Background
Nebulised HS is a relatively cheap intervention: approximately £50 for the nebuliser plus 12 doses of saline. Consequently, a large reduction in LoS is not required to suggest that the introduction of nebulised HS may be cost neutral or even cost saving. However, a broader economic evaluation that captures a wider set of costs and also includes patient outcomes is preferred. For example, if the intervention is not cost neutral, it may still be cost-effective once the value of patient health effects are also considered. Alternatively, the intervention may be cost-saving from the perspective of the hospital, but worse symptoms and more associated care following discharge may show the intervention not to be cost-effective.
Overview
A cost–utility analysis (CUA) was undertaken from the NHS perspective, with a time frame of 36 days post randomisation. The economic evaluation was originally designed to have a 28-day follow-up, but one patient in the study had a LoS of 35.7 days, so the time frame was extended to avoid censoring. A longer time frame was relevant, as there are no long-term sequelae associated with acute bronchiolitis. Given the difficulties of measuring utilities in the very young, the CUA was supplemented with a
cost–consequences analysis (CCA) which considers the secondary clinical outcome measures alongside costs to allow a more qualitative assessment of cost-effectiveness.
Resource use
The main items of resource use collected were LoS by type of ward and number of readmissions. Nursing time was not included because, although nurse time is required to set up the equipment in the intervention group, increased monitoring time may be needed in patients who are not receiving active treatment. Consequently, a detailed observational study would be required to measure these costs in both arms. It was considered that any cost difference would be small, and inconsequential compared with any difference in LoS, and that calculating any difference would incur huge costs . Furthermore, if there were no difference in LoS, then clinical practice would not change based on small differences in nursing time.
Although other costs were also considered to be negligible in comparison with the inpatient costs, ease of data collection led us to collect data on the use of nebulised saline, concomitant medications and use of primary care services in the 28 days following discharge (e.g. GP or emergency department visits). Inpatient resource use was collected by staff using the same case report forms as those used for the clinical
evaluation. Primary care resource use was collected using a patient diary, which was to be completed by the parent or guardian on a daily basis; tick boxes were available for GP contacts, NHS Direct, NHS walk-in centres, minor injury units and the emergency department.
Unit costs
All unit costs used were at 2012/13 price levels. Costs for a day in hospital were based on 2012–13 NHS Reference Costs, nebuliser costs were supplied by one of the participating hospitals, saline and medication costs were taken from theBritish National Formulary(BNF)51and primary care costs were taken from
NHS reference costs52and the Unit Costs of Health and Social Care publication produced by the Personal
The cost per day on a ward was derived using the NHS reference costs52for an admission for paediatric
acute bronchiolitis without complications (PA15B) and its associated number of bed-days. Separate costs per day for paediatric intensive care and high-dependency care are available directly from NHS reference costs.52The cost for paediatric acute bronchiolitis with complications or comorbidities (PA15A) was not
considered relevant as our separate costing of paediatric intensive care and high-dependency care captures the costs of complications.
NHS Direct costs were taken from a report by the Medical Care Research Unit, which used a Department of Health contract value to derive a cost per call.54Emergency care unit costs (defined here as walk-in centres,
minor injury units and emergency departments) relate to category 1 investigation (e.g. biochemistry) and category 3–4 treatment (e.g. oxygen).
Outcomes
For the CUA, it is usual for utilities to be calculated based on utility instruments, such as the EQ-5D, administered to patients. However, this is not possible for the participants in this trial, and even proxy completion by a parent would not be valid, as the descriptive systems of available utility instruments do not fit well with this patient group. Our original approach was to undertake a separate valuation study to estimate quality-adjusted life-year (QALY) losses related to hospitalisation and recovery and then apply these to the trial data. However, the National Institute for Health Research was not willing to fund this work, so we identified a published estimate relating to hospitalisation in paediatric populations that could be used.55
TABLE 2 Unit costs
Resource
Unit cost
(2012/13), £ Source
Nebuliser kits 44 Study hospital
Saline (4 ml) 0.45 BNF 65.513%, 6% and 7% solutions all have identical prices (£27 for 60 doses)
Inpatient day on ward 547 Derived from NHS reference costs.52
Activity-weighted average across all non-elective admissions relating to PA15B
Inpatient day on ICU 1946 Derived from NHS reference costs.52Activity-weighted average across all
paediatric intensive care categories, excluding ECMO/ECLS Inpatient day on HDU 1061 Derived from NHS reference costs.52
Activity-weighted average across all paediatric high-dependency care categories
GP attendance 45 Unit Costs of Health and Social Care 2013.53Per-patient contact lasting
11.7 minutes, including direct care staff costs and costs of qualifications NHS Direct 25 £24, 2010/11 prices.54
Inflated using Hospital and Community Health Care Pay and Prices Index53
Walk-in centre 41 Derived from NHS reference costs.52Activity-weighted average across service
type 4, admitted and non-admitted. Category 1 investigation with category 3–4 treatment
Minor injuries unit 88 Derived from NHS reference costs.52
Activity-weighted average across service type 3, admitted and non-admitted. Category 1 investigation with category 3–4 treatment
Emergency department 118 Derived from NHS reference costs.52Activity-weighted average across service
types 1 and 2, admitted and non-admitted. Category 1 investigation with category 3–4 treatment
Carrollet al.55estimated the utility decrement from full health during hospitalisation as 0.05 (with a standard
error of 0.01) using the time trade-off technique. This then needs to be combined with the general population value for infants of the same age. The best method for combining comorbidities is considered to be through multiplication of the relevant values.56Following a search of the literature, the most relevant general
population value using a paediatric utility instrument for the children recruited to the SABRE study was found to be a Health Utilities Index-II survey of 8-year-old Canadian children. The general population value in that study was 0.95 (compared with 0.82 for children of extremely low birthweight).57For the SABRE study,
therefore, the non-hospitalised utility is 0.95 (taken from Saigalet al.57), while the hospitalised utility is 0.9025
(calculated as the product of the Saigalet al.57and Carroll and Downs55utility estimates). Analysis
Differences in costs and QALYs were assessed using non-parametric permutationt-tests that allow robust comparisons of the means in the presence of non-normal data. A permutation test samples from the observed data to calculate the correct distribution of the test statistic under the null hypothesis. Paired cost and QALY data were then bootstrapped with 5000 replications and plotted on the cost-effectiveness plane. The focus of the economic analysis was the resultant cost-effectiveness acceptability curve and the probability that the intervention will be cost-effective at £20,000 per QALY.
The main cost driver was expected to be hospital costs. Deterministic sensitivity analyses were planned for the cost per day on a ward, in intensive care and in high-dependency care. Alternative plausible unit costs to our preferred ward estimate of £547 are £558 per day (with the latter also including complicated admissions) and £425 (derived using excess bed-days costs for uncomplicated admissions). Alternative plausible unit costs to our preferred intensive and high-dependency care estimates of £1946 and £1061 are £1743 and £886, respectively (derived using only the basic care categories within each type of unit).
Probabilistic sensitivity analysis is undertaken through the bootstrapping procedure described previously, thereby incorporating the sampling uncertainty related to all clinical effects and resource use items. Probabilistic sensitivity analysis using distributions around unit costs and utility values is not routinely undertaken in economic evaluations alongside trials.
Where appropriate, missing data were to be imputed using multiple imputation. This assessment would be based on the degree of missingness and the mechanism by which missing data were generated (e.g. random or non-random).