Health Technology Assessment van een beslissingsondersteunend systeem om antimicrobiële resistentie aan te pakken

Antimicrobial resistance (AMR) is one of the most pressing global health challenges worldwide. Although resistance is a natural evolutionary process, its development and spread have been markedly accelerated by inappropriate prescribing and excessive antibiotic use. AMR is already responsible for an estimated 1.27 million deaths annually, a figure expected to rise substantially in the absence of effective interventions. In addition to its clinical consequences, AMR imposes a considerable economic burden, with projected global losses reaching up to 100 trillion USD by 2050. Primary care, and paediatric primary care in particular, plays a central role in this challenge. Most childhood infections are mild and self-limiting, yet antibiotics are frequently prescribed. Approximately one in four children receives at least one antibiotic prescription each year, with an estimated one-third to one-half of these prescriptions considered inappropriate. Such prescribing is driven by 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 compromising 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 consequences of stewardship interventions to support investment and implementation decisions. This broader perspective is particularly important in resource-constrained healthcare systems, where competing priorities necessitate careful allocation of limited resources. 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 inform policy and practice, 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 examines social and behavioural dimensions through qualitative research exploring how stewardship interventions are perceived, used, and embedded in everyday clinical practice.