key: cord-0965869-jx2r8k51 authors: Huang, Yiming; Mian, Qaasim; Conradi, Nicholas; Opoka, Robert O.; Conroy, Andrea L.; Namasopo, Sophie; Hawkes, Michael T. title: Estimated Cost-effectiveness of Solar-Powered Oxygen Delivery for Pneumonia in Young Children in Low-Resource Settings date: 2021-06-24 journal: JAMA Netw Open DOI: 10.1001/jamanetworkopen.2021.14686 sha: f1a1b99d182fca9825f5d3586840741b36d4eb87 doc_id: 965869 cord_uid: jx2r8k51 IMPORTANCE: Pneumonia is the leading cause of childhood mortality worldwide. Severe pneumonia associated with hypoxemia requires oxygen therapy; however, access remains unreliable in low- and middle-income countries. Solar-powered oxygen delivery (solar-powered O(2)) has been shown to be a safe and effective technology for delivering medical oxygen. Examining the cost-effectiveness of this innovation is critical for guiding implementation in low-resource settings. OBJECTIVE: To determine the cost-effectiveness of solar-powered O(2) for treating children in low-resource settings with severe pneumonia who require oxygen therapy. DESIGN, SETTING, AND PARTICIPANTS: An economic evaluation study of solar-powered O(2) was conducted from January 12, 2020, to February 27, 2021, in compliance with the World Health Organization Choosing Interventions That Are Cost-Effective (WHO-CHOICE) guidelines. Using existing literature, plausible ranges for component costs of solar-powered O(2) were determined in order to calculate the expected total cost of implementation. The costs of implementing solar-powered O(2) at a single health facility in low- and middle-income countries was analyzed for pediatric patients younger than 5 years who required supplemental oxygen. EXPOSURES: Treatment with solar-powered O(2). MAIN OUTCOMES AND MEASURES: The incremental cost-effectiveness ratio (ICER) of solar-powered O(2) was calculated as the additional cost per disability-adjusted life-year (DALY) saved. Sensitivity of the ICER to uncertainties of input parameters was assessed through univariate and probabilistic sensitivity analyses. RESULTS: The ICER of solar-powered O(2) was estimated to be $20 (US dollars) per DALY saved (95% CI, $2.83-$206) relative to the null case (no oxygen). Costs of solar-powered O(2) were alternatively quantified as $26 per patient treated and $542 per life saved. Univariate sensitivity analysis found that the ICER was most sensitive to the volume of pediatric pneumonia admissions and the case fatality rate. The ICER was insensitive to component costs of solar-powered O(2) systems. In secondary analyses, solar-powered O(2) was cost-effective relative to grid-powered concentrators (ICER $140 per DALY saved) and cost-saving relative to fuel generator-powered concentrators (cost saving of $7120). CONCLUSIONS AND RELEVANCE: The results of this economic evaluation suggest that solar-powered O(2) is a cost-effective solution for treating hypoxemia in young children in low- and middle-income countries, relative to no oxygen. Future implementation should prioritize sites with high rates of pediatric pneumonia admissions and mortality. This study provides economic support for expansion of solar-powered O(2) and further assessment of its efficacy and mortality benefit. Our own group has experience in the implementation of SPO2 in Uganda, the Democratic Republic of the Congo, and Somalia. This experience informed the present cost-effectiveness analysis, both in terms of real-world costs of system components, as well as input parameters used to calculate health effects. Proof-of-concept was demonstrated in a pilot study of 28 patients in Jinja, Uganda. 1 We next conducted a randomized controlled non-inferiority trial comparing SPO2 to cylinder oxygen in children under 13 years of age hospitalized with hypoxemia at two hospitals in Uganda. 2 The study found that SPO2 was safe and non-inferior to cylinder oxygen with respect to duration of hospitalization (primary outcome) as well as mortality, duration of hypoxemia, and time to recovery of hypoxemia, tachypnea, and tachycardia (secondary outcomes). 2 We are currently conducting a multi-center stepped wedge cluster randomized controlled trial of SPO2 at 20 health facilities across Uganda examining the mortality benefit of SPO2. 3 The health sector represents a government-funded public health sector (e.g., the Ministry of Health of Uganda) which would be responsible for implementing and maintaining SPO2 systems. The healthcare sector perspective was included in the cost-effectiveness analysis because it informs the expenditures that would be necessary for a hospital or health system to implement SPO2, which is relevant for budgetary impacts. The societal perspective expands upon the healthcare perspective by adding costs that patient families experience when their child is admitted to hospital, and is the recommended perspective in WHO CHOICE. 4 Starting with the base case assumptions, the input parameters were varied one at a time within the range of plausible values ( Table 1 ). All other variables were held constant at the base case values. The ICER was calculated at each extremum of the range, and was plotted on a tornado plot ( Figure 1 ). The circles represent the base case and the whiskers represent the upper and lower limits of the ICER, at each extreme of the input parameter. For selected input parameters, we explored the relationship between the parameter value and the ICER by varying the parameter over its plausible range while holding the other inputs constant at their base case values. A graphical representation was used to display the independent effects of key inputs ( Figure 2 ). In computing the ICER, there is uncertainty in both the incremental costs (numerator) and health effects (denominator). These were displayed in a plane in which each point was an estimate of the ICER, based on a probabilistic sampling of the input parameters. 5 The cost-effectiveness threshold (GDP per capita) was plotted on the same plane, defining a space in which the ICER was favourable ( Figure 3A ). Next, the individual ICER estimates were used to construct a cost-effectiveness acceptability curve. The curve was constructed by varying the threshold value of the ICER and determining the posterior probability of the ICER meeting that threshold. 5 As the threshold value rises, the probability of the ICER being judged cost-effective increases. 5 The willingness-to-pay thresholds were displayed on the x-axis and the probability that SPO2 has an ICER (relative to the null case) below this threshold was plotted on the y-axis ( Figure 3B ). 1. Input parameters. Numerous assumptions for input parameters (base case and plausible range) are summarized in Table 1 . Where possible, these were taken from the literature for maximum generalizability. Where we could not find published data, we used parameters or costs based on our own experience implementing SPO2 in Uganda. 2 For sensitivity analyses, the parameters were assumed to be random variables with a Poisson, beta, or gamma probability distribution functions for frequencies, proportions, and costs or time periods, respectively (Table 1 ). We did not include effects of surges in demand (e.g., respiratory virus outbreak) or system failures (e.g., battery depletion) that could affect the cost-effectiveness of SPO2. In our experience, these are low-probability events 2 and were not included in our costeffectiveness model. 3. Comparator group. The comparator group was assumed to be the null case (no oxygen) for our primary analysis. This was based on the WHO-CHOICE methodology. 4 Ideally, the comparator group should represent the standard of care. 5 Medical oxygen is not available on the pediatric wards of many resource-limited hospitals, 6,7 justifying this comparator group. In addition to this primary analysis, we also conducted secondary analyses comparing SPO2 to grid-and fuel generatorpowered concentrators since these are alternative methods of oxygen delivery. For the DALY calculation, we neglected the YLD, such that YLL accounted for all the DALYs lost. This was based on the assumption that children who recover from pneumonia do not have residual morbidity. Two previous studies examined the long-term outcomes in hospitalized children with pneumonia and found a small increase in restrictive lung disease. 8, 9 However, given that these studies were not conducted in low-resource settings, did not clearly show that oxygen treatment was associated with subsequent pathogenesis, and did not control for environmental factors contributing to future respiratory disease, we opted to focus on mortality and forgo disability weighting among survivors. Following the recommendations of WHO-CHOICE as a standard approach to costeffectiveness analysis, 10 we assumed a time horizon of 10 years. 6 . Discounting and age-weighting of health effects. Discounting of health effects was used in the base case (discount rate 3%). This assumes a preference for present health over future years of good health. Age-weighting of DALYs was not used, as this is controversial. 10 7. Threshold for cost-effectiveness. The threshold below which the ICER must be for an intervention to be considered cost-effective was assumed to be the GDP per capita. Other cost-effectiveness studies in high-income settings have used $50 000 per DALY saved, based on renal dialysis in the USA, because there is general (political) agreement that there is willingness to pay for renal dialysis. 5 The argument that the cost-effectiveness threshold varies in poorer countries is debatable. 5 We began with the GDP per capita of Uganda, where SPO2 was pioneered. For maximum stringency, we also used the lowest GDP per capita in the world (South Sudan, GDP of $220) to evaluate the cost-effectiveness of SPO2 (vs no oxygen). Of note, despite the usefulness of a benchmark for comparison, there is no scientific justification for the GDP or any other costeffectiveness threshold over another. 8 . Use of SPO2 restricted to severe childhood pneumonia with hypoxemia at a rural or remote pediatric ward in a LMIC. The disease and patient demographic of interest was hypoxemia in children <5 years of age. Childhood pneumonia is the most common cause for hypoxemia and is a leading cause of death globally. 11 Our analysis of SPO2 cost-effectiveness was restricted to this condition and should not be extrapolated to other patient groups or clinical conditions for which the health effects may be different. Furthermore, we assumed that SPO2 would be used in a pediatrics ward in a LMIC hospital in a remote or rural location (where grid power is unreliable and access to cylinder oxygen is challenging). In this setting, a single oxygen concentrator (5L/min, two patients at a time) is generally sufficient. Base Range Distribution Reference Price A. The ICER estimate was sensitive to changes in the proportion of time without grid power, following an inverse relationship. ICER rose steeply when grid electricity was reliable. The ICER was favorable (<$604 per DALY saved) as long as the proportion of time without grid power was >1.6%. B. The ICER was relatively insensitive to variations in the price of grid electricity. Solar-powered oxygen delivery: proof of concept Solar-powered oxygen delivery in low-resource settings: a randomized clinical noninferiority trial Solar-powered oxygen delivery for the treatment of children with hypoxemia: protocol for a cluster-randomized stepped-wedge controlled trial in Uganda Choosing interventions that are cost effective (WHO-CHOICE) The limits of cost-effectiveness analysis Oxygen availability and nursing capacity for oxygen therapy in Ugandan paediatric wards Oxygen insecurity and mortality in resource-constrained healthcare facilities in rural Kenya Long-term effects of pneumonia in young children Long term sequelae from childhood pneumonia; systematic review and meta-analysis Methods and data sources for global burden of disease estimates The prevalence of hypoxaemia among ill children in developing countries: a systematic review Promoting Solar Energy through Auctions Oxygen insecurity and mortality in resource-constrained healthcare facilities in rural Kenya Feasibility study of using 2kWp residential PV system comparing with 2.5kVA gasoline generator (Case study: Baghdad city) Sustainability implications of electricity outages in sub-Saharan Africa Pump price for gasoline (US$ per liter) -Uganda Selection of a Hybrid Renewable Energy Systems for a Low-Income Household 78.2% of simulations were cost-effective using these two thresholds, respectively. B. Cost-effectiveness acceptability curve: we can be 95% confident that SPO2 will be cost-effective beyond a willingness-to-pay threshold of $849/DALY saved.