Electronic clinical outcome assessments and the European Union's clinical trial regulation: Smoothing the path to friction?

Abstract

The European Union's Clinical Trial Regulation 536/2014 (EU-CTR) sought to harmonize clinical trial rules, ensure high standards of safety, and streamline processes through its new Clinical Trials Information System (CTIS). However, confusion remains regarding submission requirements for “patient-facing documents” in Parts I and II of clinical trial applications (CTAs). Misinterpretations—particularly around what qualifies as written information—have led to unnecessary submissions of materials like eCOA or ePRO “screenshots,” which are not legally required.

The EU's EUDRALEX Volume 10 Q&A (notably Question 1.24) clarified that only patient-facing documents linked to trial endpoints, such as questionnaires, diaries, or patient cards, need inclusion in Part I alongside the protocol. There is no legal basis to demand all patient materials or their translations in Part II. Despite this clarification, member states retain autonomy under Article 26 to set national translation and document requirements, leading to inconsistent practices and continued administrative burden.

Recent initiatives, including CTR Collaborate (under the Accelerating Clinical Trials in the EU program) and MedEthics EU, seek to promote harmonization and efficient assessment. Empirical studies show that Ethics Committees (ECs) generally do not expect ePRO screenshots—most require only translated questionnaires.

EU-CTR's success depends on collective awareness and streamlined processes. With ICH E6 Revision 3 and global efforts by organizations like the WHO, there is an opportunity to balance regulatory rigor with practical efficiency—reducing redundant submissions and emphasizing participant protection as the core ethical priority.