Can you think of any diseases and health conditions that only affect residents of one country? There’s a handful of them – mostly vector-borne infectious diseases, like Hendra virus found solely in Australia, transmitted by fruit bats - or genetic conditions like PEHO syndrome, which occurs almost exclusively within Finnish populations. 

Beyond these outliers, most conditions aren’t endemic to one country and instead are found across borders. So, why then, are most clinical trials aiming to treat these conditions conducted within a single country? 

It’s tricky business setting up trials in multiple countries. Barriers to setup include complicated national ethical requirements and regulatory frameworks, patchy funding availability, logistical challenges supplying equipment, and difficulty training site personnel consistently.  

But ruling these complex study setups out entirely could block huge opportunities for clinical advances. 

Could the benefits of multinational trials outweigh the hurdles? 

In many cases, the answer must be a resounding yes. To date, over 2,600 studies registered on the ISRCTN Registry have reported recruiting patients and participants in more than one country. This accounts for nearly one in ten records. Of these, 663 are recruiting participants in more than five countries, and 271 in more than ten, making them truly multinational. 

So, what are the benefits they’re seeing? Purely from a numbers perspective, international clinical trials open themselves up to wider pools of eligible participants, resulting in increased reliability of results.  

This is particularly important in the study of rare diseases. We recently spoke with Stacey McGeown, a registered nurse, educator and co-founder of EquiPath Analytics, who is currently recruiting patients worldwide for a study which will explore the hidden burden of living with Glanzmann thrombasthenia, a rare inherited bleeding disorder. She explained that “Given the rarity of the condition, conducting research across multiple countries allows us to increase the sample size. It also enhances the diversity and representation of people living with GT, including differences in healthcare systems, social backgrounds, and access to treatment and care. Overall, this results in richer and more comprehensive data.” 

Including participants from multiple ethnicities, genomic backgrounds, and geographic regions also provides insight into how different people’s bodies might respond to newly developed or repurposed drugs. In 2023, researchers at Queen Mary University of London discovered that a drug that has been used to treat heart problems since 1998 is not effective in certain South Asian populations. A more ethnically diverse clinical trial design for the drug's development could have caught this much sooner than 25 years later.

From a patient’s perspective, safe and trustworthy clinical advancement doesn’t just benefit from international trials, it relies on them for representative populations. 

From a researcher’s perspective, international trials are also beneficial for increasing collaboration between different study teams, and for learning from each other to be able to standardise research practices globally.  

Cross-cultural challenges to solve 

There are still barriers in the way of the perfect multinational trial, though many of these are on their way to being broken down.  

Not every country has the same attitude to collaborating with patients and participants in trial design. A recent collection of articles assembled by Research Involvement & Engagement and co-produced with patients showcased how this collaboration can be undertaken creatively and in the face of social, economic, political and environmental difficulties, using real-life examples across South Africa, India, Thailand and Malaysia.  

Another concern is the geographical disparity between where research takes place and where diseases have their most substantial effects. Pilot & Feasibility Studies published an Editorial and subsequent Collection highlighting how most health research is conducted in the Global North, where only 14% of the world’s population reside, while conditions often disproportionately affect the Global South, particularly when it comes to infectious diseases. A multi-national clinical trial might not be considered truly representative if it is only recruiting patients in higher income countries. 

Combating this dissonance is crucial, but it’s important not to solve it by conducting Helicopter Research. As explained by a particularly high-profile Nature editorial in 2022, this occurs when researchers from high-income settings are ‘helicoptered’ or ‘parachuted’ (probably not literally, in most cases...) into lower-income countries or groups who are historically marginalised, like indigenous populations, without active involvement from these populations in the study design and conduct. New guidance has been created, including the Global Code of Conduct for Research in Resource-Poor Settings, which encourages collaborative research development, and transparency about inclusion and ethics, so that patients trust the research they are taking part in.  

Speaking again with Stacey McGeown, she emphasised the importance of being “respectful and mindful of cultural differences” throughout a study, which could include “rephrasing questions, offering participants choices, and allowing them the option to skip questions or pause interviews when needed”.  

Asked about what wisdom she would share with researchers new to running global studies, Stacey urged them not to be discouraged by the complex challenge of obtaining ethical approval - “It is achievable. Conducting a global study is worthwhile, as it provides more diverse and richer data”. She also praised leaps forward in technology for positively contributing to international studies, in particular conducting interviews online and being able to use tools to transcribe and analyse data from them. 

Why should cross-border trials rely on well-managed registries? 

When a clinical trial expands beyond operating solely in one country, accurate, up-to-date information in a well-managed study registry like ISRCTN becomes crucial. 

Detailed, accurate information about where a study is taking place helps regulators, researchers and the public quickly understand the trial’s geographical footprint. Often multinational studies need to be registered in multiple registries, depending on local laws, so good data management skills are required from researchers. 

Accessibly-written Plain Language Summaries play a crucial role in explaining complex studies in a clear, inclusive way that can be understood across borders so that trust can be built with patients.  

At the same time, public trial records improve the discoverability of ongoing research, making it easier for international Primary Investigators to identify relevant studies and collaborate.  

A perfect example of this comes in the form of a newly launched clinical study led by Jansen-Cilag International, investigating the use of a new medicine called Icotrokinra in patients with Crohn’s Disease. This study is recruiting patients in 24 different countries globally, and so as a result appears in three different national registries – ISRCTN (UK), ClinicalTrials.gov (USA) and ANZCTR (Australia & New Zealand). The study also appears on the UK’s Be Part of Research platform, helping a wider range of patients to discover it. 

Together, these elements ensure transparency, enable global partnerships and support the smooth delivery of multinational research, in order to ensure healthy lives and promote well-being for all at all ages, as encouraged in the third Sustainable Development Goal.