Introduction

Between 100 and 200 mature newborn infants die each year in the United Kingdom because of severe respiratory failure.1 Conventional treatment for infants in respiratory failure is ventilation with high level oxygen. Extracorporeal membrane oxygenation is a technique which oxygenates blood outside the body, obviating the need for gas exchange in the lungs, and, if necessary, providing cardiovascular support. As an expensive new technology in limited use, it was suitable for evaluation under the United Kingdom's health technology assessment model in the NHS research initiative.2 The UK collaborative randomised extracorporeal membrane oxygenation trial included an economic evaluation as an integral part of the design. Intention to treat analysis showed that extracorporeal membrane oxygenation was highly clinically effective. 34

A preliminary economic evaluation carried out before the trial suggested that extracorporeal membrane oxygenation was probably more effective and more expensive than conventional management.5 But it also showed that the existing evidence on cost effectiveness was inadequate for setting priorities because the uncertainty surrounding the data was too great.6 We report here the economic evaluation of the trial.

Subjects and methods

The economic evaluation was a cost effectiveness analysis comparing extracorporeal membrane oxygenation with conventional management based primarily on the principal clinical outcome of the trial (survival without severe disability at age 1 year). The trial protocol was developed in collaboration with health economists, who were members of the trial steering group, and an economics working party oversaw the economic evaluation. The economic evaluation was conducted from the viewpoint of the NHS and so includes only direct costs to the health service. Data on the costs to the parents and families of the infants will be discussed elsewhere.

Extracorporeal membrane oxygenation was provided in five centres, and babies were recruited from 55 UK neonatal centres. Babies were eligible for the trial if they were mature newborn infants with severe respiratory failure. They were randomised either to be transferred for extracorporeal membrane oxygenation or to receive conventional management.4 Babies in both arms of the trial received some of their care in neonatal units.

The trial data set included indicators of use of key resources, which were costed by the economics researchers using a combination of methods. Health service use was divided into three components: mode of transport used for transfers made after randomisation until discharge; services received in the initial hospital inpatient stay after randomisation, subdivided by level of intensity; and use of health services from discharge up to 1 year of age.

The babies' initial hospital treatment was described in terms of five levels: days receiving extracorporeal membrane oxygenation; days receiving maximal intensive care (more than 90% oxygen); days on a ventilator (receiving less than 90% oxygen); days on supplementary oxygen; and days in normal care.

Results

Ninety three babies were randomised to receive extracorporeal membrane oxygenation and 92 to conventional management. At 1 year of age, extracorporeal membrane oxygenation had increased survival (63 v 37), the number of survivors without severe disability (61 v 36), and the number of survivors with no disability (49 v 32). However, it also increased the number of survivors with impairment or disability (17 v 10) (table 1

The inpatient stay in the extracorporeal membrane oxygenation arm exceeded that in the conventional management arm by 1767 days (table 2) because more infants receiving conventional management died and they died early. In all, 51% (19) of the survivors who received conventional management required readmission to hospital compared with 35% (22) who received extracorporeal membrane oxygenation.

The estimated average cost for days without extracorporeal membrane oxygenation in the conventional management arm was £230. The cost in the extracorporeal membrane oxygenation arm was £205. The last estimate is lower because the infants spent the more resource intensive phase of their care receiving extracorporeal membrane oxygenation.

The estimated average total cost per day of extracorporeal membrane oxygenation was £1813. The average occupancy of the units during the trial was 14%. We estimated that average cost could fall to £1534 with 70% occupancy of the cots (table 3). In all three scenarios the average cost per day falls because the opportunity cost of increasing equipment use, up to full capacity, is zero. Although staff are involved, it is unrealistic to assume that they will be idle when throughput is low.

Table 4 shows the breakdown of the total health service costs up to 1 year of age. The total days with and without extracorporeal membrane oxygenation in each arm of the trial were multiplied by their corresponding average cost per day and summed to calculate the total cost of the initial hospital stay for each arm. The Appendix shows the data used to calculate the total transport costs and costs from discharge until age 1 year. The total costs after discharge for the survivors who received extracorporeal membrane oxygenation is almost twice that of those who received conventional management because there were almost twice as many survivors. The total cost of extracorporeal membrane oxygenation was £1 936 824 and the total cost of conventional management was £644 180.

Extracorporeal membrane oxygenation increases survival as defined in terms of the two main outcomes of the trial but at additional cost. The additional cost of extracorporeal membrane oxygenation over conventional management for every additional survivor without severe disability at 1 year of age was estimated to be £51 222. The additional cost per additional survivor with or without impairment but with no disability at one year was £75 327 (table 5).

Discussion

Extracorporeal membrane oxygenation for babies with severe respiratory failure is more costly than conventional management, and if adopted it will increase the costs of neonatal health care. Since our results showed that it is also more clinically effective, health service decision makers will have to consider the cost effectiveness when deciding whether to introduce extracorporeal membrane oxygenation.

The additional cost per additional survivor without severe disability at age 1 year was about £51 222. This figure should be compared with the incremental costs of other life extending technologies. For neonates few other technologies have been properly evaluated in randomised controlled trials, and even when trials exist comparisons have to be made with caution because the figures are often derived by different methods. A randomised controlled trial of surfactant replacement treatment for severe neonatal respiratory distress syndrome conducted in 1990 found it was highly effective. The estimated cost was £18 604 (at 1994-5 prices) per additional survivor.15

A study which set out to devise a mechanism to provide carefully established recommendations on new technologies suggested that technologies with a cost utility of £3000 to £20 000 per (quality adjusted) life year gained should be strongly recommended if the evidence came from a properly designed randomised controlled trial.16Extracorporeal membrane oxygenation resulted in more survivors with impairment or disability at 1 year than conventional management but the proportions in the two arms were similar (27% v 31%). The long term costs and benefits of caring for this group cannot yet be estimated since it will depend on the extent to which the impairment or disability affects their development. The quality of life for all the trial survivors is being assessed in four and seven year follow up studies and the cost per quality adjusted life year (QALY) will be estimated then. If survivors are shown to have a near normal life expectancy and quality of life, the cost per QALY is likely to be at the low end of the recommended range. Because of the short term perspective of our analysis, we feel that the study supports adoption of extracorporeal membrane oxygenation, but this conclusion should be treated with caution until evidence about longer term effects emerges.

If it is accepted that extracorporeal membrane oxygenation is relatively cost effective, the NHS must consider whether the results can be generalised and decide how to organise the service. The capacity of the extracorporeal membrane oxygenation centres during the trial was underused, and so costs might be lower if services were further centralised. Higher occupancy would also make more efficient use of highly trained staff. Training costs for these staff were not obtained, but these may be important if a full service was developed. Transport costs could be reduced by almost half if centres were better placed.

Our trial provides a good example of an expensive technology being introduced in the context of a carefully planned evaluation. The integration of economics into the trial design established a multidisciplinary framework for collaboration which fostered a comprehensive approach to the research question and allowed the appropriate investigations to be done. The evidence that this collaboration has produced so far suggests that extracorporeal membrane oxygenation can be as cost effective as other life extending technologies regularly used in developed countries. However, until the results of the long term follow up studies become available, this conclusion should be viewed with caution.