A randomised controlled trial and cost-effectiveness analysis of high-frequency oscillatory ventilation against conventional artificial ventilation for adults with acute respiratory distress syndrome. The OSCAR (OSCillation in ARDS) study

Abstract

BackgroundPatients with the acute respiratory distress syndrome (ARDS) require artificial ventilation but this treatment may produce secondary lung damage. High-frequency oscillatory ventilation (HFOV) may reduce this damage.ObjectivesTo determine the clinical benefit and cost-effectiveness of HFOV in patients with ARDS compared with standard mechanical ventilation.DesignA parallel, randomised, unblinded clinical trial.SettingUK intensive care units.ParticipantsMechanically ventilated patients with a partial pressure of oxygen in arterial blood/fractional concentration of inspired oxygen (P : F) ratio of 26.7 kPa (200 mmHg) or less and an expected duration of ventilation of at least 2 days at recruitment.InterventionsTreatment arm HFOV using a Novalung R100®ventilator (Metran Co. Ltd, Saitama, Japan) ventilator until the start of weaning.Control arm Conventional mechanical ventilation using the devices available in the participating centres.Main outcome measuresThe primary clinical outcome was all-cause mortality at 30 days after randomisation. The primary health economic outcome was the cost per quality-adjusted life-year (QALY) gained.ResultsOne hundred and sixty-six of 398 patients (41.7%) randomised to the HFOV group and 163 of 397 patients (41.1%) randomised to the conventional mechanical ventilation group died within 30 days of randomisation (p = 0.85), for an absolute difference of 0.6% [95% confidence interval (CI) −6.1% to 7.5%]. After adjustment for study centre, sex, Acute Physiology and Chronic Health Evaluation II score, and the initial P : F ratio, the odds ratio for survival in the conventional ventilation group was 1.03 (95% CI 0.75 to 1.40;p = 0.87 logistic regression). Survival analysis showed no difference in the probability of survival up to 12 months after randomisation. The average QALY at 1 year in the HFOV group was 0.302 compared to 0.246. This gives an incremental cost-effectiveness ratio (ICER) for the cost to society per QALY of £88,790 and an ICER for the cost to the NHS per QALY of £78,260.ConclusionsThe use of HFOV had no effect on 30-day mortality in adult patients undergoing mechanical ventilation for ARDS and no economic advantage. We suggest that further research into avoiding ventilator-induced lung injury should concentrate on ventilatory strategies other than HFOV.Trial registrationCurrent Controlled Trials ISRCTN10416500.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 23. See the NIHR Journals Library website for further project information.

Simvastatin to reduce pulmonary dysfunction in patients with acute respiratory distress syndrome: the HARP-2 RCT

“…However, we did find it difficult to achieve high rates of long-term follow-up data collection, in keeping with previous intensive care trials, 54,55 and a considerable amount of staff resource was involved in delivering this aspect of the trial. It is important to identify barriers to follow-up in these patients to inform future critical care studies.…”

“…The cost-utility analysis included only patients with complete cost and QALY data but, of those alive at 12 months, only 45% completed both the 6-and 12-month follow-up questionnaires and some data were missing from these completed questionnaires. Previous intensive care trials 54,55 have also found it difficult to achieve high rates of long-term data collection and the experience of the HARP-2 trial confirms that this is a difficult population to follow up. Furthermore, economic data are particularly likely to be missing owing to the reliance on multiple components within HRQoL and resource use questionnaires required for the calculation of QALYs and costs.…”

“…57 This approach has been used previously in economic evaluations of therapies for patients with ARDS. 54,55 Over the course of the trial it became apparent that many patients were still in hospital at 3 months and were then not administered the EQ-5D-3L at this time point. Furthermore, the timing of the discharge questionnaire varied from patient to patient.…”

Methodological Issues Surrounding the Use of Baseline Health-Related Quality of Life Data to Inform Trial-Based Economic Evaluations of Interventions Within Emergency and Critical Care Settings: A Systematic Literature Review

“…The mean time horizon for the withintrial component of the economic evaluations in the remaining 18 studies was 8 months (median 9 months and range 1 to 12 months). Some studies extrapolated outcomes beyond the trial follow-up period using decision analytic modelling methods [25,26,28] with up to 60 months [25] and lifetime [15,16,28,29] extrapolations beyond the study follow-up periods. Most economic evaluations were conducted from the perspective of the UK National Health Service (NHS) (n=4) or the NHS/Personal Social services (n=9) in accordance with NICE guidance for appraising health technologies [30].…”

“…For the purpose of this review, we measured the baseline (or first) time point for describing healthrelated quality of life as reported by individual studies; conventionally in trial-based economic evaluations this is taken as the time of randomisation. Nine (47%) of the 19 studies used the EQ-5D to measure health-related quality of life of patients, 5 (26%) used the EQ-5D in combination with another instrument (primarily the SF-12/36 [26,33,35], HUI-3 [32] and the paediatric PedsQL [36]), 1 (5%) [18] used the 15D instrument [34] and another 1 (5%) used the HUI-3 [28]. The remaining 3 (17%) studies [29] [25,27] did not report a primary health-related quality of life data collection process.…”