Conducting clinical trials across multiple countries is becoming increasingly common and useful for clinical research. However, these trials face additional challenges to those that already arise when conducted in a single country.
While concerns over logistical constraints and patient attrition persist no matter where a study is held, multinational trials present further concerns based on linguistic, cultural and regulatory differences.
Here we examine those barriers and look at how to break them down. Doing so will ensure greater inclusion and more effective trial results.
Researchers should build their cultural competency with the help of a framework, the team at Empact Consortium writes. The consortium (Enhancing Minority Participation in Clinical Trials) includes investigators from top universities that provide training to make trials more inclusive.
Culturally competent researchers will help placate patient concerns and should ensure their recruitment framework includes awareness of the 3 types of cultural barriers:
Awareness. Promotional materials for trials should be diverse linguistically and culturally, as well as being pitched at multiple education levels so more people will know about them and understand them.
Opportunity. By creating more awareness among prospective patients, researchers will have access to a larger pool of potential study patients. Once recruited, continuing to engage with them on a culturally and linguistically appropriate level will mean the difference between their completion of the study and attrition.
Acceptance. Sponsors must try to foster a culture of acceptance between patients and researchers through culturally competent communication. This includes researchers demonstrating respect and sensitivity to patients.
In a study examining the barriers blocking participation of South Asian patients in Canada and the UK in clinical trials, researchers found there was a sense of not belonging to society, distrust as to the importance or benefits of trials and also a lack of clinical trial awareness and education.
Additionally, cultural and language-related issues arose, perpetuating these aforementioned feelings and lack of trust in the trial process.
To resolve these concerns, the researchers proposed better engagement with the target population’s communities. The best route to success is to approach key figures in the community to help build trust and explain the process. This would also give researchers chance to become more culturally competent.
The study found that patients wanted and expected clearer demonstration of respect of their culture.
Building trust is also about assuaging patient fear. Disaster recovery health services provider Healthcare Ready explains that cultural barriers between the clinical research community and minority groups can prevent the latter receiving adequate treatment.
Indeed, an argument for greater inclusivity is that better primary healthcare should be available, which would also help more diverse populations access clinical trials.
It’s vital that there is greater socialization and education of both parties. Part of this requires researchers to familiarise themselves with the cultural histories of patient populations: What are their fears and doubts associated with clinical research or even Western medicine?
Exploring these differences, and acknowledging and respectfully accommodating them, enhances trust. Additionally, study processes must be made transparent for patients to understand their role and what is expected of them.
Multisector linguistic services company Language Connections notes that the challenges of multinational trials are many and complex. Translating clinical trial documents is not a straightforward project and requires greater precision than translations for text communication in other sectors. This is because people’s health is at stake — as is the quality of study results.
Finding the best “language equivalents” is essential to avoid any confusion. Once translated into the chosen language, the text needs to be translated back into English to see if any meaning has been lost or changed.
The most accurate translation requires more than substituting words. The linguistic capabilities of the translator are important, the company argues, but make up just one aspect of translation.
To be completely successful in communicating trial information, translators must show an understanding of the patient population’s culture and local regulations, as well as its history in clinical research.
With multinational trials, there are often sites in developing countries in which patients will not have received much education. This requires a thorough assessment of the patient population’s capabilities so that consent forms, for instance, are pitched at a level they can understand.
“Linguistic validation and cultural adaptation” are the guiding stars when translating materials for clinical trials, the team at Language Connections writes.
While multinational trials are increasing in popularity, they do not provide hassle-free studies. The FDA cites common concerns which include:
Those concerns go directly to the integrity of the data. This is why clinical research associate Kelly Jasko at IMARC Research highlights the importance of the FDA’s role in site and trial inspections.
The agency should always look into safety and ethics of the trial data, of course, but also consider whether only foreign data has been submitted to support an application, Jasko argues.
If data from multiple countries has been submitted, the agency will need to determine how this corresponds with data from the US. This is set out in Section 569B of the Federal Food, Drug, and Cosmetic Act, which holds data collected both inside and outside of the US to the same quality standards.
While working according to standards is vital to a successful clinical trial, it is essential that researchers balance the pursuit of harmonized standards with cultural variations in particular countries.
Christine Hauskeller. Ph.D. urges clinical teams to bridge this gap so that researchers, patients and local ethics committees are all satisfied. Each country will have specific cultural and institutional practices to which they adhere, such as patient insurance and autonomy. Failing to address these differences could affect the running of the trial as well as data capture.
Despite the number of multinational trials increasing by 50 percent from 92 countries to 140 between 2006 and 2016, logistical, regulatory and ethical concerns persist in some countries.
Take India as an example, Nicola Goatman at Medical Research Network writes. With about 67 percent of its population living in rural areas, many people lack access to healthcare resources. The result is that a large number of patients have to travel far for treatment.
Transportation issues impact trials in a number of areas around the world, including the US. The result is often damaging to study enrolment. And in a country such as India, with far fewer resources, there are also linguistic barriers, cultural differences and regulatory differences, making the risk to sponsors high.
With trials already being an expensive endeavor, sponsors might be reluctant to take on these additional risks, Goatman argues.
Regulatory differences can be difficult to navigate, says Lindsey Costello, senior project manager in outreach at Praxis Patient Recruitment. Researchers should investigate how a country’s regulations might affect any and every part of the study design.
Finding this out, Costello argues, requires open communication with regulatory agencies from the very beginning of the research and planning phases.
Communicating in a patient’s primary language is not only important for trial recruitment and enrollment, but also for informed consent. And informed consent is particularly important these days as trials have adopted a more patient-centric approach with greater patient engagement.
Jeffrey Litwin, M.D., cofounder of Patient Genesis, notes that before enrollment, patients need to read the informed consent form (ICF). This can often be around 20 pages long full of legalese and medical terminology that can be difficult to understand even when read in the patient’s primary language.
This is why it’s useful for sponsors to run a trial in a country with an existing and reliable group of translators, or where this can be quickly formed, Lisa Henderson, group content director at Applied Clinical Trials, writes.
The information most important to patients, such as benefits and risks, is often hard to find in the ICF, Henderson argues. This makes the matter of informed consent complex. And even more so when dealing with different countries, with different languages, cultures and regulations.
Sponsors and CROs need to make sure the ICF is clear and easy to read and understand even for people with low education levels, Henderson explains. Alternatively, technology such as electronic consent forms, can assist patients with comprehension tools, including videos, images and recordings.
Trials conducted in multiple countries present an untapped source of patients for many US pharma companies. Not only do international trials allow for more tests on a wider range of patients, they also provides clinical research and treatment to many developing countries that would not ordinarily receive it.
However, language barriers and cultural differences can become detrimental stumbling blocks barring the way to clinical success. To overcome these challenges, researchers must learn about and show respect for patients’ cultural needs. Plus they will have to provide clear and easy to understand information in patients’ primary languages.
Images by: elnur/©123RF Stock Photo, beer5020/©123RF Stock Photo, jackf/©123RF Stock Photo