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The last 5 years have seen considerable changes in the EU regulatory landscape, as Health Authorities work to innovate clinical trials and regulatory procedures. This is only set to continue through activities such as the Accelerating Clinical Trials (ACT EU) initiative and reform of the EU Pharmaceutical Legislation. In anticipation of these changes, 15 authors across EU Health Authorities and academia have published their vision for Clinical Evidence by 2030. This was followed by a Q&A webinar from the European Medicines Agency (EMA). Targeting clinical trial stakeholders, these updates give us an insight into future Health Authority expectations of EU clinical trials and planned regulatory support.

Six guiding principles are provided for generating excellent clinical evidence that will support regulatory decision-making:

Consult with patients to guide every step of evidence generation.
Use existing data and knowledge to inform trial planning.
Formulate clear research questions from evidence gaps.
Embrace the full spectrum of data and methods.
Plan early and collaboratively across stakeholders.
Maintain high levels of transparency.

In this article, we review how implementing these principles from clinical trial planning may support regulatory interactions and applications. To do this, we cover three key concepts: patient involvement, transparency and collaboration, and utilising Real World Data.

Figure 1. Representation of the vision for clinical evidence 2030. Figure source from Clinical Evidence 2030.

Patient Involvement

Health Authorities are increasingly advising researchers to consult with patients when planning clinical trials, as reflected in ICH E6(R3) Guidance for Good Clinical Practice:

“The design and conduct of the clinical trial may be supported by obtaining the perspectives of interested parties, such as patients and their communities, patient advocacy groups and healthcare professionals.”

The benefits of patient input are well known and wide-ranging. For example, the potential to increase recruitment rates and decrease discontinuations, leading to better quality data and outcomes for participants.

Principle 1 of ‘Clinical Evidence 2030’ additionally states the importance of engaging with patients across clinical development to address unmet patient needs. This approach has already been established within the EMA, where patient input is sought for regulatory decisions across clinical development. This includes Scientific Advice, Marketing Authorisation Applications (MAAs), and Safety Monitoring activities. Moving forward, the planned revision of EU Pharmaceutical Legislation further describes how patient representation will be increased in the assessment of MAAs. Additionally, the ACT EU group are also gaining patient input through the Multi-stakeholder Platform Advisory Group, to help improve the EU’s clinical trial environment.

With this shift towards increased patient centricity, ‘Clinical Evidence 2030’ mentions that supporting guidance is being developed. This will advise on how patient experience data can be generated, collected, and used to support regulatory decisions. Additionally, the UK Health Research Authority has created best practice resources, for researchers looking to gather patient input when planning clinical research.

Transparency and Collaboration

As a result of the Clinical Trials Regulation and ACT EU initiative, increased transparency has been a key change in the EU clinical trial landscape. Transparency is, therefore, reflected throughout ‘Clinical Evidence 2030’, being embedded into Principles 2, 3, 5, and 6 alongside collaboration.

These principles collectively acknowledge the importance of critically analysing available data resulting from the increased transparency requirements. This includes clinical data, regulatory assessments, and adverse event reports, which can help identify research gaps and avoid unintentional duplication. Subsequently, clear research questions can then be identified that guide the choice of trial design. In particular, researchers should consider whether a non-interventional trial using Real-World Data should be conducted instead of or alongside clinical trials. These points are underpinned by Principle 5, which supports early collaboration with multiple stakeholders. This can include regulators, Health Technology Assessment bodies, patients, and Health Care Professionals, ensuring all parties are aligned on the clinical strategy.

There is no doubt that following these principles will result in high quality clinical trials that increase the likelihood of successful regulatory applications. Unfortunately, the complexity and cost of collaborating with regulators as advised (e.g. through Scientific Advice, or Orphan Designation applications) can often lead to researchers not requesting this despite the advantages. Clinical Evidence 2030 calls for these processes to be further rationalised and simplified, indicating potential improvements in the future.

Additional information on navigating EU Scientific Advice is available in our previous article. Our previous whitepaper also details requirements for successful Orphan Designation applications in the EU.

Utilising Real-World Data

Principle 4 outlines the importance of considering the full spectrum of data and methods when planning a clinical trial. While acknowledging artificial intelligence as a key enabler, ‘Clinical Evidence 2030’ emphasises how using Real-World Data (RWD) can provide further evidence that supports regulatory decision-making.

RWD describes patient data collected from sources such as electronic health records, patient registries, or wearable devices, which is reflective of everyday settings. Both clinical trials and non-interventional trials can analyse RWD to then provide Real World Evidence (RWE) of product safety and efficacy in this environment. As clinical trials have become increasingly digitalised, there is more opportunity to use RWD to support regulatory applications. Additionally, access to RWD across EU countries, supported by the recent European Health Data Space Regulation, is expected to speed up clinical trial timelines. This was demonstrated in a recent report, that DARWIN EU studies have a median duration of 4 months from protocol approval to study results.

However, the current lack of harmonised EU regulatory standards and guidance makes it difficult to ensure RWD is of sufficient quality to support regulatory decisions. The EMA have made efforts to address this, such as reviewing existing guidance across the EU. This led to the publication of a reflection paper, which provided aligned guidance for using RWD in non-interventional studies. The review also identified the need for clear guidance to support RWD in clinical trials, with externally controlled clinical trials considered a priority. Additionally, the EMA have released a draft Real-World Data Chapter as part of the Data Quality Framework. This proposes recommendations to ensure data quality. Industry has also welcomed the ICH announcement outlining plans to develop RWE guidance, which will support international harmonisation on this topic.

Conclusion

The paper clearly highlights how EU Health Authorities are driving a more patient-centric and collaborative approach to clinical trials, with greater use of Real World Data. Applying the six principles to run more innovative clinical trials could help to generate data that supports regulatory decisions. Critically, this could bring treatments to patients faster, which address what really matters to them. However, Health Authorities have yet to release supporting measures, such as guidance to help researchers implement these principles. In the coming years, it will be important for researchers to consider these principles when planning clinical trials and monitor for relevant regulatory updates.

DLRC continuously reviews changes in the EU regulatory landscape to help clients deliver high-quality regulatory applications and successful interactions.

If you need expert regulatory support, contact DLRC’s team of award-winning professionals today by emailing hello@dlrcgroup.com.