Abstract Background Irritable bowel syndrome (IBS) is a common functional bowel disorder that has a considerable impact on patient quality of life and substantial societal and health care resource costs. Current treatments are often ineffective. Tricyclic antidepressants have shown promise in secondary care populations but their effectiveness in a primary care setting remains unclear. Methods ATLANTIS is a randomised, multi-centre, parallel-group, two-arm, double-blind, placebo-controlled trial of low-dose amitriptyline as a second-line treatment for IBS in primary care. Participants will be invited by letter, or recruited opportunistically, from general practices in three regions of England (West Yorkshire, Wessex, and West of England) and screened for eligibility. A total of 518 adult patients with IBS, who are symptomatic despite first-line therapies, will be randomised 1:1 to amitriptyline or identical placebo for 6 months. Treatment will commence at a dose of 10 mg (or one placebo tablet) daily at night, with dose titration up to a maximum of 30 mg at night, depending on side effects and response to treatment. Participant-reported assessments will be conducted at baseline and 3, 6, and 12 months post-randomisation. The primary objective is to determine the effectiveness of amitriptyline, compared with placebo, in improving participant-reported global symptoms of IBS at 6 months (using the IBS Severity Scoring System). Secondary outcomes include relief of IBS symptoms, effect on IBS-associated somatic symptoms (Patient Health Questionnaire-12), anxiety and depression (Hospital Anxiety and Depression Scale), ability to work and participate in other activities (Work and Social Adjustment Scale), acceptability and tolerability of treatment, self-reported health care use, health-related quality of life (EQ-5D-3L), and cost-effectiveness. A nested, qualitative study will explore patient and general practitioner experiences of treatments and trial participation, including acceptability, adherence, unanticipated effects, and implications for wider use of amitriptyline for IBS in primary care. Discussion Determining the clinical and cost-effectiveness of low-dose amitriptyline as a second-line treatment for IBS in primary care will provide robust evidence to inform management decisions. Trial registration ISRCTN ISRCTN48075063 . Registered on 7th June 2019.

BACKGROUND:Falls and fractures are a major problem. OBJECTIVES:To investigate the clinical effectiveness and cost-effectiveness of alternative falls prevention interventions. DESIGN:Three-arm, pragmatic, cluster randomised controlled trial with parallel economic analysis. The unit of randomisation was the general practice. SETTING:Primary care. PARTICIPANTS:People aged ≥ 70 years. INTERVENTIONS:All practices posted an advice leaflet to each participant. Practices randomised to active intervention arms (exercise and multifactorial falls prevention) screened participants for falls risk using a postal questionnaire. Active treatments were delivered to participants at higher risk of falling. MAIN OUTCOME MEASURES:The primary outcome was fracture rate over 18 months, captured from Hospital Episode Statistics, general practice records and self-report. Secondary outcomes were falls rate, health-related quality of life, mortality, frailty and health service resource use. Economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year and incremental net monetary benefit. RESULTS:Between 2011 and 2014, we randomised 63 general practices (9803 participants): 21 practices (3223 participants) to advice only, 21 practices (3279 participants) to exercise and 21 practices (3301 participants) to multifactorial falls prevention. In the active intervention arms, 5779 out of 6580 (87.8%) participants responded to the postal fall risk screener, of whom 2153 (37.3%) were classed as being at higher risk of falling and invited for treatment. The rate of intervention uptake was 65% (697 out of 1079) in the exercise arm and 71% (762 out of 1074) in the multifactorial falls prevention arm. Overall, 379 out of 9803 (3.9%) participants sustained a fracture. There was no difference in the fracture rate between the advice and exercise arms (rate ratio 1.20, 95% confidence interval 0.91 to 1.59) or between the advice and multifactorial falls prevention arms (rate ratio 1.30, 95% confidence interval 0.99 to 1.71). There was no difference in falls rate over 18 months (exercise arm: rate ratio 0.99, 95% confidence interval 0.86 to 1.14; multifactorial falls prevention arm: rate ratio 1.13, 95% confidence interval 0.98 to 1.30). A lower rate of falls was observed in the exercise arm at 8 months (rate ratio 0.78, 95% confidence interval 0.64 to 0.96), but not at other time points. There were 289 (2.9%) deaths, with no differences by treatment arm. There was no evidence of effects in prespecified subgroup comparisons, nor in nested intention-to-treat analyses that considered only those at higher risk of falling. Exercise provided the highest expected quality-adjusted life-years (1.120), followed by advice and multifactorial falls prevention, with 1.106 and 1.114 quality-adjusted life-years, respectively. NHS costs associated with exercise (£3720) were lower than the costs of advice (£3737) or of multifactorial falls prevention (£3941). Although incremental differences between treatment arms were small, exercise dominated advice, which in turn dominated multifactorial falls prevention. The incremental net monetary benefit of exercise relative to treatment valued at £30,000 per quality-adjusted life-year is modest, at £191, and for multifactorial falls prevention is £613. Exercise is the most cost-effective treatment. No serious adverse events were reported. LIMITATIONS:The rate of fractures was lower than anticipated. CONCLUSIONS:Screen-and-treat falls prevention strategies in primary care did not reduce fractures. Exercise resulted in a short-term reduction in falls and was cost-effective. FUTURE WORK:Exercise is the most promising intervention for primary care. Work is needed to ensure adequate uptake and sustained effects. TRIAL REGISTRATION:Current Controlled Trials ISRCTN71002650. 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. 25, No. 34. See the NIHR Journals Library website for further project information.

Objective To assess the cost-effectiveness of acupuncture in the management of chemotherapy-induced peripheral neuropathy (CIPN) in Hong Kong. Methods A within trial cost-utility analysis with the primary endpoint for the economic evaluation being the Quality Adjusted Life Year (QALY) and associated Incremental Cost Effectiveness Ratio (ICER) over 14 weeks of treatment. A secondary cost-effectiveness analysis was undertaken with the endpoint being change in pain as measured on the Brief Pain Inventory (BPI). Results Eighty-seven patients were randomised to acupuncture or usual care. Acupuncture resulted in significant improvements in pain intensity (8- and 14-week mean changes compared to usual care of −1.8 and −1.8, respectively), pain interference (8- and 14-week mean changes compared to usual care of −1.5 and −0.9, respectively) and indicators of quality of life and neurotoxicity-related symptoms. However, in the economic evaluation there was little difference in QALYs between the two arms (mean change 0.209 and 0.200 in the acupuncture and usual care arms, respectively). Also, costs yielded deterministic ICERs of HK$616,965.62, HK$824,083.44 and HK$540,727.56 per QALY gained from the health care provider perspective, the societal perspective and the patient perspective, respectively. These costs are significantly higher than the cost-effectiveness threshold of HK$180,450 that was used for the base case analysis. Conclusion While acupuncture can improve symptoms and quality of life indicators related to CIPN, it is unlikely to be a cost-effective treatment for CIPN-related pain in health care systems with limited resources. Trial registration number NCT02553863 (ClinicalTrials.gov) post-results.

INTRODUCTION:Diabetes affects more than 425 million people worldwide with a lifetime risk of diabetic foot ulcer (DFU) of up to 25%. Management includes wound debridement, wound dressings, offloading, treatment of infection and ischaemia, optimising glycaemic control; use of advanced adjuvant therapies is limited by high cost and lack of robust evidence. METHODS AND ANALYSIS:A multicentre, seamless phase II/III, open, parallel group, multi-arm multi-stage randomised controlled trial in patients with a hard-to-heal DFU, with blinded outcome assessment. A maximum of 447 participants will be randomised (245 participants in phase II and 202 participants in phase III). The phase II primary objective will determine the efficacy of treatment strategies including hydrosurgical debridement ± decellularised dermal allograft, or the combination with negative pressure wound therapy, as an adjunct to treatment as usual (TAU), compared with TAU alone, with patients randomised in a 1:1:1:2 allocation. The outcome is achieving at least 50% reduction in index ulcer area at 4 weeks post randomisation.The phase III primary objective will determine whether one treatment strategy, continued from phase II, reduces time to healing of the index ulcer compared with TAU alone, with participants randomised in a 1:1 allocation. Secondary objectives will compare healing status of the index ulcer, infection rate, reulceration, quality of life, cost-effectiveness and incidence of adverse events over 52 weeks post randomisation. Phase II and phase III primary endpoint analysis will be conducted using a mixed-effects logistic regression model and Cox proportional hazards regression, respectively. A within-trial economic evaluation will be undertaken; the primary economic analysis will be a cost-utility analysis presenting ICERs for each treatment strategy in rank order of effectiveness, with effects expressed as quality-adjusted life years.The trial has predefined progression criteria for the selection of one treatment strategy into phase III based on efficacy, safety and costs at 4 weeks. ETHICS AND DISSEMINATION:Ethics approval has been granted by the National Research Ethics Service (NRES) Committee Yorkshire and The Humber - Bradford Leeds Research Ethics Committee; approved 26 April 2017; (REC reference: 17/YH/0055). There is planned publication of a monograph in National Institute for Health Research journals and main trial results and associated papers in high-impact peer-reviewed journals. TRIAL REGISTRATION NUMBER:ISRCTN64926597; registered on 6 June 2017.

BACKGROUND:Community screening and therapeutic prevention strategies may reduce the incidence of falls in older people. The effects of these measures on the incidence of fractures, the use of health resources, and health-related quality of life are unknown. METHODS:In a pragmatic, three-group, cluster-randomized, controlled trial, we estimated the effect of advice sent by mail, risk screening for falls, and targeted interventions (multifactorial fall prevention or exercise for people at increased risk for falls) as compared with advice by mail only. The primary outcome was the rate of fractures per 100 person-years over 18 months. Secondary outcomes were falls, health-related quality of life, frailty, and a parallel economic evaluation. RESULTS:We randomly selected 9803 persons 70 years of age or older from 63 general practices across England: 3223 were assigned to advice by mail alone, 3279 to falls-risk screening and targeted exercise in addition to advice by mail, and 3301 to falls-risk screening and targeted multifactorial fall prevention in addition to advice by mail. A falls-risk screening questionnaire was sent to persons assigned to the exercise and multifactorial fall-prevention groups. Completed screening questionnaires were returned by 2925 of the 3279 participants (89%) in the exercise group and by 2854 of the 3301 participants (87%) in the multifactorial fall-prevention group. Of the 5779 participants from both these groups who returned questionnaires, 2153 (37%) were considered to be at increased risk for falls and were invited to receive the intervention. Fracture data were available for 9802 of the 9803 participants. Screening and targeted intervention did not result in lower fracture rates; the rate ratio for fracture with exercise as compared with advice by mail was 1.20 (95% confidence interval [CI], 0.91 to 1.59), and the rate ratio with multifactorial fall prevention as compared with advice by mail was 1.30 (95% CI, 0.99 to 1.71). The exercise strategy was associated with small gains in health-related quality of life and the lowest overall costs. There were three adverse events (one episode of angina, one fall during a multifactorial fall-prevention assessment, and one hip fracture) during the trial period. CONCLUSIONS:Advice by mail, screening for fall risk, and a targeted exercise or multifactorial intervention to prevent falls did not result in fewer fractures than advice by mail alone. (Funded by the National Institute of Health Research; ISRCTN number, ISRCTN71002650.).

Background and Objectives: Prospective, monthly diaries are recommended for collecting falls data but are burdensome and expensive. The aim of the article was to compare characteristics of fallers and estimates of fall rates by method of data collection. Study Design and Setting: A methodology study nested within a large cluster randomized controlled trial. We randomized 9,803 older adults from 63 general practices across England to receive one of three fall prevention interventions. Participants provided a retrospective report of falls in postal questionnaires mailed every 4 months. A separate randomization allocated participants to receive prospective monthly falls diaries for one simultaneous 4-month period. Results: Falls diaries were returned by 7,762 of 9,375 (83%); of which 6,306 (67%) participants reported the same number of falls on both data sources. Diary nonresponders were older and had poorer levels of physical and mental health. Analysis of time points where both data sources were available showed the falls rate on diaries was consistently higher than on the questionnaire (mean rate: 0.16 vs. 0.12 falls per person-month observation). Diary allocation was associated with a higher rate of withdrawal from the main trial. Conclusion: Diary completion was associated with sample attrition. We found on average a 32% difference in falls rates between the two data sources. Retrospective and prospective falls data are not consistently reported when collected simultaneously. (C) 2018 The Authors. Published by Elsevier Inc.

Introduction: Pringle manoeuvre (PM) is commonly used to prevent blood loss during liver resection. It has been suggested that isolated control of the hepatic portal vein and not clamping the hepatic artery, could potentially reduce the ischaemic reperfusion injury (IRI). We carried out a pilot randomised controlled trial (RCT) to compare the outcomes of portal vein clamping (PVC) versus PM. Method: Eighty patients were recruited in this prospective, parallel group, single blind, pilot study. The first 20 patients were part of a learning curve for PVC. The subsequent 60 patients were randomised 1:1 to PVC or PM procedure. The outcomes from main trial [PVC 30 vs. PM 30 patients] are reported. Result: There was no difference between the two groups in terms of mean age, male gender, mean BMI and major resections. There was no difference in total mean operative time (128.4 vs. 132.8 mins; P=0.711) or the total clamping time (36.3 vs. 34.9 mins; P=0.742) between PVC and PM groups. The total transection time and the estimated blood loss were higher in the PVC group, but this was not statistically significant (53.6 vs. 49.6 mins; P=0.619 and 436.7 vs. 311.6 mls; P=0.060). There were no intra-operative blood transfusions. There was no difference in post-operative peak bilirubin and peak ALT (28.8 vs. 26.7 mmol/L; P=0.706 and 327.0 vs. 336.3 U/L; P=0.919). The Clavien-Dindo complications were grade 2 (5 vs. 8), grade 3a (1 vs. 1) and grade 3b (0 vs. 1) in the PVC versus PM groups respectively. There were no 30-day mortality in both groups. Conclusion: The operating times between the two groups were similar though there was a trend towards more blood loss in the PVC group. There was no difference in IRI in this small pilot RCT. A UK wide consensus is being sought to proceed to a larger multi-centre trial.

Abstract Background There is a widespread belief that information technologies will improve diagnosis, treatment and care. Evidence about their effectiveness in health care is, however, mixed. It is not clear why this is the case, given the remarkable advances in hardware and software over the last 20 years. This review focuses on interoperable information technologies, which governments are currently advocating and funding. These link organisations across a health economy, with a view to enabling health and care professionals to coordinate their work with one another and to access patient data wherever it is stored. Given the mixed evidence about information technologies in general, and current policies and funding, there is a need to establish the value of investments in this class of system. The aim of this review is to establish how, why and in what circumstances interoperable systems affect patient safety. Methods A realist synthesis will be undertaken, to understand how and why inter-organisational systems reduce patients’ clinical risks, or fail to do so. The review will follow the steps in most published realist syntheses, including (1) clarifying the scope of the review and identifying candidate programme and mid-range theories to evaluate, (2) searching for evidence, (3) appraising primary studies in terms of their rigour and relevance and extracting evidence, (4) synthesising evidence, (5) identifying recommendations, based on assessment of the extent to which findings can be generalised to other settings. Discussion The findings of this realist synthesis will shed light on how and why an important class of systems, that span organisations in a health economy, will contribute to changes in patients’ clinical risks. We anticipate that the findings will be generalizable, in two ways. First, a refined mid-range theory will contribute to our understanding of the underlying mechanisms that, for a range of information technologies, lead to changes in clinical practices and hence patients’ risks (or not). Second, many governments are funding and implementing cross-organisational IT networks. The findings can inform policies on their design and implementation. Systematic review registration PROSPERO CRD42017073004

Introduction Poor medicines management places patients at risk, particularly during care transitions. For patients with heart failure (HF), optimal medicines management is crucial to control symptoms and prevent hospital readmission. This study explored the concept of resilience using HF as an example condition to understand how the system compensates for known and unknown weaknesses. Methods We explored resilience using a mixed-methods approach in four healthcare economies in the north of England. Data from hospital site observations, healthcare staff and patient interviews, and documentary analysis were collected between June 2016 and March 2017. Data were synthesised and analysed using framework analysis. Results Interviews were conducted with 45 healthcare professionals, with 20 patients at three time points and 189 hours of observation were undertaken. We identified four primary inter-related themes concerning organisational resilience. These were named as gaps, traps, bridges and props. Gaps were discontinuities in processes that had the potential to result in poorly optimised medicines. Traps were features of the system that could produce errors or unintended adverse medication events. Bridges were features of the medicines management system that promoted safety and continuity which ensured that, despite varying conditions, care could be delivered successfully. Props were informal, temporary or impromptu actions taken by patients or healthcare staff to avoid potential adverse events. Conclusion The numerous opportunities for HF patient safety to be compromised and for suboptimal medicines management during this common care transition are mitigated by system resilience. Cross-organisational bridges and temporary fixes or 'props' put in place by patients and carers, healthcare teams and organisations are critical for safe and optimal care to be delivered in the face of continued system pressures.

Background: Protein biomarkers with associations with the activity and outcomes of diseases are being identified by modern proteomic technologies. They may be simple, accessible, cheap and safe tests that can inform diagnosis, prognosis, treatment selection, monitoring of disease activity and therapy and may substitute for complex, invasive and expensive tests. However, their potential is not yet being realised. Design and methods: The study consisted of three workstreams to create a framework for research: workstream 1, methodology – to define current practice and explore methodology innovations for biomarkers for monitoring disease; workstream 2, clinical translation – to create a framework of research practice, high-quality samples and related clinical data to evaluate the validity and clinical utility of protein biomarkers; and workstream 3, the ELF to Uncover Cirrhosis as an Indication for Diagnosis and Action for Treatable Event (ELUCIDATE) randomised controlled trial (RCT) – an exemplar RCT of an established test, the ADVIA Centaur® Enhanced Liver Fibrosis (ELF) test (Siemens Healthcare Diagnostics Ltd, Camberley, UK) [consisting of a panel of three markers – (1) serum hyaluronic acid, (2) amino-terminal propeptide of type III procollagen and (3) tissue inhibitor of metalloproteinase 1], for liver cirrhosis to determine its impact on diagnostic timing and the management of cirrhosis and the process of care and improving outcomes. Results: The methodology workstream evaluated the quality of recommendations for using prostate-specific antigen to monitor patients, systematically reviewed RCTs of monitoring strategies and reviewed the monitoring biomarker literature and how monitoring can have an impact on outcomes. Simulation studies were conducted to evaluate monitoring and improve the merits of health care. The monitoring biomarker literature is modest and robust conclusions are infrequent. We recommend improvements in research practice. Patients strongly endorsed the need for robust and conclusive research in this area. The clinical translation workstream focused on analytical and clinical validity. Cohorts were established for renal cell carcinoma (RCC) and renal transplantation (RT), with samples and patient data from multiple centres, as a rapid-access resource to evaluate the validity of biomarkers. Candidate biomarkers for RCC and RT were identified from the literature and their quality was evaluated and selected biomarkers were prioritised. The duration of follow-up was a limitation but biomarkers were identified that may be taken forward for clinical utility. In the third workstream, the ELUCIDATE trial registered 1303 patients and randomised 878 patients out of a target of 1000. The trial started late and recruited slowly initially but ultimately recruited with good statistical power to answer the key questions. ELF monitoring altered the patient process of care and may show benefits from the early introduction of interventions with further follow-up. The ELUCIDATE trial was an ‘exemplar’ trial that has demonstrated the challenges of evaluating biomarker strategies in ‘end-to-end’ RCTs and will inform future study designs. Conclusions: The limitations in the programme were principally that, during the collection and curation of the cohorts of patients with RCC and RT, the pace of discovery of new biomarkers in commercial and non-commercial research was slower than anticipated and so conclusive evaluations using the cohorts are few; however, access to the cohorts will be sustained for future new biomarkers. The ELUCIDATE trial was slow to start and recruit to, with a late surge of recruitment, and so final conclusions about the impact of the ELF test on long-term outcomes await further follow-up. The findings from the three workstreams were used to synthesise a strategy and framework for future biomarker evaluations incorporating innovations in study design, health economics and health informatics. Trial registration: Current Controlled Trials ISRCTN74815110, UKCRN ID 9954 and UKCRN ID 11930. Funding: This project was funded by the NIHR Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 6, No. 3. See the NIHR Journals Library website for further project information.

BACKGROUND:The conventional frontline therapy for fit patients with chronic lymphocytic leukaemia (CLL) is fludarabine, cyclophosphamide and rituximab (FCR). Rituximab (Mabthera®, Roche Products Ltd) targets the CD20 antigen, which is expressed at low levels in CLL. The standard dose of rituximab in CLL (375 mg/m2 in cycle 1 and 500 mg/m2 in cycles 2-6) was selected based on toxicity data only. Small doses of rituximab (as low as 20 mg) have biological activity in CLL, with an immediate reduction in circulating CLL cells and down-regulation of CD20. Phase II trials had suggested improved efficacy with the addition of mitoxantrone to FCR. The key assumption for the Attenuated dose Rituximab with ChemoTherapy In CLL (ARCTIC) trial was that the addition of mitoxantrone to fludarabine, cyclophosphamide and low-dose rituximab would be more effective than conventional FCR. OBJECTIVES:To assess whether fludarabine, cyclophosphamide, mitoxantrone and low-dose rituximab (FCM-miniR) (100 mg of rituximab per cycle) was non-inferior to FCR in frontline CLL. Complete response (CR) rate was the primary end point, with the secondary end points being progression-free survival (PFS), overall survival (OS), overall response rate, eradication of minimal residual disease (MRD), safety and cost-effectiveness. DESIGN:ARCTIC was a UK multicentre, randomised, controlled, open, Phase IIB non-inferiority trial in previously untreated CLL. A total of 206 patients with previously untreated CLL who required treatment, according to the International Workshop on Chronic Lymphocytic Leukaemia criteria, were to be randomised to FCR or FCM-miniR. There was an independent Data Monitoring and Ethics Committee (DMEC) with a pre-planned interim efficacy assessment on 103 participants. RESULTS:The DMEC's interim analysis led to early trial closure. Although the response rates in both arms were higher than anticipated, FCM-miniR had a lower CR rate than FCR. This was partly attributable to the higher toxicity associated with mitoxantrone. A total of 100 participants completed FCR, 79 completed FCM-miniR and 21 commenced FCM-miniR but switched to FCR following DMEC recommendations. The CR rate for participants receiving FCR was 76%, compared with 55% for FCM-miniR (adjusted odds ratio 0.37; 95% confidence interval 0.19 to 0.73). Key secondary end points also showed that FCR was superior, with more participants achieving MRD negativity (57% for FCR vs. 46% for FCM-miniR). More participants experienced a serious adverse reaction with FCM-miniR compared with FCR (50% vs. 41%). At a median of 37.3 months' follow-up, the PFS and OS rates are good compared with previous studies, with no significant difference between the treatment arms. The economic analysis indicates that because FCM-miniR is less effective than FCR, FCM-miniR is not expected to be cost-effective over a lifetime horizon, producing a mean cost-saving of -£7723, a quality-adjusted life-year loss of -0.73 and a resulting incremental net monetary loss of -£6780. CONCLUSIONS:FCM-miniR is less well tolerated, with poorer response rates, than FCR, partly owing to the additional toxicity associated with mitoxantrone. In view of this, FCM-miniR will not be taken forward into a larger definitive Phase III trial. The trial demonstrated that oral FCR yields extremely high response rates compared with historical series with intravenous chemotherapy. FUTURE WORK:We shall compare the results of ARCTIC with those of the ADMIRE (Does the ADdition of Mitoxantrone Improve Response to FCR chemotherapy in patients with CLL?) trial, which compared FCR with FCM-R to assess the efficacy of low- versus standard-dose rituximab, allowing for the toxicity associated with mitoxantrone. TRIAL REGISTRATION:Current Controlled Trials ISRCTN16544962. FUNDING:This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 28. See the NIHR Journals Library website for further project information.

This paper examines government spending and economic issues related to health care services, with a particular focus on the National Health Service (NHS) in England. We begin by discussing the formation of the NHS according to noteworthy economic and political themes. We then move to a brief discussion of health care system models to make clear the NHS’s position amongst its peers. We then take an overview of key economic themes throughout the course of the NHS’s 70 year history. Next is the focal issue of expenditure. We discuss pre-NHS costs, before moving to the progression of NHS costs over its lifetime. We finally discuss economic reasons for changes in health care costs, and conclude the article by suggesting that natural rises in health care costs over time imply that efficiency is crucial for policy makers, both in the NHS context and beyond.

BackgroundOffender health is deemed a priority issue by the Department of Health. Peer support is an established feature of prison life in England and Wales; however, more needs to be known about the effectiveness of peer-based interventions to maintain and improve health in prison settings.ObjectivesThe study aimed to synthesise the evidence on peer-based interventions in prison settings by carrying out a systematic review and holding an expert symposium. Review questions were (1) what are the effects of peer-based interventions on prisoner health and the determinants of prisoner health?, (2) what are the positive and negative impacts on health services within prison settings of delivering peer-based interventions?, (3) how do the effects of peer-based approaches compare with those of professionally led approaches? and (4) what are the costs and cost-effectiveness of peer-based interventions in prison settings?Data sourcesFor the systematic review, 20 electronic databases including MEDLINE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature and EMBASE were searched from 1985. Grey literature and relevant websites were also searched. To supplement the review findings 58 delegates, representing a variety of organisations, attended an expert symposium, which provided contextual information.Review methodsTwo reviewers independently selected studies using the following inclusion criteria: population – prisoners resident in prisons and young offender institutions; intervention – peer-based interventions; comparators: review questions 3 and 4 compared peer-led and professionally led approaches; outcomes – prisoner health or determinants of health, organisational/process outcomes or views of prison populations; study design: quantitative, qualitative and mixed-methods evaluations. Two reviewers extracted data and assessed validity using piloted electronic forms and validity assessment criteria based on published checklists. Results from quantitative studies were combined using narrative summary and meta-analysis when appropriate; results from qualitative studies were combined using thematic synthesis.ResultsA total of 15,320 potentially relevant papers were identified of which 57 studies were included in the effectiveness review and one study was included in the cost-effectiveness review; most were of poor methodological quality. A typology of peer-based interventions was developed. Evidence suggested that peer education interventions are effective at reducing risky behaviours and that peer support services provide an acceptable source of help within the prison environment and have a positive effect on recipients; the strongest evidence came from the Listener scheme. Consistent evidence from many predominantly qualitative studies suggested that being a peer deliverer was associated with positive effects across all intervention types. There was limited evidence about recruitment of peer deliverers. Recurring themes were the importance of prison managerial and staff support for schemes to operate successfully, and risk management. There was little evidence on the cost-effectiveness of peer-based interventions. An economic model, developed from the results of the effectiveness review, although based on data of variable quality and a number of assumptions, showed the cost-effectiveness of peer-led over professionally led education in prison for the prevention of human immunodeficiency virus (HIV) infection.LimitationsThe 58 included studies were, on the whole, of poor methodological quality.ConclusionsThere is consistent evidence from a large number of studies that being a peer worker is associated with positive health. Peer support services can also provide an acceptable source of help within the prison environment and can have a positive effect on recipients. This was confirmed by expert evidence. Research into cost-effectiveness is sparse but a limited HIV-specific economic model, although based on a number of assumptions and evidence of variable quality, showed that peer interventions were cost-effective compared with professionally led interventions. Well-designed intervention studies are needed to provide robust evidence including assessing outcomes for the target population, economic analysis of cost-effectiveness and impacts on prison health services. More research is needed to examine issues of reach, utilisation and acceptability from the perspective of recipients and those who choose not to receive peer support.Study registrationThis study was registered as PROSPERO CRD42012002349.FundingThe National Institute for Health Research Health Services and Delivery Research programme.