BackgroundUlcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients’ quality of life. The burden for the NHS is substantial.ObjectivesTo evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities.Data sourcesPeer-reviewed publications, European Public Assessment Reports and manufacturers’ submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals.Review methodsA systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model.ResultsTen randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade®, Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira®, AbbVie) or golimumab (GOL) (Simponi®, MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32–52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8–32 and 32–52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8–32 weeks and GOL 50 mg at 32–52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32–52 weeks was significant. The greatest effects were associated with GOL (at 8–32 weeks) and ADA (at 32–52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained.LimitationsThe health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review.ConclusionsAdult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC.Study registrationThis study is registered as PROSPERO CRD42013006883.FundingThe National Institute for Health Research Health Technology Assessment programme.

ObjectivesRheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX).Data sourcesThe following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs.MethodsNetwork meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained.ResultsSixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX.ConclusionsbDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission).Study registrationThis study is registered as PROSPERO CRD42012003386.FundingThe National Institute for Health Research Health Technology Assessment programme.

A universal programme of alcohol SBI in primary care is estimated to be cost-effective, under all but the most pessimistic assumptions for programme costs and effectiveness. Policymakers should ensure that SBI programmes are routinely evaluated and followed up, given the substantial uncertainty over the effects of many of the implementation details.

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As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost-effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost-effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from the GEMINI1 trial, which is a Phase III, multicentre, randomised, doubleblind, placebo-controlled trial designed to evaluate the efficacy and safety of vedolizumab as an induction and maintenance treatment in patients with moderate-to-severe active UC who had an inadequate response to, loss of response to, or intolerance to conventional therapy or anti-Tumour necrosis factor-alpha (TNF-). The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post-hoc subgroup analyses, patients with or without prior anti-TNF-therapy, vedolizumab performed better then placebo (p-value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab and the frequency and types of adverse events were similar between the vedolizumab and placebo group but the evidence was limited to shortterm follow-up. There were a number of limitations and uncertainties in the clinical evidence base which warrant caution in its interpretation. In particular, the post-hoc subgroup analyses and high dropout rates in the maintenance phase of the GEMINI1 trial. The company also presented a network meta-analysis of vedolizumab versus other biologics therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects since fixed effects models were Key Points for Decision Makers Vedolizumab appears to be more effective in both the induction and maintenance phase compared with placebo in patients with moderate-to-severe active ulcerative colitis who have had an inadequate response to, loss of response to, or intolerance to conventional therapy or TNF-inhibitor. However, the subgroup analyses for patients with or without prior TNF-inhibitor therapy were post-hoc and the study was not powered for these assessments.  The findings of the network meta-analysis of vedolizumab versus TNF-inhibitor are limited due to a number of uncertainties in treatment effects. In addition, there is currently no head-to-head randomised 3 controlled trial comparing vedolizumab to other biologic therapies indicated for moderate-to-severe ulcerative colitis.  The National Institute for Health and Care Excellence (NICE) Appraisal Committee recommended vedolizumab within its licence indication but only if the company provides vedolizumab with the discount agr...