Effectiveness of a digital clinical decision support algorithm for guiding antibiotic prescribing in pediatric outpatient care in Rwanda: A pragmatic cluster non-randomized controlled trial

Background Poor adherence to clinical guidelines and diagnostic uncertainty are key contributors to antibiotic overprescription, accelerating antimicrobial resistance. We developed ePOCT+, a digital clinical decision support algorithm (previously published) that integrated oxygen saturation, hemoglobin measurements, and C-reactive protein testing to assist primary care clinicians in managing acutely ill children aged 14 years or below. The goal was to reduce antibiotic prescriptions without compromising clinical recovery. Methods and findings We conducted a pragmatic, open-label cluster non-randomized controlled trial in 32 Rwandan health centers allocated to two groups by geography, balancing patient volume and infrastructure. Sixteen sites used ePOCT+ throughout; the other 16 provided standard care for five months before crossing over. This design supported three comparisons: intervention–control (months 1–5), before–after (control sites pre- versus post-crossover), and longitudinal assessment (intervention sites over 10 months). ePOCT+ was deployed in a digital application; the same application (without the algorithm) served as an electronic case report form in the control arm. Outcomes were analyzed using mixed-effects logistic regression, adjusted for age, sex, district, and presenting complaints. Superiority in antibiotic prescription (primary outcome) was defined as ≥25% reduction versus routine care. Non-inferiority for clinical failure (main secondary outcome) was defined as adjusted risk ratio upper 95% CI <1.3. Several other secondary outcomes were analyzed and reported. Between December 2021 and April 2023, 59,921 consultations were enrolled and 47,822 new consultations were analyzed. ePOCT+ uptake averaged 70% across all intervention periods. In the primary per-protocol analysis, antibiotic prescriptions declined from 70.5% to 24.5% in the intervention–control comparison (absolute difference −46.0, 95% CI −52.5, −39.5) and to 27.5% in the before–after comparison (absolute difference −43.0, 95% CI −49.7, −36.4). Reductions in the intention-to-treat sensitivity analysis were −36.7 (95% CI −42.1, −31.3) in the intervention–control comparison and −26.7 (95% CI −32.2, −21.4) in the before–after comparison, respectively. Prescription rates remained low (25%–40%) throughout the longitudinal assessment. Clinical failure rates were non-inferior (per-protocol aRR 1.07, 95% CI 0.97, 1.18 and 1.00, 95% CI 0.92, 1.10 in intervention–control and before–after analyses, respectively). In the intervention–control comparison, referral rates (aRR 2.11, 95% CI 1.20, 3.70), primary hospitalizations (aRR 2.02, 95% CI 1.21, 3.38), secondary hospitalizations (aRR 1.93, 95% CI 1.17, 3.16), and severe outcomes (comprised primarily of non-referred secondary hospitalizations; aRR 1.88, 95% CI 1.11, 3.15) were higher in the intervention arm; no differences were observed in the before–after comparison, suggesting possible baseline differences in patient severity rather than intervention effects. Re-attendance rates did not differ between arms. Malaria testing among febrile cases improved (aRR 1.27, 95% CI 1.08, 1.41), while treatment adherence remained high. Study limitations included non-randomized design and self-reported outcomes. Conclusions ePOCT+ substantially reduced antibiotic prescribing in Rwandan pediatric primary care without compromising clinical recovery. Integration into Rwanda’s national electronic medical record platform is critical to ensure unified clinical and reporting functions. This could streamline service delivery, improve data quality, and promote evidence-based care at scale. Trial registration Clinicaltrials.gov NCT 05108831