A data-driven pipeline to extract potential adverse drug reactions through prescription, procedures and medical diagnoses analysis: application to a cohort study of 2,010 patients taking hydroxychloroquine with an 11-year follow-up

Pierre Sabatier (1, 2, 3) , Maxime Wack (1, 2, 3) , Jacques Pouchot (4) , Nicolas Danchin (3) , Anne-Sophie Jannot (1, 2, 3)

1 HeKA - Health data- and model- driven Knowledge Acquisition
2 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
3 HEGP - Hôpital Européen Georges Pompidou [APHP]
4 Service de Médecine Interne [CHU HEGP]

Context: Real-life data consist of exhaustive data which are not subject to selection bias. These data enable to study drug-safety profiles but are underused because of their temporality, necessitating complex models (i.e., safety depends on the dose, timing, and duration of treatment). We aimed to create a data-driven pipeline strategy that manages the complex temporality of real-life data to highlight the safety profile of a given drug. Methods: We proposed to apply the weighted cumulative exposure (WCE) statistical model to all health events occurring after a drug introduction (in this paper HCQ) and performed bootstrap to select relevant diagnoses, drugs and interventions which could reflect an adverse drug reactions (ADRs). We applied this data-driven pipeline on a French national medico-administrative database to extract the safety profile of hydroxychloroquine (HCQ) from a cohort of 2,010 patients. Results: The proposed method selected eight drugs (metopimazine, anethole trithione, tropicamide, alendronic acid & colecalciferol, hydrocortisone, chlormadinone, valsartan and tixocortol), twelve procedures (six ophthalmic procedures, two dental procedures, two skin lesions procedures and osteodensitometry procedure) and two medical diagnoses (systemic lupus erythematous, unspecified and discoid lupus erythematous) to be significantly associated with HCQ exposure. Conclusion: We provide a method extracting the broad spectrum of diagnoses, drugs and interventions associated to any given drug, potentially highlighting ADRs. Applied to hydroxychloroquine, this method extracted among others already known ADRs.

Mots clés: Hydroxychloroquine; Adverse drug reactions; Medico-administrative databases; Massive data

Domaines: Sciences du Vivant [q-bio]

Pierre Sabatier, Maxime Wack, Jacques Pouchot, Nicolas Danchin, Anne-Sophie Jannot. A data-driven pipeline to extract potential adverse drug reactions through prescription, procedures and medical diagnoses analysis: application to a cohort study of 2,010 patients taking hydroxychloroquine with an 11-year follow-up. BMC Medical Research Methodology, 2022, 22 (1), pp.166. ⟨10.1186/s12874-022-01628-3⟩. ⟨inserm-03694380⟩