A trial-based cost-effectiveness analysis of antibiotic prescription strategies for non-complicated respiratory tract infections in children
Authors: Mas-Dalmau Gemma , Pérez-Lacasta María José , Alonso-Coello Pablo , Gorrotxategi-Gorrotxategi Pedro , Argüelles-Prendes Emma , Espinazo-Ramos Oscar , Valls-Duran Teresa , Gonzalo-Alonso María Encarnación , Cortés-Viana María Pilar , Menéndez-Bada Tatiana , Vázquez-Fernández Marta Esther , Pérez-Hernández Ana Isabel , Muñoz-Ortiz Laura , Villanueva-López Carmen , Little Paul , de la Poza-Abad Mariam , Carles-Lavila Misericòrdia ,   on behalf of the DAP Paediatrics Group, Manuel-Enguidanos Josefa , Herrero-Torres Natividad , Martínez-Villamizar Lorena , Palassí-Bargalló Carme , Peix-Galito Maria Amor , Camps-Serra Francesca , Mené-Bergara Rosa , Ramírez-Álvarez Paloma , Pietrafesa-Barreiro Marisa , Ortiz-Ros Pilar , del Rey-Márquez Virgina , Barahona-Rondón Lucía , Benítez-Rubio María Rosario , Valero-Marugán Ana María , Casado-Sánchez María Laura , de Pando-Bravo Ángeles , Bengoa-Gorosabe Miren Arrate , Callén-Blecua Carmen , Hernández-Salvador Inés , Ozcoidi-Erro Irene , Blanco-González Javier Eduardo , Gutiérrez-Abad Carmelo 
Published: October 2023

Abstract
Background
Antibiotic prescription for respiratory tract infections (RTIs) in children attending primary care centres is almost double that predicted according to bacterial prevalence. Delayed antibiotic prescription (DAP) is designed to deploy a more rational use of antibiotics. While studies have evaluated DAP efficacy and safety for children with RTIs, little research has been conducted on the economic implications.

Methods
Our trial compared cost-effectiveness for DAP, immediate antibiotic prescription (IAP), and no antibiotic prescription (NAP) for children aged 2–14 years with acute uncomplicated RTIs attended to in 39 primary care centres in Spain. The main outcome was the incremental cost-effectiveness ratio (ICER), measured in euros per gained quality-adjusted life days (QALDs). Net monetary benefit (NMB) was also calculated as a tool for decision making. The analysis was performed from a societal perspective for a time horizon of 30 days, and included healthcare direct costs, non-healthcare direct and indirect costs, and the antimicrobial resistance (AMR) cost.

Results
DAP was the most cost-effective strategy, even when the cost of AMR was included. QALD values for the three strategies were very similar. IAP compared to DAP was more costly (109.68 vs 100.90 euros) and similarly effective (27.88 vs 27.94 QALDs). DAP compared to NAP was more costly (100.90 vs 97.48 euros) and more effective (27.94 vs. 27.82 QALDs). The ICER for DAP compared to NAP was 28.84 euros per QALD. The deterministic sensitivity analysis indicated that non-healthcare indirect costs had the greatest impact on the ICER. The cost-effectiveness acceptability curve showed that DAP was the preferred option in approximately 81.75% of Monte Carlo iterations, assuming a willingness-to-pay value of 82.2 euros per gained QALD.

Conclusions
When clinicians are in doubt about whether an antibiotic is needed for children with RTIs attending PC centres, those treated with the DAP strategy will have slightly better efficiency outcomes than those treated with IAP because its costs are lower than those of IAP. DAP is also the most cost-effective strategy over a time horizon of 30 days if AMR is considered, despite higher short-term costs than NAP. However, if in the long term the costs of AMR are larger than estimated, NAP could also be an alternative strategy.

Trial registration
This trial has been registered at www.clinicaltrials.gov (identifier NCT01800747; Date: 28/02/2013 (retrospectively registered).