PhD Scientific Days 2026

Pharmaceutical Sciences and Health Technologies 3.

Transitioning from Off-Label Use to On-Label Authorization: Regulatory Pathways, the Contributory Role of Real-World Evidence, and Implications for Patient Safety and Ethical Accountability

Name of the presenter

Helfrich, Dóra

Institute/workplace of the presenter

Nemzeti Népegészségügyi és Gyógyszerészeti Központ / National Center for Public Health and Pharmacy

Authors

Dóra Helfrich Dr.¹
1: Nemzeti Népegészségügyi és Gyógyszerészeti Központ / National Center for Public Health and Pharmacy

Text of the abstract

Introduction
Off-label use is common in areas with unmet medical needs, where clinical practice evolves faster than regulatory indication expansion. Although repeated off-label use can result in significant clinical experience and real-world evidence (RWE), these rarely lead to approved indications within the EU. This gap is critical, as only authorized clinical trials and on-label use provide a clear, safe, and ethically sound legal framework, particularly regarding product liability and patient protection.

Aims
This research examines how off-label clinical experience and real-world data can be integrated into clinical research processes that support regulatory approval. It also analyses how the transition from off-label use to clinical trials and approved treatment can improve ethical acceptability, patient safety, and legal clarity.

Methods
My study combines legal-regulatory and health policy analyses. It examines the interrelationships between off-label use, the collection of real-world evidence (RWE), clinical trial design, EU pharmaceutical regulations, and the legal implications of on-label use. The study includes stakeholder mapping, interviews, questionnaire analyses, and regulatory assessment. It focuses in particular on how the transition from widespread off-label use to clinical trials can improve transparency, ethical oversight, and manufacturer accountability.

Results
Among the expected outcomes is defining a structured process where sufficiently reliable real-world evidence (RWE) can justify initiating clinical trials, potentially leading to approval for the indicated use. The study also evaluates the role of real-world evidence data in clinical trials and its potential partial substitution, particularly in rare diseases and small populations. The results are expected to confirm that approved trials and subsequent on-label use provide greater assurance of ethical use, patient safety, and accountability.

Conclusion
The aim of the research is to support the development of a regulatory model that transforms off-label practices into approved therapies. Such a framework could contribute to greater regulatory coherence, stricter ethical standards, improved patient safety, and increased legal certainty for stakeholders. It could also create incentives for both marketing authorization holders and healthcare systems.

Funding
No external funding.