Deirdre B Blissett

Supported self-management for patients with moderate to severe chronic obstructive pulmonary disease (COPD): an evidence synthesis and economic analysis

BACKGROUND Self-management (SM) support for patients with chronic obstructive pulmonary disease (COPD) is variable in its coverage, content, method and timing of delivery. There is insufficient evidence for which SM interventions are the most effective and cost-effective. OBJECTIVES To undertake (1) a systematic review of the evidence for the effectiveness of SM interventions commencing within 6 weeks of hospital discharge for an exacerbation for COPD (review 1); (2) a systematic review of the qualitative evidence about patient satisfaction, acceptance and barriers to SM interventions (review 2); (3) a systematic review of the cost-effectiveness of SM support interventions within 6 weeks of hospital discharge for an exacerbation of COPD (review 3); (4) a cost-effectiveness analysis and economic model of post-exacerbation SM support compared with usual care (UC) (economic model); and (5) a wider systematic review of the evidence of the effectiveness of SM support, including interventions (such as pulmonary rehabilitation) in which there are significant components of SM, to identify which components are the most important in reducing exacerbations, hospital admissions/readmissions and improving quality of life (review 4). METHODS The following electronic databases were searched from inception to May 2012: MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Science Citation Index [Institute of Scientific Information (ISI)]. Subject-specific databases were also searched: PEDro physiotherapy evidence database, PsycINFO and the Cochrane Airways Group Register of Trials. Ongoing studies were sourced through the metaRegister of Current Controlled Trials, International Standard Randomised Controlled Trial Number database, World Health Organization International Clinical Trials Registry Platform Portal and ClinicalTrials.gov. Specialist abstract and conference proceedings were sourced through ISIs Conference Proceedings Citation Index and British Librarys Electronic Table of Contents (Zetoc). Hand-searching through European Respiratory Society, the American Thoracic Society and British Thoracic Society conference proceedings from 2010 to 2012 was also undertaken, and selected websites were also examined. Title, abstracts and full texts of potentially relevant studies were scanned by two independent reviewers. Primary studies were included if ≈90% of the population had COPD, the majority were of at least moderate severity and reported on any intervention that included a SM component or package. Accepted study designs and outcomes differed between the reviews. Risk of bias for randomised controlled trials (RCTs) was assessed using the Cochrane tool. Random-effects meta-analysis was used to combine studies where appropriate. A Markov model, taking a 30-year time horizon, compared a SM intervention immediately following a hospital admission for an acute exacerbation with UC. Incremental costs and quality-adjusted life-years were calculated, with sensitivity analyses. RESULTS From 13,355 abstracts, 10 RCTs were included for review 1, one study each for reviews 2 and 3, and 174 RCTs for review 4. Available studies were heterogeneous and many were of poor quality. Meta-analysis identified no evidence of benefit of post-discharge SM support on admissions [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.52 to 1.17], mortality (HR 1.07, 95% CI 0.74 to 1.54) and most other health outcomes. A modest improvement in health-related quality of life (HRQoL) was identified but this was possibly biased due to high loss to follow-up. The economic model was speculative due to uncertainty in impact on readmissions. Compared with UC, post-discharge SM support (delivered within 6 weeks of discharge) was more costly and resulted in better outcomes (£683 cost difference and 0.0831 QALY gain). Studies assessing the effect of individual components were few but only exercise significantly improved HRQoL (3-month St Georges Respiratory Questionnaire 4.87, 95% CI 3.96 to 5.79). Multicomponent interventions produced an improved HRQoL compared with UC (mean difference 6.50, 95% CI 3.62 to 9.39, at 3 months). Results were consistent with a potential reduction in admissions. Interventions with more enhanced care from health-care professionals improved HRQoL and reduced admissions at 1-year follow-up. Interventions that included supervised or unsupervised structured exercise resulted in significant and clinically important improvements in HRQoL up to 6 months. LIMITATIONS This review was based on a comprehensive search strategy that should have identified most of the relevant studies. The main limitations result from the heterogeneity of studies available and widespread problems with their design and reporting. CONCLUSIONS There was little evidence of benefit of providing SM support to patients shortly after discharge from hospital, although effects observed were consistent with possible improvement in HRQoL and reduction in hospital admissions. It was not easy to tease out the most effective components of SM support packages, although interventions containing exercise seemed the most effective. Future work should include qualitative studies to explore barriers and facilitators to SM post exacerbation and novel approaches to affect behaviour change, tailored to the individual and their circumstances. Any new trials should be properly designed and conducted, with special attention to reducing loss to follow-up. Individual participant data meta-analysis may help to identify the most effective components of SM interventions. STUDY REGISTRATION This study is registered as PROSPERO CRD42011001588. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Targeted case finding for chronic obstructive pulmonary disease versus routine practice in primary care (TargetCOPD): a cluster-randomised controlled trial

BACKGROUND Many individuals with chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. Health-care organisations are implementing case-finding programmes without good evidence of which are the most effective and cost-effective approaches. We assessed the effectiveness and cost-effectiveness of two alternative approaches to targeted case finding for COPD compared with routine practice. METHODS In this cluster-randomised controlled trial, participating general practices in the West Midlands, UK, were randomly assigned (1:1), via a computer-generated block randomisation sequence, to either a targeted case-finding group or a routine care group. Eligible patients were ever-smokers aged 40-79 years without a previously recorded diagnosis of COPD. Patients in the targeted case-finding group were further randomly assigned (1:1) via their household to receive either a screening questionnaire at the general practitioner (GP) consultation (opportunistic) or a screening questionnaire at the GP consultation plus a mailed questionnaire (active). Respondents reporting relevant respiratory symptoms were invited for post-bronchodilator spirometry. Patients, clinicians, and investigators were not masked to allocation, but group allocation was concealed from the researchers who performed the spirometry assessments. Primary outcomes were the percentage of the eligible population diagnosed with COPD within 1 year (defined as post-bronchodilator forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] ratio <0·7 in patients with symptoms or a new diagnosis on their GP record) and cost per new COPD diagnosis. Multiple logistic and Poisson regression were used to estimate effect sizes. Costs were obtained from the trial. This trial is registered with ISRCTN, number ISRCTN14930255. FINDINGS From Aug 10, 2012, to June 22, 2014, 74 818 eligible patients from 54 diverse general practices were randomly assigned and completed the trial. At 1 year, 1278 (4%) cases of COPD were newly detected in 32 789 eligible patients in the targeted case-finding group compared with 337 (1%) cases in 42 029 patients in the routine care group (adjusted odds ratio [OR] 7·45 [95% CI 4·80-11·55], p<0·0001). The percentage of newly detected COPD cases was higher in the active case-finding group (822 [5%] of 15 378) than in the opportunistic case-finding group (370 [2%] of 15 387; adjusted OR 2·34 [2·06-2·66], p<0·0001; adjusted risk difference 2·9 per 100 patients [95% CI 2·3-3·6], p<0·0001). Active case finding was more cost-effective than opportunistic case finding (£333 vs £376 per case detected, respectively). INTERPRETATION In this well established primary care system, routine practice identified few new cases of COPD. An active targeted approach to case finding including mailed screening questionnaires before spirometry is a cost-effective way to identify undiagnosed patients and has the potential to improve their health. FUNDING National Institute for Health Research.

The economic cost of measles: Healthcare, public health and societal costs of the 2012–13 outbreak in Merseyside, UK

BACKGROUND Measles is a highly contagious vaccine-preventable infection that caused large outbreaks in England in 2012 and 2013 in areas which failed to achieve herd protection levels (95%) consistently. We sought to quantify the economic costs associated with the 2012-13 Merseyside measles outbreak, relative to the cost of extending preventative vaccination to secure herd protection. METHODS A costing model based on a critical literature review was developed. A workshop and interviews were held with key stakeholders in the Merseyside outbreak to understand the pathway of a measles case and then quantify healthcare activity and costs for the main NHS providers and public health team incurred during the initial four month period to May 2012. These data were used to model the total costs of the full outbreak to August 2013, comprising those to healthcare providers for patient treatment, public health and societal productivity losses. The modelled total cost of the full outbreak was compared to the cost of extending the preventative vaccination programme to achieve herd protection. FINDINGS The Merseyside outbreak included 2458 reported cases. The estimated cost of the outbreak was £ 4.4m (sensitivity analysis £ 3.9 m to £ 5.2m) comprising 15% (£ 0.7 m) NHS patient treatment costs, 40% (£ 1.8m) public health costs and 44% (£ 2.0m) for societal productivity losses. In comparison, over the previous five years in Cheshire and Merseyside a further 11,793 MMR vaccinations would have been needed to achieve herd protection at an estimated cost of £ 182,909 (4% of the total cost of the measles outbreak). INTERPRETATION Failure to consistently reach MMR uptake levels of 95% across all localities and sectors (achieve herd protection) risks comparatively higher economic costs associated with the containment (including healthcare costs) and implementation of effective public health management of outbreaks. FUNDING Commissioned by the Cheshire and Merseyside Public Health England Centre.

Effect of Pay-For-Outcomes and Encouraging New Providers on National Health Service Smoking Cessation Services in England: A Cluster Controlled Study

Background Payment incentives are known to influence healthcare but little is known about the impact of paying directly for achieved outcomes. In England, novel purchasing (commissioning) of National Health Service (NHS) stop smoking services, which paid providers for quits achieved whilst encouraging new market entrants, was implemented in eight localities (primary care trusts (PCTs)) in April 2010. This study examines the impact of the novel commissioning on these services. Methods Accredited providers were paid standard tariffs for each smoker who was supported to quit for four and 12 weeks. A cluster-controlled study design was used with the eight intervention PCTs (representing 2,138,947 adult population) matched with a control group of all other (n=64) PCTs with similar demographics which did not implement the novel commissioning arrangements. The primary outcome measure was changes in quits at four weeks between April 2009 and March 2013. A secondary outcome measure was the number of new market entrants within the group of the largest two providers at PCT-level. Results The number of four-week quits per 1,000 adult population increased per year on average by 9.6% in the intervention PCTs compared to a decrease of 1.1% in the control PCTs (incident rate ratio 1∙108, p<0∙001, 95% CI 1∙059 to 1∙160). Eighty-five providers held ‘any qualified provider’ contracts for stop smoking services across the eight intervention PCTs in 2011/12, and 84% of the four-week quits were accounted for by the largest two providers at PCT-level. Three of these 10 providers were new market entrants. To the extent that the intervention incentivized providers to overstate quits in order to increase income, caution is appropriate when considering the findings. Conclusions Novel commissioning to incentivize achievement of specific clinical outcomes and attract new service providers can increase the effectiveness and supply of NHS stop smoking services.

The cost-effectiveness of domiciliary non-invasive ventilation in patients with end-stage chronic obstructive pulmonary disease: a systematic review and economic evaluation

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the U.K., domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation. DATA SOURCES Bibliographic databases, conference proceedings and ongoing trial registries up to September 2014. METHODS Standard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately. RESULTS Thirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective. LIMITATIONS Evidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data. CONCLUSIONS The cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings. FUTURE WORK RECOMMENDATIONS The results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV. STUDY REGISTRATION This study is registered as PROSPERO CRD42012003286. FUNDING The National Institute for Health Research Health Technology Assessment programme.

S82 An Economic Evaluation Of Self-management Programs Delivered At Discharge After Acute Exacerbation, In Copd Patients In The Uk

This abstract summarises independent research funded by the National Institute for Health Research (NIHR) under its HTA Programme (Ref 11/27/01). The views expressed are those of the author (s) and not necessarily those of the NHS, the NIHR or the Department of Health. Background Self-management interventions delivered to COPD patients at discharge following admission for exacerbation aim to enable patients to better manage and control their symptoms but it is not clear if they are beneficial. Our systematic review concluded that there was no evidence of a reduction in the risk of admissions or mortality but noted a dearth of good quality studies and a direction of effect for readmissions in favour of self-management. Methods A hypothetical Markov model was built to estimate the cost-effectiveness of self-management interventions in COPD patients recently discharged from hospitals, compared to usual care. It estimated the effect in terms of Quality Adjusted Life Years (QALYs) in a cohort of UK COPD patients, applying a reduced risk of admissions obtained from the hazard ratio of 0.82 (0.50, 1.36) reported in a meta-analysis in a systematic review. Due to uncertainty around this effect, extensive sensitivity analysis was conducted to estimate the likelihood being cost-effective at alternative thresholds. Results This model found that self-management delivered at discharge was more costly, but resulted in better outcomes, with a £683 cost difference and a gain of 0.0831 QALYs. To be cost-effective it would need to cost £2200 or less if the hazard ratio remained at 0.82. Sensitivity analysis found that self-management had a 68% probability of being cost-effective at a threshold of £20,000 per QALY, with most of this uncertainty being around the effect, duration of effect and cost. Conclusion If self-management interventions are effective in reducing readmissions for up to two years, they are likely to be cost-effective. This speculative economic model describes the uncertainty around this conclusion.

S83 An Economic Evaluation Of Domiciliary Non-invasive Ventilation (niv) In Patients With End-stage Copd In The Uk

This abstract summarises independent research funded by the National Institute for Health Research (NIHR) under its HTA Programme (Ref 11/27/01). The views expressed are those of the author (s) and not necessarily those of the NHS, the NIHR or the Department of Health. Background NIV is an established treatment for the management of acute exacerbation of COPD but less is known about the effectiveness of NIV in the home setting. Many clinicians consider domiciliary NIV to be cost-effective in patients that have experienced three or more exacerbations however no economic evaluations, using decision modelling have been conducted. Methods The findings of a systematic clinical review of the clinical effectiveness of domiciliary NIV in COPD were applied in a Markov model, to estimate cost-effectiveness, from a UK perspective, when compared to usual care. Outcomes were measured in Quality Adjust Life Years (QALYs). Two end-stage COPD populations were considered; patients that were stable for at least twelve weeks (stable population) and those recently discharged for exacerbation (post-admission population). Given the uncertainty around the effect of domiciliary NIV on admissions and mortality in both populations, extensive sensitivity analysis was conducted to quantify and likelihood of NIV being cost-effective at a thresholds of £30,000 per QALY and the model’s sensitivity to key parameters. Results This model indicated that domiciliary NIV is unlikely to be cost-effective in stable populations but is more likely to be cost-effective post-admission. However, there was considerable uncertainty around the results for both populations. The model was most sensitive to changes in the risk ratio for admission and the duration of the effect but was also sensitive to changes in baseline risk of admissions. Conclusion This model indicates that domiciliary NIV is unlikely to be cost-effective in stable patients but maybe cost-effective in patients with a history of admissions. This speculative economic model describes the uncertainty around these conclusions.