Using real-world data for post-market surveillance of drug safety

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After a therapeutic drug hits the market, it is crucial to continuously gather, analyze, and report data regarding its safety and potential side effects, a practice known as pharmacovigilance. Unlike clinical trials, this involves real-world data (RWD), presenting unique challenges in terms of both quality and quantity. The Belgian BELpREG project seeks to employ RWD for monitoring drug utilization during pregnancy and investigating potential safety implications for both maternal and child health. This initiative holds great promise, although it faces substantial hurdles on its path to success.

Why it is important to report adverse events?

Clinical trials are designed to assess the efficacy and safety of drugs in highly controlled settings. Before a drug is approved, it undergoes testing in thousands of patients to assess the benefit-risk balance of the product. While we commonly accept hair loss as an adverse effect of chemotherapy, we are less willing to tolerate it in a simple painkiller like paracetamol. That’s why it is crucial to continue monitoring the benefit-risk balance after a product is approved. Just as every patient is unique, so too are their reactions when taking medication. As a consequence, rare side effects may go undetected during clinical trials, only surfacing once the drug is available on the market. Some populations, for obvious reasons, are not typically included in clinical trials; pregnant women serve as a prime example. In these cases, the collection of RWD becomes even more crucial to understand whether a drug is safe to use.

“We encourage healthcare professionals and patients to report side effects.” – Peter Willems

Peter Willems, Vice President, Head International Pharmacovigilance at Johnson & Johnson and Chairman of the Board of Directors of Janssen-Cilag International NV, emphasizes the need for RWD collection in these specific populations. “Gathering post-market safety data benefits all parties involved. Clinicians can optimize patient care, the pharmaceutical industry gains additional valuable product insights to further develop new generations of products, and the government can safeguard the health of its citizens.”

BELpREG – an effort to right the wrongs

“With the BELpREG pregnancy registry, our main aim is to collect comprehensive qualitative data on medication utilization in pregnancy and mother-infant health outcomes.” –  Michael Ceulemans

From an epidemiological point of view, it is vital to collect rigorous data for many variables to accurately link drug use to adverse outcomes. At this moment, there is a scarcity of information on both the use of drugs by pregnant women as well as the safety risks for women and (unborn) infants. Michael Ceulemans is a senior postdoctoral researcher at KU Leuven, a research fellow reproductive epidemiology at Radboud University and coordinator of the recently established BELpREG pregnancy registry in Belgium. “With the BELpREG pregnancy registry, our main aim is to collect comprehensive qualitative data on medication utilization in pregnancy and mother-infant health outcomes. In later stages, we will use these data to conduct pharmacoepidemiologic safety studies.”

To ensure this national project generates enough data for meaningful conclusions, it is designed to complement existing registries from other countries or authorities. “We have constructed the system in a manner that allows for seamless data pooling with other international medication databases or registries,” says Laure Sillis, a PhD candidate and FWO fellow in strategic basic research working on the BELpREG project. “When developing the BELpREG system, we based ourselves on the international available core data elements for drug safety studies in pregnancy.” Collaboration and the involvement of a variety of disciplines are essential for such projects. Another great example in this respect is the European, IMI-funded effort, ConcePTION, where 88 private and public organizations from 22 countries collaborate to create an eco-system for research on medication use during pregnancy and lactation, with the overall aim to improve our knowledge about medication use and to empower informed decision-making for women.

“Collaboration between industry, government and academia is so important, yet remains challenging,” says Sillis. “Investing in pregnancy-related drug safety does not yet seem to be the primary focus for all stakeholders.” In their research, Sillis and her colleagues identified obstacles faced by marketing authorization holders, explaining the delay in providing essential pregnancy safety information. Unfortunately, without the willingness of partners to provide support, projects like BELpREG cannot reach their full potential and make a long-lasting difference. “In order to create impact, a sustainable pregnancy registry is needed,” says Ceulemans. The fact that the future of BELpREG has not been secured yet is a point of concern and puts Belgium behind in this area, as some neigh countries have already made significant progress in this regard.

Investing in collaboration and sustainability

“Data sharing within and between different countries and databases, but also between the industry, academic partners, and healthcare providers needs to be simplified.” – Michael Ceulemans

To obtain insights we can build upon, we need more data. “At the moment, we still witness severe underreporting of adverse drug effects by healthcare professionals and patients,” says Willems. “Understaffing and high workload in the healthcare system as well as the administrative burden of reporting adverse events are undoubtedly at play here. However, we do encourage everyone to report those adverse events as it is crucial information to develop future medicines”. To access more RWD, it is vital to enable data sharing between countries. This is particularly challenging, especially with countries like the US, China, and Russia due to varying legal frameworks. Even within the European Union, where each country has its own variation of the GDPR legislation, smooth data exchange is complex. “Procedures for data pooling or sharing need to be transparent, clear, and as simple as possible,” confirms Ceulemans. “This encompasses data exchange or linkage within and between different countries and databases, but also between the industry, academic partners, and healthcare providers.” The European Innovative Medicines Initiative (IMI) provides funding for such partnerships. All the interviewees affirm that these IMI projects undeniably enhance the development of innovative data-based research and medicine and are a valuable way of bringing stakeholders together. Quality and compatibility of the data sources are other key aspects of data alignment, yet remain challenging. Data standardization can provide a solution.

Read our article on FHIR and OMOP CDM data standards to find out more!

Besides data reporting by patient and healthcare professionals, alternative data sources also need to be explored. “We can indeed utilize data from wearables and apps,” says Willems, “but currently, the challenge lies in exploring how to extract relevant insights from the immense volume of data this will generate.”

In addition to collaboration and data linkage, there is a high need for investment in sustainable systems that can truly make a difference in patient care, especially for complex patient groups such as pregnant women. Investment in talent remains essential. “To extract valuable insights from our study data, we need people who can handle the algorithms while also understanding the medical value and relevance,” says Ceulemans. Investment needs to extend beyond talent nurturing. Projects like BELpREG serve as valuable proof-of-concept studies, assessing feasibility of data collection, analysis, and interoperability. However, to ensure their continuity and impact on healthcare, they require substantial support. “Although our current funding from KU Leuven and FWO takes care of initial program development, we can only generate valuable insights if more sustainable funds are provided,” states Ceulemans. To encourage stakeholders to invest in these projects, they must genuinely believe in the cause. We need to make it one of our main responsibilities to persuade stakeholders that post-market drug surveillance is a priority, generating economic, and more importantly, human value to our healthcare processes.