This study evaluated the cost-effectiveness of the HS (3–7%) inhalations for infant bronchiolitis versus or standard treatment without HS inhalations (controls). The main effectiveness outcome was the quality-adjusted life years (QALYs). The analysis was carried out from a societal perspective (included direct and indirect costs). The analytic horizon was an acute episode of bronchiolitis. Given the short time horizon, no type of discount to costs or results was applied.
A decision tree model was constructed to estimate de cost and effectiveness of episodes of bronchiolitis (Figure 1). We defined the following outcomes according to the natural history of bronchiolitis: death, hospitalization with or without acute complications, PICU admission with or without acute complications. Among the acute complications were included: pneumonia, atelectasis, sepsis, pleural effusions, and pneumothoraxes (11). The study protocol was reviewed and approved by the Institutional Review Board of the University of Antioquia (No 18/2015).
Model Parameters and Data Sources
To estimate the probabilities and utilities of the model (see Table 1), we performed a systematic review of systematic reviews or RCTs published or observational studies up to January, 2020. In order to identify potentially relevant studies were made searches of computerized databases (MEDLINE, CENTRAL, LILACS, and CINAHL); using the following search strategy: (3% hypertonic solution) AND (Bronchiolitis OR Bronchiolitis, Viral), limited with the terms children OR child OR pediatric OR adolescents OR infants OR preschoolers). No language restrictions were applied. To be included in the model, the studies had to be RCTs of parallel-group or cross-over design, systematic reviews or RCTs published or observational studies include children between 2 and 18 years of age. Also were included others observational clinical obtained during the review of references cited in published literature. The computerized search yield 1021 citations and a total of 75 studies were examined. Finally, the information was extracted for the construction of the economic model of 10 studies that included patients less than 18 years of age, with bronchiolitis, and with use of HS (12-19). Information regarding the effect of HS was extracted from a recent meta-analysis (10, 16) which compared HS nebulization versus normal saline inhalations or standard treatment without HS nebulization (see Table 1).
All cost and use of resources were collected directly from medical invoices of 193 patient hospitalized with diagnosis of bronchiolitis, in tertiary centers, of Rionegro, Colombia from January 2015 to December 2016(see Table 2). Details of this cost study have been previously published (20). Briefly, the direct costs considered in the analysis include medical consultation at emergency room, specialist referrals, chest physiotherapy, RSV isolation, x-ray, oxygen, nebulization, corticosteroids, bronchodilators, medical devices, hotel services at intensive care unit, hotel services in general medical ward. We use US dollars (Currency rate: US$ 1.00 = COP$ 3,000) (20) to express all costs in the study. For the valuation of the indirect costs associated with the loss of productivity of parents, the human capital method was used. The cost-opportunity of the productivity loss at the workplace and the caregiver was assessed based on the minimum wage without including the transportation assistance for the year 2019 (U$ 229.81 per month) (21). Because all patients with bronchiolitis included were children, we assumed that at least one family, member accompanies the patient permanently during hospitalization, since pediatric hospitals in the country usually allow only one companion per patient in the hospital. The cost associated with transportation and food, was assumed to correspond to 50% of minimum wage per day.
The utility values applied to QALYs calculations were collected from the literature. Baseline utility value for hospitalization was 0.95 (22-25) , whereas a 0.88 utility value was used for PICU, given hospitalization (26, 27), 0.59 for hospitalization with acute complications, and 0.5 for PICU with acute complications (28, 29). The number of QALYs was calculated as the utility value given to a particular health state multiplied by length of time spent in that state. Given that they are utilities extracted from studies in populations other than the Colombian, a range was used for the sensitivity analysis of one way and probabilistic of more or less 20% the value of the utility
The robustness of the economic model was evaluated with one-way sensitivity analyses and probabilistic sensitivity analysis according to the recommendation of consolidated health economics evaluation reporting Standards (35). Probabilistic sensitivity analysis was run by randomly sampling from each of the parameter distributions (beta distribution in the case of relative risk, and utilities, Dirichlet distribution for multinomial data in the case of transition probabilities, and gamma distribution in the case of costs). A second-order Monte Carlo simulation were used to estimated the expected costs and QALYs of the model. Net monetary benefit was calculated by multiplying effect by societal willingness to pay and subtracting cost, with a willingness to pay set at a ratio of US$ 20,000 per QALYS. Microsoft Exel ®was used in all analyzes.