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Operational complexities in international clinical trials: a systematic review of challenges and proposed solutions

Lookup NU author(s): Dr Leher Gumber, Dr Opeyemi Agbeleye, Alex InskipORCiD, Ross Fairbairn, Madeleine StillORCiD, Luke Ouma, Dr Jingky Lozano-KuehneORCiD, Michelle Bardgett, Professor John IsaacsORCiD, Professor James WasonORCiD, Professor Dawn CraigORCiD, Dr Arthur PrattORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. OBJECTIVE: International trials can be challenging to operationalise due to incompatibilities between country-specific policies and infrastructures. The aim of this systematic review was to identify the operational complexities of conducting international trials and identify potential solutions for overcoming them. DESIGN: Systematic review. DATA SOURCES: Medline, Embase and Health Management Information Consortium were searched from 2006 to 30 January 2023. ELIGIBILITY CRITERIA: All studies reporting operational challenges (eg, site selection, trial management, intervention management, data management) of conducting international trials were included. DATA EXTRACTION AND SYNTHESIS: Search results were independently screened by at least two reviewers and data were extracted into a proforma. RESULTS: 38 studies (35 RCTs, 2 reports and 1 qualitative study) fulfilled the inclusion criteria. The median sample size was 1202 (IQR 332-4056) and median number of sites was 40 (IQR 13-78). 88.6% of studies had an academic sponsor and 80% were funded through government sources. Operational complexities were particularly reported during trial set-up due to lack of harmonisation in regulatory approvals and in relation to sponsorship structure, with associated budgetary impacts. Additional challenges included site selection, staff training, lengthy contract negotiations, site monitoring, communication, trial oversight, recruitment, data management, drug procurement and distribution, pharmacy involvement and biospecimen processing and transport. CONCLUSIONS: International collaborative trials are valuable in cases where recruitment may be difficult, diversifying participation and applicability. However, multiple operational and regulatory challenges are encountered when implementing a trial in multiple countries. Careful planning and communication between trials units and investigators, with an emphasis on establishing adequately resourced cross-border sponsorship structures and regulatory approvals, may help to overcome these barriers and realise the benefits of the approach. OPEN SCIENCE FRAMEWORK REGISTRATION NUMBER: osf-registrations-yvtjb-v1.

Publication metadata

Author(s): Gumber L, Agbeleye O, Inskip A, Fairbairn R, Still M, Ouma L, Lozano-Kuehne J, Bardgett M, Isaacs JD, Wason JM, Craig D, Pratt AG

Publication type: Article

Publication status: Published

Journal: BMJ Open

Year: 2024

Volume: 14

Issue: 4

Online publication date: 15/04/2024

Acceptance date: 27/02/2024

Date deposited: 29/04/2024

ISSN (print): 2044-6055

ISSN (electronic): 2044-6055

Publisher: BMJ Publishing Group


DOI: 10.1136/bmjopen-2023-077132

PubMed id: 38626966


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Funder referenceFunder name
National Institute of Health and Care Research
National Institute of Health and Care Research (NIHR) Newcastle Biomedical Research Centre
Versus Arthritis