3 Enrollment Strategies for Global Clinical Trials

By: Aunna Nakazawa, senior director of Customer Success at OneStudyTeam

International clinical trials—especially those that include historically deprioritized countries and regions—add logistical complexity. They also hold the possibility of yielding better data (e.g. opportunities to speed up enrollment) than trials focused solely on the subset of historical “go-to” countries within clinical research. In an ever-more-interconnected world, it’s worthwhile for sponsors to invest in trials that accurately reflect our global society. However, any given trial cannot be run the same way in every country, or even at every site within a country. 

We need to take data-driven approaches to tackle global socio-economic inequities in clinical research. This article covers three important enrollment strategies for global clinical trials I have learned firsthand while helping trial teams across the globe identify, pre-screen, and enroll candidates in trials in over 75 countries.

(1) Expand your trial to sites beyond your go-to locations.

Whether or not we acknowledge it publicly, most clinical trial sponsors have tiers of preferences for trial locations. These are usually based on a variety of factors including comfort levels and resources already in place to support the varied complexities and regulatory frameworks that clinical trials must operate within. However, there are only so many patients in those go-to pools, and I have seen many previously overlooked sites deliver incredible results when given the opportunity.

One key benefit is that prioritizing new regions and/or countries can unlock important specialty areas based on disease incidence. For example, many East Asian countries have unusually high rates of hepatocellular carcinoma (HCC); for a sponsor that specializes in liver cancers, it is worth investing the resources to develop sites, teams, and capabilities in this region even if they did not previously exist. 

Another example is Behçet's disease, often referred to as “Silk Road disease” due to the high prevalence within countries along the historic trade corridor, with the highest prevalence within present-day Turkey. Prioritizing access to a trial within Turkey, as well as countries with a large Turkish diaspora—for example, Germany—would provide great benefit in yielding more opportunity for improved enrollment with the end goal of leading to cures for this rare and currently incurable disease. For niche needs like this, sponsors can also consider partnering with regional CROs for a specific trial or set of locations to minimize permanent expansion and resource expenditures.

(2) Diversify your clinical trials in multiple ways.

Diversity is a hot topic in clinical trials. But too often the conversation stops at diversity in a handful of patient demographic considerations like ethnicity and nationality. Sponsors should think about international trials as more than just pulling from multiple countries.

To improve global clinical research, consider diversity in the types of sites—a step beyond just making sure a trial checks off a certain number of regional boxes. Big academic medical centers tend to cater to more traditionally prioritized and well-resourced populations, so it is beneficial to intentionally partner with smaller, local providers as well as the large, dense sites.

Going a level deeper, the diverse identities of the principal investigators at your sites are also important. Including PIs who share both location and background with patients can instill crucial trust and confidence, especially in areas like Honduras and Guatemala where patients are wary because of the tarnished and horrific history of international trials.

(3) Learn regional nuances before you activate trials.

Leaning on local expertise to account for country- or culture-specific factors helps global operations teams plan holistically for the life of their trial. Here are some examples of different trial-related regional variations my global team has encountered:

• Pre-screening is prioritized and understood differently in the clinical trial workflow of some regions, which can limit the detail and accessibility of patient data involved in this step. For instance, we learned that in many Latin American countries, patient referrals are largely made through networks of clinicians connecting on WhatsApp groups to share key eligibility information. In Japan, much of the pre-screening process is managed through verbal communication and often does not follow a standardized format. 

• Reimbursing trial participants for things like travel expenses can sometimes require creative problem-solving to prevent extra barriers to enrollment. Our team found that prepaid debit cards are much less commonly sold and accepted in Latin America (and more generally in cash-based economies), making it more difficult to distribute and appropriately track funds to individuals.

• Regional holidays can have significant effects on recruitment, enrollment, site startup, and ongoing operations. If you are setting up a trial in a majority-Muslim country, avoid doing so during Ramadan or the weeks immediately following Eid al-Fitr; similarly, it is both strategic and respectful to local partners to schedule around Chinese New Year and Diwali in regions where these holidays are widely celebrated. Initiating a new site in August or December is nearly impossible throughout much of Europe due to cultural norms around vacations.

• Data privacy regulations can vary dramatically across national boundaries, requiring sponsors to have regional experts who can navigate the ins and outs of health information management for each site. For example, HIPAA-compliant data management will not always satisfy GDPR requirements, and vice versa. 
  

• Electronic Health Record (EHR) systems can also change data management from region to region within a trial. They are an important resource for managing and accessing detailed patient information during recruitment and enrollment, but best practices depend on factors such as siloing and access levels. Japan is a particularly unique case because they have a national EHR, so sites can pull from a centralized pool of patients. Australia has recently rolled out a national EHR system, and sponsors should stay abreast of other countries’ plans to follow suit.

International clinical trial sponsors have the opportunity to expand healthcare access in both the short and long term. Clinical trials offer enrolled patients access to treatments and care paths that would have otherwise been unavailable. Global clinical research enrollment offers new populations power and voice to be included in the outcomes and the way that therapies and medical devices are designed and developed. Together, we can develop therapies and treatments that will work for a broader range of patients.