Design, implementation, and evaluation of a pharmacist-led antiviral stewardship program in hospital settings

Thesis Abstract

The rapid emergence of antiviral resistance and rising antimicrobial burden in hospital settings necessitates optimized antiviral use and stewardship. This study addresses the gap in formalized pharmacist-led antiviral stewardship programs (AVS) by designing, implementing, and evaluating a structured intervention within tertiary care hospitals to improve appropriateness of antiviral prescribing, reduce resistance risk, and enhance patient outcomes. The aim is to develop an evidence-based AVS model that delineates roles, processes, and metrics for sustained improvement. Specific objectives include (1) to implement a pharmacist-led AVS with multidisciplinary collaboration across infectious diseases, microbiology, and pharmacy services; (2) to evaluate changes in antiviral prescribing appropriateness using predefined criteria aligned with national guidelines; (3) to assess impact on clinical outcomes such as time to antiviral optimization, length of hospital stay, and 30-day readmission rates; (4) to quantify economic implications through cost per infection averted and overall antiviral expenditure; (5) to explore stakeholder perceptions, barriers, and enablers of AVS through qualitative inquiry; and (6) to develop a scalable implementation framework for other hospital settings. The methodology adopts a mixed-methods design, integrating a quasi-experimental interrupted time series (ITS) analysis with pre/post measures and a qualitative exploration. The setting comprises three tertiary hospitals with a combined annual antiviral prescription volume of approximately 15,000 defined daily doses. The population includes all adult inpatients prescribed systemic antivirals over a 24-month period (12 months pre-intervention, 12 months post-intervention). The sample for the ITS consists of all antiviral prescription events, while qualitative sampling employs purposive selection of clinicians, pharmacists, and nursing staff (n=30) for semi-structured interviews and focus groups. Data collection instruments include (a) an AVS compliance audit checklist capturing indication, dosing, duration, drug-drug interactions, renal dosing, and de-escalation timing; (b) electronic health record-derived metrics for time to appropriate therapy, duration of antiviral use, and adverse drug events; (c) cost accounting records for antiviral expenditures; and (d) a semi-structured interview guide informed by the Theories of Planned Behavior and Normalization Process Theory to elucidate behavioral and implementation dynamics. Validity and reliability are ensured through pilot testing of instruments, triangulation across prescription data and chart reviews, and inter-rater reliability assessment (Cohen's kappa >0.8) for the audit tool. Analytical approaches include segmented ITS regression to detect level and slope changes in appropriateness and clinical outcomes post-AVS implementation; multivariate linear and logistic regression models adjusting for confounders (age, comorbidity index, severity of illness, and unit type) to estimate effect sizes; cost-effectiveness analysis to determine incremental cost per quality-adjusted life year (if feasible) and per infection averted; and thematic analysis of interview data using a constant comparative method to identify recurrent themes and barriers. A priori hypotheses anticipate significant improvements in prescribing appropriateness (level change of at least 20% and sustained trend), reductions in inappropriate antiviral duration, shorter time to optimized therapy, and favorable economic signals with potential cost savings exceeding implementation costs. Expected findings include higher rates of guideline-concordant antiviral use, reduced exposure to unnecessary antivirals, improved patient outcomes such as reduced hospital stay by 1–2 days on average, and a reduction in adverse events related to drug interactions. The study contributes to knowledge by providing a rigorous, replicable AVS model with a comprehensive implementation framework, performance metrics, and an evidence base for policy and practice guidelines in hospital pharmacotherapy. It will inform scaling strategies by identifying critical enablers and barriers, delineating roles for pharmacists, and offering a template for monitoring and evaluation. The conclusion emphasizes the potential of pharmacist-led AVS to optimize antiviral use, improve patient outcomes, and generate cost savings, with recommendations for sustaining governance structures, ongoing professional development, integration of decision-support tools, and future research to assess long-term impact and adaptability to emerging antiviral agents and resistance patterns.