Analytical framework
A budget impact analysis was performed to evaluate the potential financial impact deriving from Surfactant therapy in the market of available treatments for bronchiolitis, requiring mechanical ventilation. The analysis considered the perspective of the Colombian National Health System and was conducted over a 4-years’ time horizon. A budget impact model (BIM) was developed as a Microsoft Excel® macro-enabled workbook to evaluate the incremental budget impact of Surfactant therapy for treatment of severe bronchiolitis, requiring mechanical ventilation. The incremental budget impact was calculated by subtracting the cost of the new treatment, in which Surfactant therapy (adding to humidified oxygen or adrenaline nebulization) is reimbursed, from the cost of the conventional treatment without Surfactant therapy ( only humidified oxygen or adrenaline nebulization). Full details of all assumptions used to develop the base case analysis are provided in Table 1.
Table 1
Assumption used to develop the base case analysis
Assumption | References |
For all products compliance is considered to be 100% | Assumption based on the opinion of clinical experts |
The incidence of adverse events is equal between patients treated with ST and without ST | (6) |
The incidence of bronchiolitis is stable over the time horizon | Assumption based on the opinion of clinical experts |
The incidence of bronchiolitis requiring mechanical ventilation is stable over the time horizon | Assumption based on the opinion of clinical experts |
The market share for different types of ST are stable over the time horizon | Assumption based on the opinion of clinical experts |
Target Population
The target population is represented by infants (0 to 60 months of age), term newborn without cardiac or neurological or respiratory or another chronic disease, in pediatric intensive care unit (PICU) with a diagnosis of bronchiolitis, requiring mechanical ventilation. The size of the population for the first year was calculated applying data about the total population under 2 years of age in Colombia(7), incidence of bronchiolitis in Colombia (8), frequency of infant with bronchiolitis requiring mechanical ventilation in Colombia (4, 9). An annual population growth of 0.8% was assumed considering the average national growth rate from the period 2015–2019 (7), Table 2.
Table 2
Parameter used in the case base
Type of parameter | Base Case value | Range for one-way sensitivity analyses | Reference |
Demographics | | | |
Population | 2 327 222 | | (7) |
Annual population growth | 0.8% | | (7) |
Pediatric weight | 6.7 kg, | | (10–12) |
Epidemiology | | | |
Bronchiolitis incidence | 6.1% | 4–8% | (8) |
% bronchiolitis requiring mechanical ventilation | 7.1% | 2–10% | (4, 9) |
Cost | | | |
Survanta® (unit 25 mg), US$ | 13 | 10–15 | (14) |
Curosurf® (unit 240 mg), US$ | 37 | 30–40 | (14) |
Infasurf® (unit 105 mg), US$ | 13 | 10–20 | (14) |
Market Share | | | |
Survanta® (unit 25 mg) | 47.3% | 40–57% | (13) |
Curosurf® (unit 240 mg) | 49.2% | 45–55% | (13) |
Infasurf® (unit 105 mg) | 3.4% | 2–6% | (13) |
Intervention
Exogenous Surfactant (intratracheal administration of Surfactant) in infants less than two years old requiring mechanical ventilation. The information on effectiveness was extracted from a systematic review of three RCTs (6). In this reviw, the duration of the intensive care unit (ICU) stay was less in the ST than the control group: MD -3.31, 95% CI -6.38 -0.25 days. Serious adverse effects were not reported in these studies. Respect to the drug administration in these trials :
-
The Luchetti 1998 included infants on mechanical ventilation for 24 hours without significant improvement of their clinical status (uncorrected congenital heart disease and neuromuscular diseases were excluded by two studies). In this study, porcine surfactant (Curosurf) 50 mg/kg was administered in two to three doses through an endotracheal tube (10).
-
Luchetti 2002 included infants who had mechanical ventilation for at least 12 hours without significant improvement (uncorrected congenital heart disease and neuromuscular diseases were excluded by two studies). In this study, porcine surfactant (Curosurf) 50 mg/kg was administered in two aliquots over about five minutes through an endotracheal tube (11).
-
The Tibby 2000 study enrolled infants who were ventilated for less than 24 hours with an oxygenation index above five and a ventilation index above 2 (the study did not exclude children with chronic lung disease and prematurity history). In this study, bovine surfactant (Survanta) was administered in two doses (100 mg/ kg), 24 hours apart, through an endotracheal tube (12).
According to the Colombian market at the time of the analysis, we have 3 types of surfactant: Survanta®, Curosurf® and Infasurf® have a market shares of 47.35%, 49.20% and 3.4% respectively (13). The cost of treatment per patient was calculated:
-
the total amount of milligrams per patient/treatment was estimated for each types of surfactant according to the dosing schedules mentioned above, and assuming a patient with average weight of 6.7 kg,
-
The cost of each types of surfactant per patient was estimated by multiplying the cost per milligram of each types of surfactant, obtained from the national list of drug costs (14), by the total amount of milligrams estimated per patient/treatment calculated in the previous step
-
The final cost of treatment per patient was obtained from the sum of the results of the cost of each type of surfactant per patient multiplied by their market share.
We assumed to progressively gain market sales from surfactant therapy. In the base-case scenario the uptake rate of surfactant therapy was assumed to be 25%, increasing to 25% each year respectively, according to he estimates of the marketing authorization holder.
Time Horizon
The time horizon defined was four years. The maximum follow-up time was set to be four years A longer perspective was not considered relevant for the budget holder. All results are depicted cumulatively from 1 to 4 years
Resource Use And Cost
The costs of each outcome defined previously were estimated directly from medical invoices and electronic medical records of 193 infants admitted in tertiary centers in Rionegro, Colombia, with a diagnosis of bronchiolitis, according to the national clinical guidelines of bronchiolitis. This cost and clinical characteristics of these patients were published previously (4, 15). Brief, the direct costs considered in the analysis include medical consultation at the emergency room, specialist referrals, chest physiotherapy, diagnosis support (laboratory, electrocardiogram, x-ray, etc.), medication (oxygen, nebulization, antibiotics, corticosteroids, bronchodilators, etc.), medical devices, hotel services in the intensive care unit, and hotel services in the general medical ward. All treatment costs include the administration and preparation costs covered by the treating organization. All adverse events were assumed to be fully reversible and thus not to cause any additional costs to the hospital district. To avoid data errors during medical record abstraction, we used software (Excel MS®) with automatic calculation functions and error alerts and a review of outliers by the research team. We used US dollars (currency rate: US$ 1.00 = COP$ 3,000) (16) to express all costs in the study. For the valuation of the indirect costs associated with the loss of parents' productivity, the human capital method was used, assuming everyone receives an income of at least a legal minimum wage for formal or informal work. The cost-opportunity of the productivity loss at the workplace and the caregiver was assessed based on the minimum wage without including transportation assistance (US$ 229.81 per month). The legal minimum wage approved by the government was taken as a reference and not an average or median wage thereof, given that in Colombia, over 75% of the population has this value as their income (7). Because all patients with acute asthma episodes included in this study were children, we assumed that at least one family member accompanied the patient permanently during hospitalization, as pediatric hospitals in the country usually allow only one companion per patient in the hospital. The cost associated with transportation and food (does not include a stay), was assumed to correspond to 50% of minimum wage per day.
Sensitivity Analyses
The robustness of the base-case was evaluated with one-way sensitivity analyses. The parameters used in the analysis were varied once as detailed in Table 3. Expert opinion and literature data were used to determine ranges of parameters to be tested in the sensitivity analysis. Results of the sensitivity analysis are presented in a threshold analysis and tornado diagram showing the impact on base-case of uncertainty in the parameters used in the model. Microsoft Excel® was used in all analyses.
Table 3
Cost (US$) used in base case and sensitivity analyses
Model input | Base case value | SA range for one-way sensitivity analyses | Distribution |
Intervention cost | | | |
ST per patient day | 203 | 43–352 | γ(SD:197) |
Hospitalization cost | | | |
Daily cost in pediatric ward | 48.82 | 47,64 50.00 | γ(SD:3,20) |
Hospital length of stay (days) | 5,8 | 4,00–6,01 | γ(SD:2,03) |
PICU related cost | | | |
Daily cost in PICU | 327,35 | 326,26-328-43 | γ(SD:5,49) |
Reduction in PICU lenght of stay (days) by ST | 3.31 | 0.25–6.38 | γ(SD:1.8) |
Emergency visit prior hospitalization cost | | | |
Daily cost of emergency ward | 12,83 | 12,19 − 13,46 | γ(SD:3,20) |
Direct medical cost per patient-day | | | |
Specialist referrals | 10,67 | 10,31 − 11,01 | γ(SD:1,72) |
Chest physiotherapy | 5,15 | 4,90 − 5,39 | γ(SD:1,23) |
Chest radiography | 2,84 | 2,70 − 2,98 | γ(SD:0,73) |
Others diagnostic imaging | 0,01 | 0,0–0,022 | γ(SD:0,08) |
Complete blood cell counts | 1,12 | 1,05 − 1,17 | γ(SD:0,28) |
RSV test | 2,71 | 2,83 − 3,03 | γ(SD:2,72) |
Other laboratory tests | 4,40 | 4,23 − 4,47 | γ(SD:0,37) |
Oxygen | 1,37 | 1,28 − 1,45 | γ(SD:0,41) |
Nebulization | 16,23 | 1,28 − 1,45 | γ(SD:4,52) |
LEV | 1,10 | 1,07 − 1,13 | γ(SD:0,16) |
Antibiotics systemics | 1,21 | 1,11 − 1,30 | γ(SD:0,49) |
Systemic o Inhaled Corticosteroids | 0,08 | 0,0–0,90 | γ(SD:4,18) |
Bronchodilators | 0,04 | 0,03 − 0,04 | γ(SD:0,02) |
Other drugs | 0,65 | 0,60 − 0,68 | γ(SD:0,04) |
Medical devices | 10,24 | 9,71 − 10,76 | γ(SD:2,66) |
Indirect cost patient-day | 17,24 | 16.38-18,07 | γ(SD:4,30) |