Clinical trials increasingly have international dimensions. Whether a drug developer wants to gain approval to distribute the medication in multiple countries or a research team wants to increase the diversity of participants, the international element makes clinical trials more complex.
While any challenge can be overcome, there are a few key international issues that limit the accessibility of clinical trials and can hinder their results. Here are some of those barriers when researching abroad that sponsors and clinical research organizations are working to resolve.
One of the biggest challenges of conducting clinical trials and getting drug approval is balancing international regulations. Different countries have their own approval processes, which can keep drugs off the market as companies work to navigate them. Both trial companies and researchers are lobbying for regulation standardization to streamline these processes.
“Harmonisation of regulatory requirements to facilitate international collaboration in clinical trials...has the potential to reduce ‘drug lag’, the situation in which regulatory approval for new agents in certain countries lags behind that of the European Medicines Agency and the US Food and Drug Administration,” write Monica Tang, et al. in the British Journal of Cancer. “However, the complexity of trial-related regulatory obligations, as well as their variability between different countries and regions, increases the burden of documentation and compliance on investigators.”
Overcoming regulatory barriers is a key step in the future of clinical trials. It can allow researchers from all corners of the globe to share their data and work together to create more advanced treatments.
“To test new treatments with enough patients to be confident about the results, clinical research should not be limited to one institution, or even one country,” writes the team at Breast International Group. “The single strongest opportunity for success comes from combining resources and multi-disciplinary expertise from around the globe to establish research priorities, improve collaboration, and reduce unnecessary duplication of effort to generate results more quickly.”
While regulations can limit how clinical researchers operate and where they choose to conduct their studies, language barriers can inhibit results and participation. Inclusion based on language or ethnicity isn’t just an international problem, it is also an issue domestically.
"We know Latinos will make up a bigger and bigger share of the community living with Alzheimer's in the future," Jason Resendez, executive director at the UsAgainstAlzheimer’s Center for Brain Health Equity, tells NPR’s Josh Eibelman. "And we know that we don't have the workforce pipeline in place to accurately diagnose and enroll these folks into cutting-edge research."
Latinos represent the fastest-growing over-65 demographic. They are also 50 percent more likely to get Alzheimer’s than non-Latino whites, and many don’t speak English very well.
Trial developers tend to look for participants who have English fluency or proficiency. This can limit participation in the United States and abroad. Trial developers also operate in countries with high English-speaking rates, which typically means more affluent and urban areas.
“Patients with low English proficiency may be overlooked for cancer clinical trials,” write Jeanine Staples, et al., in Applied Cancer Research. “Unfortunately, a number of US clinical trials require English proficiency for potential participants, automatically excluding those who do not speak the language. On the other hand, those that are eligible may have a difficult time reading and understanding medical information, even when this is translated into their preferred language.”
From a clinical research perspective, this exclusion comes from a lack of resources or knowledge on how to include non-English speakers. Teams aren’t budgeting for multilingual trials, which means they lack the ability to work with people from different backgrounds.
“Researchers frequently fail to include participants who experience language barriers in their projects, in part because they lack the knowledge and experience to do so,” write Stephanie Premji, et. al in a study published in Qualitative Health Research.
In their study, they looked at the use of an interpreter for the collection of qualitative data versus the use of English-language discussions. They discovered that there are pros and cons for each. While interpreters allow participants to speak comfortably in their language — allowing for more detailed responses — some words and phrases can get lost in translation.
Not only will reducing regulations help researchers share information across borders, but it can also help companies develop inclusive practices where different ethnicities are represented in clinical trials. This is crucial for ensuring the safety of patient care.
“Japan is unique in insisting that sizeable local clinical trial data be included before drugs are approved for use,” writes Demetrius Williams at TranslateMedia. “And with good reason. Some Asian populations seem to metabolize certain antidepressants and antipsychotics better than white or black populations. Around a third of drugs licensed in Japan have a lower recommended dose compared to what is advised in the U.S.”
By failing to include different groups and ethnicities in clinical trials, researchers risk producing ineffective treatments that can actually actively harm certain groups. They risk publishing studies on medication that hasn’t been fully vetted across target populations.
“A drug may get approved on a narrow patient population’s response to the drug, but then be given after approval to a much broader patient group with much more variations in weight, age, gender, race, or other illness and organ dysfunction,” writes Mark Terry at BioSpace.
Inclusivity isn’t just a popular buzzword. It is essential for trial developers who might send their products to different markets. Even medications developed for domestic audiences should have racially and ethnically diverse elements within their studies.
“Sponsors and CROs should connect with patient advocates early in the drug development process,” says Eian Kantor at digital health company Antidote. “Advocacy groups (and individual advocates) can help shape and set the research agenda and open up dialogue around where needs are not being met in terms of current treatment options. With a deep understanding of the patient communities, they can also be key players in helping develop new methods of engaging participants in research.”
Taking steps to include more communities takes time. It takes money and energy. Doing so, however, can help build trust within these communities while also ensuring the medication created for certain treatments is more effective.
The goal of approaching international trials with an inclusive eye is to increase the overall representation of different people in the drug development process. Representation in trials increases the chances that these communities can gain access to treatment in the future. Previously underrepresented groups can be included and have a seat at the table.
“We have made unprecedented progress in the development of new agents for treatment of many hematologic disorders and malignant disorders,” says Grzegorz Nowakowski, hematologist and program director at Mayo Clinic. “However, large groups of the population do not have access to these groundbreaking treatments. People may not live near sites with clinical trial programs, or they may not be able to devote the time or travel needed to participate in the trial.”
However, representation isn’t limited to the patients. Researchers from multiple countries are calling for inclusion in the trial process. Instead of sending American researchers abroad, trial developers can work with physicians and research organizations in their target countries.
“Although the importance of clinical trials by cooperative groups is well known, a very significant issue is that researchers from emerging countries have limited participation in these kinds of studies,” write Henry Gómez, et al. in Clinical Research and Trials, an online journal. “Researchers from Latin America are aware that they have a great pool of patients and patient populations with special conditions and they have great interest in participating in clinical research; however they also are aware that they need more training.”
There are multiple levels of inclusivity to consider when conducting an international clinical trial. Developers should consider the language needs of participants — both internationally and domestically. They should involve local physicians and scientific experts from the groups they are working with. Finally, they should work to share data across borders so everyone, regardless of where they are from, can get the treatment they need.
Launching global clinical trials doesn’t just mean accessing new markets. It means bringing treatment to areas that were previously overlooked.