Joanna Picot

The effectiveness and cost-effectiveness of behavioural interventions for the prevention of sexually transmitted infections in young people aged 13-19: a systematic review and economic evaluation

OBJECTIVES To assess the effectiveness and cost-effectiveness of schools-based skills-building behavioural interventions to encourage young people to adopt and maintain safer sexual behaviour and to prevent them from acquiring sexually transmitted infections (STIs). DATA SOURCES Electronic bibliographic databases (e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, PsycINFO, CCRCT, NHS EED and DARE) were searched for the period 1985 to March 2008. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify additional published and unpublished references. REVIEW METHODS A systematic review of effectiveness and economic evaluation of cost-effectiveness were carried out. A descriptive map of studies that met inclusion criteria was produced, and keywords were developed and systematically applied to these studies to identify a policy-relevant subset of studies for the systematic review. Outcome data for variables including sexual behaviour were extracted. An economic model was developed to compare the costs and consequences of the behavioural interventions. A Bernoulli statistical model was constructed to describe the probability of STI infection. RESULTS There were few significant differences between the interventions and comparators in terms of changes in sexual behaviour outcomes, although there were some significant differences for knowledge and some measures of self-efficacy. The studies included in this review conducted relatively short follow-up assessments at a time when many young people were becoming sexually active. It is therefore possible that favourable behaviour change may have occurred, and become more cost-effective, with time, as sexual activity becomes more routine in young peoples lives. The quality of the intervention provider influenced whether or not young people found the interventions to be acceptable and engaging; enthusiasm and considerable expertise were important for effective class management and delivery of skills-building activities, and a supportive school culture was also helpful. Recognition of young peoples individual needs in relation to sexual health was another important factor. No conclusions could be drawn on the impact of the interventions on sexual health inequalities due to a lack of relevant data on socioeconomic status, gender and ethnicity. The results of the economic evaluation were considered to be illustrative, mainly due to the uncertainty of the effect of intervention on behavioural outcomes. The results were most sensitive to changes in parameter values for the intervention effect, the transmission probability of STIs and the number of sexual partners. The costs of teacher-led and peer-led behavioural interventions, based on the resources estimated from the relevant randomised controlled trials in our systematic review, were 4.30 pounds and 15 pounds per pupil, respectively. Teacher-led interventions were more cost-effective than peer-led interventions due to the less frequent need for training. The incremental cost-effectiveness of the teacher-led and peer-led interventions was 20,223 pounds and 80,782 pounds per quality-adjusted life-year gained, respectively. An analysis of individual parameters revealed that future research funding should focus on assessing the intervention effect for condom use from a school-based intervention. CONCLUSIONS School-based behavioural interventions for the prevention of STIs in young people can bring about improvements in knowledge and increased self-efficacy, but the interventions did not significantly influence sexual risk-taking behaviour or infection rates. Future investigation should include long-term follow-up to assess the extent to which safer sexual behaviour is adopted and maintained into adulthood, and prospective cohort studies are needed to look at the parameters that describe the transmission of STIs between partners. Funding should focus on the effectiveness of the interventions on influencing behaviour.

The Effectiveness of Interventions to Treat Severe Acute Malnutrition in Young Children: A Systematic Review

BACKGROUND Severe acute malnutrition (SAM) arises as a consequence of a sudden period of food shortage and is associated with loss of a persons body fat and wasting of their skeletal muscle. Many of those affected are already undernourished and are often susceptible to disease. Infants and young children are the most vulnerable as they require extra nutrition for growth and development, have comparatively limited energy reserves and depend on others. Undernutrition can have drastic and wide-ranging consequences for the childs development and survival in the short and long term. Despite efforts made to treat SAM through different interventions and programmes, it continues to cause unacceptably high levels of mortality and morbidity. Uncertainty remains as to the most effective methods to treat severe acute malnutrition in young children. OBJECTIVES To evaluate the effectiveness of interventions to treat infants and children aged < 5 years who have SAM. DATA SOURCES Eight databases (MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CAB Abstracts Ovid, Bioline, Centre for Reviews and Dissemination, EconLit EBSCO and The Cochrane Library) were searched to 2010. Bibliographies of included articles and grey literature sources were also searched. The project expert advisory group was asked to identify additional published and unpublished references. REVIEW METHODS Prior to the systematic review, a Delphi process involving international experts prioritised the research questions. Searches were conducted and two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full texts of retrieved papers by one reviewer and checked independently by a second. Included studies were mapped to the research questions. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Differences in opinion were resolved through discussion at each stage. Studies were synthesised through a narrative review with tabulation of the results. RESULTS A total of 8954 records were screened, 224 full-text articles were retrieved, and 74 articles (describing 68 studies) met the inclusion criteria and were mapped. No evidence focused on treatment of children with SAM who were human immunodeficiency virus sero-positive, and no good-quality or adequately reported studies assessed treatments for SAM among infants < 6 months old. One randomised controlled trial investigated fluid resuscitation solutions for shock, with none adequately treating shock. Children with acute diarrhoea benefited from the use of hypo-osmolar oral rehydration solution (H-ORS) compared with the standard World Health Organization-oral rehydration solution (WHO-ORS). WHO-ORS was not significantly different from rehydration solution for malnutrition (ReSoMal), but the safety of ReSoMal was uncertain. A rice-based ORS was more beneficial than glucose-based ORSs, and provision of zinc plus a WHO-ORS had a favourable impact on diarrhoea and need for ORS. Comparisons of different diets in children with persistent diarrhoea produced conflicting findings. For treating infection, comparison of amoxicillin with ceftriaxone during inpatient therapy, and routine provision of antibiotics for 7 days versus no antibiotics during outpatient therapy of uncomplicated SAM, found that neither had a significant effect on recovery at the end of follow-up. No evidence mapped to the next three questions on factors that affect sustainability of programmes, long-term survival and readmission rates, the clinical effectiveness of management strategies for treating children with comorbidities such as tuberculosis and Helicobacter pylori infection and the factors that limit the full implementation of treatment programmes. Comparison of treatment for SAM in different settings showed that children receiving inpatient care appear to do as well as those in ambulatory or home settings on anthropometric measures and response time to treatment. Longer-term follow-up showed limited differences between the different settings. The majority of evidence on methods for correcting micronutrient deficiencies considered zinc supplements; however, trials were heterogeneous and a firm conclusion about zinc was not reached. There was limited evidence on either supplementary potassium or nicotinic acid (each produced some benefits), and nucleotides (not associated with benefits). Evidence was identified for four of the five remaining questions, but not assessed because of resource limitation. LIMITATIONS The systematic review focused on key questions prioritised through a Delphi study and, as a consequence, did not encompass all elements in the management of SAM. In focusing on evidence from controlled studies with the most rigorous designs that were published in the English language, the systematic review may have excluded other forms of evidence. The systematic review identified several limitations in the evidence base for assessing the effectiveness of interventions for treating young children with severe acute malnutrition, including a lack of studies assessing the different interventions; limited details of study methods used; short follow-up post intervention or discharge; and heterogeneity in participants, interventions, settings, and outcome measures affecting generalisability. CONCLUSIONS For many of the most highly ranked questions evidence was lacking or inconclusive. More research is needed on a range of topic areas concerning the treatment of infants and children with SAM. Further research is required on most aspects of the management of SAM in children < 5 years, including intravenous resuscitation regimens for shock, management of subgroups (e.g. infants < 6 months old, infants and children with SAM who are human immunodeficiency virus sero-positive) and on the use of antibiotics.

Modelling the Cost Effectiveness of Cholinesterase Inhibitors in the Management of Mild to Moderately Severe Alzheimer's Disease

AbstractObjective: To estimate the cost effectiveness (from the UK NHS and personal social services perspective) of the cholinesterase inhibitors donepezil, rivastigmine and galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer’s disease. Patients had a mean age of 74 years, a mean disease duration of 1 year and a mean Alzheimer’s disease assessment scale-cognitive subscale score of 24. Methods: A pharmacoeconomic model was used to predict long-term outcomes over a 5-year time horizon and to estimate the cost effectiveness of cholinesterase inhibitors for the management of Alzheimer’s disease. The model structure is informed by a systematic review of the literature on the clinical and cost effectiveness of cholinesterase inhibitors and a review of the literature on the costs and outcomes associated with treatment for Alzheimer’s disease. The main outcome measure used was the cost per quality-adjusted life-year (QALY) gained. All healthcare costs (excluding cholinesterase inhibitor costs) were indexed to £ (2003 values). Drug costs are 2005 values. Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results. Results: The clinical benefits on cognition from treatment with cholinesterase inhibitors resulted in an incremental cost per QALY gained ranging from £53 780 to £74 735, over 5 years (vs usual care). Uncertainty analysis suggests that the probability of any of these treatments having an incremental cost per QALY of <£30 000 is <21%. The key determinants of cost effectiveness were the effectiveness of treatment, the mean treatment cost and the cost savings associated with an expected delay in disease progression. Conclusions: Results presented in this paper suggest that the use of cholinesterase inhibitors may not be a cost-effective use of NHS resources. Guidance from the National Institute for Health and Clinical Effectiveness (NICE) in the UK on their judgements surrounding the acceptability of technologies as an effective use of resources, indicates there would need to be special reasons for accepting cholinesterase inhibitors as a cost-effective use of NHS resources.

Adalimumab for the treatment of psoriasis

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of adalimumab for the treatment of moderate to severe plaque psoriasis based upon a review of the manufacturers submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submissions clinical evidence came from three randomised controlled trials comparing adalimumab with placebo, two extension studies and one ongoing open-label extension study. The studies were of reasonable quality and measured a range of clinically relevant outcomes. A higher proportion of patients on 40 mg adalimumab every other week achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) compared with placebo groups after 12 or 16 weeks of treatment, and there was a statistically significant difference in favour of adalimumab for the proportion of patients achieving a PASI 50 and a PASI 90. In a mixed treatment comparison, for each PASI outcome the probability of a response was greater for infliximab than for adalimumab, but the probability of response with adalimumab was greater than that with etanercept, efalizumab and non-biological systemic therapies. Adverse event rates were similar in the treatment and placebo arms and discontinuations because of adverse events were low and comparable between groups. The submissions economic model presents treatment effectiveness for adalimumab versus other biological therapies based upon utility values obtained from two clinical trials. The model is generally internally consistent and appropriate to psoriasis in terms of structural assumptions and the methods used are appropriate. The base-case incremental cost-effectiveness ratio for adalimumab compared with supportive care for patients with severe psoriasis was 30,538 pounds per quality-adjusted life-year. Scenario analysis shows that the model was most sensitive to the utility values used. Weaknesses of the clinical evidence included not undertaking a systematic review of the comparator trials, providing very little in the way of a narrative synthesis of outcome data from the key trials and not performing a meta-analysis so that the overall treatment effect of adalimumab achieved across the trials is unknown. Weaknesses of the economic model included that the assumptions made to estimate the cost-effectiveness of intermittent etanercept used inconsistent methodology for costs and benefits and there were no clear data on the amount of inpatient care required under supportive care. The NICE guidance issued as a result of the STA states that adalimumab is recommended as a treatment option for adults with plaque psoriasis in whom anti-tumour necrosis factor treatment is being considered and when the disease is severe and when the psoriasis has not responded to standard systemic therapies or the person is intolerant to or has a contraindication to these treatments.

Clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review

This review systematically assessed the evidence on the clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer. We searched eight electronic databases, including Medline and the Cochrane Library, from inception to January 2006 for systematic reviews and randomised controlled trials that reported death, heart failure, arrhythmias or measures of cardiac performance associated with cardioprotective technologies compared with standard treatment in children treated for cancer with anthracyclines. Economic evaluations were also sought. Inclusion criteria, data extraction and quality assessment were undertaken by standard methodology. Four randomised controlled trials met the inclusion criteria of the review; each had methodological limitations. No economic evaluations were identified. Studies were combined through narrative synthesis. One trial found that continuous infusion of doxorubicin did not offer any cardioprotection over rapid infusion. One suggested that continuous infusion of daunorubicin provoked less cardiotoxicity than rapid infusion. One concluded that dexrazoxane reduces cardiac injury during doxorubicin therapy and one reported a protective effect of coenzyme Q10 on cardiac function during anthracycline therapy. The evidence on the effectiveness of cardioprotective technologies in children is limited in quality and quantity thus making conclusions difficult. This is surprising given the importance of anthracycline use in children with cancer. Further long-term research, which includes relevant outcome measures, is needed to determine whether technologies influence the development of cardiac damage without limiting the antitumour efficacy of anthracyclines.

A systematic review of the clinical and cost-effectiveness of memantine in patients with moderately severe to severe Alzheimer's disease.

Alzheimer’s disease (AD) is the most common form of dementia and is characterised by a worsening of cognition, functional ability, and behaviour and mood. The objective of this study was to review the clinical and cost-effectiveness of memantine for the treatment of patients with moderately severe to severe AD. To achieve this, a systematic search and review of the clinical and cost effectiveness literature for memantine was undertaken. The literature search covered the period from the inception of MEDLINE, Cochrane Library, EMBASE and other electronic databases until July 2004. The search included randomised controlled trials (RCTs) and full economic evaluations that assessed the use of memantine in patients with moderately severe to severe AD.Two published RCTs were included in this review; in one of these trials the participants were already being treated with donepezil. The two RCTs showed benefit for patients receiving memantine compared with placebo on the outcome measures of the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia, the Clinician’s Interview-Based Impression of Change Plus Caregiver Input, and the Severe Impairment Battery, and that memantine appeared to be slightly more effective in patients already receiving a stable dose of donepezil. Five cost-effectiveness studies were included in the review. Although these studies reported cost reductions and improved outcomes with memantine, the evaluations were based on a number of assumptions.In conclusion, memantine appears to be beneficial when assessed using functional and global measurements. However, the effect of memantine on cognitive scores and behaviour and mood outcomes is less clear. Cost-effectiveness is dependent upon assumptions surrounding clinical effect and context-specific cost data.

Psychosocial aspects of DNA testing for hereditary hemochromatosis in at-risk individuals: a systematic review.

AIM To review the psychosocial benefits and harms of DNA testing for HFE-related hereditary hemochromatosis (HH) in at-risk individuals. BACKGROUND HH is a common genetic disease in people of European descent. DNA-based predisposition testing is used for diagnosis or in the context of family testing, but there are concerns about potential psychosocial consequences. METHODS Fifteen electronic databases (including Medline and Cochrane) were searched from inception to April 2007 to identify any quantitative or qualitative primary research that considered DNA testing of individuals considered at-risk of HH and reported psychosocial outcomes. Inclusion criteria, data extraction, and quality assessment were undertaken by standard methodology. RESULTS Three observational studies met the inclusion criteria of the review; each had methodological limitations. On receipt of test results, anxiety levels fell or were unchanged; general health-related quality-of-life outcomes improved in some aspects, or were unchanged with respect to pretest result values. Outcomes were not reported separately for those referred for diagnosis and those with family history of HH. Results suggest that genetic testing for HH in at-risk individuals is accompanied by few negative psychosocial outcomes. CONCLUSION The evidence on the psychosocial aspects of DNA testing for HH in at-risk individuals is limited. Further research might be required if other factors influencing the natural history of the disease phenotype are identified.

The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation.

BACKGROUND Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20-30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments. OBJECTIVES To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases. DATA SOURCES Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked. REVIEW METHODS Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted. RESULTS The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of -£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ≥ 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained. CONCLUSIONS There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection. SOURCE OF FUNDING Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation

OBJECTIVE To evaluate DNA testing for detecting hereditary haemochromatosis (HHC) in subgroups of patients suspected of having the disorder and in family members of those diagnosed with HHC. DATA SOURCES Major electronic databases, searched from inception to April 2007. REVIEW METHODS A systematic review was undertaken using a priori methods and a de novo model developed to assess costs and consequences of DNA testing. RESULTS Eleven studies were identified for estimating the clinical validity of genotyping for the C282Y mutation for the diagnosis of HHC. No clinical effectiveness studies meeting the inclusion criteria were identified. Two North American cost-effectiveness studies of reasonable quality were identified but their generalisability to the UK is not clear. Three cohort studies met the inclusion criteria for the review of psychosocial aspects. All had methodological limitations and their generalisability is difficult to determine. The clinical sensitivity of C282Y homozygosity for HHC ranged from 28.4% to 100%, or from 91.3% to 92.4% when considering only the most relevant studies. Clinical specificity ranged from 98.8% to 100%. One study found that gene testing was a cost-effective method of screening relatives of patients with haemochromatosis, whereas the other found that genotyping the spouse of a homozygote was the most cost-efficient strategy. Genetic testing for haemochromatosis appears to be well accepted, is accompanied by few negative psychosocial outcomes and may lead to reduced anxiety. The de novo economic model showed that, in people suspected of having haemochromatosis, the DNA strategy is cost saving compared with the baseline strategy using liver biopsy (cost saved per case detected 123 pounds), largely because of the reduction in liver biopsies. For family testing of siblings the DNA strategy is not cost saving because of the costs of the DNA test (additional cost per case detected 200 pounds). If the cost of the test were to reduce from 100 pounds to 60 pounds, the DNA strategy would be the cheaper one. For family testing of offspring the DNA test strategy is cheaper than the baseline biochemical testing strategy (cost saved per case detected 7982 pounds). Sensitivity analyses showed that the conclusions in each case are robust across all reasonable parameter values. CONCLUSIONS The preferred strategy in practice is DNA testing in conjunction with testing iron parameters when there is clear clinical indication of risk for haemochromatosis because of biochemical criteria or when there is familial risk for HHC. Access to genetic testing and centralisation of test provision in expert laboratories would lower the cost of testing, improve the cost-effectiveness of the strategy and improve the quality of information provided to clinicians and patients.

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

BACKGROUND Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of four biologic DMARDs [etanercept (Enbrel(®), Pfizer), abatacept (Orencia(®), Bristol-Myers Squibb), adalimumab (Humira(®), AbbVie) and tocilizumab (RoActemra(®), Roche) - with or without methotrexate where indicated] for the treatment of JIA (systemic or oligoarticular JIA are excluded). DATA SOURCES Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and the Database of Abstracts of Reviews of Effects were searched for published studies from inception to May 2015 for English-language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence. REVIEW METHODS Systematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost-utility decision-analytic model was developed to compare the estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base-case time horizon was 30 years and the model took a NHS perspective, with costs and benefits discounted at 3.5%. RESULTS Four placebo-controlled randomised controlled trials (RCTs) met the inclusion criteria for the clinical effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi)-30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar, with fewer disease flares and greater proportions of ACR Pedi-50 and -70 responses among participants randomised to continued biologic DMARDs. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that, generally, ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between the treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality-of-life studies were included, one of which informed the cost-utility model. The incremental cost-effectiveness ratios (ICERs) for adalimumab, etanercept and tocilizumab versus methotrexate were £38,127, £32,526 and £38,656 per quality-adjusted life year (QALY), respectively. The ICER for abatacept versus methotrexate as a second-line biologic was £39,536 per QALY. LIMITATIONS The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs, and clinical evidence for specific JIA subtypes is limited. CONCLUSIONS Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA who have had an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow-up are needed to establish comparative effectiveness. RCTs for JIA subtypes for which evidence is lacking are also required. STUDY REGISTRATION This study is registered as PROSPERO CRD42015016459. FUNDING The National Institute for Health Research Health Technology Assessment programme.