Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.

BACKGROUND: Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support. METHODS: In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0 or pH <7.20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>30 cm H(2)O of peak inspiratory pressure) or high FiO(2) (>0.8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827. FINDINGS: 766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622-59 200) at a discount rate of 3.5%. INTERPRETATION: We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK. FUNDING: UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.

Befriending carers of people with dementia: a cost utility analysis.

OBJECTIVE: There is very little evidence on the cost-effectiveness of social care interventions for people with dementia or their carers. The BEfriending and Costs of CAring trial (BECCA, ISRCTN08130075) aimed to establish whether a structured befriending service improved the quality of life of carers of people with dementia, and at what cost. METHODS: We performed an economic evaluation alongside a single blind, randomised controlled trial in a community setting of 236 carers of people with a primary progressive dementia. The intervention was contact with a Befriender Facilitator (BF), and offer of match with a trained lay volunteer befriender compared with no BF contact. Main outcome measures were health and social care, voluntary sector, and family care costs and quality adjusted life years (QALYs) in carers over 15 months. RESULTS: Mean QALYs per carer over 15 months were 0.017 higher in the intervention group compared with control (95%CI: -0.051, 0.083). Mean costs from a societal perspective were pound 1,813 higher (- pound 11,312, pound 14,984). The point estimate Incremental Cost Effectiveness Ratio (ICER) is thus pound 105,954 per incremental QALY gained. Probabilistic sensitivity analysis suggests a 42.2% probability that the ICER is below pound 30,000 per QALY. Inclusion of dementia patient QALYs reduces the ICER to pound 28,848 (51.4% probability below pound 30,000). CONCLUSIONS: Befriending leads to a non-significant trend towards improved carer quality of life, and there is a non-significant trend towards higher costs for all sectors. It is unlikely that befriending is a cost-effective intervention from the point of view of society.

Methods of data collection and analysis for the economic evaluation alongside a national, multi-centre trial in the UK: conventional ventilation or ECMO for Severe Adult Respiratory Failure (CESAR).

BACKGROUND: Extracorporeal Membrane Oxygenation (ECMO) is a technology used in treatment of patients with severe but potentially reversible respiratory failure. A multi-centre randomised controlled trial (CESAR) was funded in the UK to compare care including ECMO with conventional intensive care management. The protocol and funding for the CESAR trial included plans for economic data collection and analysis. Given the high cost of treatment, ECMO is considered an expensive technology for many funding systems. However, conventional treatment for severe respiratory failure is also one of the more costly forms of care in any health system. METHODS/DESIGN: The objectives of the economic evaluation are to compare the costs of a policy of referral for ECMO with those of conventional treatment; to assess cost-effectiveness and the cost-utility at 6 months follow-up; and to assess the cost-utility over a predicted lifetime. Resources used by patients in the trial are identified. Resource use data are collected from clinical report forms and through follow up interviews with patients. Unit costs of hospital intensive care resources are based on parallel research on cost functions in UK NHS intensive care units. Other unit costs are based on published NHS tariffs. Cost effectiveness analysis uses the outcome: survival without severe disability. Cost utility analysis is based on quality adjusted life years gained based on the Euroqol EQ-5D at 6 months. Sensitivity analysis is planned to vary assumptions about transport costs and method of costing intensive care. Uncertainty will also be expressed in analysis of individual patient data. Probabilities of cost effectiveness given different funding thresholds will be estimated. DISCUSSION: In our view it is important to record our methods in detail and present them before publication of the results of the trial so that a record of detail not normally found in the final trial reports can be made available in the public domain. TRIAL REGISTRATIONS: The CESAR trial registration number is ISRCTN47279827.

CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure.

BACKGROUND: An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising. METHODS/DESIGN: The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18-65 years) with severe, but potentially reversible, respiratory failure (Murray score >/= 3.0 or hypercapnea with pH < 7.2) will be randomised for consideration of extracorporeal membrane oxygenation at Glenfield Hospital, Leicester or continuing conventional care in a centre providing a high standard of conventional treatment. The central randomisation service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables. Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial. 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance (2-sided test). Secondary outcomes include patient morbidity and health status at 6 months. DISCUSSION: Analysis will be based on intention to treat. A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments.

Visiting adult patients in intensive care: the importance of relatives' travel and time costs.

UNLABELLED: Families of critically ill patients consistently rate visiting and being near their relative as very important. However, the costs incurred by families whilst visiting have received little attention. This study investigated the personal costs to informal caregivers (families, relatives and friends) visiting critically ill patients in an intensive care unit (ICU). The purpose of the study was (1) to test the feasibility of collecting data from informal caregivers visiting critically ill relatives and (2) to estimate the personal costs incurred by them. Data were collected by self-completed questionnaires over a 2-week period on out-of-pocket expenses and time foregone. RESULTS: One hundred and seven informal caregivers were invited to participate in the study. Fifty-four completed the questionnaire (response 50%). Forty-eight percent of respondents were male and 52% female. Fifty-nine percent of participants were in paid employment, and of these 16% lost wages as a result of the visit. The mean cost of time foregone was 46.21 pounds sterlings /visit (66.92 US dollars) and mean out-of-pocket expenses 29.30 pounds sterlings (42.43 US dollars). CONCLUSION: It is feasible to collect data on expenses and time foregone from informal caregivers visiting the ICU. The main out-of-pocket expense was that related to travel. More empirical work is needed across different settings to obtain more generalisable estimates of out-of-pocket expenses and time foregone.