Studying Paternal Drug Exposures and Offspring Outcomes: A Feasibility Assessment of 11 Large European Databases
Author(s)
Sandrine Colas1, Hillary Bonnet, PhD2, Laurie Fraticelli, PhD3, Emmanuelle Bignon, PhD2, Jérémy Jové, PhD2, Vera Ehrenstein, PhD4, Maria Giner-Soriano, PharmD, PhD5, Jonas Reinold, PhD6, Wiebke Schäfer, PhD6, anna-maija tolppanen, PhD7, carolyn cesta, PhD8, Jacqueline Cohen, PhD9, Romin pajouheshnia, PhD10, Josine Kuiper, PhD11, Eline Houben, PhD12, Marie-Laure Kürzinger, PhD3, Juliette Longin, PhD3, Laure carcaillon-bentata, PhD2.
1Pharmacoepidemiologist, Sanofi, Paris, France, 2Bordeaux PharmacoEpi, Bordeaux, France, 3Sanofi, Gentilly, France, 4Department of Clinical Epidemiology, Center for Population Medicine, Aarhus University & Aarhus U, Aarhus, Denmark, 5IDIAPJGol, Barcelona, Spain, 6Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany, 7School of Pharmacy, University of Eastern Finland, Kuopio, Finland, 8Karolinska Institutet, Stockholm, Sweden, 9Department of Chronic Diseases,, Norwegian Institute of Public Health, Oslo, Norway, 10RTI, Barcelona, Spain, 11PHARMO Institute, Utrecht, Netherlands, 12PHARMO Institute, utrecht, Netherlands.
1Pharmacoepidemiologist, Sanofi, Paris, France, 2Bordeaux PharmacoEpi, Bordeaux, France, 3Sanofi, Gentilly, France, 4Department of Clinical Epidemiology, Center for Population Medicine, Aarhus University & Aarhus U, Aarhus, Denmark, 5IDIAPJGol, Barcelona, Spain, 6Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany, 7School of Pharmacy, University of Eastern Finland, Kuopio, Finland, 8Karolinska Institutet, Stockholm, Sweden, 9Department of Chronic Diseases,, Norwegian Institute of Public Health, Oslo, Norway, 10RTI, Barcelona, Spain, 11PHARMO Institute, Utrecht, Netherlands, 12PHARMO Institute, utrecht, Netherlands.
OBJECTIVES: Recent studies highlight the importance of investigating the impact of paternal drug exposure on offspring. A new regulator-requested PASS, TANGO, aims to investigate the association of paternal valproate use with neurodevelopmental disorders and major congenital malformations in offspring; large databases are needed to foster statistical precision and generalizability. We assessed fitness-for-purpose of the SIGMA Consortium's large databases for investigating the impact of paternal drug exposure on offspring health.
METHODS: Eleven European databases in Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Scotland, Spain, Sweden, and the UK were evaluated for father-mother-offspring linkage availability and consistent data capture on the key variables. Feasibility was assessed based on questionnaires completed by experts with research experience using the data sources; linkage rates for CPRD were derived from literature.
RESULTS: Father-mother-offspring linkage is currently available in PHARMO, GePaRD, potentially CPRD (databases covering 25%, 20%, 25% of the Dutch, German, UK populations respectively) and in Nordic registries (100% of the Swedish, Danish, Norwegian, Finnish populations). Linkage is exact in GePaRD and Nordic registries, while CPRD and PHARMO linkage use an algorithm. Father-offspring linkage for live-birth outcomes reaches >90% in Nordic registries, 20% in PHARMO, 66% and 25% of linked mother-offspring pairs in CPRD and GePaRD. Offspring outcomes are available in all databases. Non-live-birth outcomes are available in Danish and Norwegian registries (90%), GeParD, PHARMO and CPRD (unknown rate), but not in the other databases. All databases can identify drug exposure from community pharmacy dispensing, regardless of prescriber specialty, except CPRD (only GPs).
CONCLUSIONS: From this feasibility assessment, GePaRD, Nordic registries, PHARMO and potentially CPRD have father-mother-offspring linkage. Due to a preferred exact father-offspring linkage and anticipated statistical precision, Nordic registries and GePaRD were selected for TANGO. The same conclusions may apply for other studies aimed at assessing the effects of paternal drug exposure on child health outcomes.
METHODS: Eleven European databases in Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Scotland, Spain, Sweden, and the UK were evaluated for father-mother-offspring linkage availability and consistent data capture on the key variables. Feasibility was assessed based on questionnaires completed by experts with research experience using the data sources; linkage rates for CPRD were derived from literature.
RESULTS: Father-mother-offspring linkage is currently available in PHARMO, GePaRD, potentially CPRD (databases covering 25%, 20%, 25% of the Dutch, German, UK populations respectively) and in Nordic registries (100% of the Swedish, Danish, Norwegian, Finnish populations). Linkage is exact in GePaRD and Nordic registries, while CPRD and PHARMO linkage use an algorithm. Father-offspring linkage for live-birth outcomes reaches >90% in Nordic registries, 20% in PHARMO, 66% and 25% of linked mother-offspring pairs in CPRD and GePaRD. Offspring outcomes are available in all databases. Non-live-birth outcomes are available in Danish and Norwegian registries (90%), GeParD, PHARMO and CPRD (unknown rate), but not in the other databases. All databases can identify drug exposure from community pharmacy dispensing, regardless of prescriber specialty, except CPRD (only GPs).
CONCLUSIONS: From this feasibility assessment, GePaRD, Nordic registries, PHARMO and potentially CPRD have father-mother-offspring linkage. Due to a preferred exact father-offspring linkage and anticipated statistical precision, Nordic registries and GePaRD were selected for TANGO. The same conclusions may apply for other studies aimed at assessing the effects of paternal drug exposure on child health outcomes.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
EPH220
Topic
Epidemiology & Public Health, Real World Data & Information Systems, Study Approaches
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
Mental Health (including addition), Neurological Disorders