dependence, depression and anxiety.

The next day included breakout sessions to prioritize recommendations. The meeting summary can be found at: https://heal.nih.gov/files/2020-07/HEAL%20PAIN%20OUD%20Workshop%20Summar...

A brief description of recommendations includes:

Opioid Tapering, Physical Tapering Dependence and Multimodal Care

• Engaged patients; multimodal care; safer regarding opioids; equitable care across patient phenotypes/demographics; reimbursable; acknowledgement of heterogeneity at all levels of the system (treatment, reimbursement)

Comorbid Chronic Pain and OUD

• Common transformative goal of breaking down silos to integrated care and improved patient outcomes.

Recurring themes

• Research on individuals with chronic pain and opioid use, and OUD.
• Multidisciplinary and integrated team approach to treatment
• Patient narrative driving treatment
• Adaptive Trial Design
• Implementation Research
• Access to treatment
• Stigma

Discussion:

The group discussed that pain affects all aspects of a person’s life and that many co-morbidities may be a result of the chronic pain. It is important to educate providers and the public to reduce the stigma associated with chronic pain and help people get the care they need. 
Impressions from Participants 

Dr. Darnall and Dr. Kerns shared their perceptions of the meeting as participants.

• The meeting had a very strong focus on the multi-dimensional aspects of pain across the spectrum of OUD. 
• The meeting had a strong focus on patient centered care.
• There is sufficient evidence to show that many non-pharmacological treatments help with chronic pain and it is important to focus on implementation science so that people have access to treatments.
• Accessing many non-pharmacological and behavioral treatments that are multi-session are a burden for patients and are not accessible for many patients.
• There was a focus on patient centeredness with regards to opioid prescribing and deprescribing. It is important to keep medications accessible to patients that need them.
• It is important to recognize the risk of changing a dose of opioids. When a patient’s dose of an opioid is changed, or the use is discontinued it is important that it is helping the patient. 
• Pain is often part of a complex and multidimentional
• We focus a lot on treatment outcomes, but do not focus enough on cost and feasibility so we need to shift the focus to make sure that treatments are 
• It is best to think about the person with co-ocurring conditions rather than only pain
• It’s best to assess and treat the person who has chronic pain and the multi-dimensional experience of pain rather than focusing on the pain itself.
• We need to change the way that we think about the ways of delivering care for pain and substance use disorder. Patients need to be treated as individuals. 
• This approach is articulated in the National Pain Strategy and the Institute of Medicine report.    

INTEGRATE Pain, collaboration with the IMI (EU)
Dr. Laura Wandner, Office of Pain Policy and Planning NINDS

Dr. Wandner provided an overview of IMI Paincare and the INTEGRATE-Pain Initiative, a consortium of NIH representatives and members of IMI Paincare.
IMI PainCare is composed of a public, private partnership of forty participants from fourteen countries, working in academia and the pharmaceutical industry.
Representatives of IMI PainCare and the NIH noted that  a meeting is being planned for August.

Dr. Wandner discussed the goals of the three INTEGRATE-Pain Subgroups.

Pre-Clinical Subgroup:

• Identify gaps and develop programmatic ideas for collaboration.
• Multi-center preclinical trials for therapeutics.
• Closely work with the other subgroups to facilitate back-translation.

Clinical Subgoup:

• IMI PainCare and the NIH will compare the process of selecting important pain domains and patient reported outcomes for IMI PainCare and the NIH Heal Initiative.
• Discuss Biomarker Studies.

NIH-EU/Pharma Subgroup

• Support HEAL initiative pipelines to increase the number and quality of assets.
• Interact jointly with the European Commission.

The INTEGRATE Pain Symposium will be presenting a virtual Symposium at IASP.
A virtual meeting is being planned for August to discuss scientific ideas with the goal of improving workgroup discussion. 
A description of the symposium is available on the NIH HEAL and IMI websites. 

Approval of Minutes and Closing Comments:

The minutes from the November meeting were approved with minor revisions.

Gwen Hermann shared that with all the initiatives described it is important to included patients in all steps of the development.

With no public comments, the meeting was adjourned. 

 

We certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.

Linda Porter, PhD
Designated Federal Official
Interagency Pain Research Coordinating Committee
Director, Office of Pain Policy, National Institute of Neurological Disorders and Stroke
 
Walter Koroshetz, PhD
Chair Interagency Pain Research Coordinating Committee
Director, National Institute of Neurological Disorders and Stroke
 
These minutes have been formally approved by the committee.