IPRCC Meeting - 12/03/2015

Introduction

The December 3, 2015 meeting of the Interagency Pain Research Coordinating Committee (IPRCC) was convened at 8:30 a.m. in Building 35A, Porter Neuroscience Center, 1st Floor, Room 610, on the National Institutes of Health (NIH) campus.  In accordance with Public Law 92-463, the meeting was open to the public. Walter Koroshetz, MD, Director, National Institute of Neurological Disorders and Stroke (NINDS), presided as chair.

In attendance were the following members of the IPRCC:

Federal Members: Walter Koroshetz, MD; Charles G. Helmick, III, MD; Sharon Hertz, MD; Audrey Kusiak, PhD; Richard Ricciardi, PhD, CRNP; Martha J. Somerman, DDS, PhD; Chester Buckenmaier, MD (for Maj. Gen. Paul Cordts, MD); David Thomas, PhD (ad hoc for Nora Volkow, Md, PhD)

Scientific Members: Allan Basbaum, PhD, FRS; Rami Burstein, PhD; William Maixner, DDS, PhD; Judith Paice, PhD, RN, FAAN; Richard Payne, MD

Public Members: Myra J. Christopher; Penney Cowan; Christina Spellman, PhD; Cindy Steinberg; Tina M. Tockarshewsky; Christin L. Veasley, CPRA

Ex-Officio Members: Josephine P. Briggs, MD (absent), Patricia A. Grady,  RN, FAAN,PhD, (ad hoc), David Thomas, PhD (for Nora D. Volkow, MD)

Designated Federal Official: Linda L. Porter, PhD

NIH Staff

NINDS Office of Pain Policy - Cheryse A. Sankar, PhD; Khara M. Ramos, PhD; Leah Pogorzala, PhD

IPRCC nominees pending final membership approval: Ricardo Cruciani, MD, Michael Pasternak, PhD, Cathy Glaser, and Catherine Underwood.

 

Welcome and Call to Order

Walter Koroshetz, MD, Director NINDS

After welcoming remarks, Dr. Koroshetz introduced incoming members who are awaiting final approval; Ricardo Cruciani, MD, Michael Pasternak, Cathy Glaser, and Catherine Underwood.  He then gave a brief update on selected advances in pain research. New discoveries, combined with powerful new technologies, show great promise for improving pain diagnosis and treatment, as well as for understanding basic mechanisms of pain– all of which may help reduce the heavy burden of chronic pain in America. A central concern is the need for more research related to opioids, which are used extensively and effectively to manage pain for many people, but also carry risk. The increase in deaths due to prescription opioids is a national crisis.  As with any drug, effective opioid use must involve a careful balance of safety and efficacy, at both individual and public health levels. 

Novel tools are available that enable mapping and even manipulation of neural circuits, deepening our understanding of pain processing in the nervous system. These tools include optogenetic approaches that provide precise control of individual cells in various brain regions and novel chemical transducers that can precisely alter signaling. Together, these investigative agents may find use in the not-too-distant future as part of an expanded toolbox for the treatment of pain with unprecedented specificity and low toxicity.
 
Dr. Koroshetz highlighted three recent discoveries:

1. As shown by Weng, et al.[1] (Neuron, February 2015), the ribbon-like protein Tmem100 is a potentiating modulator of TRPA1-V1 complexes in sensory neurons. Tmem100 is co-expressed and forms a complex with TRPA1 and TRPV1 in dorsal root ganglia neurons, and Tmem100-deficient mice show a reduction in inflammatory mechanical hyperalgesia in TRPA1- but not TRPV1-mediated pain. Tmem100 physically weakens the association of TRPA1 and TRPV1, interrupting a normally analgesic response. Thus, Tmem100 blockade (through various potential mechanisms) provides a new target for analgesia.
 
2. The relatively new method optogenetics allows rapid, temporally specific control of neuronal activity by targeted expression and activation of light-sensitive proteins in neurons. A recent study from Park, et al.[2] (Nature Biotechnology, November 2015) unveiled a soft, stretchable, fully implantable miniaturized system for wireless optogenetics. The approach enabled remote activation of spontaneous pain behaviors and place aversion, via nociceptive pathways expressing channelrhodopsin-2 and activated using LED devices inserted near peripheral nerves or into the epidural space. By enabling manipulation of peripheral and spinal pain circuitry, this work provides evidence for the potential widespread use of such technology in research and future clinical applications of optogenetics outside the brain.
 
3. New basic-science pain research extends understanding of microglia-to-neuron signaling in chronic pain hypersensitivity. Sorge, et al.[3] (Nature Neuroscience, 2015) showed that, unlike male mice, microglia are not required for mechanical pain hypersensitivity in female mice. Instead, female mice achieved similar levels of pain hypersensitivity using adaptive immune cells, likely T lymphocytes. This sexual dimorphism underscores the need for studying both sexes in preclinical research, especially in areas like chronic pain that disproportionately affect women. Recently, NIH has issued new policy in this arena to ensure that preclinical research considers both sexes.
 
Dr. Koroshetz briefed attendees on a recent Institute of Medicine (IOM) neuroscience forum, at which representatives from industry, government and academia explored opportunities for collaboration. The group discussed the NIH-led Accelerating Medicines Partnership (AMP) as a potential public-private partnership for advancing pain research. Potential areas related to pain include identification of pain signals through fMRI signaling, identification and validation of biomarkers, study of potential mechanisms for the placebo effect, and approaches to predict responders for stratification of clinical trial participants. Other concepts include considering pain duration as a study outcome with the goal of reducing the duration of acute pain as well as the transition to chronic pain, and use of the Federal Pain Research Strategy to identify potential research areas that are ideal for AMPs.
 

Approval of the Minutes of the April 17th, 2015 IPRCC Meeting

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

The IPRCC considered and approved the April 17, 2015 IPRCC meeting minutes.
 

Vote on the Chair

A vote was taken for Chair of the Committee, as Dr. Koroshetz had been serving as acting Chair while appointed as Acting Director of NINDS. He is now the Director of NINDS. The group unanimously voted to elect Dr. Koroshetz as Chair of the IPRCC.
 

Updates from IPRCC Members

Chronic Overlapping Pain Conditions Research Resources

Christin L. Veasley, Chronic Pain Research Alliance 

The 2011 IOM report Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research noted the increasing recognition and importance of a cluster of prevalent pain conditions that frequently co-occur and either solely or predominantly affect women. This overlap recently has been termed Chronic Overlapping Pain Conditions (COPCs) and has prompted a trans-NIH effort involving 12 Institutes and Centers (ICs).

The COPC work group to develop research resources has drawn on the experience of an NIH task force on chronic low back pain, which concluded that use of variable inclusion and exclusion criteria, case definitions, baseline assessments, and outcome measures led to difficulty in achieving consensus on research findings and an inability to provide a clear path forward. The COPC work group considered three models to derive a case definition; multiple conditions which share common mechanisms, separate primary conditions which produce overlapping symptoms, or a model that assumes a spectrum of unique and shared pathways. This third model will be used to develop a working case definition for clinical studies.

The work group reviewed and analyzed studies on overlapping conditions; a heat map was constructed to demonstrate overlap of chronic low back pain, irritable bowel syndrome, vulvodynia, and migraine, and showed the varying levels of overlap among these conditions. Toward creating a case definition, the COPC work group discussed key factors: i) diagnoses vs. symptoms vs. body sites; ii) severity criteria; and iii) standardized validated research diagnostic criteria. The group agreed to use a Complex Medical Symptoms Inventory (CMSI) as a starting point. The CMSI is easy to operationalize; can be digitized; provides a broad array of information on symptoms, chronicity, severity, and diagnoses; and eliminates the need for an index condition. A body map may be added as a companion piece in the future. After the case definition has been developed, next steps will include developing Common Data Elements for COPCs (a minimum dataset to be collected across studies).  
 
Discussion points

• The temporal nature of COPCs should be addressed, since the individual and co-morbid conditions wax and wane over time. Longitudinal, cross-sectional studies are needed to address these questions.
• Prospective environmental exposures should be addressed.
• Medications used by patients should be addressed as they have many effects and may even induce co-morbidities.
• Psychosocial factors should be considered in addition to looking at biological measures (e.g. immunological/inflammatory processes). Parameters borrowed from Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) define three biopsychosocial clusters.  
• Temporal studies may shed light on whether there are underlying contributors to COPC – such as PNS or CNS sensitivity, and immune, inflammatory, or environmental factors.
• It may be useful to consider non-pharmacological interventions, such as physical therapy, integrative approaches, and counseling.
• NIH recently announced the formation of a trans-NIH myalgic encephalomyelitis/chronic fatigue syndrome research work group, indicating increased agency focus and coordination for this frequently co-occurring pain condition. Dr. Koroshetz is leading the trans-NIH working group.
   

EvidenceNow

Richard Ricciardi, PhD, CRNP, Agency for Healthcare Research and Quality, AHRQ

AHRQ’s mission is to produce evidence on how to make health care safer, higher quality, more accessible, equitable, and affordable, and to work within HHS and with other partners to make sure that the evidence is understood and used. Primary care is a central focus for both the Affordable Care Act and AHRQ with components including patient-centered medical homes, practice facilitation as a tool for practice improvement, practice-based research networks, integration of primary care and behavioral health, care coordination, self-management support, health information technology, and team-based care and training.

Dr. Ricciardi presented an overview of an ARHQ initiative to advance heart health, as an example of dissemination and implementation of patient-centered outcomes research (PCOR). The EvidenceNow program draws from three areas of influence: i) the HHS Million Hearts campaign, ii) funding from the designated PCOR Trust Fund, and iii) AHRQ’s commitment to primary care. The EvidenceNow program aims to ensure that primary care practitioners have the latest evidence on cardiovascular health and that they use it to help their patients live healthier and longer lives by implementing PCOR findings into practice, and building primary care practitioners’ capacity to receive and incorporate future PCOR findings. A key research question centers on whether externally provided quality improvement (QI) support quickens dissemination and implementation of PCOR findings.

The $112 million, grant-based EvidenceNow effort, begun in May 2015, involves seven regional cooperatives and one site for external evaluation, and is guided by a federal interagency work group. The project expects to reach more than 1,500 small- to medium-sized primary care practices, 5,000 primary care professionals, and 8,000,000 patients. Implementation of QI interventions will begin in January 2016 and proceed through November 2017. Pain is an example of a condition that fits well within the EvidenceNow rubric.

 

Healthy People 2020

Charles Helmick, MD, Centers for Disease Control and Prevention, CDC

• The Healthy People initiative, updated each decade, presents HHS’s health objectives for the nation:
• Attain high-quality, longer lives free of preventable disease, disability, injury, and premature death
• Achieve health equity, eliminate disparities, and improve the health of all groups
• Create social and physical environments that promote good health for all
• Promote quality of life, healthy development, and healthy behaviors across all life stages

Healthy People 2020 includes four developmental objectives for high-impact chronic pain that address the domains of i) adult prevalence, ii) public awareness/knowledge, iii) self-management, and iv) impact on family/significant others.

Since the last IPRCC meeting, four National Health Information Survey (NHIS) 2016-2017 developmental questions are under consideration:

1. In the past six months, how often did you have pain? 
2. Over the past six months, how often did pain limit your life or work activities?
3. Over the past six months, how often did YOUR pain affect your family or significant others?           
4. To what extent are you able to manage your pain so that you can do the things you enjoy doing? 

Discussion points

• In response to a question as to whether the current NHIS data distinguish pain that is managed vs no pain, Dr. Helmick replied that they do not, but the 2016-17 questions can set a baseline for future questions and analyses. These questions can serve for further question development and eventually be used to derive outcomes of interventions.
• It is important to note that the four current NHIS pain questions are amid 200-300 other health questions which add context and can be interrogated to glean more information about pain at the population level.
• Surveyed individuals participate through in-person interviews; subjects are identified by the CDC National Center for Health Statistics based on census data. 35,000 adults are sampled, with oversampling of some populations for demographic purposes.
• A six, rather than the commonly used three month duration of pain for the questions was chosen after much discussion, to accommodate the spectrum of intermittent pain over six months. 
• The Healthy People 2020 effort aims to provide more granularity on the prevalence of chronic pain that was reported in the 2011 IOM report. Additional metrics would include impact, duration, co-morbidities, and the impact of chronic pain on an individual’s physical function and social and family interactions.

 

DoD Initiatives for Pain Management

Chester Buckenmaier, MD, Department of Defense, DoD

Dr. Buckenmaier provided an update on major projects of the Defense and Veterans Center for Integrated Pain Management (DVCPIM). He noted that high staff turnover in the military makes implementation progress difficult. He sought help from the IPRCC to spread awareness of new information and tools produced through the Joint Pain Education Project, a collaboration between the DoD and Department of Veterans Affairs (VA) to develop a standardized pain management curriculum to improve education and training for health care providers and patients. One such tool is an educational video on pain, which currently is played in DoD waiting rooms. The video describes how pain develops and can be managed, with the following key messages: pain is produced by the brain, it can be acute or chronic, and the brain can be re-trained to lessen the impact of pain.   

Another product is the Pain Assessment Screening Tool and Outcomes Registry (PASTOR), a 20-30 minute survey that produces a comprehensive three-page clinician report of a patient's chronic pain status. PASTOR uses NIH-developed and -tested instruments collectively known as the Patient Reported Outcomes Measurement Information System (PROMIS) to administer questions in a wide range of pain-related areas. PROMIS instruments use a technology known as Computer Adaptive Testing to administer questions in a way that allows for precision with the fewest possible number of questions.

In addition to the PROMIS instruments, PASTOR also incorporates demographics, the Defense and Veterans Pain Rating Scale (DVPRS), an anatomical map for locating pain areas, military specific pain related questions, and other measures. Taking all of these items and compiling them as one large survey, PASTOR is able to create a comprehensive view of a patient's pain status. This information is stored electronically and allows the clinician to track a patient's progress across multiple measures. 

Dr. Buckenmaier noted that non-medication-based pain therapies are important and underutilized. These include stress management, yoga, sleep, diet, physical activity, and various integrative approaches such as acupuncture. Pain management through these approaches was not addressed substantially in the recently issued Presidential Memorandum on Prescription Drug Abuse and Heroin Use.
 
Discussion points

• The educational video was well received by the committee, although some suggested that it may convey an overly optimistic view of chronic pain resolution. Future iterations might incorporate effective ways of promoting evidence-based self-management strategies for persistent chronic pain.
• The military’s performance triad focuses on nutrition, sleep, and activity. These elements are important factors in an individual’s unique response to pain, in addition to other biologically-based differences (e.g., immune system, microbiome, genetics, other). Biobank data will help construct genetic/personality profiles of vulnerable soldiers.
• Most pain care provided through the DoD is through primary care providers. Pain management is a continuum, not a single intervention or prescription.

 

Pathways to Prevention, Opioid Conference Partners Meeting

David Thomas, PhD, NIH National Institute on Drug Abuse, NIDA

Nearly 80 percent of people who reported starting heroin use in the past year had previously abused prescription pain medications,[4] and both opioid and heroin overdoses have been on a precipitous rise in recent years. Responding to the need for consensus on safe and effective treatment of chronic pain, the NIH Office of Disease Prevention’s Pathways to Prevention program sponsored a meeting in September 2014 on the Role of Opioids in the Treatment of Chronic Pain. Relevant evidence from a variety of sources was collected and reviewed as part of the process of developing evidence-based recommendations. These include AHRQ survey questions, a literature review, Patient-Centered Outcomes Research Institute (PCORI) data, study outcomes drawn from the Interagency Pain Research Portfolio database, and FDA post-market safety surveillance data. An abridged version of the meeting’s proceedings and recommendations has been published in the Annals of Internal Medicine,[5] and the full report is posted online. [6] This effort aims to be an unbiased interpretation of published evidence, conducted by a jury with no vested interest in the topic. Findings will be discussed at the Pathways to Prevention Federal Partners Meeting to be held in February 2016, followed by issuance of a white paper in March 2016. Three recommendations relevant to government action include:

• Fund research to identify which types of pain, specific diseases, and patients are most likely to benefit or incur harm from opioids.
• Fund development and evaluation of multidisciplinary pain interventions, including cost–benefit analyses and identification of barriers to dissemination.
• Fund research to develop and validate research measurement tools for identification of patient risk and outcomes (including benefit and harm) related to long-term opioid use that can be adapted to clinical settings.

Discussion points

• The Pathways to Prevention program should consider input from people with chronic pain and should work to mitigate potential stigma for people with pain being “the source of the opioid problem.”
• Relevance to past opiate-use studies as well as study of chronic pain treatment approaches in Europe may inform U.S. strategies. Dr. Somerman noted that opiate prescribing in the dental community recently has declined in the United States.
• Data on co-prescribing practices (e.g., with benzodiazepines and other medications) is important to develop preventive interventions.
• Limiting opiates addresses only one part of a complex solution that also depends on heroin cost and availability, effectiveness and availability of non-opiate pain treatments (including integrated care), and education on safe use and disposal of unused medications.

 

The President’s Memorandum on Prescription Drug Abuse

Cecilia Spitznas, PhD, White House Office of National Drug Control Policy, ONDCP

The ONDCP is a component of the Executive Office of the President. The Office coordinates drug-control activities across the federal government and produces the annual National Drug Control Strategy, which aims to:

• Prevent drug use before it ever begins through education
• Expand access to treatment for Americans struggling with addiction
• Reform our criminal justice system
• Support Americans in recovery

Signature initiatives of this strategy include efforts to combat prescription drug abuse and drugged driving. The Prescription Drug Abuse Prevention Plan invokes a coordinated federal effort targeting education, prescription drug monitoring programs (PDMPs), medication disposal,[7] and enforcement. The White House also issued a fact sheet on opioid abuse in the United States.
 
PDMPs

In 2006, only 20 states had PDMPs. Today, all but one have laws authorizing programs; 49 are operational, and 30 have some data-sharing capacity. ONDCP has urged adoption of language for the Department of Veterans Affairs to share prescription drug data with state PDMPs (although this has not been fully implemented). Data-sharing has expanded across state lines, with electronic health system integration pilot projects underway in several states. An emerging promising practice is the establishment of pharmacy/provider restriction programs, which limit patient’s access, based on unusual claims data, to a single provider and/or pharmacy.

Medication-assisted treatment (MAT) currently is available for nicotine-use disorder, alcohol-use disorder, and opioid-use disorder. To date, ODNCP activities have been conducted with existing funds, but the FY16 President’s Budget includes $11.0 billion in funding for MAT, with a focus on opioid use disorder. Current activities include i) an inventory of treatment availability and assessment of availability of ACA/state-run health marketplaces to ensure proper resourcing; and ii) language in Department of Justice (DoJ) and HHS drug-court grants to expand MAT access. In addition to currently available MAT (methadone, naltrexone, buprenorphine, and buprenorphine/naloxone), other MAT options are being studied, in addition to efforts to expand naloxone access. These include a buprenorphine implant and anti-opioid vaccines. Prevention approaches are targeted to hepatitis C and HIV infection, both co-morbidities of opioid use disorder.

In November 2015, President Obama announced release of the Presidential Memorandum -- Addressing Prescription Drug Abuse and Heroin Use. The three main points include:

• Reducing prescription pain medication and heroin overdose deaths
• Promoting the appropriate and effective prescribing of pain medications
• Improving access to treatment

Related efforts to the President’s memorandum include attention to agency and payer formularies, potentially tying DEA licensing to mandatory prescriber education, and alignment with non-traditional partners (e.g., sports associations and coaches at the high school, collegiate, and professional levels; nonprofits and non-governmental organizations). Several questions/issues are ongoing regarding implementation of the memorandum. These include:

• What is the ideal makeup of the pain/healthcare workforce?
• What training is necessary/sufficient?
• Cost-effectiveness of training
• How to engineer pharmacy-utilization controls, decision-support tools, and policies to make meaningful change
• How much MAT is enough? 
• How can we be sure overdose patients who need access to services and treatment move to long-term recovery?

 

The Secretary’s Initiative on Prescription Opioids

Richard Frank, PhD, Office of the Assistant Secretary for Planning and Evaluation, HHS

The HHS Secretary Burwell’s Initiative on Prescription Opioids identifies a small and targeted set of actions that have the highest likelihood of producing clinically meaningful intermediate and long-term outcomes. The initiative began last year, is a broad, department-wide effort, and has three priority areas:

1. Opioid prescribing practices to reduce opioid use disorders and overdose
2. Expanded use and distribution of naloxone
3. Expansion of MAT to reduce opioid use disorders and overdose

Evidence of achieving these goals includes a reduction in emergency department visits for prescription opioid drug overdose and a reduction in opioid deaths overall. The initiative has three foci for maximizing impact within three years:

1. Opioid prescribing practices

• Effort in this area is targeted to i) education (improving clinical prescribing practices through CDC-issued guidelines, which are still in development), mandatory prescriber training, and other resources and ii) PDMP programs (linked to electronic health records/information technology, increased data-sharing).
• Progress to-date includes an increase in the number of PDMPs prompted through a CDC funding announcement (17 state awards), a partnership with professional organizations for training in prescribing practices, and increased funding dedicated to expanding PDMP data access to all states for extensions.

2. Naloxone use and availability

• Effort in this area relates to the development of new, more user-friendly formulations of naloxone (auto-injectable and nasal versions of naloxone), dissemination of best practices in naloxone delivery, and expansion of naloxone use and the ability to purchase this MAT.
• Progress to-date includes issuance of grants to expand access, recent FDA approval of a nasal naloxone formulation, and identification of best practices.

3. Expanded use of MAT

• Effort in this area involves funding research to identify the most effective use of MAT, to identify and develop new MAT, and to increase access to MAT services.
• Progress to-date includes establishment of a rule-making process and altering the size limitation on buprenorphine.
• SAMHSA is awarding $11 million to 11 states to expand and enhance MAT services.
• The Health Resources and Services Administration issued a funding announcement to make $100 million in new funding available to approximately 300 Community Health Centers to expand services for those with substance use disorders, including medication-assisted treatment for opioid use disorder.
• The Centers for Medicare & Medicaid Services (CMS) is releasing guidance to help states implement comprehensive, evidence-based service delivery approaches to substance use disorder treatment.

HHS recognizes that the issue of prescription misuse is a complex problem requiring an integrated solution. It requires meaningful interoperability in health IT systems, parity legislation (expansion from 2008 law), and partnering with industry for new innovative products (e.g., MAT, overdose prevention).
 
Discussion points (combined from previous two presentations)

• IPRCC members agreed with the need to reduce mortality due to overdose of prescription opioids but expressed concern that a federal focus on addiction and misuse without a balanced focus on improved pain management may divert attention and resources from effective care for people with chronic pain. Dr. Frank recognized the dual problems of chronic pain treatment and opioid misuse, and the tension that emerges between those issues. He noted that HHS aims to avoid unintended consequences such as potential loss of access to opioids for patients who need them and that CMS is carefully monitoring this potential outcome. The National Pain Strategy, currently pending HHS clearance, also will help to align opioid use with pain care strategies.
• One IPRCC member noted that the federal government spends 4 cents per patient for pain research. More research is needed to identify alternate (non-opioid) modes of chronic pain therapy.
• NIDA has an active research program on MAT/abuse deterrents for opioids, and other NIH ICs are studying behavioral, integrative, and other treatment strategies for chronic pain.
• Interactions with industry are important to grow the pipeline of new treatments.
• Proper medication disposal is key to ensuring that medications are not available for diversion.
• There is a need to work with CMS to provide reimbursement for non-pharmacologic  treatments.

 

Update on the National Pain Strategy

Wanda Jones, Dr PH, Principal Deputy Assistant Secretary for Health, Office of the Assistant Secretary for Health, HHS

Dr. Jones reported that the National Pain Strategy (NPS) is entering departmental HHS clearance, after which it will proceed toward final release, expected in early 2016. Robust input on a draft of the NPS posted through the Federal Register in May 2015 generated more than 700 public comments, which were helpful in revising the document. Timing of the development of the NPS is apt, due to the confluence of attention to opioid overprescribing and misuse and the need for better pain care.  The NPS will be strengthened through integration with efforts to curb opioid harm, which were summarized earlier in the day.  It will provide an important piece of a comprehensive package to address both of these significant public health problems. Relieving the burden of pain through improved provider and patient education, more accessible multidisciplinary pain management strategies, and development of new therapies will mitigate the overprescribing of prescription analgesics and reduce their availability for inappropriate use.

The NPS provides a set of discrete and achievable action items for pain and pain care that address the recommendations of the 2011 IOM report on pain. The NPS objectives will increase public awareness around living with chronic pain, improve provider education for pain care, improve prevention through self-management strategies, improve care through access to patient-centered and team-based approaches to care, and increase understanding of pain prevalence and effectiveness of interventions at the population level. 

HHS recognizes that prescription opioids are an essential component of pain management and that access to safe and effective care for people suffering from pain remains a priority that needs to be balanced in parallel with efforts to minimize the harms from opioids. The overprescribing of opioids and associated rates of adverse effects must be addressed in parallel with patient needs. Policies in these areas should strike a balance between minimizing abuse of prescription drugs and the need to ensure access for their legitimate use.
 
Discussion points

• The committee members endorsed the CDC’s goal to reduce deaths due to overdose of prescription opioids.
• A committee member expressed a concern about linking the release of the NPS with that of the CDC Guideline on Opioid Prescribing for Chronic Pain. Dr. Jones noted that there are complementary roles between the NPS and the guidelines. While the exact release date of the guideline was uncertain, it might be likely that the NPS will be released slightly in advance of the guideline. Dr. Koroshetz noted that safer opioid prescribing is an essential component of the NPS and the two documents should be seen as complimentary and coordinated in their messaging.
• Dr. Jones noted that she would relay concerns to HHS that the NPS recommendations for integrated pain management be supported financially.

 

CDC Guidelines on Opioid Prescribing for Chronic Pain

Sara Patterson, MA, Associate Director for Policy, CDC – substitute for Debra Houry, MD, MPH, Director of the CDC National Center for Injury Prevention

A recent, well-publicized study determined that drug overdose is the leading driver of rising midlife mortality.[8] Opioid overdose deaths, sales, and treatment admissions have risen in parallel, according to data from CDC’s National Vital Statistics System, DEA’s Automation of Reports and Consolidated Orders System, and the Substance Abuse and Mental Health Services (SAMHSA) TEDS database. Three-quarters of people reporting use of opioids and heroin started using prescription opioids first.[9] Use of heroin has risen sharply, doubling between 2007 and 2012. Ms. Patterson reported that half of the U.S. opioids market is for chronic, non-cancer pain.

In light of these data, CDC embarked on an effort to develop prescribing guidelines for opioids for chronic pain in the primary-care (adult) setting. The CDC guidelines are not intended for cancer care, end-of-life, or palliative care situations. They are non-regulatory and do not specify standard of care – calling for providers to use their own judgment for individual patients. Clinical areas of focus include determining when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use.

To formulate these draft guidelines, CDC relied heavily on the September 2014 AHRQ systematic review, The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain. The draft summary of the recommendations in the CDC prescribing guideline center on three main areas:

• Non-opioid therapy is preferred for chronic pain outside of active cancer, palliative, and end-of-life care.
• When opioids are used, the lowest possible effective dosage should be prescribed to reduce risks of opioid use disorder and overdose.
• Providers should always exercise caution when prescribing opioids and monitor all patients closely.

Discussion points

• Committee members agreed with the CDC’s goal to stem the tide of overdose deaths due to prescription opioids.
• Committee members raised concern about the selection and representation among the membership of the expert panel and the lack of inclusion of people who suffer from pain or their advocates.
• Committee members cited limited opportunities for public comment on the draft of the guideline during its development. CDC webinars provided an avenue for comments. Some felt that this method did not provide adequate opportunity for feedback.
• Concerns were expressed over the transparency of the deliberations of the experts and the role of the federal agencies in developing the guidelines. Ms. Patterson noted that federal partners were invited to observe deliberations and agencies received the document for comment during the HHS clearance process.
• There were questions and discussion on the rationale for low or very low quality of evidence to drive strong recommendations in the draft CDC guidelines. Ms. Patterson described the Grading of Recommendations Assessment, Development and Evaluation method for appraising controlled studies and making recommendations for guidelines.
• There was concern that prescribers and payers are likely to enforce guidelines inflexibly even if they are not mandatory or standard-of-care, potentially lowering provider incentive to individualize chronic-pain care.
• A concern was raised as to whether the weak evidence made the determination of the strength of the recommendation overly dependent on the make-up of the panel. 

 

Prescribing Guidelines, the NPS, and Clinical Practice: Moderated Discussion

Judith Paice, RN, PhD, Northwestern University & Richard Payne, MD, Duke University

A list of the draft CDC opioid-prescribing recommendations was presented, after which there was further discussion of the draft CDC guidelines. It was noted that although the guidelines are not mandatory, there are many examples of publicly issued guidelines in other health areas that have introduced confusion and ambiguity for both prescribers and patients. There was concern that the CDC guidelines will be coded into policy and limit prescriber flexibility.
Specific comments were made. For example, it was noted that recommendations for “lowest effective dosing levels” will be confounded by the difficulty of predicting effective doses for an individual.
 The need to recognize hurdles to sharing and accessing PDMP data (no access to VA data was an example) was noted as were potential inconsistencies with FDA labeling.
Pain management should be viewed as a systems issue.  Limiting patient access to opioids may have unintentional consequences in that they may turn to other substance use.  
Dr. Koroshetz thanked the IPRCC members for their thoughtful contributions and discussion of the CDC guidelines.  He urged the group to keep a patient focus, noting that patients suffering from painful conditions will benefit greatly if the pain community helps drive the messaging about safe and effective opioid use.  
As an immediate action step, IPRCC members agreed to provide a scholarly critique to the CDC along with an offer to assist with balanced messaging on the dual problems of pain and opioid harm to accompany the guideline’s release. The time frame to deliver this letter was short as it was set to precede the release of the guidelines so that the CDC might consider their suggested revisions. The group agreed Dr. Judith Paice and Dr. Richard Payne will coordinate the effort. 

 

Update on the Federal Pain Research Strategy

Allan Basbaum, PhD, University of California, San Francisco

The IPRCC is overseeing development of the Federal Pain Research Strategy (FPRS), a strategic plan for pain research across federal agencies, which will help to address a subset of the mandates of the IPRCC:

• Identify gaps in basic and clinical research on the symptoms and causes of pain
• Make recommendations to ensure that the activities of the NIH and other federal agencies are free of unnecessary duplication of effort

The strategy also will complete the IOM recommendations to enhance pain research, through developing an agenda for physiological, clinical, behavioral, psychological, outcomes, and health services research as a parallel effort to the NPS.

The FPRS organizational structure consists of a steering committee and several working groups, which span the continuum of pain:

• Prevention of acute and chronic pain
• Acute pain and acute pain management
• Transition from acute to chronic pain
• Chronic pain and chronic pain management
• Disparities

The working groups (all co-chairs have been selected, and 8 to 12 members will comprise each group) will make recommendations to advance pain science, with oversight from the steering committee and a final deliverable of recommendations to the IPRCC in December 2016. The NINDS Office of Pain Policy will provide logistical support and resources. The work groups will develop recommendations which will be prioritized and provided to the federal agencies that support pain research.  The recommendations are intended to advance the science.
 
Discussion points

• At least one federal representative will be part of each working group.
• Lay members should also participate in the working groups.
• Individuals can “float” between multiple working groups.

 
Adjourn

 Following 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.
 

[1] Weng HJ, et al. Tmem100 Is a Regulator of TRPA1-TRPV1 Complex and Contributes to Persistent Pain. Neuron. 2015 Feb 18;85(4):833-46.
[2] Park SI, et al. Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. Nat Biotechnol. 2015 Nov 9.
[3] Sorge RE, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci. 2015 Aug;18(8):1081-3.
[4] Muhuri, P. et. al., Associations of Nonmedical Pain Reliever Use and Initiation of Heroin Use in the United States, CBHSQ Data Review (August 2013).  
[5] Reuben DB, et al. National Institutes of Health Pathways to Prevention Workshop: the role of opioids in the treatment of chronic pain. Ann Intern Med. 2015 Feb 17;162(4):295-300.
[6] National Institutes of Health Pathways to Prevention Workshop: the Role of Opioids in the Treatment of Chronic Pain.
[7] A NIDA SBIR grant led to development of a novel prescription drug deactivation/ disposal system, Medsway™, which is now available commercially.
[8] Case A, Deaton A. Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century. Proc Natl Acad Sci U S A. 2015 Nov 2. pii: 201518393. [Epub ahead of print]
[9] Jones CM. Heroin use and heroin use risk behaviors among nonmedical users of prescription opioid pain relievers – United States, 2002–2004 and 2008–2010. Drug Alcohol Depend. 2013 Sep 1;132(1-2):95-100.