Liver toxicity is a rare but relevant side effect of drugs. This validation study was part of a multi-center EMA Pharmacovigilance Study (Past Authorization Safety Study (PASS): Liver toxicity of agomelatine). The PASS is based on large pharmacoepidemiological databases, including GePARD from BIPS. The safety outcome, acute liver injury (ALI) is identified based on pre-specified combinations of ICD codes.

In our validation study we examined the positive predictive value of hospital discharge code combinations to describe ALI. Verification procedures included extraction of liver enzyme values and clinical information from patient Charts, performed in cooperation with the University Hospital (Klinikum Oldenburg) in Oldenburg.

The results will facilitate the use of routine data in the context of pharmacoepidemiological studies on drug safety, including estimation of bias from outcome misclassification.

• Timmer A, de Sordi D, Kappen S, Kohse KP, Schink T, Perez-Gutthann S, Jacquot E, Deltour N, Pladevall M. Validity of Hospital ICD-10-GM Codes to Identify Acute Liver Injury in Germany. Pharmacoepidemiology and Drug Safety (angenommen, Juni)
• Pladevall M, Pottegård A, Schink T, Reutfors J, Morros R, Poblador-Plou B, Timmer A, Forns J, Hellfritzsch M, Reinders T, Hägg D, Giner-Soriano M, Prados-Torres A, Cainzos-Achirica M, Hallas J, Brandt L, Cortés J, Aguado J, Perlemuter G, Falissard B, Castellsagué J, Jacquot E, Deltour N, Perez-Gutthann S. Risk of Acute Liver Injury in Agomelatine and Other Antidepressant Users in Four European Countries: A Cohort and Nested Case-Control Study Using Automated Health Data Sources. CNS Drugs 2019, 33(4), 383-395.

• Pladevall M, Pottegård A, Schink T, Reutfors J, Morros R, Poblador-Plou B, Timmer A, Forns J, Hellfitzsch M, Reinders TK, Hägg D, Giner-Soriano M, Prados-Torres A, Cainzos-Achirica M, Hallas J, Kollhorst B, Brandt L, Cortés J, Aguado J, Perlemuter G, Falissard B, Castellsagué J, Jacquot E, Deltour N, Perez-Gutthann S. Agomelatine and Other Antidepressants and the Risk of Acute Liver Injury, a Post-Authorisation Safety Study in 4 European Countries. 31st European College of Neuropsychopharmacology (ECNP 2018), Barcelona; October 6-9, 2018
• Timmer A, Kappen S, de Sordi D, Pladevall M, Perez-Gutthann S, Jacqout E, Deltour N, Schink T. Validity of Hospital ICD-10-GM Codes to Identify Acute Liver Injury. 34th International Conference on Pharmacoepidemiology and Therapeutic Risk Management (ICPE 2018), Prag; August 22-26, 2018