Clinical Trials in Times of War: A Testament to Human Resilience and Dedication

Abstract

Amidst daily news of cruel attacks on civilian life and infrastructure in Ukraine, causing significant disruptions to hospital and health services,¹ and the heroic resilience of the Ukrainian population in the face of fear and suffering, little attention has been given to the impact of war on scientific and medical research. Here, we wish to acknowledge the admirable determination and performance of Ukrainian medical centres and patients, which we encountered during the conduct of a clinical trial involving Parkinson's disease (PD).

The EPSILON trial was a phase III, 6-month double-blind, randomized, placebo-controlled, and parallel-group study, designed to evaluate the efficacy and safety of opicapone as add-on to levodopa/dopa decarboxylase inhibitor therapy in patients with early PD who do not exhibit signs of motor complications. The study was conducted in 74 European trial sites including seven Ukrainian centers in Kharkiv, Zaporizhzhia, Dnipro, Vinnytsia, Lviv, and Kyiv.

A total of 35 Ukrainian subjects were randomized (~10% of total randomized subjects in the study). Only four (11.4%) subjects did not complete the 6-month double-blind period, where one subject dropped out before the conflict begun and the other three during the conflict. This discontinuation rate was not different to the overall non-Ukrainian subjects. All our subjects, doctors/investigators, and support staff involved in the study demonstrated an unwavering commitment to the cause. They fearless kept the visits to their maximum extent possible (or beyond that), they innovatively embraced remote monitoring, telemedicine, home visits, and they even pass rivers by rowboat because of destroyed bridges just to ensure data collection. The quality and extent of the data collected despite these challenges, underscore the commitment of all involved, including Joanna Moreira who oversaw the central monitoring and operational study conduct at BIAL as the sponsor of this trial.

The dedication to the clinical trial displayed by Ukrainian patients and healthcare professionals, even in the darkest of times, is truly admirable. Their bravery and humanity exemplify the resilience of the human spirit and we wish to express our deepest respect to our Ukrainian colleagues and their patients.

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.

J.J.F.: 1A, 1B, 1C, 3A, 3B

O.R.: 1A, 3B

W.P.: 1A, 3B

J.J.F. has provided consultancy and received speaker fees from BIAL, Biogen, AbbVie, Sunovion Pharmaceuticals, Infucure, Zambon, Roche, Stada, ONO Pharma, Britannia, Neuroderm and SK Chemicals and has received grants from AbbVie, BIAL, Medtronic, and Angelini. O.R. has received honoraria for scientific advises to Alkahest, AlzProtect, Apopharma, Astrazeneca, BIAL, Biogen, Britannia, Buckwang, Cerevel, Contera, GE Healthcare, Handltherapeutic, Ionis, Jazz, Kyowa, LGD Nuvamid, Lundbeck, Merz, Neuralight, Neuratris, Neuroderm, ONO Pharma, Orion Pharma, Parexel, PD Neurotechnology, Polycaps, Roche Therapeutics, Sanofi, Scienture, Servier, Sunovion, Supernus, Synagile, Thelonius Mind, Takeda, Teva, UCB, Zambon and funding for research programs from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, The Michael J. Fox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020, Horizon Europe). W.P. received personal fees from Alterity, AbbVie, Affiris, AstraZeneca, BIAL, Biogen, Britannia, Lilly, Lundbeck, Neuroderm, Neurocrine, Denali Pharmaceuticals, Novartis, Orion Pharma, Roche, Takeda, Teva, UCB, and Zambon (consultancy and lecture fees in relation to clinical drug development programs for PD). W.P. reports also royalties from Thieme, Wiley Blackwell, Oxford University Press and Cambridge University Press and a grant support from The Michael J. Fox Foundation and EU FP7 and Horizon 2020.