IPRCC Meeting - 11/23/2020

Interagency Pain Research Coordinating Committee

 

November 23, 2020

Virtual Meeting

Introduction

On November 23, 2020, at 11:00 a.m., the Interagency Pain Research Coordinating Committee (IPRCC) convened for a virtual meeting. In accordance with Public Law 92-463, the meeting was open to the public. Walter Koroshetz, MD, Director of the National Institute of Neurological Disorders and Stroke (NINDS), presided as chair.

The following IPRCC members were in attendance:

• Federal Members: David Clark, MD, PhD; Rena D’Souza, DDS, PhD; Charles G. Helmick, II, MD; Elisabeth Kato, MD; Walter Koroshetz, MD; Helene Langevin, MD; Rigoberto Roca, MD; Shannon Zenk, PhD, RN
• 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; Irma Rodriguez
• Ex-Officio Members: Will M. Aklin, PhD (NIDA)
• Designated Federal Official: Linda L. Porter, PhD

Approval of Previous Minutes and General Updates

Linda Porter, PhD, Director, Office of Pain Policy, NINDS

Approval of Previous Minutes

IPRCC members voted to approve the minutes from the IPRCC’s previous meeting.

The U.S. Association for the Study of Pain

Dr. Porter reported that a new organization, the U.S. Association for the Study of Pain, has been established, in part to compensate for the 2019 closure of the American Pain Society. The U.S. Association for the Study of Pain aims to promote scientific advances that reduce the burden of pain. It will hold its inaugural meeting, titled “Transforming Pain Science and Care in Challenging Times,” on December 9-11, 2020.

NIH Common Fund Acute to Chronic Pain Signatures Consortium

Dr. Porter described the NIH Common Fund’s Acute to Chronic Pain Signatures consortium, which aims to discover objective biosignatures to predict susceptibility or resilience to developing chronic pain. Focused on patients with acute postsurgical pain (i.e., from either thoracic surgery or total knee replacement), the consortium will perform phenotyping/genotyping and sensory testing and will collect imaging and multiomics data (e.g., genomics, proteomics, lipidomics, and metabolomics) to identify predictors of acute-to-chronic pain transition, discover novel mechanistic therapeutic targets, and enable cohort stratification in support of clinical trials for the prevention of chronic pain. During the coming months, Institutional Review Board (IRB) approvals will enable the consortium’s Clinical Coordinating Center to begin work with two Multisite Clinical Centers (one for each type of surgery), a Data Coordination Center, three Data Generation Centers, and a Data Integration and Resource Center to provide data to the broader pain research community that will then mine the data to discover acute-to-chronic pain signatures. COVID-19 closures have delayed the launch of this consortium, but most infrastructure is in place and launch will occur when relevant academic centers receive approval to begin patient enrollment.

HEAL Initiative Updates

Walter Koroshetz, MD, Director of NINDS

Dr. Koroshetz presented an update on the National Institutes of Health (NIH) Helping to End Addiction Long-term (HEAL) Initiative. HEAL aims both to lessen the burden of pain across the United States and to ameliorate the opioid crisis. It includes several clinical programs to help advance pain research. These programs include the Effectiveness Research Network (ERN), a network of comparative effectiveness clinical trials mainly conducted by academic centers; the Pragmatic Studies for Pain Management Without Opioids (PRISM) program, which investigates nonpharmacological treatments for pain primarily within health care systems; and the Analgesic Development Program, which is a newly structured effort to generate novel nonaddictive pain therapeutics.

Dr. Koroshetz also summarized the topics to be covered during the 2021 NIH Pain Consortium Symposium and expressed confidence that the HEAL Initiative’s budget would be sustained by the U.S. Congress.

Effectiveness Research Network

Dr. Koroshetz displayed a list of ERN clinical trials that are expected to launch soon. With sample sizes ranging from 160 to 5,500 patients, these trials will investigate acute pain in adolescents, chronic pain in rural populations of older adults, knee osteoarthritis, chronic pain among veterans with opioid use disorder (OUD), acute pain among new mothers following Cesarean section, chronic pain in cancer survivors, chronic post-mastectomy pain syndrome (PMPS), and chronic musculoskeletal pain. Although the COVID-19 pandemic delayed the launch dates of these studies, Dr. Koroshetz expressed optimism that approval and widespread distribution of an effective SARS-CoV-2 vaccine will accelerate these timelines.

Pragmatic Studies for Pain Management Without Opioids

Dr. Koroshetz highlighted several PRISM trials currently in the implementation phase, including trials studying nonpharmacological options in postoperative, hospital-based, and rehabilitation pain management; fibromyalgia transcutaneous electrical nerve stimulation in physical therapy; and group-based mindfulness for patients with chronic low back pain in primary care settings. He also highlighted a pragmatic trial of acupuncture for chronic low back pain in older adults; a hybrid effectiveness-implementation trial of guided relaxation and acupuncture to treat chronic Sickle Cell disease pain in a primary care setting; and a trial of the feasibility of delivering pain consultations and physical therapy through telehealth in low socioeconomic, rural populations via Federally Qualified Health Centers (FQHCs).

Analgesic Development Program

The HEAL Initiative’s Analgesic Development Program aims to de-risk promising analgesic drug and device candidates that emerge from basic scientific research. Specifically, it utilizes federal resources to help bridge the gap between basic discovery and clinical research, thus supporting companies’ need to justify investing in optimizing assets and readying them for clinical use. The HEAL Initiative launched these efforts because major pharmaceutical companies have recently withdrawn from developing pain therapeutics, which are nevertheless urgently needed. The Program is generally divided into early-stage and late-stage programs: the former focus on assets that show promise but still require significant development (e.g., target validation), whereas the latter are intended to further develop products such as lead compounds (e.g., lead optimization and first-in-human trials). The Program is also connected to HEAL’s Early-Phase Pain Investigation Clinical Network (EPPIC-Net), which provides rigorous evaluation of therapeutic assets using a pre-established Phase II clinical trial infrastructure to establish an asset’s clinical effectiveness.

NIH Pain Consortium Symposium 2021

Dr. Koroshetz also informed IPRCC members and other participants that the virtual NIH Pain Consortium Symposium for 2021 (titled “Pain and Pandemics: Challenges and Opportunities in the Current Social and Healthcare Climate”) will occur on May 25-26. It will focus on impacts of current socioeconomic, health care, and social justice challenges on pain management, and of COVID-19 on acute and chronic pain conditions, comorbidities, and disparities, with a particular focus on vulnerable populations. Symposium presenters will also discuss interventions to reduce health disparities and increase effective pain management across populations.

Discussion

Dr. Kerns asked Dr. Koroshetz to provide an update on the HEAL Initiative’s envisioned efforts to aggregate (and, where appropriate, to harmonize) data from its various clinical trial efforts. Dr. Koroshetz reported that initial plans to establish a data repository specifically for the HEAL Initiative’s pain management studies within EPPIC-net were altered, and that the current plan—involving a contract with the University of Chicago—is to establish an integrated data repository for all HEAL programs (i.e., across pain management, OUD prevention, and treatment initiatives). Implementing these plans will be challenging, however, because data coordinating centers that have already contributed to HEAL’s efforts have been storing data in different forms, and these data will need to be transformed to fit the requirements of the new integrated HEAL repository.

Dr. Rebecca Baker, Director of the HEAL Initiative, corroborated Dr. Koroshetz’ summary, noting that the integrated HEAL repository will help ensure that primary supporting data generated by HEAL programs are made available to the research community by the time of publication, which is a requirement stipulated by the HEAL Initiative’s Data Sharing Policy.

Pain-Induced Alterations in Opioid Seeking and Motivated Behavior

Jose Moron-Concepcion, PhD, Washington University Pain Center; IPRCC Scientific Member

The United States faces a double crisis of chronic pain and OUD. During 2018, nearly 47,000 Americans died from overdoses involving opioids, with 67 percent of opioid-involved overdose deaths attributed to synthetic opioids. Simultaneously, greater than 30 percent of Americans live with some form of chronic or severe pain, and researchers consider it crucial to investigate how the OUD and chronic pain crises overlap and interact. Specifically, Dr. Moron-Concepcion’s laboratory uses animal models to explore how pain experiences affect the rewarding properties of opioids, to determine how pain impacts motivation to seek opioids, as well as various opioid-seeking behaviors.

Dr. Moron-Concepcion’s team placed male rats into an operant conditioning paradigm to determine how persistent inflammatory pain affects self-administration of heroin. The team found that under a fixed-ratio schedule, inflammatory pain increases heroin intake at high doses: rats experiencing inflammatory pain self-administered double the amount of heroin as compared to control rats, but only at the highest dose tested (i.e., 200 µg). These results may indicate that pain states affect the rewarding properties of high doses of opioids in such a way that could lead to dose escalation and subsequent overdose. To adapt this research to synthetic opioids and to explore potential sex differences, Dr. Moron-Concepcion’s team then conducted a similar study with fentanyl in both male and female rats. The team compared rates of fentanyl self-administration over time in control rats and rats experiencing inflammatory pain. Male rats experiencing inflammatory pain escalated their fentanyl doses over time, to the point of risking overdose, whereas female rats escalated their doses only slightly. These findings could indicate that males are more susceptible than females to developing opioid tolerance, which potentially increases their risk of dose escalation and overdose death via respiratory depression.

Dr. Moron-Concepcion’s team also placed rats in a progressive ratio reward schedule paradigm to determine how chronic pain-induced negative affect (e.g., anxiety, depression, or anhedonia) impacts opioid-seeking behavior. The results showed that inflammatory pain reduces motivated behaviors to obtain natural reinforcers such as sucrose pellets or food. Dr. Moron-Concepcion’s team hypothesized that the endogenous kappa opioid receptor (KOR) system inside the nucleus accumbens (NAc), which releases dynorphins and leads to dysphoria as well as analgesia, might underly pain-related negative affect. To test this hypothesis, the team injected KOR antagonists into the NAc of rats with inflammatory pain and repeated the progressive ratio reward schedule experiment. Results showed that when KOR systems are inhibited, motivation to pursue reward is maintained even during inflammatory pain. Further studies refuted the possibility that KOR inhibition maintains motivation via analgesia, indicating that pain-induced dynorphin release in the NAc KOR system generates negative affect, which decreases motivation to pursue reward. Dr. Moron-Concepcion’s team corroborated this result by using chemogenetics to silence dynorphin-containing neurons in the NAc and to confirm that inflammatory pain does not by itself decrease motivated behavior. These findings may enable development of novel treatments to prevent pain-induced negative affect that may impact subsequent alterations in opioid intake.

Discussion

Pain researchers are still exploring how KORs function as a mechanism linked to chronic pain, but they suspect that chronic pain, chronic opioid use, and negative affective comorbidities (e.g., anxiety or depression) each have the capacity on their own to increase brain kappa tone.

Dr. Moron-Concepcion’s team also plans to study how rat social interactions and environmental enrichment impacts relationships between chronic pain, opioid use, and motivational behavior.

IPRCC Member Updates

NIH: The IPRP Data Base for Pain Research: Current Status and Future Opportunities

Cheryse Sankar, PhD, Policy Analyst, OPPP; Leah Pogorzala, PhD; Policy Analyst, OPPP

The Interagency Pain Research Portfolio (IPRP) Data Base results from previous IPRCC mandates to identify critical gaps in basic/clinical research and to expand collaborative, cross-cutting research across the agencies within the IPRCC. The IPRP Data Base uses a detailed taxonomy to categorize each awarded grant (it currently shows grants awarded through 2017) according to research stage (i.e., basic, translational, or clinical), research theme and sub-theme categories, and pain conditions studied. It also provides advanced search functionality for users to explore the interagency pain research grant portfolio.

The NIH Office of Pain Policy and Planning (OPPP) frequently uses the IPRP Data Base to reply to congressional or internal NIH requests, as well as to develop the Federal Pain Research Strategy. OPPP plans to conduct an updated portfolio analysis partially to account for the HEAL Initiative programs; HEAL grants can now be tagged in the Data Base for easy querying, to allow analysis of how HEAL funding has altered the pain research landscape. IPRCC members may email feedback on the Data Base to cheryse.sankar@nih.gov or leah.pogorzala@nih.gov.

CDC: Healthy People 2030, NCHS Data Brief, CDC/NCHS/Stanford Collaboration, and 2016 Guidelines on Opioid Prescribing for Chronic Pain

Chad Helmick, MD, IPRCC member, representative from CDC

Three of the four Healthy People 2020 pain objectives are being retained for Healthy People 2030, although the phrase “high-impact chronic pain” has been updated to “chronic pain that frequently limits life or work activities” to be more understandable to non-researchers. The updated Healthy People 2030 objectives (one “core” and two “developmental”) are as follows:

• Reduce the proportion of adults with chronic pain that frequently limits life or work activities (core).
• Increase self-management of chronic pain that frequently limits life or work activities (developmental).
• Reduce the impact on loved ones of chronic pain that frequently limits life or work activities (developmental).

The National Health Interview Survey (NHIS) was updated in 2019 to incorporate two additional pain questions and a pain management question. Further pain questions—some relevant to the Healthy People 2030 objectives—will be added to NHIS every 2 years. The 2019 NHIS provides a baseline dataset of responses to 20 pain module questions that together cover all three Healthy People 2030 pain objectives.

Healthy People 2030 has a section devoted specifically to pain that, in addition to the three pain objectives listed above, lists objectives to reduce moderate and severe joint pain, and to reduce misused prescription opioids as well as rates of starting to misuse prescription opioids.

The Centers for Disease Control and Prevention (CDC) published its Data Brief 390 in November 2020, which reports that during 2019, 20.4 percent of U.S. adults (51 million) lived with chronic pain, including 7.4 percent (19 million) with high-impact chronic pain. These data will be updated biannually. A new joint effort among CDC, the National Center for Health Statistics (NCHS), and researchers from Stanford University aims to update the Institute of Medicine’s (IOM’s) previous estimates of the cost of pain to the U.S. economy. CDC is also working with the pain community to update its 2016 Guidelines on Opioids Prescribing for Chronic Pain, for 2022.

FDA: Acute Pain Guidelines

Rigoberto Roca, IPRCC nominee

The U.S. Food and Drug Administration (FDA) was mandated by the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act to develop evidence-based opioid analgesic prescribing guidelines for acute pain that results from specific conditions or procedures. FDA has contracted with the National Academies of Sciences, Engineering, and Medicine (NASEM) to help to develop these guidelines. NASEM produced a framework for FDA review, and FDA subsequently awarded a 3-year grant (to the University of Pittsburgh and the American Dental Association) to develop, disseminate, implement, and evaluate evidence-based clinical practice guidelines for the treatment of acute dental pain (both surgical and nonsurgical). The grantees will develop an implementation plan to increase uptake of the clinical practice guidelines and will evaluate the reach and impact of their dissemination and implementation strategies.

AHRQ: Systematic Reviews on Pain

Elizabeth Kato, IPRCC member

The Agency for Healthcare Research and Quality (AHRQ) is currently conducting five Systematic Reviews for pain management, which include two upcoming final reviews in support of the CDC treatment guidelines on treatment of acute pain and treatment of acute episodic migraine; two upcoming draft reviews, pursuant to the Dr. Todd Graham Pain Management Improvement Act of 2018, on integrated pain management programs, as well as on interventional treatments for acute and chronic pain; and the first Living Systematic Review on plant-based treatments for pain, which is being produced in response to a Congressional mandate.

The upcoming systematic review on treatments for acute pain will cover a specific set of acute pain conditions, including back pain, neck pain, musculoskeletal pain not otherwise included as back or neck pain, peripheral neuropathic pain, postoperative pain, dental pain, kidney stones, and Sickle cell crisis episodic pain. The review addresses a series of questions comparing the effectiveness of opioid, nonopioid, and nonpharmacological therapies as well as various control conditions such as sham treatment, waitlist, usual care, and attention control. The upcoming systematic review on treatment of acute episodic migraine addresses similar questions.

The draft review on integrated pain management programs will cover several review questions that address impacts of comprehensive pain management programs for Medicare beneficiaries with certain pain conditions; factors that may influence outcomes in studies of comprehensive or integrated pain management models; types of comprehensive, integrated approaches to pain management that have been proposed or used in clinical practice; and costs of integrated pain management programs in the Medicare or general populations.

The second draft review is still being conceptualized. It will focus on interventional treatments for acute and chronic pain within Medicare populations. Current draft questions address the effectiveness/harms of selected interventional procedures versus placebo, a sham procedure, or no intervention for Medicare beneficiaries experiencing pain. The interventions of interest include any for which an evidence review can support Medicare coverage decisions (e.g., intradiscal ozone, cooled radiofrequency ablation, vertebral augmentation procedures).

The inaugural Living Systematic Review will focus on adults with chronic pain and address the benefits and harms of cannabinoids, as well as of kratom or other plant-based substances, for treatment of chronic pain. The intended format for all Living Systematic Reviews will require AHRQ to update a list of relevant studies on a quarterly basis across a 5-year period, as well as to update the full systematic review every year during that same period. Dr. Kato encouraged IPRCC members to contact her if they would like to partner with AHRQ to help shape its data gathering, analysis, or dissemination for this Living Systematic Review.

Aside from its Systematic Reviews, AHRQ is also conducting several projects related to pain and opioid management, including one titled “Improving Management of Opioids and OUD in Older Adults.” Related to this initiative, a technical brief on Prevention, Diagnosis, and Management of Opioids, Opioids Misuse, and OUD in Older Adults was recently made publicly available via AHRQ’s Effective Health Care Program. This initiative has also launched a quality improvement project titled “Identifying and Testing Strategies for Management of Opioid Use and Misuse in Older Adults in Primary Care Practices” and has awarded three 3-year implementation grants to test models for improving management of pain, opioids, and OUD in older adults.

AHRQ has also launched the Digital Healthcare Research on Pain Management program, which is building data capacity to conduct pragmatic patient-centered outcomes research by developing an interoperable electronic (eCare) plan as well as systems to support bidirectional clinical decision support for chronic pain management.

Patient Engagement in Clinical Pain Research Studies

Introduction

Danielle Haney, Senior Policy Analyst, IPRCC

NIH Director Dr. Francis Collins, other NIH leadership, and the HEAL Initiative Multidisciplinary Working Group have established the HEAL Patient Engagement Working Group. This Working Group has undertaken a range of activities since May 2019 to better engage patients in clinical HEAL Initiative studies. The new Working Group held an Engagement Workshop in August 2020, met during September and October to define goals for itself, and is now discussing best practices with the Patient-Centered Outcomes Research Institute (PCORI) and planning a workshop for HEAL Initiative investigators to improve patient engagement.

The HEAL Patient Engagement Working Group has three overarching priorities:

1. Create a HEAL patient engagement governance structure: include internal NIH experts as well as researchers and patients; establish a HEAL Community Council (including one representative from each HEAL study) to continuously provide input to NIH; identify types of patient engagement efforts in ongoing HEAL studies.
2. Increase patient engagement in HEAL studies: require trials to develop a framework to increase patient engagement and include community panels.
3. Provide resources for the HEAL community: facilitate the development of best practices in stakeholder engagement; develop and collaborate on workshops.

The Patient Engagement Working Group held its kickoff discussion in August 2020 to consider opportunities, challenges, and benefits to incorporating patients and stakeholders in research, as well as to provide insights on virtual patient engagement, particularly in the context of COVID-19, with a primary focus on pain studies. A HEAL Virtual Workshop is planned for February/March 2020, which will showcase exemplars of patient engagement in ongoing HEAL Initiative studies and provide opportunities for sharing insights and best practices. Virtual Workshop attendees will include both HEAL investigators and members of the public.

Discussant Leads

David Williams, IPRCC Scientific Member; Gwenn Herman, IPRCC Public Member

The IPRCC highlighted the need to involve patients in key roles throughout the full research life cycle, including setting the research agenda, designing funding opportunities to ensure that grant opportunities address questions and measure outcomes that matter to patients, reviewing grant awards, designing and participating in studies, and reporting their experiences in white papers or other materials that can be disseminated to the broader patient population. Participants emphasized that funding agencies need to lead these efforts by engaging patients directly in the pre-award stages of research and requiring that grantees provide detailed plans to engage patients in their studies. IPRCC members generally agreed that PCORI’s approach to these efforts currently sets the standard, but that its efforts should be replicated and expanded by other main funding agencies, including NIH (e.g., participants suggested that NIH establish a study section to review pain research grant applications, and that patients be included in this study section).

The IPRCC highlighted various possibilities for enhancing patient engagement in pain studies:

• Ensure that patients are interested in a study’s outcomes to encourage high rates of patient participation and retention, as well as high impact of results.
• Produce clear, simple communications materials to support robust patient engagement before, during, and after studies.
• Include patients in grant oversight committees and solicit their input during the study design phase.
• Establish programs within NIH and other research-sponsoring institutions that ensure patient engagement throughout the research process.
• Improve reporting and dissemination of information on patient engagement efforts, either in peer-reviewed journals (e.g., by encouraging journal editors to increase word limits to allow such reports to be incorporated into articles) or in lay-friendly materials such as white papers that can be disseminated to patient populations and the public.
• Involve diverse patients during consultations to avoid the assumption that a small number of patients represent a broader group (e.g., establish national patient advisory boards that include diverse and geographically distributed groups of approximately 100 patients).
• Provide researchers conducting pain clinical trials with funding dedicated specifically to recruiting underrepresented and underserved populations into those studies.
• Pay/reimburse patients for their time engaging with pain research (PCORI requires that grantees pay participating patients; IPRCC members recommended also thinking of ways to reimburse patients for their involvement in pre-award activities).
• Examine how the Cochrane Collaboration as well as global pain patient advocacy efforts affiliated with the International Association for the Study of Pain (IASP) have developed over the years to gain key insights for future efforts.
• Leverage COVID-19-induced delays in launching pain clinical trials to add questions to surveys and questionnaires that capture socioeconomic risk factors for pain and disparities (e.g., to capture information more granular than race).
• Include patients in Data Safety Monitoring Boards (DSMBs) and Institutional Review Boards (IRBs) that oversee and approve clinical trials.
• Solicit input from persons with lived experiences in informing  NIH program directors about patient-centered priorities in pain research.

IPRCC members expressed interest in creating a subcommittee to further explore opportunities and challenges for pain patient engagement, using PCORI’s approach as a model but expanding it to address the priorities/challenges outlined above, and to operationalize proposed solutions.

Diversity in Pain Research: Inclusion and Retention of Diverse Populations in Clinical Pain Research Studies

Introduction

Cheryse Sankar, PhD, Policy Analyst, OPPP; Yolanda Vallejo, Program Director, NIDCR

NIH is committed to fostering a culture of diversity, equity, and inclusion that extends past its workforce to include its clinical studies research portfolio. NIH’s Pain Consortium, which aims to enhance pain research and promote collaboration among researchers across NIH Institutes and Centers with programs and activities addressing pain, has been leveraged to create a new Working Group specifically to address health disparities related to pain and to increase diversity in pain research.

The Working Group’s overarching goals are to reduce the burden of chronic pain in vulnerable populations and increase generalizability in clinical pain study outcomes. It will focus on the three main areas summarized below:

1. Increasing research on health disparities in pain
2. Enhancing inclusion and diversity in pain clinical studies and trials
3. Promoting scientific workforce diversity in pain research

To achieve its goals, the Working Group is expanding existing infrastructure at NIH focused on diversity and inclusion and is leveraging resources such as the Federal Pain Research Strategy to identify key gaps in the current pain research landscape. It is also disseminating key information to the pain health disparities and diversity communities and planning a virtual workshop that will focus on achieving health equity in the NIH HEAL Initiative. The workshop will be advertised beyond HEAL Initiative investigators to the broader pain community—it will highlight successful and innovative strategies for recruiting diverse populations into clinical studies, including those beyond the pain field.

The main topic of the IPRCC’s discussion during this meeting will be the second focus area listed above: promoting inclusion and diversity in pain clinical studies and trials. Investigators typically base their expected enrollment on past study history, and do not adequately prioritize diversity and inclusion in their patient enrollment plans and efforts. Moreover, resources such as funding and expertise for improving patient diversity and inclusion are limited. Therefore, it is crucial for NIH and its affiliates to develop a central process to monitor appropriate patient inclusion in all HEAL pain clinical trials.

Discussant Leads

Beth Darnall, IPRCC Scientific Member; Katherine Hammitt, IPRCC Public Member

The IPRCC stressed the importance of identifying root causes of low patient engagement (e.g., lower than desired recruitment and retention rates in clinical trials), particularly for vulnerable and underserved populations. Although logistical barriers (e.g., limited transportation options, work schedules that interfere with study participation) are common, discussants noted that some populations may face more fundamental (e.g., cultural) barriers that interfere with study participation. They emphasized the need to engage with underrepresented patient populations directly throughout the research life cycle (including before and during the study design phase) to ensure that specific barriers are understood and adequately addressed, both at the level of specific studies and across the entire pain field.

The IPRCC advanced various proposals for increasing the diversity of patients in pain studies:

• Appoint NIH Diversity Officers or Engagement Advisors to help answer questions and advise researchers during proposal development and throughout the funded project life cycle to integrate diverse patient populations into all levels of the research process.
• Stress the importance of diversity and inclusion among study participants within grant solicitations and consider providing extra funding to investigators who include diversity plans within their grant proposals.
• Conduct focus groups with specific patient subpopulations to gain an understanding of the barriers they face and incorporate “concierge services,” like those used by Sjögren’s Foundation, into study designs to help address those barriers. (Concierge services might include transportation assistance or mobile health delivery services and can be funded through partnerships with external stakeholders such as pharmaceutical companies.)
• Ensure that studies are designed to enable patients to participate on flexible schedules (e.g., to help accommodate participants with full-time jobs).
• Solicit input from patient subgroups of interest when designing study outcomes so that members of these subgroups perceive the value and importance of the study and thus are more likely to actively participate and remain involved.
• Consider ways to more effectively reach patients outside metropolitan areas who may lack access to the internet, or who may not feel comfortable interacting with providers virtually.
• Incorporate rural populations into studies more effectively by establishing connections with primary care providers in rural communities.
• Collaborate with the largest and most influential advocacy groups to recruit patients and solicit input from these groups to better understand what barriers affect a population of interest, as well as what remedies might address those barriers.
• Leverage the platforms of large, nationally known advocacy groups for specific pain conditions to recruit patients for studies.
• Increase compensation for patients participating in trials, both to ensure that the funds cover costs of participation and to enable individuals of lower socioeconomic status to participate. Solicit input from past participants to help determine what range of compensation is reasonable given patient burdens.
• Enlist minority patients who are enthusiastic about participation in studies to serve as peer support specialists for less experienced patients who may be willing to participate.

IPRCC members acknowledged that diversity of participants in pain clinical trials is currently not satisfactory but noted that the ideal demographic distribution among subgroups in any specific study will depend on the geographic region of the study and the demographics of patients with the condition of interest. In some cases, previously overlooked groups should be oversampled.

Enhancing Diversity in the Pain Research Workforce

Introduction

Michelle Jones-London, Chief, Office of Programs to Enhance Neuroscience Workforce Diversity, NINDS

Recognizing that diversity fosters superior science through enhanced creativity and innovation, NIH has created the Office of Workforce Diversity. NIH and health science communities more broadly should strive to increase workforce diversity to ensure that talented individuals in marginalized groups are fully engaged and can contribute to scientific progress. NIH has established funding mechanisms to create seamless transitions for biomedical career advancement and progression (including F99/K00 and K99/R00 grants for graduate students and postdocs, as well as K01, DP2, MIRA, and ESI grants for individuals seeking to obtain their first faculty positions), with a focus on individuals from underrepresented subpopulations. The NIH Loan Repayment Program can also help to support early investigators and those aspiring to pursue other biomedical careers while they work to pay off debt while pursuing long-term professional positions.

All NIH Institutes and Centers also participate in Research Supplements to Promote Diversity, a feeder program to support individuals transitioning into the biomedical research community by providing funding and mentorship opportunities; this mechanism can be used by any HEAL investigators seeking to increase the diversity of their research teams. NINDS also utilizes R25s as funding mechanisms to build a network of diverse high school and undergraduate students interested in pursuing careers in neuroscience.

NIH continues to broadly engage with stakeholders across the biomedical research community to foster diverse and inclusive biomedical research institutions that can welcome investigators from all segments of society into a fair, collaborative, and supportive environment where creativity and productivity can flourish. To develop such institutions, it is important that leadership at NIH and other key stakeholder organizations support diversity and explicitly articulate visions for inclusiveness within these organizations. An NIH program—Faculty Institutional Recruitment for Sustainable Transformation (FIRST)—has been established with the aim to create cultures of inclusive excellence at NIH-funded institutions.

Discussant Leads

Robert Kerns, IPRCC Scientific Member; Irma Rodriguez, IPRCC Public Member

The IPRCC emphasized the need to build pathways for diverse individuals into the pain research and clinical practice fields, stressing the need for institutional leaders to commit to the diversity of their organizations by setting goals, creating plans, and measuring progress. Discussants also highlighted the need to instill cultures of diversity and inclusion among educational, health care, and research institutions as they relate to pain. They focused especially on developing ways for talented and enthusiastic individuals in the pain field with diverse backgrounds to serve as mentors for high school and university students, as well as for junior faculty. They emphasized the importance of creating organizational partnerships among funding agencies, corporations, and educational institutions to help bridge gaps in the current recruitment pipelines for pain professions.

The IPRCC also proposed more specific ideas for increasing the diversity of the pain workforce:

• Establish research assistant positions or clinical internships for recent college graduates with diverse backgrounds to spark their interest in the pain field.
• Focus funding for mentorship initiatives on specific research subfields within pain and opioid areas, potentially creating a task force/committee to strategize for these efforts.
• Incorporate individuals with disabilities and chronic pain into diversity goals, recognizing the need for accommodations where appropriate.
• Create financial incentives that empower early investigators to continue within the field by instilling in them a sense of accomplishment and opportunity during their early careers.
• Devise strategies to better engage trainees and mentors who participate in mentorship programs (e.g., examine successful mentors of the past and leverage their experiences to optimize new and existing mentorship programs).
• Reinstitute the K05 funding mechanism and award it to individuals with a demonstrated history of success mentoring diverse students/postdoctoral researchers/junior faculty.
• Gather more comprehensive data on the demographic distribution of different kinds of professionals within the pain field.
• Build trust with minority communities by exhibiting a sensitivity to their needs and concerns, and by communicating with them in a way that reflects that sensitivity.
• Liaise with universities’ Offices of Diversity, Equity, and Inclusion to engage with diverse undergraduate students and to entice them to pursue careers in the pain field.
• Partner with historically black colleges and universities to build pipelines into the pain workforce and research field (potentially leveraging existing infrastructure of the NIH Blueprint ENDURE program, which partners with many universities that predominantly serve underrepresented groups).

Promoting a New Generation of Pain Researchers

Walter Koroshetz, MD, Director of NINDS

During 2020, 27 new pain researchers received their first NIH grants—an all-time high for the pain field. However, IPRCC members seek to further increase numbers of first-time pain researchers entering the field each year, as well as the amount of NIH grant funding that is awarded to investigators within 10 years of completing their terminal degree. Pain constitutes a major public health challenge, and the field of pain research must expand in order to adequately address that challenge. One particularly urgent need is to attract more physician-scientists to pursue pain research careers. NIH has partnered with external institutions such as FDA, the American Academy of Neurology, and the International Headache Society to develop outreach activities and provide training sessions to grow the pipeline of pain researchers, but additional and more comprehensive efforts (perhaps via the HEAL Initiative) are still needed.

Discussant Leads

Stephen Silberstein, External Expert; Robert Dworkin, External Expert

The IPRCC focused its discussion largely on the need to attract and engage high school, college, and graduate students, with a special emphasis on first-year medical students, who are committed to pursuing a career in medicine but may not yet have chosen a specialization. Discussants proposed various strategies for encouraging more experienced investigators (which includes mid-career investigators) to mentor junior investigators and students with a potential interest in entering the pain field. They also focused on the potential to better leverage existing funding mechanisms, or to establish new ones, that have the potential to grow the pipeline of talent entering the entire pain field, including clinical as well as basic scientific research.

The IPRCC suggested many specific ideas for promoting a new generation of pain researchers:

• Create mechanisms for junior investigators interested in specific pain subfields to serve as visiting fellows at academic centers focused on those same subfields (e.g., headache).
• Fund the formation of “mini consortia” that each focus on specific pain subfields to help direct junior investigators to the appropriate research groups based on their interest. These efforts may be especially important for clinical researchers who, early in their careers, must treat patients and therefore often have little time for research.
• Consider the possibility of establishing virtual consortia that could provide junior investigators and graduate students with the ability to participate in consortia even though they may not be able to relocate.
• Survey the younger generations of clinical and basic pain researchers (i.e., those in their 30s and 40s) to determine what they need to succeed, and what factors might, in some cases, make researchers decide to enter private practice.
• Establish grant award criteria that recognize the added value of proposals submitted jointly by senior and junior investigators with mentor-mentee relationships.
• Create a registry of distance mentors (senior clinical or basic science researchers who are willing to mentor, advise, and collaborate with younger investigators anywhere in the country using virtual platforms) for junior investigators to use in search of mentors.
• Design new courses for junior investigators, modeled on the NINDS Vail Course, in both the clinical and basic science pain fields. Establish summer fellowships allowing students to spend summers in a pain laboratory and receive a stipend.
• Create “research tracks” within university residency programs to aid junior investigators in beginning projects to be supported by T32 grants during subsequent fellowships.
• Expand funding for T32 grants in successful mentorship programs, especially those with a demonstrated history of success in training diverse candidates.
• Establish novel funding mechanisms to (1) encourage junior pain investigators, or mentors/senior investigators, to spend time advancing careers of junior investigators, (2) award travel grants for students and junior investigators to travel to conferences and meetings of pain research institutions such as the new U.S. Association for the Study of Pain (USASP), and (3) better support postdoctoral researchers so that they have incentives to pursue and remain in the pain field.
• Encourage universities to use R25 grant mechanisms to fund research projects by residents and fellows within any pain specialties.
• Expand loan repayment programs to increase the amounts paid to candidates who are focused on careers in pain research.
• Encourage USASP to connect younger generations of physician scientists with each other and facilitate networking among them.
• Identify dynamic researchers who can excite audiences about pain research and allow them to spark interest among students and junior investigators (e.g., Dr. Jeffrey Mogil’s North American Pain School program).
• Strategize about how to bridge the gap between basic and clinical pain researchers (e.g., by establishing programs like Washington University in St. Louis’ Translation Program).
• Consider opportunities to establish public-private partnerships that link academics with the private sector (e.g., pharmaceutical companies) to help fund internships/fellowships for young investigators who need to gain experience in the pain field.
• Promote career development and mentorship opportunities for HEAL investigators (e.g., those involved in EPPIC-Net).
• Increase the focus on engaging and retaining interest in pain psychology among young students, potentially leveraging connections through the U.S. Department of Veteran’s Affairs and the American Psychological Association.

Adjourn

IPRCC members concluded the meeting by praising its discussion-centric format, emphasizing the number of constructive conversations and specific proposals that emerged from discussion.

Mr. George Carter noted that this would likely be his last IPRCC meeting and emphasized that both medical associations and doctors must be strongly encouraged to properly prescribe and administer opioids to patients who need them, until alternative effective therapies are found.

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.

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