Abstract
The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors.
Highlights
Large teams involving international collaborations are a growing theme across many research disciplines and are increasingly associated with high impact science [1,2,3,4]
To categorize clinical trials by clinical specialties, we examined Medical Subject Heading (MeSH) terms, vocabulary established by the National Library of Medicine (NLM) for indexing purposes, assigned to each clinical trial based on an NLM algorithm from the condition browse fields
The slower power law decay of data from older years suggests that the distribution of unique partnering countries has become more equitable over time, i.e. the number of countries associated with trials has become less skewed with larger scale multinational clinical trials accounting for a growing fraction of all international collaboratives (Fig 3B)
Summary
Large teams involving international collaborations are a growing theme across many research disciplines and are increasingly associated with high impact science [1,2,3,4]. Past studies characterizing authorship dynamics of research publications have revealed generic structures of collaborative networks and properties of team assembly mechanisms, though unique traits exist across subject disciplines [4, 12,13,14]. We characterized the evolution, trial demographics, network properties, and geographic constraints of multinational clinical research, defined as interventional trials with clinical sites enrolling patients in more than one country. Our criteria for multinational clinical trials does not rely on authorship affiliations, the conventional method of analyzing collaborative ties, given the high incidence of non-publication in clinical trials and the likely involvement of international authors that are not directly involved in patient recruitment [15]
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