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Background: A new regulation, (EU) No 536/2014, which replaces earlier national laws on clinical trials, has been implemented since 31 January 2022 with coordinated reviews of multinational trial applications. The legal text encourages the inclusion of all Member States (MSs) where the trial is intended to be conducted in the initial application, allowing sponsors the flexibility to submit either full applications (including scientific aspects in Part I and national aspects in Part II) or partial applications (Part I only). Both full and partial MSs should be included in subsequent substantial modification applications to harmonize the approval process.

Aim: This thesis examines the extent to which sponsors of trials in the EU/EEA submit partial trial applications and analyzes the challenges these applications faced.

Method: A systematic review was conducted on all initial multinational trial applications (n=1 914) submitted to the Clinical Trials Information System (CTIS) between 31 January 2022 and 30 September 2024.

Result: The proportion of partial applications submitted per quarter declined over time, from 27% in 2022 to 2% in 2024. Partial MSs were more likely to be withdrawn after the initial application (accounting for 76% of all withdrawals) compared to those receiving full applications. Sponsors explained that CTIS-related issues caused the withdrawal of partial MSs in 58% of cases. These issues mostly prevented sponsors from submitting urgent modifications before all partial MSs received Part II, which could be submitted by the sponsors later according to regulations. Smaller countries were primarily affected by this forced withdrawal, suggesting that sponsors prioritize setting up trial sites in larger MSs with higher potential to recruit more subjects.

Conclusion: This study identifies the need for improvements in CTIS, harmonisation of partial application process and inclusion of smaller member states to streamline clinical drug trials and improve patients' access to innovative treatments in the EU/EEA.