Hurdles for the Delivery of Multinational Randomized Clinical Trials

REMAP-CAP contributed to important work on improving how clinical trials are conducted across borders. Conducting clinical research, especially during a public health emergency such as a pandemic, requires navigating a complex web of ethical, administrative, regulatory, and logistical (EARL) requirements. In this publication, we aimed to provide insights into where improvements could be made and analyzed EARL timelines in different countries, such as time to first patient enrollment. The results show the extraordinary amount of work of all teams across Europe. It was found that some countries, such as the UK and also France, were able to accelerate timelines substantially during the COVID-19 pandemic. In other settings, there were still challenges, particularly in long contracting timelines. We hope that these findings spark further conversation about how we can collectively streamline EARL processes to ensure that patients across Europe can keep benefitting from innovative research.

  • 02 July 2025
  • Denise van Hout; Paul Mouncey; David Harrison; Marc Bonten; Lennie Derde and the REMAP-CAP European Regional Investigators
  • JAMA Network Open

BACKGROUND
This cohort study used data from the ongoing Randomized Embedded Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia to enable comparison of EARL procedures for multiple protocols across 19 European countries in the pre–COVID-19 pandemic (February 19, 2016 to March 10, 2020) and COVID-19 pandemic (March 11, 2020, to May 4, 2023) periods. Data were analyzed from November 2024 to March 2025 with contracts and protocol submissions as the units of analysis.

Time to (1) site contract completion, (2) regulatory and ethical approval (TTA), and (3) first patient in (FPI). The UKwas compared with non-UK countries because of its distinct research infrastructure.

RESULTS
There were 257 fully signed first contracts with study sites for analysis. In the UK, contract completion times decreased by 97%(95%CI, 95%to 98%), from a median (IQR) of 196 (154 to 250) days in the pre–COVID-19 pandemic period to 5 (1 to 11) days during the COVID-19 pandemic. In non-UK countries, median (IQR) contract completion times were 224 (119 to 412) days and 183 (62 to 291) days before and during the COVID-19 pandemic, respectively (relative difference, −18%; 95% CI, −43%to 52%). In total, 44 interventions in 16 domains were submitted, yielding 232 protocol approvals for analysis. During the COVID-19 pandemic, median (IQR) TTA was 8 (5 to 31) days in the UK and 115 (47 to 103) days in non-UK countries (median difference, 107 days; 95%CI, 76 to 123 days), with large variation across non-UK countries. Time between approval and FPI during the COVID-19 pandemic was, on average, 3 months faster in the UK compared with non-UK countries (median difference, 90 days; 95%CI, 42 to 141 days).

CONCLUSIONS
This study found that EARL procedures were lengthy and variable between countries, reflecting different interpretations of trial regulations, with faster processes in the UK. These findings underscore the need to streamline processes across European countries to improve trial efficiency, in particular during future public health emergencies such as pandemics.

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