Challenges and opportunities for research clinicians interested in pain: results of a survey.

The National Institutes of Health and its independent advisors recognize the need to develop a strong pain research workforce and provide opportunities, particularly for clinicians, to pursue research careers. A survey was conducted to better understand the challenges facing the clinical pain research community. Respondents reported that time and funding to pursue research were the most critical factors either enabling or holding them back from a research career. Respondents who received some kind of formal research training or mentorship were more likely than those who did not to have federal research funding and to be at more advanced stages of their careers. The findings point to a need for all stakeholders in the pain research community to help formalize research training and provide funding or protected time to support the ambitions of aspiring researchers.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Access to and Models of Care.

Rising compounding prevalence of inflammatory bowel disease (IBD) (Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18:56-66.) and pandemic-exacerbated health system resource limitations have resulted in significant variability in access to high-quality, evidence-based, person-centered specialty care for Canadians living with IBD. Individuals with IBD have identified long wait times, gaps in biopsychosocial care, treatment and travel expenses, and geographic and provider variation in IBD specialty care and knowledge as some of the key barriers to access. Care delivered within integrated models of care (IMC) has shown promise related to impact on disease-related outcomes and quality of life. However, access to these models is limited within the Canadian healthcare systems and much remains to be learned about the most appropriate IMC team composition and roles. Although eHealth technologies have been leveraged to overcome some access challenges since COVID-19, more research is needed to understand how best to integrate eHealth modalities (i.e., video or telephone visits) into routine IBD care. Many individuals with IBD are satisfied with these eHealth modalities. However, not all disease assessment and monitoring can be achieved through virtual modalities. The need for access to person-centered, objective disease monitoring strategies, inclusive of point of care intestinal ultrasound, is more pressing than ever given pandemic-exacerbated restrictions in access to endoscopy and cross-sectional imaging. Supporting learning healthcare systems for IBD and research relating to the strategic use of innovative and integrative implementation strategies for evidence-based IBD care interventions are greatly needed. Data derived from this research will be essential to appropriately allocating scarce resources aimed at improving person-centred access to cost-effective IBD care.

Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures.

ABSTRACT: Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Impact of preventive pill-based treatment on migraine days: A secondary outcome study of the Childhood and Adolescent Migraine Prevention (CHAMP) trial and a comparison of self-report to nosology-derived assessments.

OBJECTIVE: To examine group differences in self-reported migraine days among youth who completed the Childhood and Adolescent Migraine Prevention (CHAMP) trial prior to its closure and explore the relationship between self-reported and "nosology-derived" (i.e., International Classification of Headache Disorders, 3rd edition [ICHD-3]) migraine days. BACKGROUND: The CHAMP trial compared amitriptyline and topiramate to placebo for migraine prevention in youth and proposed to analyze change in migraine days as a secondary outcome. There is considerable variability in the field regarding what constitutes a "migraine day," how this is determined and reported in trials, and how consistent these measures are with diagnostic nosology. METHODS: CHAMP trial completers (N = 175) were randomized to receive amitriptyline (n = 77), topiramate (n = 63), or placebo (n = 35). Participants maintained daily headache diaries where they reported each day with headache and if they considered that headache to be a migraine. For each headache day, participants completed a symptom record and reported about symptoms such as pain location(s) and presence of nausea/vomiting or photophobia and phonophobia. We examined group differences in self-reported migraine days at trial completion (summed from trial weeks 20-24) compared to baseline. We also used an algorithm to determine whether participants' symptom reports met ICHD-3 criteria for migraine without aura, and examined the association between self-reported and "nosology-derived" migraine days. RESULTS: Results showed no significant differences between groups in self-reported migraine days over the course of the trial. Self-reported and "nosology-derived" migraine days during the baseline and treatment phases were strongly associated (r's = 0.73 and 0.83, respectively; p's < 0.001). CONCLUSION: Regardless of treatment, CHAMP trial completers showed clinically important reductions in self-reported migraine days over the course of the trial (about 3.8 days less). The strong association between self-reported and "nosology-derived" migraine days suggests youth with migraine can recognize a day with migraine and reliably report their headache features and symptoms. Greater rigor and transparency in the calculation and reporting of migraine days in trials is needed.

Health care utilization differences between First Nations people and the general population with inflammatory bowel disease: a retrospective cohort study from Saskatchewan, Canada.

BACKGROUND: Indigenous people in Canada often face barriers to access specialized care, with limited data in evaluating health care utilization among Indigenous people with inflammatory bowel disease (IBD). We aimed to compare health care utilization between First Nations patients and those in the general population diagnosed with IBD in Saskatchewan. METHODS: We conducted a patient-oriented, population-based, retrospective cohort study by linking administrative health databases of Saskatchewan between fiscal years 1998/99 and 2017/18. We designed and completed this study in partnership with Indigenous patients and family advocates. We applied a validated algorithm to identify IBD incident cases and then used the self-declared First Nations status variable to divide those cases. We applied a 1:5 ratio for age and sex matching and used Cox proportional models to assess associations. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. RESULTS: We created a matched cohort with 696 IBD incident cases: 116 First Nations patients and 580 patients in the general population. We observed differences between the groups for IBD-specific hospital admissions (HR 1.33, 95% CI 1.01-1.75), IBD-related hospital admissions (HR 1.55, 95% CI 1.20-2.01), medication claims for IBD (HR 0.52, 95% CI 0.41-0.65) and 5-aminosalicylic acid claims (HR 0.56, 95% CI 0.45-0.71) adjusting by rural or urban residence and diagnosis type. There were no significant differences in the hazard rate of outpatient gastroenterology visits (HR 1.13, 95% CI 0.90-1.41), colonoscopies (HR 1.14, 95% CI 0.92-1.41) and surgeries for IBD (HR 1.14, 95% CI 0.80-1.64). INTERPRETATION: We identified that First Nations patients diagnosed with IBD had a higher rate of hospital admissions owing to IBD than patients in the general population diagnosed with IBD. We also found an inverse association between First Nations status and having prescription medication claims for IBD.

A Review of Potential National Chronic Pain Surveillance Systems in the United States.

Pain has been established as a major public health problem in the United States (U.S.) with 50 million adults experiencing chronic pain and 20 million afflicted with high-impact chronic pain (ie, chronic pain that interferes with life or work activities). High financial and social costs are associated with chronic pain. Over the past 2 decades, pain management has been complicated by the marked increase in opioids prescribed to treat chronic noncancer pain and by the concurrent opioid crisis. Monitoring the prevalence of chronic pain and pain management is especially important because pain management is changing in uncertain ways. We review potential U.S. chronic pain surveillance systems, present potential difficulties of chronic pain surveillance, and explore how to address chronic pain surveillance in the current opioid era. We consider case definitions, severity, anatomic site, and varieties of chronic pain management strategies in reviewing and evaluating national surveys for chronic pain surveillance. Based on the criteria evaluated, the National Health Interview Survey offers the best single source for pain surveillance as the pain-related questions administered are brief, valid, and cover a broad scope of pain-related phenomena. PERSPECTIVE: This review article describes data sources that can be leveraged to conduct national chronic pain surveillance in the United States, explores case defining or pain-related questions administered, and evaluates them against 8 surveillance attributes.

Trajectory of treatment response in the child and adolescent migraine prevention (CHAMP) study: A randomized clinical trial.

OBJECTIVE: Identify preventive medication treatment response trajectories among youth participating in the Childhood and Adolescent Migraine Prevention study. METHODS: Data were evaluated from 328 youth (ages 8-17). Childhood and Adolescent Migraine Prevention study participants completed headache diaries during a 28-day baseline period and a 168-day active treatment period during which youth took amitriptyline, topiramate, or placebo. Daily headache occurrence trajectories were established across baseline and active treatment periods using longitudinal hierarchical linear modeling. We tested potential treatment group differences. We also compared final models to trajectory findings from a clinical trial of cognitive behavioral therapy plus amitriptyline for youth with chronic migraine to test for reproducibility. RESULTS: Daily headache occurrence showed stability across baseline. Active treatment models revealed decreases in headache frequency that were most notable early in the trial period. Baseline and active treatment models did not differ by treatment group and replicated trajectory cognitive behavioral therapy plus amitriptyline trial findings. CONCLUSIONS: Replicating headache frequency trajectories across clinical trials provides strong evidence that youth can improve quickly. Given no effect for medication, we need to better understand what drives this clinically meaningful improvement. Results also suggest an expected trajectory of treatment response for use in designing and determining endpoints for future clinical trials.Trial Registration. ClinicalTrials.gov Identifier: NCT01581281.

Increasing Prevalence and Stable Incidence Rates of Inflammatory Bowel Disease Among First Nations: Population-Based Evidence From a Western Canadian Province.

BACKGROUND: There is limited to no evidence of the prevalence and incidence rates of inflammatory bowel disease (IBD) among Indigenous peoples. In partnership with Indigenous patients and family advocates, we aimed to estimate the prevalence, incidence, and trends over time of IBD among First Nations (FNs) since 1999 in the Western Canadian province of Saskatchewan. METHODS: We conducted a retrospective population-based study linking provincial administrative health data from the 1999-2000 to 2016-2017 fiscal years. An IBD case definition requiring multiple health care contacts was used. The prevalence and incidence data were modeled using generalized linear models and a negative binomial distribution. Models considered the effect of age groups, sex, diagnosis type (ulcerative colitis [UC], Crohn disease [CD]), and fiscal years to estimate prevalence and incidence rates and trends over time. RESULTS: The prevalence of IBD among FNs increased from 64/100,000 (95% confidence interval [CI], 62-66) in 1999-2000 to 142/100,000 (95% CI, 140-144) people in 2016-2017, with an annual average increase of 4.2% (95% CI, 3.2%-5.2%). Similarly, the prevalence of UC and CD, respectively, increased by 3.4% (95% CI, 2.3%-4.6%) and 4.1% (95% CI, 3.3%-4.9%) per year. In contrast, the incidence rates of IBD, UC, and CD among FNs depicted stable trends over time; no statistically significant changes were observed in the annual change trend tests. The ratio of UC to CD was 1.71. CONCLUSIONS: We provided population-based evidence of the increasing prevalence and stable incidence rates of IBD among FNs. Further studies are needed in other regions to continue understanding the patterns of IBD among Indigenous peoples.

Multimodal Assessment of Medication Adherence Among Youth With Migraine: An Ancillary Study of the CHAMP Trial.

OBJECTIVE: Examine preventive medication adherence among youth with migraine. METHODS: Adherence (self-report, pill count, and blood serum drug levels) was assessed as an ancillary study that utilized data from 328 CHAMP Study participants (ages 8-17). CHAMP was a multisite trial of preventive medications. Participants completed a prospective headache diary during a six-month active treatment period during which youth took amitriptyline, topiramate, or placebo pill twice daily. Self-reported medication adherence was collected via daily diary. At monthly study visits, pill count measures were captured. At trial month 3 (trial midpoint) and 6 (end of active trial), blood serum drug levels were obtained. Self-report and pill count adherence percentages were calculated for the active trial period, at each monthly study visit, and in the days prior to participants' mid-trial blood draw. Percentages of nonzero drug levels were calculated to assess blood serum drug level data. Adherence measures were compared and assessed in context of several sociodemographic factors. Multiple regression analyses investigated medication adherence as a predictor of headache outcomes. RESULTS: Self-report and pill count adherence rates were high (over 90%) and sustained over the course of the trial period. Serum drug level adherence rates were somewhat lower and decreased significantly (from 84% to 76%) across the trial period [t (198) = 3.23, p = .001]. Adherence measures did not predict headache days at trial end; trial midpoint serum drug levels predicted headache-related disability. CONCLUSIONS: Youth with migraine can demonstrate and sustain relatively high levels of medication adherence over the course of a clinical trial.

NIH's Helping to End Addiction Long-termSM Initiative (NIH HEAL Initiative) Clinical Pain Management Common Data Element Program.

The Helping to End Addiction Long-term Initiative (NIH HEAL Initiative) is an aggressive trans-NIH effort to speed solutions to stem the national opioid public health crisis, including through improved pain management. Toward this end, the NIH HEAL Initiative launched a common data element (CDE) program to ensure that NIH-funded clinical pain research studies would collect data in a standardized way. NIH HEAL Initiative staff launched a process to determine which pain-related core domains should be assessed by every clinical pain study and what questionnaires are required to ensure that the data is collected uniformly. The process involved multiple literature reviews, and consultation with experts inside and outside of NIH and the investigators conducting studies funded by the initiative. Ultimately, 9 core pain domains, and questionnaires to measure them, were chosen for studies examining acute pain and chronic pain in adults and pediatric populations. These were augmented with dozens of study-specific supplemental questionnaires to enable uniform data collection methods of outcomes outside of the core domains. The selection of core domains will ensure that valuable clinical pain data generated by the initiative is standardized, useable for secondary data analysis, and useful for guiding future research, clinical practice decisions, and policymaking. PERSPECTIVE: The NIH HEAL Initiative launched a common data element program to ensure that NIH-funded clinical pain research studies would collect data in a standardized way. Nine core pain domains and questionnaires to measure them were chosen for studies examining acute pain and chronic pain in adults and pediatric populations.

Prevalence of Headache Days and Disability 3 Years After Participation in the Childhood and Adolescent Migraine Prevention Medication Trial.

Importance: Migraine is a common neurological disease that often begins in childhood and continues into adulthood; approximately 6 million children and adolescents in the United States cope with migraine, and many frequently experience significant disability and multiple headache days per week. Although pharmacological preventive treatments have been shown to offer some benefit to youth with migraine, additional research is needed to understand whether and how these benefits are sustained. Objective: To survey clinical status of youth with migraine who participated in the 24-week Childhood and Adolescent Migraine Prevention (CHAMP) trial over a 3-year follow-up period. Design, Setting, and Participants: This survey study used internet-based surveys collected from youth ages 8 to 17 years at 3, 6, 12, 18, 24, and 36 months after completion of the CHAMP trial, which randomized participants to amitriptyline, topiramate, or placebo. At the end of the trial, the study drug was stopped, and participants received clinical care of their choice thereafter. The CHAMP trial was conducted between May 2012 and November 2015, and survey follow-up was conducted June 2013 to June 2018. Participants in this survey study were representative of those randomized in the trial. Data were analyzed from March 2020 to April 2021. Exposures: Survey completion. Main Outcomes and Measures: Headache days, disability (assessed using the Pediatric Migraine Disability Scale [PedMIDAS]), and self-report of ongoing use of prescription preventive medication. Results: A total of 205 youth (mean [SD] age, 14.2 [2.3] years; 139 [68%] girls; mean [SD] history of migraine, 5.7 [3.1] years) participated in the survey. Retention of participants was 189 participants (92%) at month 6, 182 participants (88%) at month 12, 163 participants (80%) at month 18, 165 participants (80%) at month 24, and 155 participants (76%) at month 36. Over the course of the 3-year follow-up, participants consistently maintained meaningful reductions in headache days (mean [SD] headache days per 28 days: CHAMP baseline, 11.1 [6.0] days; CHAMP completion, 5.0 [5.7] days; 3-year follow-up, 6.1 [6.1] days) and disability (mean [SD] score: CHAMP baseline, 40.9 [26.4]; CHAMP completion, 17.9 [22.1]; 3-year follow-up, 12.3 [20.0]). At 3 years after completion of the CHAMP trial, headache days were approximately 1.5 per week (changed from about 3 per week at trial baseline) and disability had improved from the moderate range to the low mild range on the PedMIDAS. Longitudinal analyses showed that amitriptyline and topiramate did not explain intercept random effects for either mean rate of headache days per week (amitriptyline: estimate [SE], 0.07 [0.05]; P = .16; topiramate: estimate [SE], 0.04 [0.05]; P = .50) or headache disability PedMIDAS total score (amitriptyline: estimate [SE], 0.25 [0.38]; P = .52; topiramate: estimate [SE], -0.09 [0.39]; P = .82) changes over time. Of 153 participants who reported on prescription drug use at 3 years, only 1 participant (1%) reported using prevention medication, and most participants reported no medication use at most time points. Conclusions and Relevance: These findings suggest that children and adolescents with longer than 5 years history of migraine who participated in the CHAMP trial may sustain positive clinical outcomes over time, even after discontinuing preventive pill-based treatment. This survey study could inform use and discontinuation timing of pharmacological preventive therapies for migraine in youth ages 8 to 17 years. Research is needed to examine mechanisms of treatment improvement and maintenance for preventive therapies, as well as placebo, in the pediatric population.

Impact of carbonation on neurogenic dysphagia and an exploration of the clinical predictors of a response to carbonation.

BACKGROUND: The need for effective compensatory strategies in neurogenic dysphagia management has led to the exploration of sensory enhancement strategies (SES), such as carbonated liquids. Despite some positive findings, evidence related to the efficacy of carbonation as an SES is limited. AIMS: To determine if carbonated thin liquids reduced dysphagia symptoms and to explore clinical factors associated with response to carbonation. METHODS & PROCEDURES: Participants (n = 29) with neurogenic dysphagia demonstrating deep penetration or aspiration on thin liquids during videofluoroscopic swallow studies (VFSS) completed a set protocol: discrete sips of non-carbonated thin fluids (DS-NC) followed by discrete sips of carbonated thin fluids (DS-C) and then consecutive sips of carbonated fluids (CS-C). The impact of carbonation was identified through changes to swallow physiology (videofluoroscopy dysphagia scale-VDS) and depth of airway compromise (penetration-aspiration scale-PAS). Demographic variables including genetic taste type, cranial nerve function and key results from the VDS were examined for association with carbonation response using both individual parameter analysis and exploratory cluster analysis. OUTCOMES & RESULTS: Significant (p < 0.05) improvements in PAS scores were noted in DS-C and CS-C conditions compared with DS-NC. Total VDS score was also significantly (p < 0.05) reduced (i.e., improved function) in the DS-NC condition. Individual variability in response to carbonation was noted and no clear clinical factors associated with carbonation response in the current set of parameters were identified. CONCLUSION & IMPLICATIONS: Findings support that carbonated thin fluids sometimes result in neurogenic dysphagia symptom reduction. However, identifying the clinical characteristics of patients who may benefit from trials of carbonation needs further investigation.

Prevalence and Profile of High-Impact Chronic Pain in the United States.

The multidimensional nature of chronic pain is not reflected by definitions based solely on pain duration, resulting in high prevalence estimates limiting effective policy development. The newly proposed concept of high-impact chronic pain (HICP) incorporates both disability and pain duration to identify a more severely impacted portion of the chronic pain population yet remains uncharacterized at the population level. As such, we used the 2011 National Health Interview Survey (N = 15,670) to 1) assess the likelihood of disability in the overall chronic pain population, 2) estimate the prevalence of HICP, and 3) characterize the disability, health status, and health care use profile of this population in the United States. Overall, chronic pain, defined as pain experienced on most days or every day in the previous 3 months, was strongly associated with an increased risk of disability after controlling for other chronic health conditions (odds ratio = 4.43; 95% confidence interval = 3.73-5.26), where disability was more likely in those with chronic pain than in those with stroke or kidney failure, among others. HICP affected 4.8% of the U.S. adult population, or approximately 10.6 million individuals, in 2011. The HICP population reported more severe pain and more mental health and cognitive impairments than persons with chronic pain without disability, and was also more likely to report worsening health, more difficulty with self-care, and greater health care use. HICP clearly represents a more severely impacted portion of the chronic pain population. Understanding this heterogeneity will contribute to developing more effective legislation promoting safe and cost-effective approaches to the prevention and treatment of chronic pain. PERSPECTIVE: HICP is a powerful new classification that differentiates those with debilitating chronic pain from those with less impactful chronic pain. By addressing the multidimensionality of chronic pain, this classification will improve clinical practice, research, and the development of effective health policy.

Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults - United States, 2016.

Chronic pain, one of the most common reasons adults seek medical care (1), has been linked to restrictions in mobility and daily activities (2,3), dependence on opioids (4), anxiety and depression (2), and poor perceived health or reduced quality of life (2,3). Population-based estimates of chronic pain among U.S. adults range from 11% to 40% (5), with considerable population subgroup variation. As a result, the 2016 National Pain Strategy called for more precise prevalence estimates of chronic pain and high-impact chronic pain (i.e., chronic pain that frequently limits life or work activities) to reliably establish the prevalence of chronic pain and aid in the development and implementation of population-wide pain interventions (5). National estimates of high-impact chronic pain can help differentiate persons with limitations in major life domains, including work, social, recreational, and self-care activities from those who maintain normal life activities despite chronic pain, providing a better understanding of the population in need of pain services. To estimate the prevalence of chronic pain and high-impact chronic pain in the United States, CDC analyzed 2016 National Health Interview Survey (NHIS) data. An estimated 20.4% (50.0 million) of U.S. adults had chronic pain and 8.0% of U.S. adults (19.6 million) had high-impact chronic pain, with higher prevalences of both chronic pain and high-impact chronic pain reported among women, older adults, previously but not currently employed adults, adults living in poverty, adults with public health insurance, and rural residents. These findings could be used to target pain management interventions.

Prescription Drug Coverage for Treatment of Low Back Pain Among US Medicaid, Medicare Advantage, and Commercial Insurers.

Importance: Despite unprecedented injuries and deaths from prescription opioids, little is known regarding medication coverage policies for the treatment of chronic noncancer pain among US insurers. Objective: To assess medication coverage policies for 62 products used to treat low back pain. Design, Setting, and Participants: A cross-sectional study of health plan documents from 15 Medicaid, 15 Medicare Advantage, and 20 commercial health plans in 2017 from 16 US states representing more than half the US population and 20 interviews with more than 43 senior medical and pharmacy health plan executives from representative plans. Data analysis was conducted from April 2017 to January 2018. Main Outcomes and Measures: Formulary coverage, utilization management, and patient out-of-pocket costs. Results: Of the 62 products examined, 30 were prescription opioids and 32 were nonopioid analgesics, including 10 nonsteroidal anti-inflammatory drugs, 10 antidepressants, 6 muscle relaxants, 4 anticonvulsants, and 2 topical analgesics. Medicaid plans covered a median of 19 opioids examined (interquartile range [IQR], 12-27; median, 63%; IQR, 40%-90%) and a median of 22 nonopioids examined (IQR, 21-27; median, 69%; IQR, 66%-83%). Medicare Advantage plans covered similar proportions (median [IQR], opioids: 17 [15-22]; 57% [50%-73%]; nonopioids: 22 [22-26]; 69% [69%-81%]), while commercial plans covered more opioids (median [IQR], 23 [21-25]; 77% [70%-84%]) and nonopioids (median [IQR], 26 [24-27]; 81% [74%-85%]). Utilization management strategies were common for opioids in Medicaid plans (median [IQR], 15 [11-20] opioids; 91% [74%-97%]), Medicare Advantage plans (median [IQR], 15 [9-18] opioids; 100% [100%-100%]), and commercial plans (median [IQR], 16 [11-20] opioids; 74% [53%-94%]), generally relying on 30-day quantity limits rather than prior authorization. Step therapy was especially uncommon. Many of the nonopioids examined also were subject to utilization management, especially quantity limits (24%-32% of products across payers) and prior authorization (median [IQR], commercial plans: 2 [0-3] nonopioids; 9% [0%-11%]; Medicare Advantage plans: 4 [3-5] nonopioids; 19% [10%-23%]; Medicaid plans: 6 [1-13] nonopioids; 38% [2%-52%]). Among commercial plans, the median plan placed 18 opioids (74%) and 20 nonopioids (81%) in tier 1, which was associated with a median out-of-pocket cost of $10 (IQR, $9-$10) per 30-day supply. Key informant interviews revealed an emphasis on increasing opioid utilization management and identifying high-risk prescribers and patients, rather than promoting comprehensive strategies to improve treatment of chronic pain or better integrating pharmacologic and nonpharmacologic alternatives to opioids. Conclusions and Relevance: Given the effect of coverage policies on drug utilization and health outcomes, these findings provide an important opportunity to evaluate how formulary placement, utilization management, copayments, and integration of nonpharmacologic treatments can be optimized to improve pain care while reducing opioid-related injuries and deaths.

Coverage of Nonpharmacologic Treatments for Low Back Pain Among US Public and Private Insurers.

Importance: Despite epidemic rates of addiction and death from prescription opioids in the United States, suggesting the importance of providing alternatives to opioids in the treatment of pain, little is known regarding how payers' coverage policies may facilitate or impede access to such treatments. Objective: To examine coverage policies for 5 nonpharmacologic approaches commonly used to treat acute or chronic low back pain among commercial and Medicare Advantage insurance plans, plus an additional 6 treatments among Medicaid plans. Design, Setting, and Participants: Cross-sectional study of 15 commercial, 15 Medicaid, and 15 Medicare Advantage health plans for the 2017 calendar year in 16 states representing more than half of the US population. Interviews were conducted with 43 senior medical and pharmacy health plan executives from representative plans. Main Outcomes and Measures: Medical necessity and coverage status for the treatments examined, as well as the use of utilization management tools and cost-sharing magnitude and structure. Results: Commercial and Medicare insurers consistently regarded physical and occupational therapy as medically necessary, but policies varied for other therapies examined. Payers most commonly covered physical therapy (98% [44 of 45 plans]), occupational therapy (96% [43 of 45 plans]), and chiropractic care (89% [40 of 45 plans]), while transcutaneous electrical nerve stimulation (67% [10 of 15 plans]) and steroid injections (60% [9 of 15 plans]) were the most commonly covered among the therapies examined for Medicaid plans only. Despite evidence in the literature to support use of acupuncture and psychological interventions, these therapies were either not covered by plans examined (67% of all plans [30 of 45] did not cover acupuncture) or lacked information about coverage (80% of Medicaid plans [12 of 15] lacked information about coverage of psychological interventions). Utilization management tools, such as prior authorization, were common, but criteria varied greatly with respect to which conditions and what quantity and duration of services were covered. Interviewees represented 6 Medicaid managed care organizations, 2 Medicare Advantage or Part D plans, 9 commercial plans, and 3 trade organizations (eg, Blue Cross Blue Shield Association). Interviews with plan executives indicated a low level of integration between the coverage decision-making processes for pharmacologic and nonpharmacologic therapies for chronic pain. Conclusions and Relevance: Wide variation in coverage of nonpharmacologic treatments for low back pain may be driven by the absence of best practices, the administrative complexities of developing and revising coverage policies, and payers' economic incentives. Such variation suggests an important opportunity to improve the accessibility of services, reduce opioid use, and ultimately improve the quality of care for individuals with chronic, noncancer pain while alleviating the burden of opioid addiction and overdose.

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine.

BACKGROUND: Which medication, if any, to use to prevent the headache of pediatric migraine has not been established. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment. RESULTS: A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt. CONCLUSIONS: There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281 ).

United States National Pain Strategy for Population Research: Concepts, Definitions, and Pilot Data.

UNLABELLED: National Pain Strategy population research objectives include: estimating chronic pain prevalence, studying pain treatment with electronic health care data, and developing metrics to assess progress in reducing chronic pain impact. In this article, the National Pain Strategy Population Research Workgroup reviews concepts relevant to achieving these aims. High-impact chronic pain was defined as persistent pain with substantial restriction of life activities lasting 6 months or more. In pilot work, we tested a brief assessment of high-impact chronic pain, and used electronic health records data to describe pain-related health care. A mail survey of adult health plan enrollees (N = 770) reported that 14% had high-impact chronic pain. Relative to persons with lower-impact chronic pain, those with high-impact chronic pain were more often frequent users of health care for pain, reported lower quality of life, greater pain-related interference with activities, and more often reported pain at multiple anatomic locations. Analyses of health care data (N = 289,464) reported that pain patients had higher health care costs compared with others and that pain services were typically delivered in primary care. These results support the feasibility of developing data on chronic pain through national health interview surveys and large electronic health care databases. PERSPECTIVE: Pilot analyses supported the feasibility of brief chronic pain assessments suitable for national health surveys and use of electronic health care databases to develop data regarding trends in the delivery of pain treatments, costs, and effectiveness. These methods are relevant to achieving the aims of the US National Pain Strategy.

Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations.

There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for "precision medicine" or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.