ObjectivesTo evaluate the long-term cost-effectiveness of collaborative care (vs usual care) for treating depression in patients with diabetes and/or coronary heart disease (CHD).Setting36 primary care general practices in North West England.Participants387 participants completed baseline assessment (collaborative care: 191; usual care: 196) and full or partial 4-month follow-up data were captured for 350 (collaborative care: 170; usual care: 180). 62% of participants were male, 14% were non-white. Participants were aged ≥18 years, listed on a Quality and Outcomes Framework register for CHD and/or type 1 or 2 diabetes mellitus, with persistent depressive symptoms. Patients with psychosis or type I/II bipolar disorder, actively suicidal, in receipt of services for substance misuse, or already in receipt of psychological therapy for depression were excluded.InterventionCollaborative care consisted of evidence-based low-intensity psychological treatments, delivered over 3 months and case management by a practice nurse and a Psychological Well Being Practitioner.Outcome measuresAs planned, the primary measure of cost-effectiveness was the incremental cost-effectiveness ratio (cost per quality-adjusted life year (QALY)). A Markov model was constructed to extrapolate the trial results from short-term to long-term (24 months).ResultsThe mean cost per participant of collaborative care was £317 (95% CI 284 to 350). Over 24 months, it was estimated that collaborative care was associated with greater healthcare usage costs (net cost £674 (95% CI −30 953 to 38 853)) and QALYs (net QALY gain 0.04 (95% CI −0.46 to 0.54)) than usual care, resulting in a cost per QALY gained of £16 123, and a likelihood of being cost-effective of 0.54 (willingness to pay threshold of £20 000).ConclusionsCollaborative care is a potentially cost-effective long-term treatment for depression in patients with comorbid physical and mental illness. The estimated cost per QALY gained was below the threshold recommended by English decision-makers. Further, long-term primary research is needed to address uncertainty associated with estimates of cost-effectiveness.Trial registration numberISRCTN80309252; Post-results.

Background Bipolar disorder (BD) costs the English economy an estimated £5.2billion/year, largely through incomplete recovery. This analysis estimated the cost-effectiveness of group psychoeducation (PEd), versus group peer support (PS), for treating BD. Methods A 96-week pragmatic randomised controlled trial (RCT), conducted in NHS primary care. The primary analysis compared PEd with PS, using multiple imputed datasets for missing values. An economic model was used to compare PEd with treatment as usual (TAU). The perspective was Health and Personal Social Services. Results Participants receiving PEd (n=153) used more (costly) health-related resources than PS (n=151) (net cost per person £1098 (95% CI, £252-£1943)), with a quality-adjusted life year (QALY) gain of 0.023 (95% CI, 0.001-0.056). The cost per QALY gained was £47,739. PEd may be costeffective (versus PS) if decision makers are willing to pay at least £37,500 per QALY gained. PEd costs £10,765 more than PS to avoid one relapse. The economic model indicates that PEd may be costeffective versus TAU if it reduces the probability of relapse (by 15%) or reduces the probability of and increases time to relapse (by 10%). Limitations Participants were generally inconsistent in attending treatment sessions and low numbers had complete cost/QALY data. Factors contributing to pervasive uncertainty of the results are discussed. Conclusions This is the first economic evaluation of PEd versus PS in a pragmatic trial. PEd is associated with a modest improvement in health status and higher costs than PS. There is a high level of uncertainty in the data and results.

BackgroundBipolar disorder (BD) costs £5.2B annually, largely as a result of incomplete recovery after inadequate treatment.ObjectivesA programme of linked studies to reduce relapse and suicide in BD.DesignThere were five workstreams (WSs): a pragmatic randomised controlled trial (RCT) of group psychoeducation (PEd) versus group peer support (PS) in the maintenance of BD (WS1); development and feasibility RCTs of integrated psychological therapy for anxiety in bipolar disorder (AIBD) and integrated for problematic alcohol use in BD (WS2 and WS3); survey and qualitative investigations of suicide and self-harm in BD (WS4); and survey and qualitative investigation of service users’ (SUs) and psychiatrists’ experience of the Mental Capacity Act 2005 (MCA), with reference to advance planning (WS5).SettingParticipants were from England; recruitment into RCTs was limited to certain sites [East Midlands and North West (WS1); North West (WS2 and WS3)].ParticipantsAged ≥ 18 years. In WS1–3, participants had their diagnosis of BD confirmed by the Structural Clinical Interview for theDiagnostic and Statistical Manual of Mental Disorders.InterventionsIn WS1, group PEd/PS; in WS3 and WS4, individual psychological therapy for comorbid anxiety and alcohol use, respectively.Main outcome measuresIn WS1, time to relapse of bipolar episode; in WS2 and WS3, feasibility and acceptability of interventions; in WS4, prevalence and determinants of suicide and self-harm; and in WS5, professional training and support of advance planning in MCA, and SU awareness and implementation.ResultsGroup PEd and PS could be routinely delivered in the NHS. The estimated median time to first bipolar relapse was 67.1 [95% confidence interval (CI) 37.3 to 90.9] weeks in PEd, compared with 48.0 (95% CI 30.6 to 65.9) weeks in PS. The adjusted hazard ratio was 0.83 (95% CI 0.62 to 1.11; likelihood ratio testp = 0.217). The interaction between the number of previous bipolar episodes (1–7 and 8–19, relative to 20+) and treatment arm was significant (χ2 = 6.80, degrees of freedom = 2;p = 0.034): PEd with one to seven episodes showed the greatest delay in time to episode. A primary economic analysis indicates that PEd is not cost-effective compared with PS. A sensitivity analysis suggests potential cost-effectiveness if decision-makers accept a cost of £37,500 per quality-adjusted life-year. AIBD and motivational interviewing (MI) cognitive–behavioural therapy (CBT) trials were feasible and acceptable in achieving recruitment and retention targets (AIBD:n = 72, 72% retention to follow-up; MI-CBT:n = 44, 75% retention) and in-depth qualitative interviews. There were no significant differences in clinical outcomes for either trial overall. The factors associated with risk of suicide and self-harm (longer duration of illness, large number of periods of inpatient care, and problems establishing diagnosis) could inform improved clinical care and specific interventions. Qualitative interviews suggested that suicide risk had been underestimated, that care needs to be more collaborative and that people need fast access to good-quality care. Despite SUs supporting advance planning and psychiatrists being trained in MCA, the use of MCA planning provisions was low, with confusion over informal and legally binding plans.LimitationsInferences for routine clinical practice from WS1 were limited by the absence of a ‘treatment as usual’ group.ConclusionThe programme has contributed significantly to understanding how to improve outcomes in BD. Group PEd is being implemented in the NHS influenced by SU support.Future workFuture work is needed to evaluate optimal approaches to psychological treatment of comorbidity in BD. In addition, work in improved risk detection in relation to suicide and self-harm in clinical services and improved training in MCA are indicated.Trial registrationCurrent Controlled Trials ISRCTN62761948, ISRCTN84288072 and ISRCTN14774583.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 6, No. 6. See the NIHR Journals Library website for further project information.

Objectives: To assess the efficacy and tolerability of lurasidone versus other atypical antipsychotic monotherapy agents in patients with bipolar depression, using a Bayesian network meta-analysis. Methods: Fourteen randomised clinical trials (6221 patients) of lurasidone, quetiapine (extended release and immediate release), aripiprazole, olanzapine, and ziprasidone for bipolar depression were included. Efficacy assessments included change in the Montgomery-Åsberg Depression Rating Scale (MADRS), rates of response (!50% improvement in MADRS) and remission (MADRS 12 at study endpoint), and change in the Clinical Global Impressions-Bipolar Disorder-Severity (CGI-BP-S) scale. Tolerability outcomes included weight, somnolence, extrapyramidal symptoms (EPS), and all-cause discontinuation. Changes from baseline or odds ratios (OR) with 95% credible intervals (CrI) were evaluated. Results: Improvement in the MADRS associated with lurasidone treatment was significantly greater than placebo (-4.70, 95%CrI:-7.20,-2.21), aripiprazole (-3.62, 95%CrI:-7.04,-0.20), and ziprasidone (-3.38, 95%CrI:-6.68,-0.11), but not olanzapine (-0.15, 95%CrI:-3.12, 2.74) or quetiapine (0.10, 95%CrI:-2.68, 2.84). Results for improvement in the CGI-BP-S, and for response and remission were similar. Lurasidone was associated with less weight gain than olanzapine (-2.54 kg, 95%CrI:-3.42,-1.67) and quetiapine (-0.83kg, 95%CrI:-1.59,-0.08); and with lower rates of somnolence than quetiapine (OR: 0.33, 95%CrI: 0.11, 0.82) and ziprasidone (OR: 0.34, 95%CrI: 0.09, 0.93). No significant differences among atypical antipsychotic agents were observed in rates of discontinuation or in rates of EPS. Conclusions: In this network meta-analysis, lurasidone was found to be more efficacious than aripiprazole and ziprasidone, and was associated with less weight gain than quetiapine and olanzapine and less somnolence than quetiapine and ziprasidone.

BackgroundAbdominal aortic aneurysm (AAA) repair aims to prevent premature death from AAA rupture. Elective repair is currently recommended when AAA diameter reaches 5.5 cm (men) and 5.0 cm (women). Applying population-based indications may not be appropriate for individual patient decisions, as the optimal indication is likely to differ between patients based on age and comorbidities.ObjectiveTo develop an Aneurysm Repair Decision Aid (ARDA) to indicate when elective AAA repair optimises survival for individual patients and to assess the cost-effectiveness and associated uncertainty of elective repair at the aneurysm diameter recommended by the ARDA compared with current practice.Data sourcesThe UK Vascular Governance North West and National Vascular Database provided individual patient data to develop predictive models for perioperative mortality and survival. Data from published literature were used to model AAA growth and risk of rupture. The cost-effectiveness analysis used data from published literature and from local and national databases.MethodsA combination of systematic review methods and clinical registries were used to provide data to populate models and inform the structure of the ARDA. Discrete event simulation (DES) was used to model the patient journey from diagnosis to death and synthesised data were used to estimate patient outcomes and costs for elective repair at alternative aneurysm diameters. Eight patient clinical scenarios (vignettes) were used as exemplars. The DES structure was validated by clinical and statistical experts. The economic evaluation estimated costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) from the NHS, social care provider and patient perspective over a lifetime horizon. Cost-effectiveness acceptability analyses and probabilistic sensitivity analyses explored uncertainty in the data and the value for money of ARDA-based decisions. The ARDA outcome measures include perioperative mortality risk, annual risk of rupture, 1-, 5- and 10-year survival, postoperative long-term survival, median life expectancy and predicted time to current threshold for aneurysm repair. The primary economic measure was the ICER using the QALY as the measure of health benefit.ResultsThe analysis demonstrated it is feasible to build and run a complex clinical decision aid using DES. The model results support current guidelines for most vignettes but suggest that earlier repair may be effective in younger, fitter patients and ongoing surveillance may be effective in elderly patients with comorbidities. The model adds information to support decisions for patients with aneurysms outside current indications. The economic evaluation suggests that using the ARDA compared with current guidelines could be cost-effective but there is a high level of uncertainty.LimitationsLack of high-quality long-term data to populate all sections of the model meant that there is high uncertainty about the long-term clinical and economic consequences of repair. Modelling assumptions were necessary and the developed survival models require external validation.ConclusionsThe ARDA provides detailed information on the potential consequences of AAA repair or a decision not to repair that may be helpful to vascular surgeons and their patients in reaching informed decisions. Further research is required to reduce uncertainty about key data, including reintervention following AAA repair, and assess the acceptability and feasibility of the ARDA for use in routine clinical practice.FundingThe National Institute for Health Research Health Technology Assessment programme.

The economic evidence is dominated by comparisons of interventions to placebo, with implicit comparisons of different therapies. There is a lack of evaluations of service model innovations to deliver complex packages of care for psoriasis. Primary and secondary integrated clinical and economic research is needed to address the limitations and to identify patient preferences and barriers/facilitators to treatment.

IntroductionDulaglutide is a novel onceweekly administered glucagon-like peptide 1 receptor agonist (GLP-1 RA) for the management of type 2 diabetes mellitus (T2DM). The objective of this analysis was to estimate the cost-effectiveness of dulaglutide 1.5 mg versus exenatide QW for the management of T2DM in France.MethodsThe QuintilesIMS CORE Diabetes Model was used to estimate the expected lifetime direct medical costs and outcomes of T2DM from the perspective of the French National Health Service. In the absence of head-to-head data, relative efficacy was derived from a network meta-analysis. Patient cohort characteristics were derived from the AWARD-2 trial. All patients were assumed to remain on treatment for 2 years before escalating to insulin therapy. Costs included treatment costs and costs associated with long-term complications of T2DM. Utilities were estimated based on a recent systematic review. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analysis (PSA) were conducted. Cost-effectiveness acceptability curves (CEACs) were generated.ResultsDulaglutide 1.5 mg was associated with lower costs (lifetime costs €41,562 vs €43,021) and increased health benefits (lifetime quality-adjusted life years: QALYs 9.804 vs 9.757) versus exenatide QW for the treatment of T2DM in France. OWSA and PSA indicated that results were robust across a range of plausible input parameters. The CEAC indicated a 99.5% probability that dulaglutide would be considered cost-effective at a willingness to pay of €30,000.ConclusionDulaglutide 1.5 mg reduced expected costs and increased expected QALYs when compared against exenatide QW for the treatment of T2DM in France. Compared with exenatide QW, dulaglutide 1.5 mg can provide additional health benefits for patients with T2DM and may result in cost savings for payers.FundingEli Lilly.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0321-0) contains supplementary material, which is available to authorized users.

BackgroundOver 70% of the health-care budget in England is spent on the care of people with long-term conditions (LTCs), and a major cost component is unscheduled health care. Psychological morbidity is high in people with LTCs and is associated with a range of adverse outcomes, including increased mortality, poorer physical health outcomes, increased health costs and service utilisation.ObjectivesThe aim of this programme of research was to examine the relationship between psychological morbidity and use of unscheduled care in people with LTCs, and to develop a psychosocial intervention that would have the potential to reduce unscheduled care use. We focused largely on emergency hospital admissions (EHAs) and attendances at emergency departments (EDs).DesignA three-phase mixed-methods study. Research methods included systematic reviews; a longitudinal prospective cohort study in primary care to identify people with LTCs at risk of EHA or ED admission; a replication study in primary care using routinely collected data; an exploratory and feasibility cluster randomised controlled trial in primary care; and qualitative studies to identify personal reasons for the use of unscheduled care and factors in routine consultations in primary care that may influence health-care use. People with lived experience of LTCs worked closely with the research team.SettingPrimary care. Manchester and London.ParticipantsPeople aged ≥ 18 years with at least one of four common LTCs: asthma, coronary heart disease, chronic obstructive pulmonary disease (COPD) and diabetes. Participants also included health-care staff.ResultsEvidence synthesis suggested that depression, but not anxiety, is a predictor of use of unscheduled care in patients with LTCs, and low-intensity complex interventions reduce unscheduled care use in people with asthma and COPD. The results of the prospective study were that depression, not having a partner and life stressors, in addition to prior use of unscheduled care, severity of illness and multimorbidity, were independent predictors of EHA and ED admission. Approximately half of the cost of health care for people with LTCs was accounted for by use of unscheduled care. The results of the replication study, carried out in London, broadly supported our findings for risk of ED attendances, but not EHAs. This was most likely due to low rates of detection of depression in general practitioner (GP) data sets. Qualitative work showed that patients were reluctant to use unscheduled care, deciding to do so when they perceived a serious and urgent need for care, and following previous experience that unscheduled care had successfully and unquestioningly met similar needs in the past. In general, emergency and primary care doctors did not regard unscheduled care as problematic. We found there are missed opportunities to identify and discuss psychosocial issues during routine consultations in primary care due to the ‘overmechanisation’ of routine health-care reviews. The feasibility trial examined two levels of an intervention for people with COPD: we tried to improve the way in which practices manage patients with COPD and developed a targeted psychosocial treatment for patients at risk of using unscheduled care. The former had low acceptability, whereas the latter had high acceptability. Exploratory health economic analyses suggested that the practice-level intervention would be unlikely to be cost-effective, limiting the value of detailed health economic modelling.LimitationsThe findings of this programme may not apply to all people with LTCs. It was conducted in an area of high social deprivation, which may limit the generalisability to more affluent areas. The response rate to the prospective longitudinal study was low. The feasibility trial focused solely on people with COPD.ConclusionsPrior use of unscheduled care is the most powerful predictor of unscheduled care use in people with LTCs. However, psychosocial factors, particularly depression, are important additional predictors of use of unscheduled care in patients with LTCs, independent of severity and multimorbidity. Patients and health-care practitioners are unaware that psychosocial factors influence health-care use, and such factors are rarely acknowledged or addressed in consultations or discussions about use of unscheduled care. A targeted patient intervention for people with LTCs and comorbid depression has shown high levels of acceptability when delivered in a primary care context. An intervention at the level of the GP practice showed little evidence of acceptability or cost-effectiveness.Future workThe potential benefits of case-finding for depression in patients with LTCs in primary care need to be evaluated, in addition to further evaluation of the targeted patient intervention.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.