Skip to main content

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

Periodic Reporting for period 3 - 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)

Reporting period: 2021-04-01 to 2022-03-31

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.
In its first three years, ConcePTION has made progress in all its major objectives of the project. In WP1, the 5 demonstration project (DP) protocols have been finalised and successfully prepared, along with statistical analysis plans (SAPs) for outcome algorithm design, drug utilisation studies and drug safety studies. In WP2, the Core Data Elements (CDE) for pregnancy pharmacovigilance were defined, which have already been used by UK Epilepsy and Pregnancy Register and by TIS Leuven (Teratology Information Services). They have also prepared and uploaded the protocols for demonstration projects and the framework for the ConcePTION data collection app. In WP3, a Physiology-Based PharmacoKinetic (PBPK) model for healthy reference individual and model template for lactating women has been developed for multiple compounds. They have also made progress in the use of the Göttingen minipig as a reliable animal lactation model along with the completion of the first in vivo study with Amoxicillin in domestic pig/minipig. Additionally, progress was made in the preparation for an Innovation Task Force meeting with EMA.

In WP4, all demonstration projects have been approved. The standard procedures for shipping of breast milk samples have been developed and implemented and the analytical validity for 4 compounds and 1 metabolite have been demonstrated. WP5 has developed a prototype of the knowledge bank and its front page was released during Y3 of the project. While WP6 has been providing constant support to the consortium to prepare for the Innovation Task Force (ITF) meetings with EMA, in WP7, the data catalogue based on FAIR principles was prepared and the data quality framework established and deployed. The ConcePTION Common Data Model (CDM) (along with the ConcePTION network, tools, and data) has been 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). It was also utilised for several industry studies: EMA/2017/09/PE/04 retinoids project, CONSIGN, ACCESS, Early Covid Vaccine Monitoring project), MINERVA project for EMA, VAC4EU, and LifeCycle. The sustainability task force of ConcePTION (WP8) has taken steps towards drafting the sustainability plan. Specific deliverables crucial to the functioning of the learning healthcare system have been identified for each WP. In addition, the continuity and sustainability needs were defined for each WP and its deliverables.

Finally, the consortium prepared a presentation for IMI’s independent experts during the mid-term review on October 2021. The overall assessment of the experts was positive and concluded that the project has achieved most of its objectives and milestones for the period with relatively minor deviations. The experts also agreed on that the project has progressed satisfactorily. The ConcePTION project will likely provide results with significant immediate or potential impact in the next reporting period(s).
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.
ConcePTION ecosystem workflow
ConcePTION ecosystem infographic
ConcePTION project logo