A Pilot, Predictive Surveillance Model in Pharmacovigilance Using Machine Learning Approaches.

INTRODUCTION: The identification of a new adverse event (AE) caused by a drug product is one of the key activities in the pharmaceutical industry to ensure the safety profile of a drug product. Machine learning (ML) has the potential to assist with signal detection and supplement traditional pharmacovigilance (PV) surveillance methods. This pilot ML modeling study was designed to detect potential safety signals for two AbbVie products and test the model's capability of detecting safety signals earlier than humans. METHODS: Drug X, a mature product with post-marketing data, and Drug Y, a recently approved drug in another therapeutic area, were selected. Gradient boosting-based ML approaches (e.g., XGBoost) were applied as the main modeling strategy. RESULTS: For Drug X, eight true signals were present in the test set. Among 12 potential new signals generated, four were true signals with a 50.0% sensitivity rate and a 33.3% positive predictive value (PPV) rate. Among the remaining eight potential new signals, one was confirmed as a signal and detected six months earlier than humans. For Drug Y, nine true signals were present in the test set. Among 13 potential new signals generated, five were true signals with a 55.6% sensitivity rate and a 38.5% PPV rate. Among the remaining eight potential new signals, none were confirmed as true signals upon human review. CONCLUSION: This model demonstrated acceptable accuracy for safety signal detection and potential for earlier detection when compared to humans. Expert judgment, flexibility, and critical thinking are essential human skills required for the final, accurate assessment of adverse event cases.

Zonisamide and associated oligohidrosis and hyperthermia.

Zonisamide is an antiepileptic agent that is indicated as adjunctive therapy for the treatment of partial seizures in adults. Oligohidrosis has been reported in a small number of patients receiving zonisamide and, in a proportion of these patients, hyperthermia has occurred. Most reports of hyperthermia have been in children, typically occurring during the summer months. However, the mechanism of zonisamide-associated oligohidrosis is not fully understood. Thirteen events of oligohidrosis, or hyperthermia, associated with zonisamide were reported in the US during the 3 years after zonisamide was approved, an estimated incidence of 1 case per 4590 patient-years. These events happened mostly in children. In Japan, all reported cases of zonisamide-associated oligohidrosis or hyperthermia have been in children, with an incidence of 1 case per 10,000 pediatric-years during the first 11 years of marketing. In each case, oligohidrosis was reversible upon discontinuation of zonisamide. Ensuring that children remain cool and well hydrated during hot weather can minimize the potential for hyperthermia resulting from oligohidrosis.