The impact of double-blind placebo- controlled food challenge (DBPCFC) on the socioeconomic cost of food allergy in Europe.

BACKGROUND: Double-blind placebo controlled food challenge (DBPCFC) is the gold standard diagnostic test in food allergy because it minimizes diagnostic bias. OBJECTIVE: To investigate the potential effect of diagnosis on the socioeconomic costs of food allergy. METHODS: A prospective longitudinal cost analysis study was conducted in Spain and Poland within the EuroPrevall project. Food-allergic patients were enrolled into the study and in all cases diagnosis was confirmed through a standardized DBPCFC. Data were collected through a self-administered survey on all aspects of health and social care resource use, costs of living, and costs of leisure activities. Costs were measured before and 6 months after the DBPCFC and reported in international dollars with 2007 as the benchmark year. RESULTS: Forty-two patients were enrolled. Twenty-one patients had a negative DBPCFC and the suspected food was reintroduced into their diet. Comparing total direct costs before and after the DBPCFC, the reactive group spent a significantly higher amount (median increase of $813.1 over baseline), while the tolerant group's spending decreased by a median of $87.3 (P = .031). The amount of money spent on food 6 months after diagnosis was also significantly higher in the reactive group (P = .040). Finally, a larger, but not statistically significant, decrease in total indirect costs was observed in the tolerant group compared with the reactive group ($538.3 vs $32.3). CONCLUSION: DBPCFC has an impact on indirect and direct costs of living. The main contribution to this increase was money spent on food.

Cognitive behaviour therapy for improving social recovery in psychosis: a report from the ISREP MRC Trial Platform Study (Improving Social Recovery in Early Psychosis).

BACKGROUND: This study reports on a preliminary evaluation of a cognitive behavioural intervention to improve social recovery among young people in the early stages of psychosis showing persistent signs of poor social functioning and unemployment. The study was a single-blind randomized controlled trial (RCT) with two arms, 35 participants receiving cognitive behaviour therapy (CBT) plus treatment as usual (TAU), and 42 participants receiving TAU alone. Participants were assessed at baseline and post-treatment. METHOD: Seventy-seven participants were recruited from secondary mental health teams after presenting with a history of unemployment and poor social outcome. The cognitive behavioural intervention was delivered over a 9-month period with a mean of 12 sessions. The primary outcomes were weekly hours spent in constructive economic and structured activity. A range of secondary and tertiary outcomes were also assessed. RESULTS: Intention-to-treat analysis on the combined affective and non-affective psychosis sample showed no significant impact of treatment on primary or secondary outcomes. However, analysis of interactions by diagnostic subgroup was significant for secondary symptomatic outcomes on the Positive and Negative Syndrome Scale (PANSS) [F(1, 69)=3.99, p=0.05]. Subsequent exploratory analyses within diagnostic subgroups revealed clinically important and significant improvements in weekly hours in constructive and structured activity and PANSS scores among people with non-affective psychosis. CONCLUSIONS: The primary study comparison provided no clear evidence for the benefit of CBT in a combined sample of patients. However, planned analyses with diagnostic subgroups showed important benefits for CBT among people with non-affective psychosis who have social recovery problems. These promising results need to be independently replicated in a larger, multi-centre RCT.

Integrating children's services in England: national evaluation of children's trusts.

BACKGROUND: Poor co-ordination of services can have severe consequences for disadvantaged children with complex needs. Since 2003 national and local governments in England embarked on sweeping reforms aimed at improving and integrating local health, education and social services for children. These were to be organized locally by children's trusts and piloted by 35 children's trust pathfinders. METHODS: This study described and compared the experience of integrating children's services in all 35 children's trust pathfinders, covering 20% of children in England. It had a prospective mixed-methods design. Over 3 years we interviewed 147 managers and professionals working in the children's trusts, including 172 semi-structured interviews, carried out two questionnaire surveys of the 35 children's trusts and analysed official documents. RESULTS: In most areas different agencies jointly commissioned children's services, especially for mental health, disabilities and multi-purpose children's centres, and increasingly pooled finances. Provision of multi-agency and multi-professional services was increasing. Professionals generally supported these changes but found them stressful. All children's trusts appointed directors of children's services and established boards representing multiple agencies. Systems for sharing information about individual children were mostly in place but were still underused. Health services were generally less involved in joint work than were local authorities' education and social care services, with notable exceptions. Areas where local authorities and health authorities shared geographical boundaries made most progress. Some children's trusts made few changes beyond their statutory obligations. CONCLUSION: Children's trusts enabled major changes to services in areas where local actors and organizations were motivated and empowered. In other areas the remit of children's trusts was often too broad and vague to overcome entrenched organizational and professional divisions and interests. Policymakers need to balance facilitation of change in areas with dynamic change agents with methods for ensuring that dormant areas and agencies are not left behind.

Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of bone morphogenetic protein (BMP) for the treatment of spinal fusions and the healing of fractures compared with the current standards of care. DATA SOURCES: Electronic databases, related journals and references from identified studies were searched in January 2006, with an updated search only for randomised controlled trials (RCTs) in November 2006. REVIEW METHODS: A systematic review of available data was conducted. The data from selected studies were then analysed and graded according to quality and processed to give a value to the efficacy of BMP. Existing models were modified or updated to evaluate the cost-effectiveness of BMP for open tibial fractures and spinal fusion. RESULTS: All selected trials were found to have several methodological weaknesses. Insufficient sample size in most trials, meant that patient baseline comparability between trial arms was not achieved and the statistical power to detect a moderate effect was low. Data did indicate that BMP increased fracture union among patients with acute tibial fractures and found that high-dose BMP is more effective than a lower dose for open tibial fractures. The healing rate in the BMP group was not found to be statistically significantly different from that in the autogenous bone grafting group for patients with tibial non-union fractures, but BMP reduced the number of secondary interventions in patients with acute tibial fractures compared with controls. There was very limited evidence that BMP in scaphoid non-union was safe and may help to accelerate non-union healing when used in conjunction with either autograft or allograft. There was evidence that BMP-2 is more effective than autogenous bone graft for radiographic fusion in patients with single-level degenerative disc disease. No significant difference was found when BMP-7 was compared with autograft for degenerative spondylolisthesis with spinal stenosis and spondylolysis. The use of BMP was associated with a reduced operating time, improvement in clinical outcomes and a shorter hospital stay as compared with autograft. The proportion of secondary interventions tended to be lower in the BMP group than the control, but not of statistical significance. Trial data on time to return to work postoperatively were sometimes difficult to interpret because of unclear or inappropriate data analysis methods. The incremental cost of BMP for open tibial fractures was estimated to be about 3.5 million pounds per year in the UK. The estimated incremental cost per quality-adjusted life-year (QALY) gained is 32,603 pounds. The probability that cost per QALY gained is less than 30,000 pounds for open tibial fracture is 35.5%. The cost-effectiveness ratio is sensitive to the price of BMP and the severity of open tibial fractures. The use of recombinant human bone morphogenetic protein for spinal fusion surgery may increase the cost to the UK NHS by about 1.3 million pounds per year. The estimated incremental cost per QALY gained was about 120,390 pounds. The probability that BMP is cost-effective (i.e. cost/QALY less than 30,000 pounds) was only 6.4%. From the societal perspective, the estimated total cost of using BMP for spinal fusion is about 4.2 million pounds per year in the UK. CONCLUSIONS: Additional BMP treatment plus conventional intervention is more effective than conventional intervention alone for union of acute open tibial fractures. The cost-effectiveness of additional BMP may be improved if the price of BMP is reduced or if BMP is mainly used in severe cases. BMP may eliminate the need for autogenous bone grafting so that costs and complications related to harvesting autograft can be avoided. In non-unions, there is no evidence that BMP is more or less effective than bone graft; however, it is currently used when bone graft and other treatments have failed. The use of BMP-2 in spinal fusion surgery seems to be more effective than autogenous bone graft in terms of radiographic spinal fusion among patients with single-level degenerative disc disease. There is a lack of evidence about the effectiveness of BMP for other spinal disorders including spondylolisthesis and spinal stenosis. There was limited evidence showing that BMP is associated with greater improvement in clinical outcomes. According to the results of economic evaluation, the use of BMP for spinal fusion is unlikely to be cost-effective. The following areas would benefit from further research: clinical trials of BMP that include formal economic evaluation, a multicentre RCT of fracture non-union and of interbody and/or posterolateral spinal fusion, trials of non-tibial acute long bone fractures, and RCTs comparing BMP-2, BMP-7 and controls.

Postnatal support for mothers living in disadvantaged inner city areas: a randomised controlled trial.

STUDY OBJECTIVE: To evaluate the effect of two forms of postnatal social support for disadvantaged inner city mothers on maternal and child health outcomes. DESIGN: Randomised controlled trial with economic and process evaluations and follow up at 12 and 18 months. The two intervention groups received either the offer of a year of monthly supportive listening home visits by a support health visitor (SHV), or a year of support from community groups providing drop in sessions, home visiting and/or telephone support (CGS). Each was compared with a control group that received standard health visitor services. SETTING: Two disadvantaged boroughs of London, United Kingdom. PARTICIPANTS: 731 women from culturally diverse backgrounds with infants. MAIN RESULTS: At 12 and 18 months, there was little impact for either intervention on the main outcomes: child injury (SHV: relative risk 0.99; 95% confidence intervals 0.68 to 1.45, CGS: 0.91; 0.61 to1.36), maternal smoking (SHV: 0.86; 0.62 to 1.19, CGS: 0.97; 0.72 to 1.33) or maternal depression (SHV: 0.86; 0.62 to1.19, CGS: 0.93; 0.69 to 1.27). SHV women had different patterns of health service use (with fewer taking their children to the GP) and had less anxious experiences of motherhood than control women. User satisfaction with the SHV intervention was high. Uptake of the CGS intervention was low: 19%, compared with 94% for the SHV intervention. CONCLUSIONS: There was no evidence of impact on the primary outcomes of either intervention among this culturally diverse population. The SHV intervention was associated with improvement in some of the secondary outcomes.

Randomised controlled trial and cost consequences study comparing initial physiotherapy assessment and management with routine practice for selected patients in an accident and emergency department of an acute hospital.

OBJECTIVE: The Department of Health is reviewing the effectiveness of accident and emergency (A&E) departments. This study aimed to compare health and economic effects of physiotherapy initial assessment and management with routine practice in an A&E department. METHODS: Randomised controlled trial and cost and consequences study. Patients presenting at A&E were eligible if suspected at triage to have soft tissue injury without fracture. The efficacy end point was "days to return to usual activities". Secondary end points included patient satisfaction with their care and further health outcomes and cost data. RESULTS: 766 of 844 (915) patients were randomised. The median days before return to usual activities (available for 73% of those randomised) was greater in the physiotherapist group (41 days compared with 28.5 days; hazard ratio 0.85 p = 0.071). The physiotherapy group expressed greater satisfaction with their A&E care (on a scale of 1 to 5, median was 4.2 compared with 4.0, p<0.001), were more likely to be given advice and reassurance, and more likely to be provided with aids and appliances. Costs were the same between the two arms. CONCLUSION: There is evidence that physiotherapy leads to a prolonged time before patients return to usual activities. This study shows no clear danger from physiotherapy intervention and long term outcomes may be different but given these findings, a best estimate is that introducing physiotherapist assessment will increase costs to the health service and society. Routine care should continue be provided unless there is some reason why it is not feasible to do so and an alternative must be found.

The Social Support and Family Health Study: a randomised controlled trial and economic evaluation of two alternative forms of postnatal support for mothers living in disadvantaged inner-city areas.

OBJECTIVES: To determine whether increased postnatal support could influence maternal and child health outcomes. DESIGN: This was a randomised controlled trial comparing maternal and child health outcomes for women offered either of the support interventions with those for control women receiving standard services only. Outcome data were collected through questionnaires distributed 12 and 18 months postrandomisation. Process data were also collected. There was also an integral economic evaluation. SETTING AND PARTICIPANTS: Women living in deprived enumeration districts in selected London boroughs were eligible for the trial if they gave birth between 1 January and 30 September 1999. RESULTS: The 731 participants were found to be well matched in terms of socio-economic characteristics and health and support variables (14% of the participants were non-English speaking). Response rates at the two follow-up points were 90% and 82%. At both points there were no differences that could not be attributed to chance on the primary outcomes of maternal depression, child injury or maternal smoking. At the first follow-up, there was reduced use of general practitioners by support health visitor (SHV) children, but increased use of NHS health visitors and social workers by mothers. At the second follow-up, both community group support (CGS) and SHV mothers had less use of midwifery services (fewer were pregnant), and SHV mothers were less worried about their child's health and development. Uptake of the CGS intervention was low: 19%, compared with 94% for the SHV intervention. Satisfaction with the intervention among women in the SHV group was high. Based on the assumptions and conditions of the costing methods, the economic evaluation found no net economic cost or benefit of choosing either of the two interventions. CONCLUSIONS: There was no evidence of impact on the primary outcomes of either intervention. The SHV intervention was popular with women, and was associated with improvement in some of the secondary outcomes. This suggests that greater emphasis on the social support role of health visitors could improve some measures of family well-being. Possible areas for future research include a systematic review of social support and its effect on health; developing and testing other postnatal models of support that match more closely the age of the baby and the changing patterns of mothers' needs; evaluating other strategies for mobilising 'non-professional' support; developing and testing more culturally specific support interventions; developing more culturally appropriate standardised measures of health outcomes; providing longer term follow-up of social support interventions; and exploring the role of social support on the delay in subsequent pregnancy.

Factors affecting the outcome of maternity care. 1. Relationship between staffing and perinatal deaths at the hospital of birth.

This is the first of two papers describing a retrospective study of maternity hospitals in an English health region using data for the years 1977-83. The research was designed to investigate the relationship between resources (such as staff and equipment) and the outcomes of births at maternity units. Considerable variation in medical and nursing staffing levels in the units in the study was observed. Regression analysis suggests that, after taking account of differences in very low weight births at each unit, the level of paediatric staffing at a maternity unit is a significant factor in explaining differences in "in house" mortality. There was no identifiable relationship between staff categories other than paediatricians and the rate of perinatal death at the hospital of delivery. As selective referral and transfers between hospitals may affect the interpretation of these findings, a second paper follows presenting the results of a further analysis that adjusts both resources and outcomes to take account of neonatal transfers.

Factors affecting the outcome of maternity care. II. Neonatal outcomes and resources beyond the hospital of birth.

Analysis of data about perinatal mortality and indicators of resources at maternity hospitals in the West Midlands region between 1977 and 1983 showed that paediatric staff ratios were inversely related to in-house mortality rates. In this paper, the outcomes for and resources used by transferred babies are added to those of the hospital of birth for three of the study years--1978, 1980, and 1982. Patterns of transfer differ between units and over time in the region, and a regional neonatal intensive care policy was introduced in 1980. Analysis of the new variables showed that in 1978 paediatric staffing was significantly inversely related to neonatal mortality. In later years, neonatal mortality of births at maternity units is explained entirely by the proportion of low or very low weight births.

Cost effectiveness of surfactant replacement in preterm babies.

Surfactant replacement in preterm babies has been shown in recent years in randomised controlled trials to be an effective treatment for respiratory distress syndrome (RDS). It is expensive and, because it increases survival, it has implications for the costs of neonatal services. We used evidence about resource use obtained from trials of surfactant and other studies on the economics of surfactant to assess the cost effectiveness of different policies for its use. For the smallest babies, surfactant is likely to increase overall costs of neonatal care, but also to reduce the ratio of costs to survival, whether surfactant is given prophylactically or as a treatment for established RDS. It is less clear what the optimal policy should be for babies of more than around 31 weeks' gestation. Comparison of the relative cost effectiveness of policies of early prophylactic surfactant and surfactant for later treatment of RDS, and of different dosage policies, is currently being conducted in the context of 2 large multicentre trials. No policy for surfactant use should be considered in isolation from the availability of effective obstetric interventions which have been shown to reduce the risk of RDS in preterm babies and which will therefore reduce the need for surfactant.

Cataract surgery in a community hospital outreach clinic: patients' costs and satisfaction.

A cataract day surgery service for the population of central Norfolk, UK, was provided by the main ophthalmic department in a district general hospital and in an outreach clinic in a community hospital 40 km distant. The outreach clinic aimed to extend the accessibility of this particular service in a rural area where many patients faced long journeys to the main hospital. Samples of 201 patients attending the main hospital for day cataract surgery and 198 patients attending the outreach clinic for the same procedure were identified. Patients were interviewed and given questionnaire forms to establish their general health before the operation, their arrangements to get to hospital and their satisfaction with the clinic and the care they had received. The sample of patients attending the outreach clinic was slightly older, less affluent and in slightly poorer general health than the patients attending the main hospital. The two samples were similar in terms of visual acuity after the operation, complication rates, satisfaction with the outcome of the operation and subsequent use of health services. The journey to hospital was quicker, more convenient and less costly for the outreach clinic patients than the main hospital patients. The net benefit to patients of the outreach clinic was estimated as pounds sterling 39,000 per annum. Satisfaction with administrative matters, facilities at the two clinics and the care received was high in both samples, but patients were significantly more satisfied with arrangements at the smaller outreach clinic. This evidence suggests that an outreach clinic in a small community hospital can provide cataract day surgery under local anaesthesia as effectively as a district centre, at a reduced social cost and with positive social benefits. Further study of heath service costs is vital, but political pressure to acknowledge patient preferences for more local services is growing.

Conflicting conclusions from two systematic reviews of epidural steroid injections for sciatica: which evidence should general practitioners heed?

Systematic reviews and meta-analyses are becoming increasingly important in informing clinical practice and commissioning. Two systematic reviews of a treatment for low back pain and sciatica using epidural steroid injections, published in the same year, arrived at conflicting conclusions. Only one was reported in a digest for evidence-based medicine. This paper aims to find the reasons for the discordance between the reviews, and draw conclusions for users of reviews. Using comparative analysis of two published systematic reviews and their source material, it was found that the two reviews had the same overall aims and met the criteria for review methods. They differed in their choice of methods, including the judgement of quality of studies for inclusion and for summing-up evidence. Estimation of summary odds ratios in one review led to stronger conclusions about effectiveness. In conclusion, the choice of methods for systematic review may alter views about the current state of evidence. Users should be aware that systematic reviews include an element of judgement, whatever method is used.

Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a complex procedure of life support in severe but potentially reversible respiratory failure, used particularly in mature newborn infants. Although the number of babies requiring ECMO is small, and the ECMO policy invasive and potentially expensive, its benefits may be high. OBJECTIVES: To determine whether ECMO used for neonatal infants with severe respiratory failure is clinically effective and cost-effective compared to a policy of conventional ventilatory support. SEARCH STRATEGY: The Cochrane Neonatal Group Specialised Register, the Cochrane Controlled Trials Register, and MEDLINE were searched for 1974 to 2001. SELECTION CRITERIA: All randomised trials comparing neonatal ECMO to conventional ventilatory support. DATA COLLECTION AND ANALYSIS: The authors independently evaluated the trials for methodological quality and appropriateness for inclusion in the Review (without consideration of their results), and then independently extracted the data. MAIN RESULTS: The three trials from the USA and one from the UK recruited clinically similar groups of babies. Two trials excluded infants with congenital diaphragmatic hernias. In two, transfer for ECMO implied transport over a considerable distance. One study included an economic evaluation. Two trials had follow up information. All except the UK trial had very small numbers of patients. Two of the trials used conventional randomisation with low potential for bias. The other two used less usual designs which have led to difficulties in their interpretation. All four trials showed a strong benefit of ECMO on mortality (RR 0.44; 95% CI 0.31 to 0.61), especially for babies without congenital diaphragmatic hernia (RR 0.33, 95% CI 0.21 to 0.53). Only the UK trial provided information about death or disability at one and four years, and showed benefit of ECMO at one year (RR 0.56, 95% CI 0.40 to 0.78), and at four years (RR 0.62, 95% CI 0.45 to 0.86). Overall nearly half of the children had died or were severely disabled at four years of age, reflecting the severity of their underlying conditions. Based on economic analysis from the UK trial, the ECMO policy is as cost-effective as other intensive care technologies in common use. REVIEWER'S CONCLUSIONS: A policy of using ECMO in mature infants with severe but potentially reversible respiratory failure would result in significantly improved survival without increased risk of severe disability amongst survivors. For babies with diaphragmatic hernia ECMO offers short term benefits but the overall effect of employing ECMO in this group is not clear. Further studies are needed to refine ECMO techniques; to consider the optimal timing for introducing ECMO; to identify which infants are most likely to benefit; and to address the longer term implications of neonatal ECMO during later childhood and adult life.

A critical review of cost reduction in neonatal intensive care. I. The structure of costs.

Neonatal intensive care is expensive. In the current era of intense cost containment in hospital care, neonatologists and hospital administrators are under intense pressure to find strategies for cost reduction for neonatal services. Few neonatal clinicians are trained in economics, management, or accounting, and few hospital administrators are familiar with neonatal intensive care. In this review, we describe the structure and sources of hospital costs and the accounting systems needed to isolate and measure such costs. We discuss where efficiencies might be found and consider specific issues in capitated settings such as health maintenance organizations in the United States, the Canadian health care system and the National Health System in the United Kingdom.

A critical review of cost reduction in neonatal intensive care. II. Strategies for reduction.

Neonatal intensive care is extremely expensive; there is both a financial and an ethical obligation to practice efficiently. In the current era of intense cost containment in hospital care, neonatologists and hospital administrators are under pressure to find strategies for cost reduction for neonatal services. In this review, we address reducing discretionary admissions, the high costs of low-cost testing, minimizing use of selected high-cost technologies (ventilators and parenteral nutrition), shortening length of stay, and optimizing nursing allocation.

Reducing the incidence of infection after caesarean section: implications of prophylaxis with antibiotics for hospital resources.

OBJECTIVES: To estimate the cost effectiveness of giving prophylactic antibiotics routinely to reduce the incidence of wound infection after caesarean section. DESIGN: Estimation of cost effectiveness was based, firstly, on a retrospective overview of 58 controlled trials and, secondly, on evidence about costs derived from data and observations of practice. SETTING: Trials included in the overview were from obstetric units in several different countries, including the United Kingdom. The costing study was based on data referring to the John Radcliffe Maternity Hospital, Oxford. SUBJECTS: A total of 7777 women were included in the 58 controlled trials comparing the effects of giving routine prophylactic antibiotics at caesarean section with either treatment with a placebo or no treatment. Cost estimates were based on data on 486 women who had caesarean sections between January and September 1987. MAIN OUTCOME MEASURE: Cost effectiveness of prophylaxis with antibiotics. RESULTS: The odds of wound infection are likely to be reduced by between about 50 and 70% by giving antibiotics routinely at caesarean section. Forty one (8.4%) women who had caesarean section were coded by the Oxford obstetric data system as having developed wound infection. The additional average cost of hospital postnatal care for women with wound infection (compared with women who had had caesarean section and no wound infection) was estimated to be 716 pounds; introducing routine prophylaxis with antibiotics would reduce average costs of postnatal care by between 1300 pounds and 3900/100 pounds caesarean sections (at 1988 prices), depending on the cost of the antibiotic used and its effectiveness. CONCLUSIONS: The results suggest that giving antibiotics routinely at caesarean section will not only reduce rates of infection after caesarean section but also reduce costs.

Effects of feedback of information on clinical practice: a review.

OBJECTIVE: To establish what is known about the role of feedback of statistical information in changing clinical practice. DESIGN: Review of 36 studies of interventions entailing the use of statistical information for audit or practice review, which used a formal research design. SUBJECTS: Papers identified from computer searches of medical and health service management publications, of which 36 describing studies of interventions designed to influence clinical care and including information feedback from clinical or administrative data systems were reviewed. MAIN OUTCOME MEASURES: Evidence for effect of information feedback on change in clinical practice. RESULTS: Information feedback was most likely to influence clinical practice if it was part of strategy to target decision makers who had already agreed to review their practice. A more direct effect was discernable if the information was presented close to the time of decision making. The questions of the optimum layout and quantity of information were not addressed; the 36 papers were insufficient for defining good formats for information to be used for audit or quality assurance. CONCLUSIONS: Given the cost of information processing and the current emphasis on closing the audit loop in the health services, it is important that the use of information in the audit process should be critically evaluated.

Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR).

OBJECTIVES: To determine the comparative effectiveness and cost-effectiveness of conventional ventilatory support versus extracorporeal membrane oxygenation (ECMO) for severe adult respiratory failure. DESIGN: A multicentre, randomised controlled trial with two arms. SETTING: The ECMO centre at Glenfield Hospital, Leicester, and approved conventional treatment centres and referring hospitals throughout the UK. PARTICIPANTS: Patients aged 18-65 years with severe, but potentially reversible, respiratory failure, defined as a Murray lung injury score > or = 3.0, or uncompensated hypercapnoea with a pH < 7.20 despite optimal conventional treatment. INTERVENTIONS: Participants were randomised to conventional management (CM) or to consideration of ECMO. MAIN OUTCOME MEASURES: The primary outcome measure was death or severe disability at 6 months. Secondary outcomes included a range of hospital indices: duration of ventilation, use of high frequency/oscillation/jet ventilation, use of nitric oxide, prone positioning, use of steroids, length of intensive care unit stay, and length of hospital stay - and (for ECMO patients only) mode (venovenous/veno-arterial), duration of ECMO, blood flow and sweep flow. RESULTS: A total of 180 patients (90 in each arm) were randomised from 68 centres. Three patients in the conventional arm did not give permission to be followed up. Of the 90 patients randomised to the ECMO arm, 68 received that treatment. ECMO was not given to three patients who died prior to transfer, two who died in transit, 16 who improved with conventional treatment given by the ECMO team and one who required amputation and could not therefore be heparinised. Ninety patients entered the CM (control) arm, three patients later withdrew and refused follow-up (meaning that they were alive), leaving 87 patients for whom primary outcome measures were available. CM consisted of any treatment deemed appropriate by the patient's intensivist with the exception of extracorporeal gas exchange. No CM patients received ECMO, although one received a form of experimental extracorporeal arteriovenous carbon dioxide removal support (a clear protocol violation). Fewer patients in the ECMO arm than in the CM arm had died or were severely disabled 6 months after randomisation, [33/90 (36.7%) versus 46/87 (52.9%) respectively]. This equated to one extra survivor for every six patients treated. Only one patient (in the CM arm) was known to be severely disabled at 6 months. Patients allocated to ECMO incurred average total costs of 73,979 pounds compared with 33,435 pounds for those undergoing CM (UK prices, 2005). A lifetime model predicted the cost per quality-adjusted life-year (QALY) of ECMO to be 19,252 pounds (95% confidence interval 7622 pounds to 59,200 pounds) at a discount rate of 3.5%. Lifetime QALYs gained were 10.75 for the ECMO group compared with 7.31 for the conventional group. Costs to patients and their relatives, including out of pocket and time costs, were higher for patients allocated to ECMO. CONCLUSIONS: Compared with CM, transferring adult patients with severe but potentially reversible respiratory failure to a single centre specialising in the treatment of severe respiratory failure for consideration of ECMO significantly increased survival without severe disability. Use of ECMO in this way is likely to be cost-effective when compared with other technologies currently competing for health resources. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47279827.