International clinical trials present unique challenges and benefits for investigators and the patients they are ultimately working to help. During the session Providing Novel Therapies to the World: International Considerations in Access and Regulatory Approval, three experts discussed the intricacies of performing these studies.

“You shouldn’t do any study unless the study cohort reflects the affected patient population,” said John Galvin, MD, lead medical director for graft-versus-host disease (GVHD) at Incyte Pharmaceuticals. “This has been a challenge for a lot of clinical trials, but certainly in the transplant setting.”

International studies can help address this issue. Additionally, international studies enhance the diversity of sites and investigators. This broader expertise can lead to more insightful study designs and improved data interpretation, Galvin explained. Logistically, international studies can recruit patients faster and include a larger patient population.

However, these benefits come with challenges and risks. Although establishing a representative study cohort may seem straightforward, it has historically been difficult, Galvin noted. Further, including multiple regions and sites complicates reaching a consensus on the standard of care and endpoints, and enrolling more patients and achieving faster accrual require additional resources and regionally specific data.

Collaboration and innovation can address these risks and challenges. The research community can implement new methods to improve access, develop new endpoints and study designs, and aim to obtain better regional data, Galvin said.

Charles Crawley, MD, chair of the National institute for Health and Care Excellence (NICE) Technology Appraisal Committee B in the United Kingdom, discussed the role and evidence considerations for health technology assessment (HTA).

“Regulators such as the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are responsible for licensing drugs, and their primary questions are: ‘Does the drug work?’ and ‘Is the drug safe?’ The outcome of their deliberations impacts whether the drug can be sold,” Crawley said. “Health technology assessment asks slightly different questions, which are: ‘How well does the drug work?’ and ‘Is it value for money?’ The outcome of our discussions determines whether the drug should be paid for.”

To determine a drug’s value, the needed data includes the proportion of people who are in better health states after taking the drug, how long people survive in those health states, the quality of life associated with those health states, and the associated costs, he explained.

While high-quality randomized controlled trials provide the best evidence for assessing the relative treatment effect, they are very resource intensive. Consequently, not all of the aforementioned questions can be addressed. Thus, the data from these trials must be flexible, accessible, and open to reanalysis, Crawley said. Additionally, all available evidence, including real-world evidence, should be utilized to determine the benefit.

Anna Newton, MPH, senior director within the Real-World Evidence team at Lumanity, discussed the role of real-world evidence in regulatory and HTA decision-making.

In the last five years, there have been several publications by decision-making bodies reflecting the increased use of real-world evidence to support decision-making. While these guidelines are helpful, there’s still a series of trade-offs in considerations that need to be thought through when sourcing for real-world data, Newton said. This can be thought of as three essential categories.

The first is finding the right data. This is fit-for-purpose data to support a specific study design. The second is the right level of engagement across stakeholders to validate the study design. The third is the operations needed to execute the study design. Each category has a series of questions that should be further considered.

“Identifying which real-world evidence will be accepted by decision-makers is more than just finding the data and saying, ‘Alright, let’s design this study.’ It’s a complex and nuanced process, but it is possible,” Newton said.

This and other sessions at the 2025 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT® and CIBMTR® will be available for on-demand viewing for registered attendees following the live presentation.