Evaluating the cost-effectiveness of new treatment strategies for the management of young infants with low- or moderate-mortality risk signs of possible serious bacterial infection: framework and study methodology for randomised controlled trials in

Background: The World Health Organization (WHO) is coordinating two randomised controlled trials (RCTs) across three sites in Africa (Ethiopia, Nigeria, and Tanzania) and four in Asia (one in Bangladesh, two in India, and one in Pakistan) to generate evidence on the optimal place of treatment for young infants (YIs) with a single low-mortality risk sign of possible serious bacterial infection (PSBI) and switching antibiotic therapy from injectable to oral in YIs with moderate-mortality risk signs of PSBI. We present the framework and methodology used to compare the costs and evaluate the cost-effectiveness (CE) of these strategies. Methods: Cost analysis will be conducted from societal (hospital and household) perspectives. Hospital medical costs (staff, medicines, and consumables) and operational costs (inpatient bed costs, non-consumables, training, and communication) will be collected through hospital surveys. Household costs, including medical payments for treatment (registration, consultations, medications, consumables) and non-medical costs (transport, food, and wage loss), will be collected through household surveys. In both RCTs, combined hospital and household (including medical and non-medical) costs for all randomised sick YIs (SYIs) will be used, with an intention-to-treat approach, to calculate the cost per SYI in each study arm. Effectiveness measures, based on the absence of adverse outcomes, will be used to determine incremental CE ratios and incremental net benefits. Separate societal and payer/provider perspectives will be considered, and site-specific willingness-to-pay thresholds will be estimated. The household's medical and non-medical costs, along with their share of societal costs, will estimate the household burden per treated child. Conclusions: This CE framework will evaluate thresholds for new PSBI treatment strategies in YIs, integrating health system and household perspectives. It will seek to identify safe, cost-effective approaches to reduce economic burdens, inform national budgetary impact, and potentially prompt WHO guideline revisions to improve infant care in low-resource settings globally.