Exclusion of Children with Malnutrition, HIV and Sickle Cell Disease from Paediatric Trials in Sub-Saharan Africa: An Analysis of Trials Registered Between 2010 and 2023

The rapid growth of clinical trials in sub-Saharan Africa (sSA) since 2010 has increased opportunities to evaluate interventions for children. However, children with common comorbidities—malnutrition, HIV infection, and sickle cell disease (SCD)—may be systematically excluded, limiting the applicability of trial findings. We quantified the extent of such exclusions and identified trial characteristics associated with exclusion. We analysed phase 2–4 interventional trials registered between 2010 and 2023 in ClinicalTrials.gov, the International Standard Randomized Controlled Trials Number, and the Pan-African Clinical Trials Registry. Eligibility criteria were reviewed and trials classified as including, excluding, probably including, or probably excluding each condition. Exclusion proportions were calculated among trials not primarily targeting these populations. Associations between exclusion and trial characteristics (phase, period, disease area, design, and intervention type) were examined. Among 1,276 trials, primary exclusion rates were 37.0% (95% CI: 34.3–39.7) for malnutrition, 41.2% (38.4–44.1) for HIV, and 35.1% (32.5–37.9) for SCD. Exclusion varied by trial phase, intervention type, and disease area. Children with these high-risk conditions remain substantially underrepresented in paediatric trials in sSA, undermining generalisability and equity. More inclusive trial designs are needed.