The response to COVID-19 resulted in never-before-seen collaboration and innovation among the global healthcare community. The landmark Phase 3 clinical trial of Pfizer-BioNTech’s COVID-19 vaccine enrolled more than 46,000 patients in 153 sites across six countries. The trial was conducted with extraordinary speed while maintaining the highest quality and safety standards for participants.
If necessity is the mother of invention, then the success of this trial is a testament to the resilience of our industry. Unfortunately, most clinical trials are not as successful. Nearly 80% of trials fail to finish on schedule, with 20% delayed six months or more. The reasons are complex, but chief among them: a disheartening 85% of clinical trials cannot retain enough patients, with more than two-thirds of trial sites failing to meet targeted patient enrollment.
Trial sponsors and clinical research organizations (CROs) face unique challenges when recruiting and maintaining participation in clinical trials. Even greater obstacles exist in trials requiring patients to travel across borders to participate. The pharmaceutical industry has made tremendous strides in this area, but our work continues, as improving access to life-saving clinical trials is vital from both a commercial and ethical perspective.
The Need for Cross-border Travel Support
Clinical trial participation can create a heavy burden for patients and their caregivers. Traveling or temporarily relocating to a foreign country creates an additional series of challenges requiring creative solutions. According to a 2020 study examining clinical trial access in the European Union, the logistical and financial burdens on patients were perceived as the biggest challenge to participating in cross-border clinical trials. In the same study, 92% of survey respondents said cross-border trials are necessary, and 91% agreed increasing access to cross-border clinical trials could improve treatment and care.
Children and those suffering from rare or ultra-rare diseases are the most vulnerable of these patients, and access to life-saving clinical trials is nearly impossible without outside support and financial coordination. These patients face even greater complexities, as it is not uncommon for there to be a limited number of sites for these trials. For pediatric patients, entire families may need to relocate for the duration of the trial.
Most CROs and trial sponsors lack the logistics expertise or resources required to recruit and retain patients in global studies. The most common logistical challenges disrupting cross-border trial participation are language and cultural differences, governmental and regulatory documentation, financial considerations and variances in the cost of living, and personal safety and geopolitical constraints. Luckily, none of these challenges are insurmountable.
Overcoming Language and Cultural Barriers
All respondents in the 2020 EU study ranked language as a top issue impeding participation in cross-border clinical trials. Concerns centered around the ability of a patient to communicate with medical professionals and give informed consent, as well as navigating daily life in a new country.
Many patients and caregivers require interpretation and translation support throughout their participation in a clinical trial. Having an ongoing relationship with a local advocate who speaks the language of the patient and understands the nuances of their culture lays the foundation for a strong connection, one that significantly improves the patient experience and likely supports their ability and willingness to continue participating in a clinical trial.
Coordination of a single cross-border trip often requires knowledge of several languages, in addition to an understanding of different cultural norms. In one case, an immigrant family living in Israel could not travel to Russia so their son, a pediatric patient, could participate in a clinical trial for his rare disease. The family did not speak Hebrew, which made finding a suitable solution on their own nearly impossible.
In this case, a patient coordinator contacted Israel’s Minister of Health and secured permission for the life-saving trial medication to be imported under the care of a local physician who spoke Russian. This solution was made possible by a team of global coordinators who could collectively translate details about the condition of the patient and his urgent medical needs.
Securing Required Documentation
Once a patient commits to participating in a clinical trial involving cross-border travel, their caregivers, already managing fears and treatments related to the health of their loved one, are faced with a daunting to-do list. In many cases, the first step is securing approval for travel and often extended stay in the trial country. Because policies vary by country, the time required to secure official travel documents also varies. For example, in the United States, foreign patients must often obtain a B2 temporary visitor’s visa before entering the country for medical treatment. The application process can take weeks to several months. Participants must also provide documentation that they meet country-specific immunization requirements, which the pandemic has only complicated.
The health insurance of the patient is also a huge consideration: patients and caregivers want to be sure they are covered in the event of unexpected sickness, travel delays, cancellations, or accidental injury while in a foreign country for treatment. These common logistical issues can inhibit trial enrollment when patients and caregivers perceive them as additional and avoidable sources of stress. However, when clinical trial sponsors and CROs invest in and promote patient support services, patient coordinators can assist in securing necessary travel documents, which alleviates participant fears and reduces the responsibilities often placed on trial site coordinators.
Addressing Economic Disparity
Cross-border patients must manage new forms of currency, fluctuating exchange rates, and unexpected expenses. Patients participating in clinical trials in countries with higher living costs than their home countries are especially impacted by financial pressures. In Brazil, where banks are sensitive to money laundering, it is not uncommon for a wire transfer to a patient or caregiver account to be flagged as suspicious, adding pressure to the complexities of stipends and reimbursements. In Argentina, inflation can cause prices to double in as little as three months, skyrocketing living expenses and making an original travel budget obsolete.
Although some countries reimburse (or require reimbursement) for citizens incurring cross-border healthcare costs, many patients and caregivers cannot pay for their expenses upfront. In addition to rapid reimbursements, patient coordinators can also oversee prepayment for transportation and lodging and, when necessary, help manage stipends to cover daily living expenses and offset lost wages for missed work.
Prioritizing Patient Health and Safety
The COVID-19 pandemic disrupted many planned and ongoing clinical trials on other diseases around the globe. Although some CROs quickly pivoted and utilized telehealth to access trial participants, patients in poor or unstable countries were likely deterred by either unreliable or a total lack of access to the internet.
Geopolitical conflicts such as military engagements and diplomatic crises between nations can also impact participant access to life-saving clinical trials. In countries that have poor diplomatic relationships, laws may prevent patients from entering countries for medical care. Even when no conflicts exist, some governments refuse to cooperate with countries that have opposing ideologies.
Internal conflicts within a country can also create unexpected circumstances for trial sponsors and CROs. In one extreme example, a patient, caregiver, and driver in Rio de Janeiro were caught in machine-gun crossfire between the army and a local gang. They were forced to hide under their car until the shooting stopped. The local patient coordinator began using armored vehicles to transport patients safely throughout the region to avoid similar potentially life-threatening situations.
Optimism for Improving Clinical Trial Performance
Collaboration and innovation among the global healthcare community during the COVID-19 pandemic created a positive ripple effect. The success of Pfizer and BioNTech’s COVID-19 mRNA vaccine trials have inspired new trials and modalities for those seeking to solve existing health problems. According to the New York Times, several recent clinical trials have begun investigating the use of mRNA technology in flu vaccines. Advancements in technology and communications, collaboration, and a better understanding of how to support trial participants can improve clinical trial recruitment, retention, and outcomes—and without question, help save countless lives.
Trial sponsors and CROs who invest in patient support services can better anticipate and overcome the logistical challenges of cross-border travel and prevent patients from participating in their studies. As patient coordinators earn the trust of both patients and their caregivers, they build meaningful relationships that increase the likelihood a patient will complete a trial.