Using RWD in Non-Interventional Studies

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On 3 May 2024, the European Medicines Agency (EMA) initiated a public consultation to review draft recommendations published in its reflection paper on “the use of real-world data (RWD) in non-interventional studies (NIS) to generate real-world evidence (RWE)” (1). The paper discusses methodological aspects of NIS using RWD, such as claims databases, hospital data, electronic health records (EHR), registries, and medical health data, to generate RWE for regulatory decision-making. The paper is part of the Methodology Working Party Workplan 2022–2024 and the joint Heads of Medicines Agency (HMA)-EMA Big Data Steering Group plan 2023–2025 (2,3).

Non-interventional studies

According to EMA, a clinical trial is defined as a clinical study where:

• the assignment of the subject to a particular therapeutic strategy is decided in advance and does not fall within the normal clinical practice of the member state concerned
• the decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical study
• diagnostic or monitoring procedures in addition to normal clinical practice are applied to the subjects. RWD are data that describe patient characteristics (including treatment utilization and outcomes) in routine clinical practice (1).

A NIS is a clinical study that does not fulfil any of the above conditions, based on Article 48 of Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use (4).

Key topics discussed in the reflection paper

The reflection paper discusses feasibility assessment, bias, confounding, and data quality and provides guidance on four key areas:

• study design
• governance and transparency
• data quality
• statistical analyses.

The paper also recognizes the importance of using protocol formats when designing NIS for RWD generation. For example, applying the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) Checklist for Study Protocols and The HARmonized Protocol Template to Enhance Reproducibility (HARPER) protocol template (5,6).

In March 2024, the US Food and Drug Administration (FDA) published its draft guidance on Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological Products, which is open for consultation until 18 June 2024 (7). EMA’s guidance closely aligns with FDA’s; however, the regulatory agencies’ definition of NIS differs and further clarification and standardization will help drive the utilization of RWD moving forward (8).

EMA promotes the use of RWD in decision-making

EMA’s Regulatory Science Strategy to 2025 promotes using high-quality RWD in decision-making (9). To this end, EMA aims to create a flexible framework to deliver rapid access to and analysis of RWD throughout a product’s lifecycle; to develop computing capacity and skills in the agency to analyze large amounts of healthcare data, and to implement processes to feed data into regulatory assessments.

In March 2024, EMA launched its RWD catalogues to help regulators, pharmaceutical companies, and researchers identify and use RWD to investigate the safety and effectiveness of medicines (10). The catalogue of RWD sources replaces the ENCePP Resources Database. The data are searchable and can be exported by registered entities.

In April 2024, EMA’s Real-World Evidence Team (TDA-RWE) of the Data Analytics and Methods Task Force released new guidance detailing the types of studies that can be performed for RWE generation and how it can be used to support regulatory decision-making (11). The regulators recognize that RWD provides additional benefits compared to traditional randomized control trials. For instance, it can be generated quickly and reduce the risk of data duplication, RWD can be used to fill in knowledge gaps and provide tailored analyses to the committee’s questions (11).

Future implication

The draft reflection paper highlights the importance that EMA places on RWD and its potential impact on decision-making. It also establishes a framework for scientific and methodological rigour, helps to improve the transparency of data collection and analysis, and ultimately should increase the reliability of RWD generated by the industry.

The reflection paper will be presented at the multi-stakeholder joint HMA-EMA workshop on RWE methods on 14 June 2024 (12). Stakeholders are invited to provide feedback on the draft reflection paper by 31 Aug. 2024.

References

1. EMA. Reflection Paper on the Use of Real-World Data in Non-Interventional Studies to Generate Real-World Evidence. Draft Reflection Paper. EMA.europa.eu. 15 April 2024.
2. EMA. Revised Consolidated 3-Year Work Plan for the Methodology Working Party (MWP). Work Programme. EMA.europa.eu. 15 Jan. 2024
3. HMA/EMA Joint Big Data Steering Group. Big Data Workplan 2023–2025. Work Programme. EMA.europa.eu. January 2024.
4. EMA. Regulation (EU) No 536/2014 on Clinical Trials on Medicinal Products for Human Use. 16 April 2014.
5. ENCePP. ENCePP Checklist for Study Protocols. ENCepp.europa.eu, 15 Oct. 2018.
6. Wang, S.V.; Pottegård, A.; Crown, P.; et al. HARmonized Protocol Template to Enhance Reproducibility of Hypothesis Evaluating Real-World Evidence Studies on Treatment Effects: A Good Practices Report of a Joint ISPE/ISPOR Task Force. Pharmacoepidemiol. Drug Saf. 2023 Jan, 32 (1), 44–55.
7. FDA. Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological Products. Guidance Document, March 2024.
8. McCully, S. What’s in a Name? Towards Standardizing the Terminology of Real-World Data and Real-World Evidence. The Evidence Base, 30 Jan. 2024.
9. EMA. Decision-Making. EMA.europa.eu. 18 Nov. 2019.
10. EMA. HMA-EMA Catalogues of Real-World Data Sources and Studies. Webinar. EMA.europa.eu. 4 March 2024.
11. EMA. Real-World Evidence Provided by EMA. Support for Regulatory Decision-Making. EMA.europa.eu. 10 April 2024.
12. EMA. Joint HMA-EMA Big Data Steering Group Workshop on RWE Methods. Event, 14 June 2024.

About the author

Cheryl Barton is founder and director of PharmaVision, Pharmavision.co.uk.

Article details

Pharmaceutical Technology Europe
Vol. 36, No. 6
June 2024
Pages: 10–11

Citation

When referring to this article, please cite it as Barton, C. Using RWD in Non-Interventional Studies. Pharmaceutical Technology Europe, 2024, 36 (6), 10–11.