Periodic Reporting for period 4 - ConcePTION (Building an ecosystem for better monitoring and communicating of medication safety in pregnancy and breastfeeding: validated and regulatory endorsed workflows for fast, optimised evidence generation)
Periodo di rendicontazione: 2022-04-01 al 2023-03-31
More than 5 million women get pregnant in the EU every year and more than 90% take at least one medicine during pregnancy. Yet there is almost no evidence-based information available on most medicines to guide a woman’s fully informed decision. Even less information is available regarding medicine exposure through breast feeding. As few as 5% of available medicines have been adequately monitored, tested and labelled for use in pregnant and breastfeeding women. On average, it takes an estimated 27 years to determine the teratogen status of a novel medicine. The field, while inherently difficult to study, has suffered from a lack of systematically gathered insights that could lead to more effective data generation methodologies. Fragmentation and misinformation abounds, resulting in confusing and contradictory communication and perception of risks by both health professionals and women and their families. Obtaining reliable safety information for pregnant or breastfeeding women can take 20 or more years to collect after a medicine is on the market, if it arrives at all.
Building on (1) the rising awareness of the problem, and (2) the exponential growth and innovation in capture and use of health, surveillance and digital patient-generated data, ConcePTION will create a paradigm shift in how we generate and disseminate evidence on the effects of medicine in pregnancy. We aim to establish a trusted ecosystem that can efficiently, systematically, and in an ethically responsible manner, generate and disseminate reliable evidence-based information regarding effects of medicines used during pregnancy and breastfeeding to women and their healthcare providers. This will be achieved by generating, cataloguing, linking, collecting and analysing pharmacovigilance, modelling, routine healthcare, pregnant women and their children through a large network. Conception will validate non-clinical models that predict medicine transfer to breastmilk using a multipronged approach consisting of in vivo, in vitro and in silico models, and will establish the first Europe-wide research biobank to measure medicine levels in human breast milk.
Building on (1) the rising awareness of the problem, and (2) the exponential growth and innovation in capture and use of health, surveillance and digital patient-generated data, ConcePTION will create a paradigm shift in how we generate and disseminate evidence on the effects of medicine in pregnancy. We aim to establish a trusted ecosystem that can efficiently, systematically, and in an ethically responsible manner, generate and disseminate reliable evidence-based information regarding effects of medicines used during pregnancy and breastfeeding to women and their healthcare providers. This will be achieved by generating, cataloguing, linking, collecting and analysing pharmacovigilance, modelling, routine healthcare, pregnant women and their children through a large network. Conception will validate non-clinical models that predict medicine transfer to breastmilk using a multipronged approach consisting of in vivo, in vitro and in silico models, and will establish the first Europe-wide research biobank to measure medicine levels in human breast milk.
In its four years, the ConcePTION project has made significant advancements across various work packages (WPs) to accomplish its objectives. The primary focus of WP1 was to define evidence elements and create a comprehensive glossary of potentially harmful medicines. Progress was made in the completion of Statistical Analysis Plans, finalization of code books, selection of Data Acquisition Partners, and resolution of script-related issues. Year 4 witnessed substantial progress in defining evidence elements, developing algorithms, conducting drug utilization studies, and advancing demonstration projects within WP1.WP2 achieved progress in conducting demonstration studies and the development of the LifeTIME system for monitoring offspring health. The Core Data Elements (CDE) tables were uploaded to the ENTIS website, and two stakeholders (UK Epilepsy and Pregnancy Register and TIS Leuven - Teratology Information Services) utilized the CDE for building new pregnancy databases. Significant advancements were made in WP3 in the development of in vitro and in vivo models for studying drug effects. Furthermore, preparations were underway for an Innovation Task Force meeting with the European Medicines Agency (EMA). WP4 successfully approved all demonstration projects and implemented standard procedures for shipping breast milk samples. Analytical validity was demonstrated for four compounds and one metabolite, with ongoing development and validation of the bioanalytical method for the fifth compound, prednisolone. WP5 developed a prototype of the knowledge bank and engaged in communication campaigns. A new process, involving the compilation of existing evidence synthesis from local knowledge banks was considered. The communication campaign design, including toolkit content was presented to an external audience during a webinar in March 2023. WP6 provided support for Innovation Task Force (ITF) meetings with EMA. Collaboration with work packages 1, 2, 3, and 7 was ongoing to identify potential candidates for ITF discussions and develop ITF submission dossier packages. WP7 prepared a data catalogue based on FAIR principles and established the ConcePTION data quality framework. The ConcePTION Common Data Model (CDM) was adopted in various applications, including public funding studies in the Netherlands and Norway, as well as industry studies. The deployment of the ConcePTION CDM within EMA-tendered projects around measurement of the impact of additional risk minimization activities continued in year 4. The data quality pipeline has been transformed in an online certified education course for researchers for VAC4EU and ConcePTION members and currently is being included in the EMA requested Big Data Curriculum for regulators. WP8 focused on sustainability planning and engaged stakeholders. The sustainability core team categorized project outputs into two overarching groups: knowledge generation and knowledge dissemination. Sustainability activities will be a key focus during the final year of the project.
In ConcePTION we believe there is an important societal obligation to radically and rapidly reduce uncertainty about the effects of medicine use during pregnancy and breastfeeding. Even though studies are performed to test the safety, quality and efficacy of medicines before launch, ConcePTION is the first large European project that specifically focuses on pregnant and breastfeeding women. The project unites an unprecedented 88 organizations from 22 countries around a common goal, including the European Medicines Agency, pharmaceutical companies, academia, public health organizations, and teratology networks. Through better use of existing health data from routine clinical practice together with enhanced methods to collect patient-reported data, and with new research capabilities to predict and measure maternal medicine in breastmilk, the team aims to close the knowledge and information gap that will in turn lead to improved healthcare for this underserved segment of the population.
In year 1, Use of the ConcePTION ecosystem (network, tools, data, common data model) was already adopted in two applications for public funding in the Netherlands (the AAAA study on the safety of anti-hypertensive drugs) and in Norway (PREGNANT-COVID), and the use is actively promoted and enquired by several private organizations. In year 2, the ecosystem was utilised through WP7; EMA/2017/09/PE/04 retinoids project, CONSIGN, ACCESS, Early Covid Vaccine Monitoring project), MINERVA project for EMA, VAC4EU, and LifeCycle. The WP2 Core Data Elements (CDE) was used by UK Epilepsy and Pregnancy Register and by TIS Leuven (Teratology Information Services) and exchange of expertise was carried out through WP2 with the global initiative VAMPSS and Ubomi Buhle South African Pregnancy Exposure Registry. In year 3 and 4, the ConcePTION project has made remarkable progress in various work packages, including the definition of evidence elements, conducting demonstration studies, developing models for studying drug effects, and establishing a data quality framework. Key milestones include the publication of core data elements for pregnancy pharmacovigilance, successful approval of demonstration projects, and the development of a knowledge bank and communication campaigns.
In year 1, Use of the ConcePTION ecosystem (network, tools, data, common data model) was already adopted in two applications for public funding in the Netherlands (the AAAA study on the safety of anti-hypertensive drugs) and in Norway (PREGNANT-COVID), and the use is actively promoted and enquired by several private organizations. In year 2, the ecosystem was utilised through WP7; EMA/2017/09/PE/04 retinoids project, CONSIGN, ACCESS, Early Covid Vaccine Monitoring project), MINERVA project for EMA, VAC4EU, and LifeCycle. The WP2 Core Data Elements (CDE) was used by UK Epilepsy and Pregnancy Register and by TIS Leuven (Teratology Information Services) and exchange of expertise was carried out through WP2 with the global initiative VAMPSS and Ubomi Buhle South African Pregnancy Exposure Registry. In year 3 and 4, the ConcePTION project has made remarkable progress in various work packages, including the definition of evidence elements, conducting demonstration studies, developing models for studying drug effects, and establishing a data quality framework. Key milestones include the publication of core data elements for pregnancy pharmacovigilance, successful approval of demonstration projects, and the development of a knowledge bank and communication campaigns.