Methods for pragmatic randomized clinical trials of pain therapies: IMMPACT statement.

ABSTRACT: Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the appropriate level of flexibility in treatment delivery, integrating information on concomitant treatments and adherence, and choosing comparator conditions and outcome measures. Ensuring data quality in real-world clinical settings is another challenging goal. Furthermore, current trials in the field would benefit from analysis methods that allow for a differentiated understanding of effects across patient subgroups and improved reporting of methods and context, which is required to assess the generalizability of findings. At the same time, a range of novel methodological approaches provide opportunities for enhanced efficiency and relevance of pragmatic trials to stakeholders and clinical decision making. In this study, best-practice considerations for these and other concerns in pragmatic trials of pain treatments are offered and a number of promising solutions discussed. The basis of these recommendations was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks.

Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations.

ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.

A patient activation intervention in primary care for patients with chronic pain on long term opioid therapy: results from a randomized control trial.

BACKGROUND: Given significant risks associated with long-term prescription opioid use, there is a need for non-pharmacological interventions for treating chronic pain. Activating patients to manage chronic pain has the potential to improve health outcomes. The ACTIVATE study was designed to evaluate the effectiveness of a 4-session patient activation intervention in primary care for patients on long-term opioid therapy. METHODS: The two-arm, pragmatic, randomized trial was conducted in two primary care clinics in an integrated health system from June 2015-August 2018. Consenting participants were randomized to the intervention (n = 189) or usual care (n = 187). Participants completed online and interviewer-administered surveys at baseline, 6- and 12- months follow-up. Prescription opioid use was extracted from the EHR. The primary outcome was patient activation assessed by the Patient Activation Measure (PAM). Secondary outcomes included mood, function, overall health, non-pharmacologic pain management strategies, and patient portal use. We conducted a repeated measure analysis and reported between-group differences at 12 months. RESULTS: At 12 months, the intervention and usual care arms had similar PAM scores. However, compared to usual care at 12 months, the intervention arm demonstrated: less moderate/severe depression (odds ratio [OR] = 0.40, 95%CI 0.18-0.87); higher overall health (OR = 3.14, 95%CI 1.64-6.01); greater use of the patient portal's health/wellness resources (OR = 2.50, 95%CI 1.42-4.40) and lab/immunization history (OR = 2.70, 95%CI 1.29-5.65); and greater use of meditation (OR = 2.72; 95%CI 1.61-4.58) and exercise/physical therapy (OR = 2.24, 95%CI 1.29-3.88). At 12 months, the intervention arm had a higher physical health measure (mean difference 1.63; 95%CI: 0.27-2.98). CONCLUSION: This trial evaluated the effectiveness of a primary care intervention in improving patient activation and patient-reported outcomes among adults with chronic pain on long-term opioid therapy. Despite a lack of improvement in patient activation, a brief intervention in primary care can improve outcomes such as depression, overall health, non-pharmacologic pain management, and engagement with the health system. TRIAL REGISTRATION: The study was registered on 10/27/14 on ClinicalTrials.gov (NCT02290223).

Cluster-Randomized Comparative Effectiveness Trial of Physician-Directed Clinical Decision Support Versus Patient-Directed Education to Promote Appropriate Use of Opioids for Chronic Pain.

We compared the effectiveness of physician-directed clinical decision support (CDS) administered via electronic health record versus patient-directed education to promote the appropriate use of opioids by conducting a cluster-randomized trial involving 82 primary care physicians and 951 of their patients with chronic pain. Primary outcomes were satisfaction with patient-physician communication consumer assessment of health care providers and system clinician and group survey (CG-CAHPS) and pain interference patient-reported outcomes measurement information system. Secondary outcomes included physical function (patient-reported outcomes measurement information system), depression (PHQ-9), high-risk opioid prescribing (>90 morphine milligram equivalents per day [≥90 mg morphine equivalent/day]), and co-prescription of opioids and benzodiazepines. We used multi-level regression to compare longitudinal difference-in-difference scores between arms. The odds of achieving the maximum CG-CAHPS score were 2.65 times higher in the patient education versus the CDS arm (P = .044; 95% confidence interval [CI] 1.03-6.80). However, baseline CG-CAHPS scores were dissimilar between arms, making these results challenging to interpret definitively. No difference in pain interference was found between groups (Coef = -0.64, 95% CI -2.66 to 1.38). The patient education arm experienced higher odds of Rx ≥ 90 milligrams morphine equivalent/day (odds ratio = 1.63; P = .010; 95% CI 1.13, 2.36). There were no differences between groups in physical function, depression, or co-prescription of opioids and benzodiazepines. These results suggest that patient-directed education may have the potential to improve satisfaction with patient-physician communication, whereas physician-directed CDS via electronic health records may have greater potential to reduce high-risk opioid dosing. More evidence is needed to ascertain the relative cost-effectiveness between strategies. PERSPECTIVE: This article presents the results of a comparative-effectiveness study of 2 broadly used communication strategies to catalyze dialog between patients and primary care physicians around chronic pain. The results add to the decision-making literature and offer insights about the relative benefits of physician-directed versus patient-directed interventions to promote the appropriate use of opioids.

Cannabinoid Therapy: Attitudes and Experiences of People With Chronic Pain.

OBJECTIVE: Clinical trials of cannabinoids for chronic pain have mixed and often inconclusive results. In contrast, many prospective observational studies show the analgesic effects of cannabinoids. This survey study aimed to examine the experiences/attitudes of individuals with chronic pain who are currently taking, have previously taken, or never taken cannabinoids for chronic pain to inform future research. METHODS: This study is based on a cross-sectional, web-based survey of individuals with self-reported chronic pain. Participants were invited to participate through an email that was distributed to the listservs of patient advocacy groups and foundations that engage individuals with chronic pain. RESULTS: Of the 969 respondents, 444 (46%) respondents reported currently taking, 213 (22%) previously taken, and 312 (32%) never taken cannabinoids for pain. Participants reported using cannabinoids to treat a wide variety of chronic pain conditions. Those currently taking cannabinoids (vs previously) more frequently reported: (1) large improvements from cannabinoids in all pain types, including particularly difficult-to-treat chronic overlapping pain conditions (eg, pelvic pain), (2) improvements in comorbid symptoms (eg, sleep), and (3) lower interference from side effects. Those currently taking cannabinoids reported more frequent and satisfactory communication with clinicians regarding cannabinoid use. Those never taken cannabinoids reported a lack of suggestion/approval of a clinician (40%), illegality (25%), and lack of FDA regulation (19%) as reasons for never trying cannabinoids. CONCLUSION: These findings underscore the importance of conducting high-quality clinical trials that include diverse pain populations and clinically relevant outcomes that if successful, could support FDA approval of cannabinoid products. Clinicians could then prescribe and monitor these treatments similarly to other chronic pain medications.

Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement.

ABSTRACT: Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care. This article summarizes methodological considerations for pragmatic trials, mainly concerning methods of fundamental importance to the internal validity of trials. The relationship between these methods and common pragmatic trials methods and goals is considered, recognizing that the resulting trial designs are highly dependent on the specific research question under investigation. The basis of this statement was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) systematic review of methods and a consensus meeting. The meeting was organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The consensus process was informed by expert presentations, panel and consensus discussions, and a preparatory systematic review. In the context of pragmatic trials of pain treatments, we present fundamental considerations for the planning phase of pragmatic trials, including the specification of trial objectives, the selection of adequate designs, and methods to enhance internal validity while maintaining the ability to answer pragmatic research questions.

Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations.

Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, "precision pain medicine"). Precision pain medicine, currently an aspirational goal, would consist of empirically based algorithms that determine the optimal treatments, or treatment combinations, for specific patients (ie, targeting the right treatment, in the right dose, to the right patient, at the right time). Answering this question of "what works for whom" will certainly improve the clinical care of patients with pain. It may also support the success of novel drug development in pain, making it easier to identify novel treatments that work for certain patients and more accurately identify the magnitude of the treatment effect for those subgroups. Significant preliminary work has been done in this area, and analgesic trials are beginning to utilize precision pain medicine approaches such as stratified allocation on the basis of prespecified patient phenotypes using assessment methodologies such as quantitative sensory testing. Current major challenges within the field include: 1) identifying optimal measurement approaches to assessing patient characteristics that are most robustly and consistently predictive of inter-patient variation in specific analgesic treatment outcomes, 2) designing clinical trials that can identify treatment-by-phenotype interactions, and 3) selecting the most promising therapeutics to be tested in this way. This review surveys the current state of precision pain medicine, with a focus on drug treatments (which have been most-studied in a precision pain medicine context). It further presents a set of evidence-based recommendations for accelerating the application of precision pain methods in chronic pain research. PERSPECTIVE: Given the considerable variability in treatment outcomes for chronic pain, progress in precision pain treatment is critical for the field. An array of phenotypes and mechanisms contribute to chronic pain; this review summarizes current knowledge regarding which treatments are most effective for patients with specific biopsychosocial characteristics.

Patient Responses to the Term Pain Catastrophizing: Thematic Analysis of Cross-sectional International Data.

Pain catastrophizing is understood as a negative cognitive and emotional response to pain. Researchers, advocates and patients have reported stigmatizing effects of the term in clinical settings and the media. We conducted an international study to investigate patient perspectives on the term pain catastrophizing. Open-ended electronic patient and caregiver proxy surveys were promoted internationally by collaborator stakeholders and through social media. 3,521 surveys were received from 47 countries (77.3% from the U.S.). The sample was mainly female (82.1%), with a mean age of 41.62 (SD 12.03) years; 95% reported ongoing pain and pain duration > 10 years (68.4%). Forty-five percent (n = 1,295) had heard of the term pain catastrophizing; 12% (n = 349) reported being described as a 'pain catastrophizer' by a clinician with associated high levels of feeling blamed, judged, and dismissed. We present qualitative thematic data analytics for responses to open-ended questions, with 32% of responses highlighting the problematic nature of the term. We present the patients' perspective on the term pain catastrophizing, its material effect on clinical experiences, and associations with negative gender stereotypes. Use of patient-centered terminology may be important for favorably shaping the social context of patients' experience of pain and pain care. PERSPECTIVE: Our international patient survey found that 45% had heard of the term pain catastrophizing, about one-third spontaneously rated the term as problematic, and 12% reported the term was applied to them with most stating this was a negative experience. Clinician education on patient-centered terminology may improve care and reduce stigma.

Benefit-risk assessment and reporting in clinical trials of chronic pain treatments: IMMPACT recommendations.

ABSTRACT: Chronic pain clinical trials have historically assessed benefit and risk outcomes separately. However, a growing body of research suggests that a composite metric that accounts for benefit and risk in relation to each other can provide valuable insights into the effects of different treatments. Researchers and regulators have developed a variety of benefit-risk composite metrics, although the extent to which these methods apply to randomized clinical trials (RCTs) of chronic pain has not been evaluated in the published literature. This article was motivated by an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting and is based on the expert opinion of those who attended. In addition, a review of the benefit-risk assessment tools used in published chronic pain RCTs or highlighted by key professional organizations (ie, Cochrane, European Medicines Agency, Outcome Measures in Rheumatology, and U.S. Food and Drug Administration) was completed. Overall, the review found that benefit-risk metrics are not commonly used in RCTs of chronic pain despite the availability of published methods. A primary recommendation is that composite metrics of benefit-risk should be combined at the level of the individual patient, when possible, in addition to the benefit-risk assessment at the treatment group level. Both levels of analysis (individual and group) can provide valuable insights into the relationship between benefits and risks associated with specific treatments across different patient subpopulations. The systematic assessment of benefit-risk in clinical trials has the potential to enhance the clinical meaningfulness of RCT results.

Mindfulness-based therapy compared to cognitive behavioral therapy for opioid-treated chronic low back pain: Protocol for a pragmatic randomized controlled trial.

OBJECTIVE: Chronic low back pain (CLBP) is disabling and costly. Existing therapies have proven suboptimal, with many patients resorting to long-term opioid therapy, which can cause harms. Cognitive behavioral (CBT) and mindfulness-based (MBT) therapies can be effective and offer unique skills for safe pain coping. This article describes the protocol for a study evaluating comparative effectiveness of CBT and MBT in adults with opioid-treated CLBP. DESIGN: Pragmatic, multi-center randomized controlled trial (RCT). SETTINGS: Community and outpatient care. PARTICIPANTS: Planned enrollment of 766 adults (383/group) with CLBP treated with long-term opioids (≥3 months; ≥15 mg/day morphine-equivalent dose). INTERVENTIONS: CBT or MBT consisting of eight weekly therapist-led, two-hour group sessions, and home practice (≥30 min/day, 6 days/week) during the 12-month study. MAIN OUTCOME MEASURES: Main outcome measures, collected by self-report at baseline, then three, six, nine and 12 months post-entry, include co-primary measures: pain intensity (Numeric Rating Scale) and function (Oswestry Disability Index), and secondary measures: quality of life (Medical Outcomes Study) and average daily opioid dose (Timeline Followback). Baseline scores of depression, anxiety, and opioid misuse questionnaires will be assessed as potential contributors to the heterogeneity of treatment response. Intention-to-treat, linear mixed-effects analysis will examine treatment effectiveness. Qualitative data will augment the quantitative measures. CONCLUSIONS: This will be the largest RCT comparing CBT and MBT in opioid-treated CLBP. It will provide evidence on the impact of these interventions, informing clinical decisions about optimal therapy for safe, effective care, improving quality of life and decreasing opioid-related harm among adults with refractory CLBP.

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

Research approaches for evaluating opioid sparing in clinical trials of acute and chronic pain treatments: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations.

ABSTRACT: Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.

Language Matters: It Is Time We Change How We Talk About Addiction and its Treatment.

The way we communicate about addiction, its treatment, and treatment outcomes matters to individuals affected by addiction, their families, and communities. Stigmatizing language can worsen addiction-related stigma and outcomes. Although non-professional terminology may be used by individuals with addiction, the role of clinicians, educators, researchers, policymakers, and community and cultural leaders is to actively work toward destigmatization of addiction and its treatment, in part through the use of non-stigmatizing language. Role-modeling better approaches can help us move away from the inaccurate, outdated view of addiction as a character flaw or moral failing deserving of punishment, and toward that of a chronic disease requiring long-term treatment. Non-stigmatizing, non-judgmental, medically-based terminology and the adoption of person-first language can facilitate improved communication as well as patient access to and engagement with addiction care. Person-first language, which shifts away from defining a person through the lens of disease (eg, the term "a person with addiction" is recommended over the terms "addict" or "addicted patient"), implicitly acknowledges that a patient's life extends beyond a given disease. While such linguistic changes may seem subtle, they communicate that addiction, chronic pain and other diseases are only one aspect of a person's health and quality of life, and can promote therapeutic relationships, reduce stigma and health and disparities in addiction care. This article provides examples of stigmatizing terms to be avoided and recommended replacements to facilitate the dialogue about addiction in a more intentional, therapeutic manner.

Ensuring Patient Protections When Tapering Opioids: Consensus Panel Recommendations.

Long-term opioid therapy has the potential for serious adverse outcomes and is often used in a vulnerable population. Because adverse effects or failure to maintain benefits is common with long-term use, opioid taper or discontinuation may be indicated in certain patients. Concerns about the adverse individual and population effects of opioids have led to numerous strategies aimed at reductions in prescribing. Although opioid reduction efforts have had generally beneficial effects, there have been unintended consequences. Abrupt reduction or discontinuation has been associated with harms that include serious withdrawal symptoms, psychological distress, self-medicating with illicit substances, uncontrolled pain, and suicide. Key questions remain about when and how to safely reduce or discontinue opioids in different patient populations. Thus, health care professionals who reduce or discontinue long-term opioid therapy require a clear understanding of the associated benefits and risks as well as guidance on the best practices for safe and effective opioid reduction. An interdisciplinary panel of pain clinicians and one patient advocate formulated recommendations on tapering methods and ongoing pain management in primary care with emphasis on patient-centered, integrated, comprehensive treatment models employing a biopsychosocial perspective.

The Concerns About Pain (CAP) Scale: A Patient-Reported Outcome Measure of Pain Catastrophizing.

Pain catastrophizing has been recognized as an important and consistent psychosocial predictor of nearly every key pain-related outcome. The purpose of this study was to develop a new measure of pain catastrophizing using modern psychometric methodology. People with chronic pain (N = 795) responded to thirty items. Data were analyzed using item response theory, including assessment of differential item functioning and reliability. Sensitivity to change and validity were examined using data collected from patients undergoing spinal fusion surgery (n = 184) and participating in an ongoing longitudinal aging with a disability survey study (n = 1,388). The final 24-item bank had no items with significant local dependence, misfit, or differential item functioning. Results provided strong evidence of reliability and validity. Six- and 2-item short forms were developed for use when computer adaptive testing is not feasible or desirable. The item bank was named the University of Washington Concerns About Pain scale because the term "catastrophizing" was considered stigmatizing by people with chronic pain. Guidance for score interpretation was developed with extensive feedback from individuals with chronic pain. The Concerns About Pain item bank, short forms, and user manuals are free and publicly available to all users and can be accessed online at https://uwcorr.washington.edu/measures/. PERSPECTIVE: This article presents the development of the University of Washington Concerns About Pain scale, the first item response theory-based item bank of pain catastrophizing. The measure is intended for clinicians interested in improving outcomes of patients with chronic pain and for researchers who study impact of and treatment interventions aimed at reducing pain catastrophizing.

Interpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations.

Interpreting randomized clinical trials (RCTs) is crucial to making decisions regarding the use of analgesic treatments in clinical practice. In this article, we report on an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, the purpose of which was to recommend approaches that facilitate interpretation of analgesic RCTs. We review issues to consider when drawing conclusions from RCTs, as well as common methods for reporting RCT results and the limitations of each method. These issues include the type of trial, study design, statistical analysis methods, magnitude of the estimated beneficial and harmful effects and associated precision, availability of alternative treatments and their benefit-risk profile, clinical importance of the change from baseline both within and between groups, presentation of the outcome data, and the limitations of the approaches used.

Improving Study Conduct and Data Quality in Clinical Trials of Chronic Pain Treatments: IMMPACT Recommendations.

The estimated probability of progressing from phase 3 analgesic clinical trials to regulatory approval is approximately 57%, suggesting that a considerable number of treatments with phase 2 trial results deemed sufficiently successful to progress to phase 3 do not yield positive phase 3 results. Deficiencies in the quality of clinical trial conduct could account for some of this failure. An Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting was convened to identify potential areas for improvement in trial conduct in order to improve assay sensitivity (ie, ability of trials to detect a true treatment effect). We present recommendations based on presentations and discussions at the meeting, literature reviews, and iterative revisions of this article. The recommendations relate to the following areas: 1) study design (ie, to promote feasibility), 2) site selection and staff training, 3) participant selection and training, 4) treatment adherence, 5) data collection, and 6) data and study monitoring. Implementation of these recommendations may improve the quality of clinical trial data and thus the validity and assay sensitivity of clinical trials. Future research regarding the effects of these strategies will help identify the most efficient use of resources for conducting high quality clinical trials. PERSPECTIVE: Every effort should be made to optimize the quality of clinical trial data. This manuscript discusses considerations to improve conduct of pain clinical trials based on research in multiple medical fields and the expert consensus of pain researchers and stakeholders from academia, regulatory agencies, and industry.

Patient Advisory Committee for a Chronic Opioid Therapy Risk Reduction Evaluation: Engaging Diverse Patients.

BACKGROUND: Active patient engagement in research is critically important, but can be difficult in controversial areas where patients have conflicting perspectives. OBJECTIVES: In this Lesson's Learned report, we describe engagement of patients with divergent views in guiding a controlled interrupted time series evaluation of chronic opioid therapy risk reduction initiatives implemented by a large health plan. METHODS: A nine-person Patient Advisory Committee (PAC) advised the scientific team on the evaluation and reporting of results on diverse outcomes important to patients, including pain and function, opioid use disorder, overdose, motor vehicle accidents, and medically attended injuries. Patients were selected with varied perspectives on opioid prescribing for chronic pain. Multiple strategies facilitated PAC engagement: making room for personal experience; investing upfront in setting the stage for working together including an initial face to face meeting; clarifying shared values; and including individuals skilled in group process and collaboration. PAC meetings were organized separately from regular meetings of the scientific team. RESULTS: Shared values identified to guide the research were: Safety, respect, autonomy, compassion, knowledge and teamwork. PAC guidance altered key scientific decisions regarding assessment of patient outcomes, doctor-patient collaboration, and analytic approaches. CONCLUSIONS: Separate meetings of the PAC and scientific team enhanced opportunities for patients to influence the study design, analyses and interpretation of evaluation results. Convening a large group of patients with diverse perspectives and experiences was productive and influential in guiding the evaluation. Patient selection and building rapport allowed PAC members with divergent perspectives to work together effectively.

Patients' Experience With Opioid Tapering: A Conceptual Model With Recommendations for Clinicians.

Clinical guidelines discourage prescribing opioids for chronic pain, but give minimal advice about how to discuss opioid tapering with patients. We conducted focus groups and interviews involving 21 adults with chronic back or neck pain in different stages of opioid tapering. Transcripts were qualitatively analyzed to characterize patients' tapering experiences, build a conceptual model of these experiences, and identify strategies for promoting productive discussions of opioid tapering. Analyses revealed 3 major themes. First, owing to dynamic changes in patients' social relationships, emotional state, and health status, patients' pain and their perceived need for opioids fluctuate daily; this finding may conflict with recommendations to taper by a certain amount each month. Second, tapering requires substantial patient effort across multiple domains of patients' everyday lives; patients discuss this effort superficially, if at all, with clinicians. Third, patients use a variety of strategies to manage the tapering process (eg, keeping an opioid stash, timing opioid consumption based on planned activities). Recommendations for promoting productive tapering discussions include understanding the social and emotional dynamics likely to impact patients' tapering, addressing patient fears, focusing on patients' best interests, providing anticipatory guidance about tapering, and developing an individualized tapering plan that can be adjusted based on patient response. Perspective: This study used interview and focus group data to characterize patients' experiences with opioid tapering and identify communication strategies that are likely to foster productive, patient-centered discussions of opioid tapering. Findings will inform further research on tapering and help primary care clinicians to address this important, often challenging topic.