Supportive Self-Management Program for People With Chronic Headaches and Migraine: A Randomized Controlled Trial and Economic Evaluation.

BACKGROUND AND OBJECTIVES: Chronic headache disorders are a major cause of pain and disability. Education and supportive self-management approaches could reduce the burden of headache disability. We tested the effectiveness of a group educational and supportive self-management program for people living with chronic headaches. METHODS: This was a pragmatic randomized controlled trial. Participants were aged 18 years or older with chronic migraine or chronic tension-type headache, with or without medication overuse headache. We primarily recruited from general practices. Participants were assigned to either a 2-day group education and self-management program, a one-to-one nurse interview, and telephone support or to usual care plus relaxation material. The primary outcome was headache related-quality of life using the Headache Impact Test (HIT)-6 at 12 months. The primary analysis used intention-to-treat principles for participants with migraine and both baseline and 12-month HIT-6 data. RESULTS: Between April 2017 and March 2019, we randomized 736 participants. Because only 9 participants just had tension-type headache, our main analyses were on the 727 participants with migraine. Of them, 376 were allocated to the self-management intervention and 351 to usual care. Data from 586 (81%) participants were analyzed for primary outcome. There was no between-group difference in HIT-6 (adjusted mean difference = -0.3, 95% CI -1.23 to 0.67) or headache days (0.9, 95% CI -0.29 to 2.05) at 12 months. The Chronic Headache Education and Self-management Study intervention generated incremental adjusted costs of £268 (95% CI, £176-£377) (USD383 [95% CI USD252-USD539]) and incremental adjusted quality-adjusted life years (QALYs) of 0.031 (95% CI -0.005 to 0.063). The incremental cost-effectiveness ratio was £8,617 (USD12,322) per QALY gained. DISCUSSION: These findings conclusively show a lack of benefit for quality of life or monthly headache days from a brief group education and supportive self-management program for people living with chronic migraine or chronic tension-type headache with episodic migraine. TRIAL REGISTRATION INFORMATION: Registered on the International Standard Randomized Controlled Trial Number registry, ISRCTN79708100 16th December 2015 doi.org/10.1186/ISRCTN79708100. The first enrollment was April 24, 2017. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a brief group education and self-management program does not increase the probability of improvement in headache-related quality of life in people with chronic migraine.

Testing a support programme for opioid reduction for people with chronic non-malignant pain: the I-WOTCH randomised controlled trial protocol.

INTRODUCTION: Chronic non-malignant pain has a major impact on the well-being, mood and productivity of those affected. Opioids are increasingly prescribed to manage this type of pain, but with a risk of other disabling symptoms, when their effectiveness has been questioned. This trial is designed to implement and evaluate a patient-centred intervention targeting withdrawal of strong opioids in people with chronic pain. METHODS AND ANALYSIS: A pragmatic, multicentre, randomised controlled trial will assess the clinical and cost-effectiveness of a group-based multicomponent intervention combined with individualised clinical facilitator led support for the management of chronic non-malignant pain against the control intervention (self-help booklet and relaxation compact disc). An embedded process evaluation will examine fidelity of delivery and investigate experiences of the intervention. The two primary outcomes are activities of daily living (measured by Patient-Reported Outcomes Measurement Information System Pain Interference Short Form (8A)) and opioid use. The secondary outcomes are pain severity, quality of life, sleep quality, self-efficacy, adverse events and National Health Service (NHS) healthcare resource use. Participants are followed up at 4, 8 and 12 months, with a primary endpoint of 12 months. Between-group differences will indicate effectiveness; we are looking for a difference of 3.5 points on our pain interference outcome (scale 40 to 77). We will undertake an NHS perspective cost-effectiveness analysis using quality adjusted life years. ETHICS AND DISSEMINATION: Full approval was given by Yorkshire & The Humber - South Yorkshire Research Ethics Committee on 13 September, 2016 (16/YH/0325). Appropriate local approvals were sought for each area in which recruitment was undertaken. The current protocol version is 1.6 date 19 December 2018. Publication of results in peer- reviewed journals will inform the scientific and clinical community. We will disseminate results to patient participants and study facilitators in a study newsletter as well as a lay summary of results on the study website. TRIAL REGISTRATION NUMBER: ISRCTN49470934; Pre-results.

Development of an education and self-management intervention for chronic headache - CHESS trial (Chronic Headache Education and Self-management Study).

BACKGROUND: Self-management interventions are well recognised and widely used in chronic conditions. Their application to chronic headaches has been limited and generally of low quality. We describe here our process for developing an evidence based, and theory driven, education and self-management intervention for those living with chronic headache. METHODS: Our intervention was designed using several core information sources; the results of three systematic reviews, qualitative material from those living with chronic headaches, our knowledge from existing self-management interventions; and finally collaborative input from a multidisciplinary team of clinicians, academics, patients, and charity partners. We manualised the intervention and associated training as a package for use in a feasibility study. We made adaptations for its use in a randomised controlled trial. RESULTS: We piloted the intervention in four groups with a total of 18 participants. Qualitative feedback from 12 participants and five facilitators allowed the intervention to be refined for the main randomised controlled trial. Some of the key changes included shortening of the overall intervention, changes to the originally planned facilitators and spreading the facilitator training over three days rather than two. We are now testing the final revised intervention in a randomised controlled trial of its clinical and cost effectiveness. The group component of the intervention is delivered over two days with the first day focused on living, understanding and dealing with chronic headaches and the second day exploring how to adapt and take control of one's life with chronic headaches. CONCLUSION: Our pilot work indicates that our intervention is feasible to deliver, and with the relevant changes would be acceptable for use with this population. Our randomised control trial is ongoing. We anticipate publishing final results in 2021. TRIAL REGISTRATION: ISRCTN79708100. Registered 16th December 2015, http://www.isrctn.com/ISRCTN79708100.

Lessons learnt from a discontinued randomised controlled trial: adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica (Subcutaneous Injection of Adalimumab Trial compared with Control: SCIATiC).

BACKGROUND: Adalimumab, a biological treatment targeting tumour necrosis factor α, might be useful in sciatica. This paper describes the challenges faced when developing a new treatment pathway for a randomised controlled trial of adalimumab for people with sciatica, as well as the reasons why the trial discussed was stopped early. METHODS: A pragmatic, parallel group, randomised controlled trial with blinded (masked) participants, clinicians, outcome assessment and statistical analysis was conducted in six UK sites. Participants were identified and recruited from general practices, musculoskeletal services and outpatient physiotherapy clinics. They were adults with persistent symptoms of sciatica of 1 to 6 months' duration with moderate to high level of disability. Eligibility was assessed by research physiotherapists according to clinical criteria, and participants were randomised to receive two doses of adalimumab (80 mg then 40 mg 2 weeks later) or saline placebo subcutaneous injections in the posterior lateral thigh. Both groups were referred for a course of physiotherapy. Outcomes were measured at baseline, 6-week, 6-month and 12-month follow-up. The main outcome measure was disability measured using the Oswestry Disability Index. The planned sample size was 332, with the first 50 in an internal pilot phase. RESULTS: The internal pilot phase was discontinued after 10 months from opening owing to low recruitment (two of the six sites active, eight participants recruited). There were several challenges: contractual delays; one site did not complete contract negotiations, and two sites signed contracts shortly before trial closure; site withdrawal owing to patient safety concerns; difficulties obtaining excess treatment costs; and in the two sites that did recruit, recruitment was slower than planned because of operational issues and low uptake by potential participants. CONCLUSIONS: Improved patient care requires robust clinical research within contexts in which treatments can realistically be provided. Step changes in treatment, such as the introduction of biologic treatments for severe sciatica, raise complex issues that can delay trial initiation and retard recruitment. Additional preparatory work might be required before testing novel treatments. A randomised controlled trial of tumour necrosis factor-α blockade is still needed to determine its cost-effectiveness in severe sciatica. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN14569274 . Registered on 15 December 2014.

A realist evaluation of social prescribing: an exploration into the context and mechanisms underpinning a pathway linking primary care with the voluntary sector.

This article adopts a realist approach to evaluate a social prescribing pilot in the areas of Hackney and City in London (United Kingdom). It unpacks the contextual factors and mechanisms that influenced the development of this pilot for the benefits of GPs, commissioners and practitioners, and reflects on the realist approach to evaluation as a tool for the evaluation of health interventions. Primary care faces considerable challenges including the increase in long-term conditions, GP consultation rates, and widening health inequalities. With its emphasis on linking primary care to non-clinical community services via a social prescribing coordinator (SPC), some models of social prescribing could contribute to reduce the burden on primary care, tackle health inequalities and encourage people to make greater use of non-clinical forms of support. This realist analysis was based on qualitative interviews with users, commissioners, a GP survey, focus groups and learning events to explore stakeholders' experience. To enable a detailed analysis, we adapted the realist approach by subdividing the social prescribing pathway into stages, each with contextual factors, mechanisms and outcomes. SPCs were pivotal to the effective functioning of the social prescribing service and responsible for the activation and initial beneficial impact on users. Although social prescribing shows significant potential for the benefit of patients and primary care, several challenges need to be considered and overcome, including 'buy in' from some GPs, branding, and funding for the third sector in a context where social care cuts are severely affecting the delivery of health care. With its emphasis on context and mechanisms, the realist evaluation approach is useful in understanding how to identify and improve health interventions, and analyse in greater detail the contribution of different stakeholders. As the SPC is central to social prescribing, more needs to be done to understand their role conceptually and practically.

The impact of a social prescribing service on patients in primary care: a mixed methods evaluation.

BACKGROUND: Social prescribing is targeted at isolated and lonely patients. Practitioners and patients jointly develop bespoke well-being plans to promote social integration and or social reactivation. Our aim was to investigate: whether a social prescribing service could be implemented in a general practice (GP) setting and to evaluate its effect on well-being and primary care resource use. METHODS: We used a mixed method evaluation approach using patient surveys with matched control groups and a qualitative interview study. The study was conducted in a mixed socio-economic, multi-ethnic, inner city London borough with socially isolated patients who frequently visited their GP. The intervention was implemented by 'social prescribing coordinators'. Outcomes of interest were psychological and social well-being and health care resource use. RESULTS: At 8 months follow-up there were no differences between patients referred to social prescribing and the controls for general health, depression, anxiety and 'positive and active engagement in life'. Social prescribing patients had high GP consultation rates, which fell in the year following referral. The qualitative study indicated that most patients had a positive experience with social prescribing but the service was not utilised to its full extent. CONCLUSION: Changes in general health and well-being following referral were very limited and comprehensive implementation was difficult to optimise. Although GP consultation rates fell, these may have reflected regression to the mean rather than changes related to the intervention. Whether social prescribing can contribute to the health of a nation for social and psychological wellbeing is still to be determined.

Subcutaneous Injection of Adalimumab Trial compared with Control (SCIATiC): a randomised controlled trial of adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica.

BACKGROUND: Biological treatments such as adalimumab (Humira®; AbbVie Ltd, Maidenhead, UK) are antibodies targeting tumour necrosis factor alpha, released from ruptured intervertebral discs, which might be useful in sciatica. Recent systematic reviews concluded that they might be effective, but that a definitive randomised controlled trial was needed. Usual care in the NHS typically includes a physiotherapy intervention. OBJECTIVES: To test whether or not injections of adalimumab plus physiotherapy are more clinically effective and cost-effective than injections of saline plus physiotherapy for patients with sciatica. DESIGN: Pragmatic, parallel-group, randomised controlled trial with blinded participants and clinicians, and an outcome assessment and statistical analysis with concurrent economic evaluation and internal pilot. SETTING: Participants were referred from primary care and musculoskeletal services to outpatient physiotherapy clinics. PARTICIPANTS: Adults with persistent symptoms of sciatica of 1-6 months' duration and with moderate to high levels of disability. Eligibility was assessed by research physiotherapists according to clinical criteria for diagnosing sciatica. INTERVENTIONS: After a second eligibility check, trial participants were randomised to receive two doses of adalimumab (80 mg and then 40 mg 2 weeks later) or saline injections. Both groups were referred for a course of physiotherapy. MAIN OUTCOME MEASURES: Outcomes were measured at the start, and after 6 weeks' and 6 months' follow-up. The main outcome measure was the Oswestry Disability Index (ODI). Other outcomes: leg pain version of the Roland-Morris Disability Questionnaire, Sciatica Bothersomeness Index, EuroQol-5 Dimensions, 5-level version, Hospital Anxiety and Depression Scale, resource use, risk of persistent disabling pain, pain trajectory based on a single question, Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia and adverse effects. SAMPLE SIZE: To detect an effect size of 0.4 with 90% power, a 5% significance level for a two-tailed t-test and 80% retention rate, 332 participants would have needed to be recruited. ANALYSIS PLAN: The primary effectiveness analysis would have been linear mixed models for repeated measures to measure the effects of time and group allocation. An internal pilot study would have involved the first 50 participants recruited across all centres. The primary economic analysis would have been a cost-utility analysis. RESULTS: The internal pilot study was discontinued as a result of low recruitment after eight participants were recruited from two out of six sites. One site withdrew from the study before recruitment started, one site did not complete contract negotiations and two sites signed contracts shortly before trial closure. In the two sites that did recruit participants, recruitment was slow. This was partly because of operational issues, but also because of a low rate of uptake from potential participants. LIMITATIONS: Although large numbers of invitations were sent to potential participants, identified by retrospective searches of general practitioner (GP) records, there was a low rate of uptake. Two sites planned to recruit participants during GP consultations but opened too late to recruit any participants. CONCLUSION: The main failure was attributable to problems with contracts. Because of this we were not able to complete the internal pilot or to test all of the different methods for primary care recruitment we had planned. A trial of biological therapy in patients with sciatica still needs to be done, but would require a clearer contracting process, qualitative research to ensure that patients would be willing to participate, and simpler recruitment methods. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14569274. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 60. See the NIHR Journals Library website for further project information.

Novel Three-Day, Community-Based, Nonpharmacological Group Intervention for Chronic Musculoskeletal Pain (COPERS): A Randomised Clinical Trial.

BACKGROUND: Chronic musculoskeletal pain is the leading cause of disability worldwide. The effectiveness of pharmacological treatments for chronic pain is often limited, and there is growing concern about the adverse effects of these treatments, including opioid dependence. Nonpharmacological approaches to chronic pain may be an attractive alternative or adjunctive treatment. We describe the effectiveness of a novel, theoretically based group pain management support intervention for chronic musculoskeletal pain. METHODS AND FINDINGS: We conducted a multi-centre, pragmatic, randomised, controlled effectiveness and cost-effectiveness (cost-utility) trial across 27 general practices and community musculoskeletal services in the UK. We recruited 703 adults with musculoskeletal pain of at least 3 mo duration between August 1, 2011, and July 31, 2012, and randomised participants 1.33:1 to intervention (403) or control (300). Intervention participants were offered a participative group intervention (COPERS) delivered over three alternate days with a follow-up session at 2 wk. The intervention introduced cognitive behavioural approaches and was designed to promote self-efficacy to manage chronic pain. Controls received usual care and a relaxation CD. The primary outcome was pain-related disability at 12 mo (Chronic Pain Grade [CPG] disability subscale); secondary outcomes included the CPG disability subscale at 6 mo and the following measured at 6 and 12 mo: anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), pain acceptance (Chronic Pain Acceptance Questionnaire), social integration (Health Education Impact Questionnaire social integration and support subscale), pain-related self-efficacy (Pain Self-Efficacy Questionnaire), pain intensity (CPG pain intensity subscale), the census global health question (2011 census for England and Wales), health utility (EQ-5D-3L), and health care resource use. Analyses followed the intention-to-treat principle, accounted for clustering by course in the intervention arm, and used multiple imputation for missing or incomplete primary outcome data. The mean age of participants was 59.9 y, with 81% white, 67% female, 23% employed, 85% with pain for at least 3 y, and 23% on strong opioids. Symptoms of depression and anxiety were common (baseline mean HADS scores 7.4 [standard deviation 4.1] and 9.2 [4.6], respectively). Overall, 282 (70%) intervention participants met the predefined intervention adherence criterion. Primary outcome data were obtained from 88% of participants. There was no significant difference between groups in pain-related disability at 6 or 12 mo (12 mo: difference -1.0, intervention versus control, 95% CI -4.9 to 3.0), pain intensity, or the census global health question. Anxiety, depression, pain-related self-efficacy, pain acceptance, and social integration were better in the intervention group at 6 mo; at 12 mo, these differences remained statistically significant only for depression (-0.7, 95% CI -1.2 to -0.2) and social integration (0.8, 95% CI 0.4 to 1.2). Intervention participants received more analgesics than the controls across the 12 mo. The total cost of the course per person was £145 (US$214). The cost-utility analysis showed there to be a small benefit in terms of quality-adjusted life years (QALYs) (0.0325, 95% CI -0.0074 to 0.0724), and on the cost side the intervention was a little more expensive than usual care (i.e., £188 [US$277], 95% CI -£125 [-US$184] to £501 [US$738]), resulting in an incremental cost-effectiveness ratio of £5,786 (US$8,521) per QALY. Limitations include the fact that the intervention was relatively brief and did not include any physical activity components. CONCLUSIONS: While the COPERS intervention was brief, safe, and inexpensive, with a low attrition rate, it was not effective for reducing pain-related disability over 12 mo (primary outcome). For secondary outcomes, we found sustained benefits on depression and social integration at 6 and 12 mo, but there was no effect on anxiety, pain-related self-efficacy, pain acceptance, pain intensity, or the census global health question at 12 mo. There was some evidence that the intervention may be cost-effective based on a modest difference in QALYs between groups. TRIAL REGISTRATION: ISRCTN Registry 24426731.

Effectiveness and cost-effectiveness of a novel, group self-management course for adults with chronic musculoskeletal pain: study protocol for a multicentre, randomised controlled trial (COPERS).

INTRODUCTION: Chronic musculoskeletal pain is a common condition that often responds poorly to treatment. Self-management courses have been advocated as a non-drug pain management technique, although evidence for their effectiveness is equivocal. We designed and piloted a self-management course based on evidence for effectiveness for specific course components and characteristics. METHODS/ANALYSIS: COPERS (coping with persistent pain, effectiveness research into self-management) is a pragmatic randomised controlled trial testing the effectiveness and cost-effectiveness of an intensive, group, cognitive behavioural-based, theoretically informed and manualised self-management course for chronic pain patients against a control of best usual care: a pain education booklet and a relaxation CD. The course lasts for 15 h, spread over 3 days, with a -2 h follow-up session 2 weeks later. We aim to recruit 685 participants with chronic musculoskeletal pain from primary, intermediate and secondary care services in two UK regions. The study is powered to show a standardised mean difference of 0.3 in the primary outcome, pain-related disability. Secondary outcomes include generic health-related quality of life, healthcare utilisation, pain self-efficacy, coping, depression, anxiety and social engagement. Outcomes are measured at 6 and 12 months postrandomisation. Pain self-efficacy is measured at 3 months to assess whether change mediates clinical effect. ETHICS/DISSEMINATION: Ethics approval was given by Cambridgeshire Ethics 11/EE/046. This trial will provide robust data on the effectiveness and cost-effectiveness of an evidence-based, group self-management programme for chronic musculoskeletal pain. The published outcomes will help to inform future policy and practice around such self-management courses, both nationally and internationally. TRIAL REGISTRATION: ISRCTN24426731.

Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials: a consensus study.

BACKGROUND: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. METHOD: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers' Handbook, and the process was repeated. RESULTS: The recommendations are that meta-analysts report both confirmatory and exploratory findings for sub-groups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based a-priori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. CONCLUSIONS: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies.