IPRCC Meeting - 11/18/2019

Administrative Note: This meeting summary was prepared by Alison Davis, Rose Li and Associates, Inc., under contract to the National Institute of Neurological Disorders and Stroke (NINDS). The views expressed in this document reflect both individual and collective opinions of the meeting participants and not necessarily those of NINDS. Review of earlier versions of this meeting summary by the following individuals is gratefully acknowledged: Nancy Tuvesson.

Introductory Remarks

Walter Koroshetz, MD, Director of the National Institute of Neurological Disorders and Stroke

Dr. Walter Koroshetz, Director of NINDS and Chair of the Interagency Pain Research Coordinating Committee (IPRCC), opened the meeting and recognized the ongoing diligent efforts of the NINDS Office of Pain Policy and Planning. He noted that several IPRCC member nominees are still awaiting formal appointment, and he thanked IPRCC member Dr. Martha Somerman, who is retiring from her NIH leadership role as Director of NIH’s National Institute of Dental and Craniofacial Research. Dr. Linda Porter, Director of the Office of Pain Policy and Planning and IPRCC Executive Officer, requested and received IPRCC approval of the May 2019 IPRCC meeting summary.

The following IPRCC members were in attendance:

• Federal Members: David Clark, MD, PhD; Charles G. Helmick, II, MD; Sharon Hertz, MD; Walter Koroshetz, MD; Martha J. Somerman, DDS, PhD 
• Scientific Members: Daniel B. Carr, MD; Beth Darnall, PhD;  Christine Goertz, DC, PhD;  Robert D. Kerns, PhD; Jose Moron-Concepcion, PhD; Christine Nai-Mei Sang, MD, MPH; David A. Williams, PhD 
• Public Members: James Broatch; George Carter; Katherine Hammitt; Gwenn Herman; Sue Pinkham
• Ex-Officio Members: Will M. Aklin, PhD (NIDA); Tara Schwetz, PhD (NINR)
• Designated Federal Official: Linda L. Porter, PhD

IPRCC Overview

Walter Koroshetz, MD, Director, NINDS and Linda Porter, PhD, Director, NINDS Office of Pain Policy and Planning and IPRCC Executive Officer

The 2010 Patient Protection and Affordable Care Act required the Department of Health and Human Services (HHS) to enlist the Institute of Medicine (IOM; now the National Academy of Medicine) to examine pain as a public health problem via (1) convening the IOM Conference on Pain (which culminated in the 2011 publication of Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research) and (2) establishing the IPRCC to coordinate all efforts across federal agencies and other departments that support research related to pain. The IPRCC first met in 2012 and since then has convened routinely. The IOM report articulated the need to “develop a comprehensive, population health-level strategy for pain prevention, treatment, management, education, reimbursement, and research that includes specific goals, actions, time frames, and resources,” which in 2016 resulted in issuance of the National Pain Strategy (NPS), “the government’s first broad-ranging effort to improve  how pain is perceived, assessed, and treated: a significant step toward the ideal state of pain care.” The NPS employs a multifaceted approach spanning six areas: population research, public education, professional education, services and payment, prevention and care, and disparities. In 2017, the IPRCC announced the follow-on Federal Pain Research Strategy. This long-term strategic plan involves the efforts of scientific experts, patient advocates, and federal representatives to identify and prioritize research recommendations to coordinate and advance the federal pain research agenda as well as to “make recommendations to ensure that the activities of the National Institutes of Health and other Federal agencies are free of unnecessary duplication of effort.” The interagency IPRCC investment is reflected in the  IPRP Data Base, a tool for ongoing, thematic portfolio analyses through coded terms such as “risk factors;” “use of services, treatments, and interventions;” “basic to clinical;” and others, including “pain mechanisms” (which currently has received the majority of funding). Annual reports of pain-related science advances are posted on the IPRCC website to increase public and scientific awareness of the impact of federal spending on pain research.

Support Act and Expanded IPRCC Mandates

Linda Porter, PhD, Director, NINDS Office of Pain Policy and Planning and IPRCC Executive Officer

Per the 2010 federal mandate, Congress reauthorizes the IPRCC every 2 years. The IPRCC charter was recently revised according to the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act, expanding the original IPRCC mandate. Three key additions include: (1) summarizing advances and best practices for nonpharmacological treatments and non-addictive medical products and other drugs or devices approved by the U.S. Food and Drug Administration (FDA); (2) identifying gaps in clinical research, especially related to biomarkers, screening models, epidemiological data on acute and chronic pain, and risk factors/early warning signs for substance use disorders (SUDs, presumably including those related to tobacco and alcohol) in people with acute or chronic pain; and (3) making recommendations directly to the NIH Director on how best to disseminate information about care and epidemiological data related to acute and chronic pain. The IPRCC continues to consider and address the responsible use of opioids, and as mandated by the SUPPORT for Patients and Communities Act, FDA has issued guidelines on tapering opioid dosing. The U.S. Agency for Healthcare Research and Quality (AHRQ) is developing a comprehensive review of nonpharmacological treatments for pain, which will be released in early 2020. The NIH Helping to End Addiction Long-term (HEAL) initiative is investing in research to understand pain treatment in people with a history of SUDs. 

Support Act and FDA Mandate to Develop Evidence-Based Opioid Analgesic Prescribing Guidelines for Indication-Specific Treatment of Acute Pain

Sharon Hertz, MD, IPRCC Representative from FDA

Prescription pain reliever misuse remains a serious health problem in the United States, especially among young adults. According to the 2018 National Survey on Drug Use and Health, of the 9.9 million people ages 12 and older who misused prescription pain relievers in the past year, the vast majority obtained them from a friend or relative. A 2017 study concluded that 50 percent of people reported excess supply of opioid analgesics after post-surgical treatment of acute pain; many people are hesitant to give up medications they anticipate needing at a later date. Non-secure storage and lack of disposal increase access by other individuals. States are addressing the issue of excess supply in blunt ways. More than 20 states have passed legislation limiting opioid prescription duration to 1 week or less, and some states (e.g., Oregon) have proposed tapering chronic-pain patients receiving Medicaid support to opioid doses of zero beginning in 2020. Other practices, such as manufacturing quotas, do not account for variation among individuals, conditions, or reasons for use—and as such may lead to inadequate treatment of pain or other negative unintended consequences, such as suicide. 

The SUPPORT for Patients and Communities Act (H.R. 6) became law in October 2018. Under Section 3002 of SUPPORT, FDA is tasked with developing evidence-based, opioid analgesic–prescribing guidelines for the indication-specific treatment of acute pain for therapeutic areas without such guidelines. With assistance from a contract with the National Academies of Science, Engineering, and Medicine (NASEM), FDA is developing a framework for writing these prescribing guidelines. One strategy is to collaborate with professional societies to develop evidence-based guidelines for different medical indications. Two 2019 NASEM workshops have explored ways to prioritize surgical procedures and medical conditions for which opioid analgesics are prescribed and considered clinically necessary, as well as to articulate research needs for filling evidence gaps. FDA is also taking other additional actions including clarifying its regulation of non-addictive pain products and post-market authorities; expanding distribution and recall authority for controlled substances; reviewing the effectiveness and impact of abuse-deterrent opioid formulations; restricting entrance of illicit drugs; and mandating safety-enhancing packaging/disposal systems to mitigate potential abuse. For example, FDA is making available blister packs containing fewer (<30) immediate-release opioid tablets toward “right-sizing” delivery of acute-pain treatment. 

Discussion Points

• Racial bias in prescribing practices can also affect access, storage, and distribution of unused drugs.
• Application of population-based prescribing methods by definition leaves 10 percent of people undertreated.
• Defining prescribing practices by procedure overlooks several sources of variation; for example, by individual and by institution. 
• The Pain Management Best Practices Inter-Agency Task Force issued recommendations in May 2019 that address gaps or inconsistencies for managing chronic and acute pain.
• FDA established a Risk Evaluation and Mitigation Strategies program for opioid analgesics.

Healthy People 2030 Pain Objectives

Chad Helmick, MD, IPRCC representative from CDC

Healthy People (HP) 2020 designated a set of national health objectives: (1) attain high-quality, longer lives free of preventable disease, disability, injury, and premature death; (2) achieve health equity, eliminate disparities, and improve the health of all groups; (3) create social and physical environments that promote good health for all; and (4) promote quality of life, healthy development, and healthy behaviors across all life stages. HP2020 also includes four developmental objectives for pain: (1) decrease the prevalence of adults having high-impact chronic pain; (2) increase self-management of high-impact chronic pain; (3) reduce impact of high-impact chronic pain on family/significant others; and (4) increase public awareness/knowledge of high-impact chronic pain. The National Health Interview Survey (NHIS) has monitored the health of the nation since 1957, to identify and address evolving health trends. These questions have helped define pain experiences more precisely—an important task based on significant interindividual variation of pain sensation and reporting. The HP program relies upon NHIS data, which were reported in 2018 in the widely read Morbidity and Mortality Weekly Report, noting that chronic pain affects 50 million adults (21 percent of the U.S. population) and that high-impact chronic pain affects 20 million adults (8 percent of the U.S. population). 

Development of the HP 2030 objectives is under way, and the overall number of objectives has been reduced by about 30 percent. The fourth pain objective to increase public awareness has been eliminated, and the NHIS time horizon for assessing/reporting pain experiences was changed slightly from 6 months to 3 months. The NHIS underwent a major redesign in 2019 to feature content to be included annually as well as content that will rotate on and off the questionnaire with a pre-established periodicity. The new NHIS adult survey will feature rotating content questions on chronic pain every 2 years, including the addition of 10 NHIS questions each for pain and pain management, reflecting a significant focus upon pain in HP2030. Notably, these questions aim to measure functional outcomes of pain (e.g., effect on life, work, relationships) as well as pain location (body region). An additional significant change from HP 2020 to HP 2030 is the elevation of pain as its own topic area (along with arthritis and osteoporosis). 

Discussion Points

• In addition to pain statistics, stories about how people are living with pain are important. Clear messaging resonates with stakeholders of all types.
• Pediatric pain is not included in HP objectives and thus not assessed on a national scale despite some existing and limited surveys. 
• The proposed HP 2030 pain-management questions do not address medications (although the opioid-use questions do). 
•  Stakeholder engagement and representation is important for informing policy: what proportion of people writing guidelines (e.g., CDC guidelines) have ever experienced serious pain?
  • As a result, some CDC guidelines may not reflect the reality of people who experience specific types of pain, such as that associated with sickle-cell disease (SCD). 
  • Some U.S. subpopulations are disproportionately affected by certain types of pain, and they do not always have a voice in shaping effective guidelines and their implementation.
  • The current CDC guidelines will be re-reviewed in 2021, offering an opportunity to include more pain patients in the discussions.

Update on HEAL Clinical and Preclinical Pain Research Programs

Walter Koroshetz, MD, Director, NINDS

In FY 2019, NIH funded $945 million in research (~375 awards across 41 states) through the NIH HEAL initiative. This research investment covers multiple pain conditions, including diverse strategies for addressing opioid use disorders (OUDs) and pain treatment. Future HEAL funds have been embedded into the NIH base budget ($250 million annually for several years to support existing awards and to make room for new funding opportunities in future years). The first round of HEAL funding occurred very rapidly for both NIH and applicants, and FY 2020 and FY 2021 funding will aim to address opportunities missed with the FY 2019 awards. The HEAL initiative addresses both pain management and treatments for misuse and addiction, and it extends from discovery projects to implementation and dissemination efforts. Examples of funded research include the following:

• The NIH Common Fund’s “Acute to Chronic Pain Signatures” program aims to follow patients with onset of acute pain from surgery or trauma to develop signatures predictive of transition versus resilience to chronic pain . Of two planned cohorts across multiple sites, the first cohort will include people who have received a total knee replacement, and the second (pending) may include people with peri-operative pain or musculoskeletal trauma.
• The “Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain” program seeks to accelerate the scientific discovery and/or validation of novel treatment targets for acute and chronic pain conditions. These 22 awards are investigating a wide array of pain targets in circuits within primary sensory nerves, dorsal root ganglia, trigeminal ganglia, the spinal cord, and the brain.
• The “Preclinical Screening Platform for Pain” program aims to identify and profile non-addictive therapeutics for pain by evaluating assets submitted by the research community: (1) test potential non-addictive treatments for acute pain, (2) develop and acquire animal models that more closely mimic human pain conditions, and (3) use these models to test and characterize promising non-addictive therapeutic strategies.
• The “Early Phase Pain Investigation Clinical Network” (EPPIC NET) program is a network to advance new treatments for pain by conducting early-phase clinical trials with adults and children. It consists of 12 specialized research hubs, a clinical coordinating center, and a data coordinating center.
• The “Pain Management Effectiveness Research Network” (ERN) is a multi-institution effort to conduct phase 3 clinical trials for efficacy of pharmacologic and nonpharmacologic therapies for acute and chronic pain. Behavioral interventions are a particular focus of ERN trials.
• The “Pragmatic and Implementation Studies for the Management of Pain” (PRISM) program is conducting clinical research in real-world settings to integrate evidence-based interventions into health care systems.

Discussion Points

• The same pain populations continue to be studied; there is a need to expand clinical investigations both to additional subpopulations and to people suffering from less-commonly studied conditions. 
• Several non-NIH federal agencies were involved in HEAL planning, including the U.S. Centers for Medicare and Medicaid Services, FDA, Department of Defense, and Department of Veterans Affairs.
• The IPRCC database includes research investments across federal agencies. Creative use of data visualization tools may help various stakeholders understand and potentially evaluate the multiple types of funding and topics funded across the federal pain research investment.

HEAL Scope and Diversity

Danielle Haney, PhD, Policy Analyst, NINDS Office of Pain Policy and Planning and Michael Oshinsky, PhD, NINDS Program Director

The HEAL research portfolio was assessed to determine diversity and scope within and across programs—toward identifying redundancy and locating gaps. In the clinical arena, current studies are investigating various conditions including musculoskeletal pain, procedural pain, chronic pain, SCD pain, neuropathic pain, cancer pain, chronic low-back pain, and comorbid pain/OUD. HEAL investigators will convene in January 2020 to discuss this last topic. The broad range of projects identified through portfolio analyses of the investment include e-self-management, mindfulness, and prognostic and diagnostic biomarkers. For preclinical and translational work, several studies across pain types (and Institute and Center funding) are uncovering several new targets, and various devices are being tested for a range of pain applications (many through the federal Small Business Innovation Research program or as cooperative agreements). Some of these are optimization projects that aim to accelerate the “hit-to-lead” process for testing in humans. To leverage existing data sets, the NIH Common Fund’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) program aims to accelerate development of therapeutic devices that modulate electrical activity in nerves to improve organ function. SPARC projects span a range of organs in multiple mammalian model systems: a January 2019 meeting gathered community input on best practices for preclinical research on pain.

Discussion Points

• NIH is beginning to see some applications regarding the effects of the microbiome on pain. 
• Despite aggressive efforts to publicize NIH funding opportunities, many potential applicants are underinformed, which can limit the range of projects and topical areas that can be funded. 
• Pain and pain management in long-term opioid users is an underfunded area.

Discussion of HEAL Pain Research Portfolio

Daniel Carr, MD and Robert Kerns, PhD, Scientific Members, IPRCC

Data

A contractor was hired to provide advice on establishing a data center to manage the disparate types of findings derived from HEAL research. Under construction, this data center will collate all data from individual projects and make them publicly available to researchers, including those beyond the HEAL research community. Some exceptions include data from clinical trials that cannot be released immediately and certain projects with their own data centers. A data platform and data policy are in place (stipulating immediate publication and release), and pre-publication data sharing is encouraged. Ongoing discussions are refining criteria for minimal data elements that can enable secondary studies and meta-analyses. Discussions are also under way about the capture of negative data (e.g., unused industry compounds). 

Funding Announcements

There is widespread agreement that the FY 2019 HEAL funding period (from announcement to awards) was difficult for everyone to navigate, based upon the extremely tight window of time for all steps of the process to occur. Similar time constraints will cause struggles for FY 2020 awards, but the FY 2021 funding cycle is expected to be more manageable. 

Research Gaps

Despite intense efforts by NIH staff and leadership, many researchers remain unaware of funding opportunities. This problem is not limited to the HEAL initiative. NIH is considering ways to use evidence-based, unbiased algorithms to conduct gap analyses. To this end, establishment of the IPRCC database has been helpful, as would creative use of text-mining tools to guide research priority-setting (NIH’s Office of Portfolio Analysis has this expertise). There is great interest in involving affected populations more directly in shaping the pain research agenda. Additional steps might go beyond traditional indicators such as disease burden (number of people affected and money spent) to ensure representation for all pain-affected conditions.

Pain Measurement

Although the analgesic research and treatment community remains interested in use of a pain-intensity index, there has been a shift toward measuring functional impact. Many researchers and clinicians focus instead on the frequency and intensity of interference with life activities, employing function-based pain scales. Moreover, many clinicians help individuals set personal goals, toward individualized care rather than universal practices. Additional education for providers might expand use of function-based pain scales.

New Targets and Repurposed Treatments

Ketamine has emerged as a useful agent for various conditions, including depression, anxiety, and pain. However, advancing testing and use into new clinical areas remains difficult because ketamine is off-patent and thus an unattractive commercial prospect. FDA has started a process to integrate biomarkers into clinical trials, and the newly funded HEAL initiative program, Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions  should promote progress in this area.  

FDA Research to Support Development of Guidelines for Acute Pain Management

Sharon Hertz, MD, IPRCC Representative from FDA

Under Section 3002 of SUPPORT, FDA is tasked with developing evidence-based, opioid analgesic–prescribing guidelines for the indication-specific treatment of acute pain (for therapeutic areas without such guidelines). The agency is conducting several projects to inform this process, four of which are described briefly below.

• A project at the University of Pennsylvania aims to develop and implement an innovative and scalable approach for patient-centered, opioid-prescribing guidelines for specific procedures associated with acute pain in orthopedic, neurosurgery, and emergency medicine settings. An automated text-messaging platform will collect data on patient-reported outcomes and opioid consumption, toward generating electronic health record (EHR) prescribing defaults across specialties.  
• Another project used 2014 claims-based data (preceding prescribing limits) from a large U.S. nationwide commercial insurer to investigate the relationship between the number-of-days initial supply of opioid analgesic prescriptions and refills in a primary-care setting across a range of pain conditions. The findings highlight the need to tailor prescribing strategies to individuals and conditions because the adjusted probability of a refill varied considerably across conditions but the initial prescriptions of ≤7 days’ duration were generally sufficient for many people.
• A third project reviewed postsurgical opioid analgesic refills in Sentinel, FDA’s distributed data system and also found substantial variation (ranging from a few days to a few weeks) in the relationship between post-procedure days’ supply and probability of refill. This study assumed that a 20 percent refill rate was an adequate target but recognized the consequent undertreatment of some individuals whose circumstances may not be representative of population averages. 
• A new project about to get under way is the “FDA/Yale-Mayo Clinic Centers of Excellence in Regulatory Science and Innovation Collaboration.” This project will collect real-world evidence to understand the relationship between prescriber-usage instructions, amount dispensed, and actual-use patterns of short-acting opioid and non-opioid analgesics. Data will be collected (and linked to EHRs and pharmacy data) via a novel patient-centered health data-sharing platform (a mobile-device application, “Hugo”).

Discussion Points

• Individuals have distinct features that affect pain and health outcomes. For example, a dental extraction may be very different in an individual with an autoimmune condition that affects oral health. 

• The use of automated data-collection systems (and EHR data) poses limitations including an inability to monitor actual patient behavior (vs. pharmacy data), to monitor cash purchases, and to distinguish refills for a different condition rather than evidence of more need to manage surgical pain.
• Employing a public-health lens is important for looking beyond physiological substrates. Also contributory are host-, environmental, and social factors.

NIH Common Fund Health Care Systems Collaboratory—Collaborative Care for Chronic Pain in Primary Care

Lynn DeBar, PhD, Kaiser Health Research

The NIH Health Care Systems (HCS) Research Collaboratory was developed by the NIH Common Fund in 2012 and is administered by the National Center for Complementary and Integrative Health and the National Institute on Aging. Its goal is to engage health care delivery organizations, such as clinics or hospitals, as research partners in the conduct of pragmatic clinical trials. Overall objectives of this approach, as related to pain management, include scaling and sustaining nondrug approaches to chronic pain management in routine clinical care. Doing so involves complex challenges around engaging primary-care providers and aligning insurance benefits and available services with the most effective and safe evidence-based treatments—recognizing that health care systems are complex, adaptive systems. In current health care environments, primary-care providers experience burnout, in large part from an increasing number of administrative tasks and reimbursement challenges. Moreover, pain is the primary reason that patients seek medical care, and primary-care providers are typically the first point of contact with such patients despite lack of specific training in pain medicine.

PPACT is a large-scale pragmatic clinical trial (850 patients) conducted in three regions of Kaiser Permanente health systems: Northwest, Georgia, and Hawaii (which reflect real-world variation in staffing, pain cases, and other variables). The PPACT trial is evaluating integration of different kinds of pain-management services within a primary-care environment compared with usual care in the same settings. The trial combines several treatment approaches, including physical therapy and psychological interventions, and has a per-patient intervention cost of ~ $2,000. Patients (many of whom have multiple conditions including depression and posttraumatic stress disorder) were encouraged to assume a more active role in managing their pain, and primary-care providers received additional support and guidance in treating patients with chronic pain. Outcome measures include assessment of pain (using the PEG scale), opioid medication use, receipt of benzodiazepines, pain-related health services, and cost. Results showed a modest decrease in both pain score and benzodiazepine receipt but no independent effect on opioid use. Pragmatic clinical trials are by nature complex, and they also exist within the backdrop of a very dynamic health care landscape. As such, assessment of outcomes is difficult because of the various real-world confounding variables. The “mind/body separation” in health care systems and associated issues related to stigma remains a persistent challenge for clinical studies of chronic pain: Multi-level stakeholder engagement is a critical component for efficient and effective operation of pragmatic clinical trials. In summary, PPACT findings indicate that primary care-embedded behavioral treatment can achieve sustained impact in patients with chronic pain, yet caveats include variability in local/regional health care systems and the fact that stakeholder engagement is complex and time-consuming but important for success at various levels. Successful implementation of integrated care must appreciate local needs and practices: (1) employing automation and technology (e.g., telehealth) for tasks amenable to it, (2) being flexible about types of conditions and staff available to deliver treatments, and (3) empowering both patient and provider in self-care and harnessing the placebo effect, respectively. It may be, for example, that patients could choose from an array of placebo interventions (with similar effect sizes) based upon personal preference, potentially enhancing their efficacy. Wide adoption of integrative modalities will likely hinge on contextual application of components that are effective in certain settings and continued efforts to destigmatize nonpharmacological treatment approaches.

The Patient-Centered Outcomes Research Institute’s Investment in Pain and Opioid Research

Penny Mohr, Senior Advisor, PCORI

The mission of the Patient-Centered Outcomes Research Institute (PCORI) is to help people make informed health care decisions and to improve health care delivery and outcomes by producing and promoting high-integrity, evidence-based information from research guided by patients, caregivers, and the broader health care community. As part of the pain ecosystem, PCORI activities complement those of federal agencies—addressing acute pain, chronic pain, the transition from acute to chronic pain, as well as cross-cutting areas. PCORI’s primary approach is comparative effectiveness research (CER), and through intensive stakeholder-driven processes, it has identified two strategic priorities: chronic pain (as of November 2019 investing $189 million in 43 CER studies, including those on acute pain) and the opioid crisis ($135 million, 28 CER studies). PCORI employs a patient-centered, multi-pronged approach to addressing both areas and spanning the care continuum from prevention treatment of OUD. PCORI-funded studies are usually quite large, address questions at multiple levels (i.e., policy, provider, patient), and include patient-centered outcomes such as pain, function, and quality of life. There is a concerted effort to include understudied populations including those with co-occurring mental-health disorders and SUDs. PCORI funds several types of research projects, including investigator-initiated studies, targeted projects, and pragmatic clinical trials. PCORI has learned of the value of early and continued stakeholder engagement, beginning with workshops to shape research priorities. PCORI has observed enhanced dissemination of study results through inclusion of patients as part of research teams. Examples of PCORI-funded studies for acute pain, chronic pain, and cross-cutting areas are described below.

Acute Pain

• The “Provider-Targeted Behavioral Interventions to Prevent Unsafe Opioid Prescribing for Acute Non-Cancer Pain in Primary Care” study is using a CER approach to test provider-targeted behavioral interventions using EHR-based prompts, feedback, and alerts. The goal is to prevent unsafe opioid prescribing, encourage non-opioid management, and improve pain in patients with acute non-cancer pain. Results are expected in March 2021.
• The “Life STORRIED” study is using a CER approach to assess enhanced opioid-risk communication strategies for pain management after acute care. Results are expected in January 2020.

Chronic Pain

• The “Pain-Cognitive Behavioral Therapy and Chronic Pain Self-Management Within the Context of Opioid Reduction” study will use a patient-centered approach to voluntary opioid reduction in combination with nonpharmacologic behavioral treatments to improve pain management. Results are expected in February 2024.
• The “SMART LBP: Optimized Multidisciplinary Treatment Programs for Nonspecific Chronic Low Back Pain” study is comparing the effectiveness of first-line treatments for chronic low-back pain and determining what sequence of treatments is most beneficial for patients who do not respond to the first treatment attempted. Results are expected in March 2025.

Cross-Cutting Areas

• The “Evaluating the Impact of Medicaid Reimbursement Changes on Opioid Prescribing and Patient Outcomes Among Patients with Low Back Pain” study is evaluating state Medicaid policies (comparing Oregon and California) that limit access to long-term opioids for the treatment of low-back pain while expanding access to alternative, evidence-based nonpharmacologic therapies. Results are expected in January 2024. 
• The “National Patient-Centered Clinical Research Network” (PCORNet) is a network of networks with access to secure, curated data from millions of patients across the largest health systems in the United States. It can be used by researchers nationwide, and various stakeholders (i.e., patients, caregivers, researchers, clinicians, health plans, and health system leaders) all play key roles in its development and ongoing activities.

HEAL and Other Pain Research: Gaps and IPRCC Observations and Recommendations

Daniel Carr, MD, Scientific Member, IPRCC

The moderated group discussion attempted to synthesize the day’s discussions into articulation of pain research gaps. 

1. There is a need for a shift in the way pain, which is often an invisible condition, is conceptualized and addressed in the United States. A large diversity of stakeholders affected by pain—patients and caregivers, providers of various specialties, payers, and various public audiences including the media—contribute to both our understanding of pain and its impacts as well as our collective ability to manage those impacts. Issues to consider include viewing pain and pain management through the lenses of individuals, populations, and conditions (and multiple, co-occurring conditions). Such considerations will affect the study and development of tailored approaches rather than universal policies that currently have an uneven impact on targeted beneficiaries. Developing and promoting common standards and an understandable, simplified, yet precise nomenclature for pain (including increased adoption of function-based pain scales) could improve communication between patients and providers, and intermediary audiences such as the media. Also helpful might be novel data visualization tools to convey stories and statistics graphically, such as “the neuroscience of pain” that blends basic science, clinical conditions, psychosocial components, and integrative modalities. Two particularly pressing areas include achieving (1) a broader consensus (and its communication) of the continued need for opioid therapy among certain individuals and pain populations and (2) reduced stigma around use of evidence-based nonpharmacological approaches. These gaps cannot be filled without consideration of the roles of service delivery and reimbursement, that is, where “the rubber hits the road.” Publication of early results of PCORI studies, if appropriate based on study design, may also be beneficial.
2. Related to promoting a deeper national appreciation of pain and its impacts is understanding the role of variation through study of subpopulations and a multitude of conditions that feature pain. Because social determinants of health are known to affect pain development and treatment response, research should assure that vulnerable populations are studied as well as consulted about their experiences with pain and sequelae. Pediatric populations remain underserved by pain research, although some emerging and academically led collaborations are beginning to address this gap. Of urgent importance is a focused research effort to study co-occurring pain, mental-health conditions, and SUDs (particularly OUD). The interplay of these factors in real-world settings may be best understood through collaborative-care models, likely in primary-care settings.
3. Enhanced stakeholder engagement, especially during the process of setting research priorities, will likely help to fill both gaps described above. Patients in particular can convey the multifaceted effects of pain, on not only biology but also mental health, functionality, and interpersonal relationships. These efforts will likely increase return on investment by expediting dissemination of results (and myth-busting where relevant). NIH currently addresses stakeholder concerns through the HEAL initiative’s multidisciplinary working group and by hosting many workshops open to the public.
4. The field should continue to study and define basic mechanisms of pain (e.g., through “natural” studies of anesthesia/nociceptive block, microbiome, cultural trauma, and other topics). New preclinical models are needed (HEAL is addressing this).
5. Continued attention to safety in addition to efficacy for pain-management strategies is important, especially toward the intersection of pain, OUD and abuse of other substances, and psychiatric conditions.

No public comments were submitted. The meeting was adjourned.