Digital monitoring of medication safety in children: an investigation of ADR signalling techniques in Malaysia.

Background: Digital solutions can help monitor medication safety in children who are often excluded in clinical trials. The lack of reliable safety data often leads to either under- or over-dose of medications during clinical management which make them either not responding well to treatment or susceptible to adverse drug reactions (ADRs).

Aim: This study investigated ADR signalling techniques to detect serious ADRs in Malaysian children aged from birth to 12 years old using an electronic ADRs' database.

Methods: Four techniques (Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS)) were tested on ADR reports submitted to the National Pharmaceutical Regulatory Agency between 2016 and 2020. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the techniques were compared.

Results: A total of 31 medicine-Important Medical Event pairs were found and examined among the 3152 paediatric ADR reports. Three techniques (PRR, ROR, MGPS) signalled oculogyric crisis and dystonia for metoclopramide. BCPNN and MGPS signalled angioedema for paracetamol, amoxicillin and ibuprofen. Similar performances were found for PRR, ROR and BCPNN (sensitivity of 12%, specificity of 100%, PPV of 100% and NPV of 21%). MGPS revealed the highest sensitivity (20%) and NPV (23%), as well as similar specificity and PPV (100%).

Conclusions: This study suggests that medication safety signalling techniques could be applied on electronic health records to monitor medication safety issues in children. Clinicians and medication safety specialist could prioritise the signals for further clinical consideration and prompt response.