Health technology assessment of a decision support system to tackle antimicrobial resistance

Antimicrobial resistance (AMR) is one of the most pressing global health challenges today. Although resistance is a natural evolutionary process, its emergence and spread have been greatly accelerated by inappropriate prescribing and excessive antibiotic use. AMR already accounts for an estimated 1.27 million deaths worldwide each year, a figure projected to rise sharply if no effective action is taken. Beyond its health impact, AMR also imposes a substantial economic burden, with global losses estimated to reach up to 100 trillion USD by 2050. Primary care, and paediatric primary care in particular, lies at the centre of this challenge. While most childhood infections are mild and self-limiting, antibiotic prescribing remains common. Approximately one in four children receives at least one antibiotic prescription annually, and between one-third and one-half of these prescriptions are considered inappropriate. Such prescribing persists due to a combination of diagnostic uncertainty, parental concern, and time pressure during routine consultations. To address these challenges, the ARON trial was conducted: a pragmatic cluster-randomised controlled trial including 6,750 acutely ill children in Belgian primary care. The trial evaluated a multifaceted antibiotic stewardship intervention combining a validated clinical decision tree, point-of-care C-reactive protein (CRP) testing, and structured safety-netting advice for parents delivered through an information booklet. The intervention demonstrated that antibiotic prescribing could be safely reduced without adverse effects on clinical outcomes, by strengthening clinical assessment and reducing diagnostic uncertainty. However, evidence of clinical effectiveness alone is insufficient to inform healthcare decision-making. Policymakers also require insight into the economic, social, and behavioural implications of stewardship interventions to justify investments and guide implementation. This broader perspective is particularly important in settings of constrained healthcare resources, where competing priorities necessitate careful allocation decisions. This thesis therefore adopts a comprehensive Health Technology Assessment (HTA) framework to evaluate the broader value of antibiotic stewardship interventions in primary care. By integrating clinical, economic, and socio-behavioural perspectives, it aims to generate a multidimensional evidence base to support informed policy decisions, contributing both to high-quality patient care and to the long-term preservation of antibiotic effectiveness. The thesis is structured in two parts. The first part focuses on economic evaluation, including a systematic review of economic evaluations of point-of-care interventions addressing AMR in primary care; an assessment of challenges in measuring health-related quality of life in young children with acute infection; a trial-based cost-effectiveness analysis of the ARON intervention; a long-term agent-based simulation model estimating its impact on AMR levels; and a budget impact analysis of implementing CRP point-of-care testing in Belgian primary care. The second part addresses social and behavioural dimensions through qualitative research examining how stewardship interventions are perceived, used, and integrated into everyday clinical practice.