Cognitive Behavioral Program for the Prevention of Depression in At-Risk Adolescents: Isolating the Effects of Dose.

The current study estimated effects of intervention dose (attendance) of a cognitive behavioral prevention (CBP) program on depression-free days (DFD) in adolescent offspring of parents with a history of depression. As part of secondary analyses of a multi-site randomized controlled trial, we analyzed the complete intention-to-treat sample of 316 at-risk adolescents ages 13-17. Youth were randomly assigned to the CBP program plus usual care (n=159) or to usual care alone (n=157). The CBP program involved 8 weekly acute sessions and 6 monthly continuation sessions. Results showed that higher CBP program dose predicted more DFDs, with a key threshold of approximately 75% of a full dose in analyses employing instrumental variable methodology to control multiple channels of bias. Specifically, attending at more than 75% of acute phase sessions led to 45.3 more DFDs over the 9-month period post randomization, which accounted for over 12% of the total follow-up days. Instrument sets were informed by study variables and external data including weather and travel burden. In contrast, conventional analysis methods failed to find a significant dose-outcome relation. Application of the instrumental variable approach, which better controls the influence of confounding, demonstrated that higher CBP program dose resulted in more DFDs.

Factors Affecting Post-trial Sustainment or De-implementation of Study Interventions: A Narrative Review.

In contrast to traditional randomized controlled trials, embedded pragmatic clinical trials (ePCTs) are conducted within healthcare settings with real-world patient populations. ePCTs are intentionally designed to align with health system priorities leveraging existing healthcare system infrastructure and resources to ease intervention implementation and increase the likelihood that effective interventions translate into routine practice following the trial. The NIH Pragmatic Trials Collaboratory, funded by the National Institutes of Health (NIH), supports the conduct of large-scale ePCT Demonstration Projects that address major public health issues within healthcare systems. The Collaboratory has a unique opportunity to draw on the Demonstration Project experiences to generate lessons learned related to ePCTs and the dissemination and implementation of interventions tested in ePCTs. In this article, we use case studies from six completed Demonstration Projects to summarize the Collaboratory's experience with post-trial interpretation of results, and implications for sustainment (or de-implementation) of tested interventions. We highlight three key lessons learned. First, ineffective interventions (i.e., ePCT is null for the primary outcome) may be sustained if they have other measured benefits (e.g., secondary outcome or subgroup) or even perceived benefits (e.g., staff like the intervention). Second, effective interventions-even those solicited by the health system and/or designed with significant health system partner buy-in-may not be sustained if they require significant resources. Third, alignment with policy incentives is essential for achieving sustainment and scale-up of effective interventions. Our experiences point to several recommendations to aid in considering post-trial sustainment or de-implementation of interventions tested in ePCTs: (1) include secondary outcome measures that are salient to health system partners; (2) collect all appropriate data to allow for post hoc analysis of subgroups; (3) collect experience data from clinicians and staff; (4) engage policy-makers before starting the trial.

Graded chronic pain scale revised: validation in a Veteran sample.

OBJECTIVE: The Graded Chronic Pain Scale (GCPS) is frequently used in pain research and treatment to classify mild, bothersome, and high impact chronic pain. This study's objective was to validate the revised version of the GCPS (GCPS-R) in a US Veterans Affairs (VA) healthcare sample to support its use in this high-risk population. METHODS: Data were collected from Veterans (n = 794) via self-report (GCPS-R and relevant health questionnaires) and electronic health record extraction (demographics and opioid prescriptions). Logistic regression, adjusting for age and gender, was used to test for differences in health indicators by pain grade. Adjusted odds ratio (AOR) with 95% confidence intervals (CIs) were reported with CIs not including an AOR of 1 indicating that the difference exceeded chance. RESULTS: In this population, the prevalence of chronic pain (pain present most or every day, prior 3 months) was 49.3%: 7.1% with mild chronic pain (mild pain intensity and lower interference with activities); 23.3% bothersome chronic pain (moderate to severe pain intensity with lower interference); and 21.1% high impact chronic pain (higher interference). Results of this study mirrored findings in the non-VA validation study; differences between bothersome and high impact were consistent for activity limitations and present but not fully consistent for psychological variables. Those with bothersome chronic pain or high impact chronic pain were more likely to receive long-term opioid therapy compared to those with no/mild chronic pain. CONCLUSIONS: Findings highlight categorical differences captured with the GCPS-R, and convergent validity supports use of the GCPS-R in US Veterans.

A Primary Care-Based Cognitive Behavioral Therapy Intervention for Long-Term Opioid Users With Chronic Pain : A Randomized Pragmatic Trial.

BACKGROUND: Chronic pain is common, disabling, and costly. Few clinical trials have examined cognitive behavioral therapy (CBT) interventions embedded in primary care settings to improve chronic pain among those receiving long-term opioid therapy. OBJECTIVE: To determine the effectiveness of a group-based CBT intervention for chronic pain. DESIGN: Pragmatic, cluster randomized controlled trial. (ClinicalTrials.gov: NCT02113592). SETTING: Kaiser Permanente health care systems in Georgia, Hawaii, and the Northwest. PARTICIPANTS: Adults (aged ≥18 years) with mixed chronic pain conditions receiving long-term opioid therapy. INTERVENTION: A CBT intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorist, nurse, physical therapist, and pharmacist) versus usual care. MEASUREMENTS: Self-reported pain impact (primary outcome, as measured by the PEGS scale [pain intensity and interference with enjoyment of life, general activity, and sleep]) was assessed quarterly over 12 months. Pain-related disability, satisfaction with care, and opioid and benzodiazepine use based on electronic health care data were secondary outcomes. RESULTS: A total of 850 patients participated, representing 106 clusters of primary care providers (mean age, 60.3 years; 67.4% women); 816 (96.0%) completed follow-up assessments. Intervention patients sustained larger reductions on all self-reported outcomes from baseline to 12-month follow-up; the change in PEGS score was -0.434 point (95% CI, -0.690 to -0.178 point) for pain impact, and the change in pain-related disability was -0.060 point (CI, -0.084 to -0.035 point). At 6 months, intervention patients reported higher satisfaction with primary care (difference, 0.230 point [CI, 0.053 to 0.406 point]) and pain services (difference, 0.336 point [CI, 0.129 to 0.543 point]). Benzodiazepine use decreased more in the intervention group (absolute risk difference, -0.055 [CI, -0.099 to -0.011]), but opioid use did not differ significantly between groups. LIMITATION: The inclusion of only patients with insurance in large integrated health care systems limited generalizability, and the clinical effect of change in scores is unclear. CONCLUSION: Primary care-based CBT, using frontline clinicians, produced modest but sustained reductions in measures of pain and pain-related disability compared with usual care but did not reduce use of opioid medication. PRIMARY FUNDING SOURCE: National Institutes of Health.

"I really had somebody in my corner." Patient experiences with a pharmacist-led opioid tapering program.

BACKGROUND: Opioid tapering has been identified as an effective strategy to prevent the dangers associated with long-term opioid therapy for patients with chronic pain. However, many patients are resistant to tapering, and conversations about tapering can be challenging for health care providers. Pharmacists can play a role in supporting both providers and patients with the process of opioid tapering. OBJECTIVE: Qualitatively describe patient experiences with a unique phone-based and pharmacy-led opioid tapering program implemented within an integrated health care system. METHODS: In-depth telephone interviews with patients who completed the program were recorded, transcribed, and analyzed. Themes were identified through a constant comparative approach. RESULTS: We completed 25 interviews; 80% of patients were women (20), with a mean age of 58 years, and 72% (18) had been using opioids for pain management for 10 or more years. Most (60%) described a positive and satisfying experience with the tapering program. Strengths of the program reported by patients included a patient-centered and compassionate taper approach, flexible taper pace, easy access to knowledgeable pharmacist advocates, and resultant improvements in quality of life (e.g., increased energy). Challenges reported included: unhelpful or difficult-to-access nonpharmacological pain management options, negative quality of life impacts (e.g., inability to exercise), and lack of choice in the taper process. At the end of tapering, most patients (72%) described their pain as reduced or manageable rather than worse and expressed willingness to use the program in the future if a need should arise. CONCLUSIONS: Patients in a pharmacist-led opioid tapering program appreciated the program's individualized approach to care and access to pharmacist' expertise. Most interviewed patients successfully reduced their opioid use and recommended that the program should continue as an offered service. To improve the program, patients suggested increased personalization of the taper process and additional support for withdrawal symptoms and nonpharmacological pain management.

Pre-implementation formative evaluation of cooperative pain education and self-management expanding treatment for real-world access: A pragmatic pain trial.

OBJECTIVE: Cognitive behavioral therapy for chronic pain (CBT-CP) is an evidence-based treatment for improving functioning and pain intensity for people with chronic pain with extensive evidence of effectiveness. However, there has been relatively little investigation of the factors associated with successful implementation and uptake of CBT-CP, particularly clinician and system level factors. This formative evaluation examined barriers and facilitators to the successful implementation and uptake of CBT-CP from the perspective of CBT-CP clinicians and referring primary care clinicians. METHODS: Qualitative interviews guided by the Consolidated Framework for Implementation Research were conducted at nine geographically diverse Veterans Affairs sites as part of a pragmatic clinical trial comparing synchronous, clinician-delivered CBT-CP and remotely delivered, technology-assisted CBT-CP. Analysis was informed by a grounded theory approach. RESULTS: Twenty-six clinicians (CBT-CP clinicians = 17, primary care clinicians = 9) from nine VA medical centers participated in individual qualitative interviews conducted by telephone from April 2019 to August 2020. Four themes emerged in the qualitative interviews: (1) the complexity and variability of referral pathways across sites, (2) referring clinician's lack of knowledge about CBT-CP, (3) referring clinician's difficulty identifying suitable candidates for CBT-CP, and (4) preference for interventions that can be completed from home. CONCLUSIONS: This formative evaluation identified clinician and system barriers to widespread implementation of CBT-CP and allowed for refinement of the subsequent implementation of two forms of CBT-CP in an ongoing pragmatic trial. Identification of relative difference in barriers and facilitators in the two forms of CBT-CP may emerge more clearly in a pragmatic trial that evaluates how treatments perform in real-world settings and may provide important information to guide future system-wide implementation efforts.

Economic Evaluation: A Randomized Pragmatic Trial of a Primary Care-based Cognitive Behavioral Intervention for Adults Receiving Long-term Opioids for Chronic Pain.

BACKGROUND: Chronic pain is prevalent and costly; cost-effective nonpharmacological approaches that reduce pain and improve patient functioning are needed. OBJECTIVE: Report the incremental cost-effectiveness ratio (ICER), compared with usual care, of cognitive behavioral therapy aimed at improving functioning and pain among patients with chronic pain on long-term opioid treatment. DESIGN: Economic evaluation conducted alongside a pragmatic cluster randomized trial. SUBJECTS: Adults with chronic pain on long-term opioid treatment (N=814). INTERVENTION: A cognitive behavioral therapy intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorists, nurses) with additional support from physical therapists, and pharmacists. OUTCOME MEASURES: Cost per quality adjusted life year (QALY) gained, and cost per additional responder (≥30% improvement on standard scale assessment of Pain, Enjoyment, General Activity, and Sleep). Costs were estimated as-delivered, and replication. RESULTS: Per patient intervention replication costs were $2145 ($2574 as-delivered). Those costs were completely offset by lower medical care costs; inclusive of the intervention, total medical care over follow-up was $1841 lower for intervention patients. Intervention group patients also had greater QALY and responder gains than did controls. Supplemental analyses using pain-related medical care costs revealed ICERs of $35,000, and $53,000 per QALY (for replication, and as-delivered intervention costs, respectively); the ICER when excluding patients with outlier follow-up costs was $106,000. LIMITATIONS: Limited to 1-year follow-up; identification of pain-related utilization potentially incomplete. CONCLUSION: The intervention was the optimal choice at commonly accepted levels of willingness-to-pay for QALY gains; this finding was robust to sensitivity analyses.

Treating Persistent Pain: A Nurse Co-Led, Interdisciplinary Model for Primary Care.

The public health crisis of chronic pain has only increased in recognition since the Institute of Medicine's (IOM) Relieving Pain in America (2011) called for a cultural transformation in the way pain is viewed, treated, and put forward specific recommendations for action. The National Pain Strategy (NPS) provides a roadmap for putting these recommendations into practice. We implemented a program that placed nurses and behavioral specialists at the head of an interdisciplinary team utilizing best practices. In this program, nurses enacted the NPS recommendations to advance care for patients with persistent pain on long-term opioid treatment. This program promoted professional growth in nurses along with fostering success for patients. Compared with patients receiving usual care, patients in the program achieved greater reductions in pain severity, pain-related disability, and pain-related functional interference and reported greater satisfaction with pain-related care and primary care services. This article will detail the NPS-aligned practice approaches these nurses and their teams used, describe the training for the nurses, and speak to opportunities to enhance the nurse's capacity for this role in hopes of providing a model for the future implementation of an NPS-based approach by nurses.

Characteristics of Patients with Non-Cancer Pain and Perceived Severity of COVID-19 Related Stress.

Synopsis Patients with non-cancer pain reported increased pain and pain interference during the first months of the COVID-19 pandemic. We determined if pain, prescription opioid use, and comorbidities were associated with perceived COVID-19-related stress as the pandemic peaked. Analysis of survey data revealed that depression/anxiety, pain severity, and pain interference were most strongly and consistently associated with greater stress due to COVID-19 related changes in lifestyle, worsening of emotional/mental health and worsening pain. Identifying specific stressful experiences that most impacted patients with non-cancer pain may help target public health and treatment interventions. Background: During the first months of the COVID-19 pandemic, patients with chronic pain reported increased pain severity and interference. This study measured the association between pain, prescription opioid use, and comorbidities with perceived COVID-19-related stress as the pandemic peaked in the United States. Methods: From 9/2020 to 3/2021, the first 149 subjects from a prospective cohort study of non-cancer pain, completed a survey which contained the Complementary and Integrative Research (CAIR) Pandemic Impact Questionnaire (C-PIQ). Respondents also reported whether the pandemic has contributed to their pain or opioid use. Bivariate comparisons explored patient characteristics with each CAIR domain. Results: Respondents mean age was 54.6 (±11.3) years, 69.8% were female, 64.6% were White. Respondent characteristics were not associated with reading/watching/thinking about the pandemic or with worry about health. Depression/anxiety (p=0.003), using any prescription opioid in the prior three months (p=0.009), higher morphine milligram equivalent used (p=0.005), higher pain severity (p=0.011), and higher pain interference (p=0.0004) were all positively and significantly associated with moderate to severe stress due to COVID-19 related lifestyle changes. Depression/anxiety, pain severity, and pain interference were positively associated with COVID-19-related worsening emotional/mental health. Depression/anxiety were significantly (p<0.0001) associated with reporting that the pandemic made their pain worse. Conclusion: Depression, anxiety, pain severity, and pain interference were most strongly and consistently associated with COVID-19 changes in way of life, worsening of emotional/mental health, and worsening pain. Identifying specific stressful experiences that most impacted patients with noncancer pain may inform public health and treatment interventions.

"We Need to Taper." Interviews with Clinicians and Pharmacists About Use of a Pharmacy-Led Opioid Tapering Program.

OBJECTIVE: To identify factors that influence or interfere with referrals by primary care providers (PCPs) to a pharmacist-led telephone-based program to assist patients undergoing opioid tapering. The Support Team Onsite Resource for Management of Pain (STORM) program provides individualized patient care and supports PCPs in managing opioid tapers. DESIGN: Qualitative interviews were conducted with referring PCPs and STORM staff. Interview guides addressed concepts from the RE-AIM framework, focusing on issues affecting referral to the STORM program. SETTING: An integrated healthcare system (HCS) in the Northwest United States. SUBJECTS: Thirty-five interviews were conducted with 20 PCPs and 15 STORM staff. METHODS: Constant comparative analysis was used to identify key themes from interviews. A codebook was developed based on interview data and a qualitative software program was used for coding, iterative review, and content analysis. Representative quotes illustrate identified themes. RESULTS: Use of the STORM opioid tapering program was influenced by PCP, patient, and HCS considerations. Factors motivating use of STORM included lack of PCP time to support chronic pain patients requiring opioid tapering and the perception that STORM is a valued partner in patient care. Impediments to referral included PCP confidence in managing opioid tapering, patient resistance to tapering, forgetting about program availability, and PCP resistance to evolving guidelines regarding opioid tapering goals. CONCLUSIONS: PCPs recognized that STORM supported patient safety and reduced clinician burden. Utilization of the program could be improved through ongoing PCP education about the service and consistent co-location of STORM pharmacists within primary care clinics.

Factors associated with opioid-tapering success: A mixed methods study.

OBJECTIVE: Opioid tapering is recommended when risks of chronic opioid use outweigh benefits. Little is known about patient characteristics or factors related to tapering success. We sought to identify characteristics that predict a 50% reduction in opioid use and qualitatively characterize factors that impact tapering success. METHODS: We used multilevel hierarchical modeling to identify predictors of a 50% reduction in opioid use among Kaiser Permanente Northwest patients who underwent pharmacist-led tapering between 2012 and 2017. We conducted qualitative interviews among patients and pharmacists to identify factors influencing tapering success. RESULTS: We identified 1384 patients who, on average, were dispensed 207 milligram morphine equivalents per day at baseline. After 12 months, 56% of patients reduced their opioid use by 50%. Increased odds of 50% reduction were associated with younger age 21-49 years (Odds ratio [OR] 1.32, P = 0.004); previous surgery (OR 2.24, P < 0.001); increased number of Addiction Medicine encounters (OR 1.25, P = 0.011); substance use disorder (OR 1.62, P = 0.001); anxiety (OR 1.32, P = 0.003); non-narcotic analgesic (OR 1.22, P = 0.025) or antipsychotic medication use (OR 1.53, P = 0.006); and opioid days supplied in the previous year (OR 1.08, P < 0.001). Patients and pharmacists noted that success was influenced by patients' willingness or resistance to change opioid use, the level of patient engagement achieved through communication with their provider, aspects of the tapering process such as pace, and external factors including health issues or caregiving responsibilities. CONCLUSIONS: Over one-half of patients who underwent tapering reduced their opioid use by 50%. Patient demographic and clinical characteristics were predictive of tapering success; however, patients and pharmacists noted that patient willingness, motivation, and personal circumstances also influence tapering outcome. Opioid tapering requires an individualized approach. Both clinical factors and personal circumstances should be considered when opioid tapering is being discussed as a possible solution for a patient.

Satisfaction with Primary Care Providers and Health Care Services Among Patients with Chronic Pain: a Mixed-Methods Study.

BACKGROUND: Chronic pain is a prevalent health concern in the United States (US) and a frequent reason for patients to seek primary care. The challenges associated with developing effective pain management strategies can be perceived as a burden on the patient-provider relationship. OBJECTIVE: This study explored the relationship between patients' overall satisfaction with their primary care providers (PCPs) and their satisfaction with their chronic pain treatment, as well as the provider behaviors that contributed to chronic pain patients' satisfaction with their PCPs. DESIGN: Concurrent nested mixed-methods design PARTICIPANTS: 97 patients with chronic pain who were assigned to the usual care arm of the Pain Program for Active Coping and Training (PPACT) study. APPROACH: We analyzed phone interview and survey data (n = 97). Interviews assessed provider behaviors that led to patient satisfaction. Interview transcripts were analyzed based on a content analysis approach. Survey responses assessed patient satisfaction with primary care and pain services. We calculated a Pearson's correlation coefficient using five response categories. KEY RESULTS: Interviews revealed that high satisfaction with primary care was driven by five concrete PCP behaviors: (1) listening, (2) maintaining communication with patients, (3) acting as an access point to comprehensive pain care, (4) providing an honest assessment of the possibilities of pain care, and (5) taking time during consultations with patients. In surveys, participants reported higher satisfaction with their primary care services than with the pain services they received; these variables were only moderately correlated (r = 0.586). CONCLUSIONS: Results suggest that patients with chronic pain can view the relationship with their PCPs as positive, even in the face of low satisfaction with their pain treatment. The expectations that these patients held of PCPs could be met regardless of providers' ability to successfully relieve chronic pain.

Identifying Multisite Chronic Pain with Electronic Health Records Data.

BACKGROUND: Multisite chronic pain (MSCP) is associated with increased chronic pain impact, but methods for identifying MSCP for epidemiological research have not been evaluated. OBJECTIVE: We assessed the validity of identifying MSCP using electronic health care data compared with survey questionnaires. METHODS: Stratified random samples of adults served by Kaiser Permanente Northwest and Washington (N = 2,059) were drawn for a survey, oversampling persons with frequent use of health care for pain. MSCP and single-site chronic pain were identified by two methods, with electronic health care data and with self-report of common chronic pain conditions by survey questionnaire. Analyses were weighted to adjust for stratified sampling. RESULTS: MSCP was somewhat less common when ascertained by electronic health records (14.7% weighted prevalence) than by survey questionnaire (25.9% weighted prevalence). Agreement of the two MSCP classifications was low (kappa agreement statistic of 0.21). Ascertainment of MSCP with electronic health records was 30.9% sensitive, 91.0% specific, and had a positive predictive value of 54.5% relative to MSCP identified by self-report as the standard. After adjusting for age and gender, patients with MSCP identified by either electronic health records or self-report showed higher levels of pain-related disability, pain severity, depressive symptoms, and long-term opioid use than persons with single-site chronic pain identified by the same method. CONCLUSIONS: Identification of MSCP with electronic health care data was insufficiently accurate to be used as a surrogate or screener for MSCP identified by self-report, but both methods identified persons with heightened chronic pain impact.

Co-Operative Pain Education and Self-management (COPES) Expanding Treatment for Real-World Access (ExTRA): Pragmatic Trial Protocol.

BACKGROUND: Given access barriers to cognitive behavioral therapy for chronic pain (CBT-CP), this pragmatic superiority trial will determine whether a remotely delivered CBT-CP intervention that addresses these barriers outperforms in-person and other synchronous forms of CBT-CP for veterans with musculoskeletal pain. DESIGN: This pragmatic trial compares an asynchronous form of CBT-CP that uses interactive voice response (IVR) to allow patients to participate from their home (IVR CBT-CP) with synchronous CBT-CP delivered by a Department of Veterans Affairs (VA) clinician. Veterans (n=764; 50% male) with chronic musculoskeletal pain throughout nine VA medical centers will participate. The primary outcome is pain interference after treatment (4 months). Secondary outcomes, including pain intensity, depression symptom severity, sleep, self-efficacy, and global impression of change, are also measured after treatment. Where possible, outcomes are collected via electronic health record extraction, with remaining measures collected via IVR calls to maintain blinding. Quantitative and qualitative process evaluation metrics will be collected to evaluate factors related to implementation. A budget impact analysis will be performed. SUMMARY: This pragmatic trial compares the outcomes, cost, and implementation of two forms of CBT-CP as delivered in the real-world setting. Findings from the trial can be used to guide future policy and implementation efforts related to these interventions and their use in the health system. If one of the interventions emerges as superior, resources can be directed to this modality. If both treatments are effective, patient preferences and health care system factors will take precedence when making referrals. Implications of COVID-19 on treatment provision and trial outcomes are discussed.

Core Outcome Measures for Chronic Musculoskeletal Pain Research: Recommendations from a Veterans Health Administration Work Group.

OBJECTIVE: Chronic musculoskeletal pain (CMSP) disorders are among the most prevalent and disabling conditions worldwide. It would be advantageous to have common outcome measures when comparing results across different CMSP research studies. METHODS: The Veterans Health Administration appointed a work group to recommend core outcome measures for assessing pain intensity and interference as well as important secondary domains in clinical research. The work group used three streams of data to inform their recommendations: 1) literature synthesis augmented by three recently completed trials; 2) review and comparison of measures recommended by other expert groups; 3) two Delphi surveys of work group members. RESULTS: The single-item numerical rating scale and seven-item Brief Pain Inventory interference scale emerged as the recommended measures for assessing pain intensity and interference, respectively. The secondary domains ranked most important included physical functioning and depression, followed by sleep, anxiety, and patient-reported global impression of change (PGIC). For these domains, the work group recommended the Patient-Reported Outcome Information System four-item physical function and sleep scales, the Patient Health Questionnaire two-item depression scale, the Generalized Anxiety Disorder two-item anxiety scale, and the single-item PGIC. Finally, a single-item National Health Interview Survey item was favored for defining chronic pain. CONCLUSIONS: Two scales comprising eight items are recommended as core outcome measures for pain intensity and interference in all studies of chronic musculoskeletal pain, and brief scales comprising 13 additional items can be added when possible to assess important secondary domains.

Addressing guideline and policy changes during pragmatic clinical trials.

While conducting a set of large-scale multi-site pragmatic clinical trials involving high-impact public health issues such as end-stage renal disease, opioid use, and colorectal cancer, there were substantial changes to both policies and guidelines relevant to the trials. These external changes gave rise to unexpected challenges for the trials, including decisions regarding how to respond to new clinical practice guidelines, increased difficulty in implementing trial interventions, achieving separation between treatment groups, and differential responses across sites. In this article, we describe these challenges and the approaches used to address them. When deliberating appropriate action in the face of external changes during a pragmatic clinical trial, we recommend considering the well-being of the participants, clinical equipoise, and the strength and quality of the evidence associated with the change; involving those charged with data and safety monitoring; and where possible, planning for potential external changes as the trial is being designed. Any solution must balance the primary obligation to protect the well-being of participants with the secondary obligation to protect the integrity of the trial in order to gain meaningful answers to important public health questions.

The Mediating Effect of Sleep Disturbance on the Relationship Between Nonmalignant Chronic Pain and Suicide Death.

IMPORTANCE: Few studies have examined the relationship between nonmalignant chronic pain (NMCP) and suicide death, and even fewer have specifically explored what role sleep disturbance might play in the association between NMCP and suicide death. OBJECTIVE: To assess whether sleep disturbance mediates the relationship between NMCP and suicide death. DESIGN: This case-control study included 2,674 individuals who died by suicide between 2000 and 2013 (cases) and 267,400 matched individuals (controls). SETTING: Eight Mental Health Research Network (MHRN)-affiliated healthcare systems. PARTICIPANTS: All cases and matched controls were health plan members for at least 10 months during the year prior to the index date. MAIN OUTCOMES AND MEASURES: Sociodemographic data and diagnosis codes for NMCP and sleep disorders were extracted from the MHRN's Virtual Data Warehouse. Suicide mortality was identified using International Statistical Classification of Diseases and Related Health Problems (ICD)-10 codes from official government mortality records matched to health system records. RESULTS: After accounting for covariates, there was a significant relationship between NMCP and sleep disturbance; those who were diagnosed with NMCP were more likely to develop subsequent sleep disturbance. Similarly, sleep disturbance was significantly associated with suicide death. Finally, a significant indirect effect of NMCP on suicide death, through sleep disturbance, and a nonsignificant direct effect of NMCP on suicide death provide support for a fully mediated model. CONCLUSIONS AND RELEVANCE: There is a need for clinicians to screen for both sleep disturbance and suicidal ideation in NMCP patients and for health systems to implement more widespread behavioral treatments that address comorbid sleep problems and NMCP.

Automating Collection of Pain-Related Patient-Reported Outcomes to Enhance Clinical Care and Research.

INTRODUCTION: Chronic pain is highly prevalent, and the ability to routinely measure patients' pain and treatment response using validated patient-reported outcome (PRO) assessments is important to clinical care. Despite this recognition, systematic use in everyday clinical care is rare. AIMS: The aims of this study were to (1) describe infrastructure designed to automate PRO data collection, (2) compare study-enhanced PRO completion rates to those in clinical care, and (3) evaluate patient response rates by method of PRO administration and sociodemographic and/or clinical characteristics. SETTING: The Pain Program for Active Coping and Training (PPACT) is a pragmatic clinical trial conducted within three regions of the Kaiser Permanente health care system. PROGRAM DESCRIPTION: PPACT evaluates the effect of integrative primary care-based pain management services on outcomes for chronic pain patients on long-term opioid treatment. We implemented a tiered process for quarterly assessment of PROs to supplement clinical collection and ensure adequate trial data using three methods: web-based personal health records (PHR), automated interactive voice response (IVR) calls, and live outreach. PROGRAM EVALUATION: Among a subset of PPACT participants examined (n = 632), the tiered study-enhanced PRO completion rates were higher than in clinical care: 96% completed ≥ 1 study-administered PRO with mean of 3.46 (SD = 0.85) vs. 74% completed in clinical care with a mean of 2.43 (SD = 2.08). Among all PPACT participants at 3 months (n = 831), PRO completion was 86% and analyses of response by key characteristics found only that participant age predicted an increased likelihood of responding to PHR and IVR outreach. DISCUSSION: Adherence to pain-related PRO data collection using our enhanced tiered approach was high. No demographic or clinical identifiers other than age were associated with differential response by modality. Successful ancillary support should employ multimodal electronic health record functionalities for PRO administration. Using automated modalities is feasible and may facilitate better sustainability for regular PRO administration within health care systems. Clinical Trials Registration Number: NCT02113592.

Comparative Effectiveness of Usual Care With or Without Chiropractic Care in Patients with Recurrent Musculoskeletal Back and Neck Pain.

BACKGROUND: Chiropractic care is a popular alternative for back and neck pain, with efficacy comparable to usual care in randomized trials. However, the effectiveness of chiropractic care as delivered through conventional care settings remains largely unexplored. OBJECTIVE: To evaluate the comparative effectiveness of usual care with or without chiropractic care for patients with chronic recurrent musculoskeletal back and neck pain. STUDY DESIGN: Prospective cohort study using propensity score-matched controls. PARTICIPANTS: Using retrospective electronic health record data, we developed a propensity score model predicting likelihood of chiropractic referral. Eligible patients with back or neck pain were then contacted upon referral for chiropractic care and enrolled in a prospective study. For each referred patient, two propensity score-matched non-referred patients were contacted and enrolled. We followed the participants prospectively for 6 months. MAIN MEASURES: Main outcomes included pain severity, interference, and symptom bothersomeness. Secondary outcomes included expenditures for pain-related health care. KEY RESULTS: Both groups' (N = 70 referred, 139 non-referred) pain scores improved significantly over the first 3 months, with less change between months 3 and 6. No significant between-group difference was observed. (severity - 0.10 (95% CI - 0.30, 0.10), interference - 0.07 (- 0.31, 0.16), bothersomeness - 0.1 (- 0.39, 0.19)). After controlling for variances in baseline costs, total costs during the 6-month post-enrollment follow-up were significantly higher on average in the non-referred versus referred group ($1996 [SD = 3874] vs $1086 [SD = 1212], p = .034). Adjusting for differences in age, gender, and Charlson comorbidity index attenuated this finding, which was no longer statistically significant (p = .072). CONCLUSIONS: We found no statistically significant difference between the two groups in either patient-reported or economic outcomes. As clinical outcomes were similar, and the provision of chiropractic care did not increase costs, making chiropractic services available provided an additional viable option for patients who prefer this type of care, at no additional expense.

Clinical Policy Recommendations from the VHA State-of-the-Art Conference on Non-Pharmacological Approaches to Chronic Musculoskeletal Pain.

As a large national healthcare system, Veterans Health Administration (VHA) is ideally suited to build on its work to date and develop a safe, evidence-based, and comprehensive approach to the care of chronic musculoskeletal pain conditions that de-emphasizes opioid use and emphasizes non-pharmacological strategies. The VHA Office of Health Services Research and Development (HSR&D) held a state-of-the-art (SOTA) conference titled "Non-pharmacological Approaches to Chronic Musculoskeletal Pain Management" in November 2016. Goals of the conference were (1) to establish consensus on the current state of evidence regarding non-pharmacological approaches to chronic musculoskeletal pain to inform VHA policy in this area and (2) to begin to identify priorities for the future VHA research agenda. Workgroups were established and asked to reach consensus recommendations on clinical and research priorities for the following treatment strategies: psychological/behavioral therapies, exercise/movement therapies, manual therapies, and models for delivering multimodal pain care. Participants in the SOTA identified nine non-pharmacological therapies with sufficient evidence to be implemented across the VHA system as part of pain care. Participants further recommended that effective integration of these non-pharmacological approaches across the VHA and especially into VHA primary care, pain care, and mental health settings should be a priority, and that these treatments should be offered early in the course of pain treatment and delivered in a team-based, multimodal treatment setting concurrently with active self-care and self-management approaches. In addition, we recommend that VHA leadership and policy makers systematically address the barriers to implementation of these approaches by expanding opportunities for clinician and veteran education on the effectiveness of these strategies; supporting and funding further research to determine optimal dosage, duration, sequencing, combination, and frequency of treatment; emphasizing multimodal care with rigorous evaluation grounded in team-based approaches to test integrated models of delivery and stepped-care approaches; and working to address socioeconomic and cultural barriers to veterans' access to non-pharmacological approaches.