Jake Jordan

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three non-adjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective. Of those trialled, the semi-bespoke MAD is an appropriate first choice. Trial registration number ISRCTN02309506.

Clinical effectiveness and cost-effectiveness results from the randomised controlled Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea–hypopnoea (TOMADO) and long-term economic analysis of oral devices and continuous positive airway pressure

BACKGROUND Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness (EDS), impairs quality of life (QoL) and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment is clinically effective but undermined by intolerance, and its cost-effectiveness is borderline in milder cases. Mandibular advancement devices (MADs) are another option, but evidence is lacking regarding their clinical effectiveness and cost-effectiveness in milder disease. OBJECTIVES (1) Conduct a randomised controlled trial (RCT) examining the clinical effectiveness and cost-effectiveness of MADs against no treatment in mild to moderate OSAH. (2) Update systematic reviews and an existing health economic decision model with data from the Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and newly published results to better inform long-term clinical effectiveness and cost-effectiveness of MADs and CPAP in mild to moderate OSAH. TOMADO A crossover RCT comparing clinical effectiveness and cost-effectiveness of three MADs: self-moulded [SleepPro 1™ (SP1); Meditas Ltd, Winchester, UK]; semibespoke [SleepPro 2™ (SP2); Meditas Ltd, Winchester, UK]; and fully bespoke [bespoke MAD (bMAD); NHS Oral-Maxillofacial Laboratory, Addenbrookes Hospital, Cambridge, UK] against no treatment, in 90 adults with mild to moderate OSAH. All devices improved primary outcome [apnoea-hypopnoea index (AHI)] compared with no treatment: relative risk 0.74 [95% confidence interval (CI) 0.62 to 0.89] for SP1; relative risk 0.67 (95% CI 0.59 to 0.76) for SP2; and relative risk 0.64 (95% CI 0.55 to 0.76) for bMAD (p < 0.001). Differences between MADs were not significant. Sleepiness [as measured by the Epworth Sleepiness Scale (ESS)] was scored 1.51 [95% CI 0.73 to 2.29 (SP1)] to 2.37 [95% CI 1.53 to 3.22 (bMAD)] lower than no treatment (p < 0.001), with SP2 and bMAD significantly better than SP1. All MADs improved disease-specific QoL. Compliance was lower for SP1, which was unpopular at trial exit. At 4 weeks, all devices were cost-effective at £20,000/quality-adjusted life-year (QALY), with SP2 the best value below £39,800/QALY. META-ANALYSIS A MEDLINE, EMBASE and Science Citation Index search updating two existing systematic reviews (one from November 2006 and the other from June 2008) to August 2013 identified 77 RCTs in adult OSAH patients comparing MAD with conservative management (CM), MADs with CPAP or CPAP with CM. MADs and CPAP significantly improved AHI [MAD -9.3/hour (p < 0.001); CPAP -25.4/hour (p < 0.001)]. Effect difference between CPAP and MADs was 7.0/hour (p < 0.001), favouring CPAP. No trials compared CPAP with MADs in mild OSAH. MAD and CPAP reduced the ESS score similarly [MAD 1.6 (p < 0.001); CPAP 1.6 (p < 0.001)]. LONG-TERM COST-EFFECTIVENESS An existing model assessed lifetime cost-utility of MAD and CPAP in mild to moderate OSAH, using the revised meta-analysis to update input values. The TOMADO provided utility estimates, mapping ESS score to European Quality of Life-5 Dimensions three-level version for device cost-utility. Using SP2 as the standard device, MADs produced higher mean costs and mean QALYs than CM [incremental cost-effectiveness ratio (ICER) £6687/QALY]. From a willingness to pay (WTP) of £15,367/QALY, CPAP is cost-effective, although the likelihood of MADs (p = 0.48) and CPAP (p = 0.49) being cost-effective is very similar. Both were better than CM, but there was much uncertainty in the choice between CPAP and MAD (at a WTP £20,000/QALY, the probability of being the most cost-effective was 47% for MAD and 52% for CPAP). When SP2 lifespan increased to 18 months, the ICER for CPAP compared with MAD became £44,066. The ICER for SP1 compared with CM was £1552, and for bMAD compared with CM the ICER was £13,836. The ICER for CPAP compared with SP1 was £89,182, but CPAP produced lower mean costs and higher mean QALYs than bMAD. Differential compliance rates for CPAP reduces cost-effectiveness so MADs become less costly and more clinically effective with CPAP compliance 90% of SP2. CONCLUSIONS Mandibular advancement devices are clinically effective and cost-effective in mild to moderate OSAH. A semi-bespoke MAD is the appropriate first choice in most patients in the short term. Future work should explore whether or not adjustable MADs give additional clinical and cost benefits. Further data on longer-term cardiovascular risk and its risk factors would reduce uncertainty in the health economic model and improve precision of effectiveness estimates. TRIAL REGISTRATION This trial is registered as ISRCTN02309506. 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. 18, No. 67. See the NIHR Journals Library website for further project information.

Laparoscopic versus open colorectal resection for cancer and polyps: A cost-effectiveness study

Background Available evidence that compares outcomes from laparoscopic and open surgery for colorectal cancer shows no difference in disease free or survival time, or in health-related quality of life outcomes, but does not capture the short term benefits of laparoscopic methods in the early postoperative period. Aim To explore the cost-effectiveness of laparoscopic colorectal surgery, compared to open methods, using quality of life data gathered in the first 6 weeks after surgery. Methods Participants were recruited in 2006–2007 in a district general hospital in the south of England; those with a diagnosis of cancer or polyps were included in the analysis. Quality of life data were collected using EQ-5D, on alternate days after surgery for 4 weeks. Costs per patient, from a National Health Service perspective (in British pounds, 2006) comprised the sum of operative, hospital, and community costs. Missing data were filled using multiple imputation methods. The difference in mean quality adjusted life years and costs between surgery groups were estimated simultaneously using a multivariate regression model applied to 20 imputed datasets. The probability that laparoscopic surgery is cost-effective compared to open surgery for a given societal willingness-to-pay threshold is illustrated using a cost-effectiveness acceptability curve. Results The sample comprised 68 laparoscopic and 27 open surgery patients. At 28 days, the incremental cost per quality adjusted life year gained from laparoscopic surgery was £12,375. At a societal willingness-to-pay of £30,000, the probability that laparoscopic surgery is cost-effective, exceeds 65% (at £20,000 ≈60%). In sensitivity analyses, laparoscopic surgery remained cost-effective compared to open surgery, provided it results in a saving ≥£699 in hospital bed days and takes no more than 8 minutes longer to perform. Conclusion The study provides formal evidence of the cost-effectiveness of laparoscopic approaches and supports current guidelines that promote use of laparoscopy where suitably trained surgeons are available.

Holistic needs assessment and care plans for women with gynaecological cancer: do they improve cancer-specific health-related quality of life? A randomised controlled trial using mixed methods

Objectives Holistic needs assessment (HNA) and care planning are proposed to address unmet needs of people treated for cancer. We tested whether HNA and care planning by an allied health professional improved cancer-specific quality of life for women following curative treatment for stage I–III gynaecological cancer. Methods Consecutive women were invited to participate in a randomised controlled study (HNA and care planning vs usual care) at a UK cancer centre. Data were collected by questionnaire at baseline, 3 and 6 months. The outcomes were 6-month change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (version 3), global score (primary) and, in EORTC subscales, generic quality of life and self-efficacy (secondary). The study was blinded for data management and analysis. Differences in outcomes were compared between groups. Health service utilisation and quality-adjusted life years (QALY) (from Short Form-6) were gathered for a cost-effectiveness analysis. Thematic analysis was used to interpret data from an exit interview. Results 150 women consented (75 per group); 10 undertook interviews. For 124 participants (61 intervention, 63 controls) with complete data, no statistically significant differences were seen between groups in the primary endpoint. The majority of those interviewed reported important personal gains they attributed to the intervention, which reflected trends to improvement seen in EORTC functional and symptom scales. Economic analysis suggests a 62% probability of cost-effectiveness at a £30 000/QALY threshold. Conclusion Care plan development with an allied health professional is cost-effective, acceptable and useful for some women treated for stage I–III gynaecological cancer. We recommend its introduction early in the pathway to support person-centred care.

Follow-up care after treatment for prostate cancer: protocol for an evaluation of a nurse-led supported self-management and remote surveillance programme

BackgroundAs more men survive a diagnosis of prostate cancer, alternative models of follow-up care that address men’s enduring unmet needs and are economical to deliver are needed. This paper describes the protocol for an ongoing evaluation of a nurse-led supported self-management and remote surveillance programme implemented within the secondary care setting.Methods/designThe evaluation is taking place within a real clinical setting, comparing the outcomes of men enrolled in the Programme with the outcomes of a pre-service change cohort of men, using a repeated measures design. Men are followed up at four and 8 months post recruitment on a number of outcomes, including quality of life, unmet need, psychological wellbeing and activation for self-management. An embedded health economic analysis and qualitative evaluation of implementation processes are being undertaken.DiscussionThe evaluation will provide important information regarding the effectiveness, cost effectiveness and implementation of an integrated supported self-management follow-up care pathway within secondary care.

Measuring health related quality of life of care home residents, comparison of self-report with staff proxy responses for EQ-5D-5L and HowRu: protocol for assessing proxy reliability in care home outcome testing

Introduction Research into interventions to improve health and well-being for older people living in care homes is increasingly common. Health-related quality of life (HRQoL) is frequently used as an outcome measure, but collecting both self-reported and proxy HRQoL measures is challenging in this setting. This study will investigate the reliability of UK care home staff as proxy respondents for the EQ-5D-5L and HowRu measures. Methods and analysis This is a prospective cohort study of a subpopulation of care home residents recruited to the larger Proactive Healthcare for Older People in Care Homes (PEACH) study. It will recruit residents ≥60 years across 24 care homes and not receiving short stay or respite care. The sample size is 160 participants. Resident and care home staff proxy EQ-5D-5L and HowRu responses will be collected monthly for 3 months. Weighted kappa statistics and intraclass correlation adjusted for clustering at the care home level will be used to measure agreement between resident and proxy responses. The extent to which staff variables (gender, age group, length of time caring, role, how well they know the resident, length of time working in care homes and in specialist gerontological practice) influence the level of agreement between self-reported and proxy responses will be considered using a multilevel mixed-effect regression model. Ethics and dissemination The PEACH study protocol was reviewed by the UK Health Research Authority and University of Nottingham Research Ethics Committee and was determined to be a service development project. We will publish this study in a peer-reviewed journal with international readership and disseminate it through relevant national stakeholder networks and specialist societies.

Optimal healthcare delivery to care homes in the UK: a realist evaluation of what supports effective working to improve healthcare outcomes

Abstract Introduction care home residents have high healthcare needs not fully met by prevailing healthcare models. This study explored how healthcare configuration influences resource use. Methods a realist evaluation using qualitative and quantitative data from case studies of three UK health and social care economies selected for differing patterns of healthcare delivery to care homes. Four homes per area (12 in total) were recruited. A total of 239 residents were followed for 12 months to record resource-use. Overall, 181 participants completed 116 interviews and 13 focus groups including residents, relatives, care home staff, community nurses, allied health professionals and General Practitioners. Results context-mechanism-outcome configurations were identified explaining what supported effective working between healthcare services and care home staff: (i) investment in care home-specific work that legitimises and values work with care homes; (ii) relational working which over time builds trust between practitioners; (iii) care which ‘wraps around’ care homes; and (iv) access to specialist care for older people with dementia. Resource use was similar between sites despite differing approaches to healthcare. There was greater utilisation of GP resource where this was specifically commissioned but no difference in costs between sites. Conclusion activities generating opportunities and an interest in healthcare and care home staff working together are integral to optimal healthcare provision in care homes. Outcomes are likely to be better where: focus and activities legitimise ongoing contact between healthcare staff and care homes at an institutional level; link with a wider system of healthcare; and provide access to dementia-specific expertise.

Gastroenterologist and nurse management of symptoms after pelvic radiotherapy for cancer: An economic evaluation of a clinical randomized controlled trial (the ORBIT study)

Background Over 20 distressing gastrointestinal symptoms affect many patients after pelvic radiotherapy, but in the United Kingdom few are referred for assessment. Algorithmic-based treatment delivered by either a consultant gastroenterologist or a clinical nurse specialist has been shown in a randomized trial to be statistically and clinically more effective than provision of a self-help booklet. In this study, we assessed cost-effectiveness. Methods Outcomes were measured at baseline (pre-randomization) and 6 months. Change in quality-adjusted life years (QALYs) was the primary outcome for the economic evaluation; a secondary analysis used change in the bowel subset score of the modified Inflammatory Bowel Disease Questionnaire (IBDQ-B). Intervention costs, British pounds 2013, covered visits with the gastroenterologist or nurse, investigations, medications and treatments. Incremental outcomes and incremental costs were estimated simultaneously using multivariate linear regression. Uncertainty was handled non-parametrically using bootstrap with replacement. Results The mean (SD) cost of treatment was £895 (499) for the nurse and £1101 (567) for the consultant. The nurse was dominated by usual care, which was cheaper and achieved better outcomes. The mean cost per QALY gained from the consultant, compared to usual care, was £250,455; comparing the consultant to the nurse, it was £25,875. Algorithmic care produced better outcomes compared to the booklet only, as reflected in the IBDQ-B results, at a cost of ~£1,000. Conclusion Algorithmic treatment of radiation bowel injury by a consultant or a nurse results in significant symptom relief for patients but was not found to be cost-effective according to the National Institute for Health and Care Excellence (NICE) criteria.

S1 TOMADO: A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea

Introduction Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness (EDS), impairs quality of life (Qol), and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure therapy is effective but undermined by intolerance and cost effectiveness is borderline in milder cases. Mandibular Advancement Devices (MADs) are another treatment option but evidence is lacking regarding their effectiveness compared to no treatment in milder disease. This study compared clinical and cost effectiveness of a range of MADs and no treatment in these patients. Methods This 4-period, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with mild to moderate OSAH and EDS (Apnoea-Hypopnoea Index (AHI) 5-<30/hour; Epworth Sleepiness Scale score (ESS) > = 9) underwent 6 weeks of treatment with three non-adjustable MADs: self-moulded (SP1); semi-bespoke (SP2); fully-bespoke (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment and analysed by intention to treat. Secondary outcomes included ESS and QoL. Cost effectiveness was evaluated using validated tools, treatment costs and healthcare usage. Results Ninety patients were recruited. Sixteen withdrew before trial end. Seven did not complete any treatment and were excluded from analyses. All devices reduced AHI against no treatment, by 26% (95%CI 11%, 38%, p = 0.001) for SP1 to 36% (95%CI 24%, 45%, p < 0.001) for bMAD. ESS was 1.51 (SP1) to 2.37 (bMAD) lower versus no treatment (p < 0.001 for all). Compliance was lower for SP1 which was unpopular at trial exit. All devices were cost-effective compared with no treatment at a willingness to pay (WTP) of £20,000/quality-adjusted life year (QALY), based on mean costs and QALYs. SP2 was most cost-effective up to a WTP of £39,800/QALY after which, bMAD superseded it. Serious adverse events occurred in four patients (4%). Conclusions Mandibular Advancement Devices achieve clinically important improvements in mild to moderate OSAH syndrome and are cost effective. A semi-bespoke non-adjustable MAD would appear to be the appropriate first choice in most patients. Future work should explore whether adjustable MADs give additional clinical and cost benefits in this patient group. Funding NIHR Health Technology Assessment Programme, UK.