Cost-effectiveness of out-of-hospital continuous positive airway pressure for acute respiratory failure: decision analytic modelling using data from a feasibility trial.

BACKGROUND: Standard prehospital management for Acute respiratory failure (ARF) involves controlled oxygen therapy. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment, however, it is uncertain whether this could improve outcomes and provide value for money. This study aimed to evaluate the cost-effectiveness of prehospital CPAP in ARF. METHODS: A cost-utility economic evaluation was performed using a probabilistic decision tree model synthesising available evidence. The model consisted of a hypothetical cohort of patients in a representative ambulance service with undifferentiated ARF, receiving standard oxygen therapy or prehospital CPAP. Costs and quality adjusted life years (QALYs) were estimated using methods recommended by NICE. RESULTS: In the base case analysis, using CPAP effectiveness estimates form the ACUTE trial, the mean expected costs of standard care and prehospital CPAP were £15,201 and £14,850 respectively and the corresponding mean expected QALYs were 1.190 and 1.128, respectively. The mean ICER estimated as standard oxygen therapy compared to prehospital CPAP was £5685 per QALY which indicated that standard oxygen therapy strategy was likely to be cost-effective at a threshold of £20,000 per QALY (67% probability). The scenario analysis, using effectiveness estimates from an updated meta-analysis, suggested that prehospital CPAP was more effective (mean incremental QALYs of 0.157), but also more expensive (mean incremental costs of £1522), than standard care. The mean ICER, estimated as prehospital CPAP compared to standard care, was £9712 per QALY. At the £20,000 per QALY prehospital CPAP was highly likely to be the most cost-effective strategy (94%). CONCLUSIONS: Cost-effectiveness of prehospital CPAP depends upon the estimate of effectiveness. When based on a small pragmatic feasibility trial, standard oxygen therapy is cost-effective. When based on meta-analysis of heterogeneous trials, CPAP is cost-effective. Value of information analyses support commissioning of a large pragmatic effectiveness trial, providing feasibility and plausibility conditions are met.

Is a definitive trial of prehospital continuous positive airway pressure versus standard oxygen therapy for acute respiratory failure indicated? The ACUTE pilot randomised controlled trial.

OBJECTIVES: To determine the feasibility of a large-scale definitive multicentre trial of prehospital continuous positive airway pressure (CPAP) in acute respiratory failure. DESIGN: A single-centre, open-label, individual patient randomised, controlled, external pilot trial. SETTING: A single UK Ambulance Service, between August 2017 and July 2018. PARTICIPANTS: Adults with respiratory distress and peripheral oxygen saturations below British Thoracic Society target levels despite controlled oxygen treatment. INTERVENTIONS: Patients were randomised to prehospital CPAP (O-Two system) versus standard oxygen therapy in a 1:1 ratio using simple randomisation. PRIMARY AND SECONDARY OUTCOME MEASURES: Feasibility outcomes comprised recruitment rate, adherence to allocated treatment, retention and data completeness. The primary clinical outcome was 30-day mortality. RESULTS: 77 patients were enrolled (target 120), including 7 cases with a diagnosis where CPAP could be ineffective or harmful. CPAP was fully delivered in 74% (target 75%). There were no major protocol violations. Full data were available for all key outcomes (targets ≥90%). Overall 30-day mortality was 27.3%. Of these deceased patients, 14/21 (68%) either did not have a respiratory condition or had ceiling of treatment decisions implemented excluding hospital non-invasive ventilation and critical care. CONCLUSIONS: Recruitment rate was below target and feasibility was not demonstrated. Limited compliance with CPAP, and difficulty in identifying patients who could benefit from CPAP, indicate that prehospital CPAP is unlikely to materially reduce mortality. A definitive effectiveness trial of CPAP is therefore not recommended. TRIAL REGISTRATION NUMBER: ISRCTN12048261; Post-results.

Pre-hospital CPAP for acute respiratory failure: the ACUTE feasibility and pilot randomised controlled trial.

INTRODUCTION: Acute respiratory failure (ARF) is a common and life-threatening medical emergency. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment; however, it is uncertain whether this could improve important outcomes in NHS ambulance services. The ACUTE study aimed to assess the feasibility of a large-scale pragmatic trial of pre-hospital CPAP. METHODS: The study was a pilot randomised controlled trial of the O-Two system CPAP mask versus standard oxygen therapy, with concealed allocation in identical sealed boxes. Feasibility objectives estimated the incidence of eligible patients; the proportion recruited and allocated to treatment appropriately; adherence to allocated treatment; and retention and data completeness. The primary clinical endpoint was 30-day mortality. Ancillary studies included an ARF incidence study, ARF diagnostic agreement study, clinician perceptions of CPAP mixed methods study and investigation of allocation concealment. RESULTS: Over 12 months, 77 patients were enrolled (target 120). CPAP was fully delivered in 74% (target 75%). There were no major protocol violations/non-compliances. Full data were available for all key outcomes (targets ≥ 90%). Thirty-day mortality was 27.3%. Of deceased patients, 14/21 (68%) either did not have a respiratory condition or had ceiling of treatment decisions implemented excluding hospital NIV and critical care. CONCLUSION: The ACUTE trial recruitment rate was below the target rate and feasibility was not demonstrated. Identification of patients who might benefit from pre-hospital CPAP was challenging. It appeared difficult to exclude conditions where CPAP would not work, or might be harmful, and to select appropriate patients where there was a meaningful chance of success, or where the potential advantages of pre-hospital CPAP would outweigh the burdens of more advanced and aggressive treatment. The limited compliance with CPAP, and the difficulty in identifying patients who could benefit from CPAP, indicate that pre-hospital CPAP is unlikely to materially reduce mortality. A definitive effectiveness trial of CPAP in the NHS is therefore not recommended.

The ACUTE (Ambulance CPAP: Use, Treatment effect and economics) feasibility study: a pilot randomised controlled trial of prehospital CPAP for acute respiratory failure.

BACKGROUND: Acute respiratory failure (ARF) is a common and life-threatening medical emergency. Standard prehospital management involves controlled oxygen therapy and disease-specific ancillary treatments. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment that could be delivered by emergency medical services. However, it is uncertain whether this treatment could work effectively in United Kingdom National Health Service (NHS) ambulance services and if it represents value for money. METHODS: An individual patient randomised controlled external pilot trial will be conducted comparing prehospital CPAP to standard oxygen therapy for ARF. Adults presenting to ambulance service clinicians will be eligible if they have respiratory distress with peripheral oxygen saturation below British Thoracic Society (BTS) target levels, despite titrated supplemental oxygen. Enrolled patients will be allocated (1:1 simple randomisation) to prehospital CPAP (O_two system) or standard oxygen therapy using identical sealed boxes. Feasibility outcomes will include incidence of recruited eligible patients, number of erroneously recruited patients and proportion of cases adhering to allocation schedule and treatment, followed up at 30 days and with complete data collection. Effectiveness outcomes will comprise survival at 30 days (definitive trial primary end point), endotracheal intubation, admission to critical care, length of hospital stay, visual analogue scale (VAS) dyspnoea score, EQ-5D-5L and health care resource use at 30 days. The cost-effectiveness of CPAP, and of conducting a definitive trial, will be evaluated by updating an existing economic model. The trial aims to recruit 120 patients over 12 months from four regional ambulance hubs within the West Midlands Ambulance Service (WMAS). This sample size will allow estimation of feasibility outcomes with a precision of < 5%. Feasibility and effectiveness outcomes will be reported descriptively for the whole trial population, and each trial arm, together with their 95% confidence intervals. DISCUSSION: This study will determine if it is feasible, acceptable and cost-effective to undertake a full-scale trial comparing CPAP and standard oxygen treatment, delivered by ambulance service clinicians for ARF. This will inform NHS practice and prevent inappropriate prehospital CPAP adoption on the basis of limited evidence and at a potentially substantial cost. TRIAL REGISTRATION: ISRCTN12048261. Registered on 30 August 2017. http://www.isrctn.com/ISRCTN12048261.

A coproduced patient and public event: An approach to developing and prioritizing ambulance performance measures.

BACKGROUND: Patient and public involvement (PPI) is recognized as an important component of high-quality health services research. PPI is integral to the Pre-hospital Outcomes for Evidence Based Evaluation (PhOEBE) programme. The PPI event described in detail in this article focusses on the process of involving patients and public representatives in identifying, prioritizing and refining a set of outcome measures that can be used to support ambulance service performance measurement. OBJECTIVE: To obtain public feedback on little known, complex aspects of ambulance service performance measurement. DESIGN: The event was codesigned and coproduced with the PhOEBE PPI reference group and PhOEBE research team. The event consisted of brief researcher-led presentations, group discussions facilitated by the PPI reference group members and electronic voting. SETTING AND PARTICIPANTS: Data were collected from eighteen patient and public representatives who attended an event venue in Yorkshire. RESULTS: The results of the PPI event showed that this interactive format and mode of delivery was an effective method to obtain public feedback and produced a clear indication of which ambulance performance measures were most highly favoured by event participants. DISCUSSION AND CONCLUSIONS: The event highlighted valuable contributions the PPI reference group made to the design process, supporting participant recruitment and facilitation of group discussions. In addition, the positive team working experience of the event proved a catalyst for further improvements in PPI within the PhOEBE project.