Commentary: Regulatory challenges of exposomic research in the EHDS era

Advancing the use of health data in a secure and collaborative manner is critical for driving innovation in exposome research. The European Health Data Space (EHDS) is an EU initiative designed to facilitate the secure sharing and utilization of health data for healthcare, research, and policymaking across member states. It will play a pivotal role in reshaping data access and analysis across borders, and is expected to streamline cross-border studies through data catalogs and one-stop-shop health data access points, unlocking new research opportunities

By Juha Pajula (HEDIMED researcher and supporting member of TEHDAS2)

The EHDS will introduce significant changes in the secondary use of health data

Once operational, EHDS will introduce significant changes in the secondary use of health data. Firstly, it will shift data analytics from local research infrastructures and personal machines to secure processing environments (SPEs) certified by EHDS actors. Secondly, it aims to enable cross-border data analytics throughout Europe under a one-stop-shop principle. For exposome research, this presents both opportunities and challenges.

Regulatory challenges in exposome research

Exposome research faces complex regulatory challenges when integrating data from diverse sources, including common health measurements, genome-based risk assessments, and various exposomic data types ranging from soil samples to satellite-imaging-based environmental indicators. Many exposomic investigations rely on birth or patient cohorts followed for decades, with data collected specifically for research purposes. In such cases, key regulatory considerations include GDPR compliance and obtaining patient consent for data collection and usage.

A challenge with EHDS arises when exposomic cohorts are enriched with health data from healthcare systems. This includes using registers and electronic health records to gather information about subjects’ interactions with their local healthcare systems, such as service usage or common diagnoses.

When patient data is collected during routine doctor visits, it is primarily for treating symptoms (i.e., “primary use”). Any other use is considered “secondary use” under EHDS regulations. This real-world data is valuable for exposomic studies, particularly in mapping environmental and genetic factors to specific diseases or symptoms. However, EHDS mandates that all processing of such real-world data must occur within closed, secure processing environments (SPEs), preventing studies from being conducted in the traditional manner. In practice, this means that all subject-level analyses of exposomic factors must be performed within these closed environments. While some exposome studies can rely on aggregated data, such as regional pollution level averages, subject-level analysis is typically necessary to achieve groundbreaking results.

GDPR stays as the guardian of data protection, while EHDS advances cross-border data exchange – working together to safeguard public health through improved data sharing.

Hedimed researcher Juha Pajula introducing exposome related insights into the EHDS at the EHEN Stakeholder Event in Brussels, in November 2024.

Opportunities for cross-border research

One of the most significant opportunities presented by EHDS is the ability to make cross-border data requests through a central service. Researchers will be able to request access to real-world datasets with a single application to the relevant Health Data Access Body (HDAB). This will significantly reduce bureaucratic hurdles, which currently complicate European-wide exposome studies. At present, extending research across multiple countries requires navigating a complex set of agreements regarding data use, transfer, and storage under various national legislations. EHDS aims to overcome these barriers by aligning national laws on the secondary use of health data, enforcing strict rules for secure data storage and processing.

Illustration of TEHDAS’ proposal on HealthData@EU architecture for secondary use of health data (From: https://www.sitra.fi/en/publications/advancing-data-sharing-to-improve-health-for-all-in-europe/#ensuring-secure-data-processing-is-crucial)

Handling Complex Data in EHDS

One key consideration with EHDS relates to complex data that is not initially classified as health data but may become so when combined with exposomic health data. A prime example is satellite-imaging-based environmental indicators, where the actual satellite data cannot be delivered to an SPE due to its immense size and the computational power required for processing. Currently, due to GDPR requirements, these indicators are typically generated in multiple phases. First, satellite image-based indicators are derived from dedicated maps created within secure environments without direct access to raw satellite imaging data. These indicator maps are then transferred to cohort owner premises (or directly to the SPE), where subject-level indicators are generated using geographical coordinates of participants’ homes, workplaces, or other relevant locations. Once processed, these indicators can be integrated with exposomic health data for further analysis.

Limitations and Future of SPEs

The first SPE solutions are mostly built as isolated virtual machines without external access, managed or certified by local HDABs. Common issues include limited computing power, lack of AI analytics capabilities, and restricted access, leading to a suboptimal user experience. Additionally, specialized research tools often face slow approval processes for integration into SPEs. However, it is expected that these environments will evolve over time, offering improved functionalities and greater flexibility as more use cases are tested.

HEDIMED’s Approach to Data Analytics and Dissemination

The HEDIMED project employs a dual approach to data analytics and results dissemination. First, it has developed a proof of concept (PoC) setup for a researcher- friendly centralized environment, that maintains high security. While the HEDIMED Research Platform would not – as of writing – fulfill the proposed EHDS regulation requirements, it has the potential to be adapted to meet the requirements. Its key advantage lies in offering researchers an opportunity to familiarize themselves with analytics in a centralized computing environment similar to those mandated under EHDS regulations.

Second, HEDIMED has explored innovative methods to ensure the rapid dissemination of research results and enhance public understanding of complex scientific data through interactive, visually engaging graphics. The HEDIMED Public Platform allows stakeholders—including researchers, policymakers, and the general public—to access visualized research outcomes efficiently. This initiative transforms intricate exposomic and immune-mediated disease data into accessible formats, facilitating informed decision-making and broader public awareness. Additionally, HEDIMED has investigated methodologies for automated transfers of results between analytics and dissemination environments.

Implementation Timeline for EHDS

The EHDS Act (https://www.europarl.europa.eu/doceo/document/TA-9-2024-0331-FNL-COR01_EN.pdf ) is set to enter into force at February 2025. This means that implementing acts should be ready in February 2027 and whole Regulation applicable in all member countries by 2029. To support this action, various parallel supporting activities and funding have been announced. One significant action is the TEHDAS2 Joint Action project (https://tehdas.eu/) which aims to help all member countries to align with EHDS in a coherent manner and to avoid variation in interpretations of the Act within the national legislations.

The International Human Exposome Network (IHEN)

The exposome research community is also establishing the International Human Exposome Network (IHEN) (https://humanexposome.net/). IHEN aims to expand knowledge about exposomic factors affecting human health, deepening our understanding of the connections between health and the environment in which we live.