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. 2021 Aug;22(5-6):419-425.
doi: 10.1080/21678421.2021.1879866. Epub 2021 Feb 3.

Challenges and opportunities for Multi-National Investigator-Initiated clinical trials for ALS: European and United States collaborations

Paul Lingor  1 , Jan C Koch  2 , Jeffrey M Statland  3 , Sumaira Hussain  4 , Christiane Hennecke  5 , Joanne Wuu  4 , Thomas Langbein  6 , Raees Ahmed  5 , René Günther  7 , Benjamin Ilse  8 , Jan Kassubek  9 , Katja Kollewe  10 , Josua Kuttler  2 , Andreas Leha  11 , Teresa Lengenfeld  2 , Thomas Meyer  12 , Christoph Neuwirth  13 , Ralf Tostmann  5 , Michael Benatar  4
Affiliations

Challenges and opportunities for Multi-National Investigator-Initiated clinical trials for ALS: European and United States collaborations

Paul Lingor et al. Amyotroph Lateral Scler Frontotemporal Degener. 2021 Aug.

Abstract

An inherent challenge to clinical trials that aim to test the efficacy of experimental therapeutics for patients with amyotrophic lateral sclerosis (ALS) is the relative rarity of the disease. A promising solution to this problem is a multi-center approach that ideally includes sites distributed across a broad geographic area. In support of such an approach, the European E-RARE program and the United States National Institutes of Health (NIH) partnered to support the investigator-initiated ROCK-ALS trial (Eudra-CT-Nr.: 2017-003676-31, NCT03792490) as a multi-national collaboration between centers in Europe and North America that is led by European investigators. During the set-up of this international trial, however, a number of unanticipated legal, administrative, and financial complexities emerged that required significant adaptation of the proposed trial scheme. Here, we report our experience navigating these obstacles and describe the potential solutions that we explored. Our experience may inform future efforts to implement multi-national investigator-initiated trials that involve both European and United States centers.

Keywords: Clinical trial; international; rare disease; regulatory; sister trials.

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Conflict of interest statement

Declaration of interests

All authors have contributed to design aspects (PL, JCK, MB) , administrative preparation (CH, TLa, RA, RT) or local implementation (SH, JW, ER, RG, BI, JKa, KK, JKu, AL, TLe, TM, CN, JS) of the ROCK-ALS trial (Eudra-CT-Nr.: 2017-003676-31, NCT03792490).

Figures

Figure 1:
Figure 1:. Concepts for the integration of academic European and US centers in clinical trials.
A: one trial, one sponsor: a joint clinical trial in Europe and the US is supported by a single sponsor that could be located in either country. B: one trial, two sponsors: a joint clinical trial with one sponsor located in Europe and another based in the US. Responsibilities are split between the two sponsors. C: two trials, two sponsors: two separate clinical trials with independent sponsors are conducted in the US and in Europe, but both share the same trial protocol and agree on a subsequent combined analysis of data and joint publication.
See this image and copyright information in PMC

References

    1. Jansen-van der Weide MC, Gaasterland CMW, Roes KCB, Pontes C, Vives R, Sancho A, et al. Rare disease registries: potential applications towards impact on development of new drug treatments. Orphanet J Rare Dis. BioMed Central; 2018. September 5;13(1):154. - PMC - PubMed
    1. Kaji R, Imai T, Iwasaki Y, Okamoto K, Nakagawa M, Ohashi Y, et al. Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study. Journal of Neurology, Neurosurgery & Psychiatry. BMJ Publishing Group Ltd; 2019. April;90(4):451–7. - PMC - PubMed
    1. Lingor P, Weber M, Camu W, Friede T, Hilgers R, Leha A, et al. ROCK-ALS: Protocol for a randomized, placebo-controlled, double-blind phase IIa trial of safety, tolerability and efficacy of the Rho kinase (ROCK) inhibitor fasudil in amyotrophic lateral sclerosis. Front Neurol. Frontiers; 2019;10. - PMC - PubMed
    1. Gainotti S, Petrini C. Insurance Policies for Clinical Trials in the United States and in some European Countries. J Clinic Res Bioeth. 2010;01(01):1–8.
    1. Viertes Gesetz zur Änderung arzneimittelrechtlicher und anderer Vorschriften. Bundesgesetzblatt Bonn; December 23, 2016. pp. 3048–65.

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