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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 2 - 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: 2020-04-01 to 2021-03-31

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.
The first year ConcePTION focused on an assessment of available systems, data, and methods and constructing the foundations of all of the dimensions (societal and ethical, technical, data, evidence generation, communication & evidence dissemination and sustainability) of the new ConcePTION ecosystem. During the second year much work was conducted on different tasks contributing to the workflow and building of the ConcePTION ecosystem. The work done can be represented broadly along these themes:

- Ethical and societal: Foundational work was conducted on the governance, privacy aspects and ethics of using such data within the ConcePTION ecosystem.

- Technical: a task management system, catalogue and platform were identified, assessed and put in service to support the work in the ecosystem. A common data model was defined for routine health care and surveillance data. All work packages described their data collections, the modality of analysing and archiving data, and a distributed data network approach was set-up.

- Data: different data sources that would be able to provide evidence on effects of drugs in pregnancy and lactation were identified ranging from animals, pharmacovigilance data, data on reported pregnancies, data on congenital anomaly surveillance, registries, plus routine electronic health care data. For the latter, several data access providers covering data on more than 2 million pregnancies per year are actively engaged in implementing ConcePTION tools.

- Evidence generation: In year 1, protocols were written to collect and use data from the different data sources and to assess its quality. In year 2, WP1 completed a report on the core evidence elements and analytical standards for informing Healthcare providers (HCPs) and patients on risks associated with exposure during pregnancy and lactation; and WP6 has developed a report explaining the regulatory procedures regarding the use of medicines in pregnancy and lactation. In addition, a report with toolbox of methodologies and approaches for WPs to engage stakeholders regarding new evidence on the use of medicines in pregnancy and lactation was developed.

- Evidence dissemination: In year 1, a baseline assessment and online survey was conducted on the way information is currently provided to pregnant women. In year 2, a dedicated communication plan was developed.

- Advancing clinical and healthcare practice: WP5 has laid the groundwork in Task 5.1 and 5.2 to be able to create the open access digital knowledge bank. WP3 has further worked on developing an advanced technology on how compound milk transfer can be better characterised in animals in order to conduct human lactation studies and WP4 has laid the groundwork for centralised an EU centralised breast milk biobank by reviewing literature and Standard Operating Procedures (SOPs).

- Sustainability: In year 1, models for sustainability of the ecosystem were developed and several interactions with potential users of the ecosystem were undertaken. In year 2, the sustainability mandate was adopted. Preliminary steps towards drafting a sustainability plan were undertaken along two lines: (1) sustainability of the ecosystem and its impact on evidence generation for drug safety in pregnancy and lactation and (2) specific outcomes of the different WPs; the community (WP6), the tools and infrastructure (biobank (WP4), the drug information databank (WP5), the data source catalogue (WP7) and the evidence generation workflows and templates.
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