Clinical trials, both ongoing and new, were greatly affected by the COVID-19 pandemic and the public health measures taken to control its spread. This produced a shift in the acceptance of decentralized clinical trials (DCTs), leading to a significant surge in their adoption.

With improved guidance and the maturation of digital health technologies (DHTs), decentralized clinical trials are here to stay. This is excellent news in many ways: DCTs provide a path to addressing tough, longstanding challenges in clinical trials. Properly planned and executed, DCTs allow for accelerated cohort recruitment and clinical development timelines. Additional benefits include enhanced retention, better participant adherence, greater diversity, and more representative patient access, leading to a more robust evidence base.

However, DCTs are also associated with a significant increase in complexity. Challenges range from regulatory compliance to data collection and patient engagement. The use of DHTs can add another layer of complexity. Things become even more intricate when trials are conducted across multiple countries, cultures, languages, and even language variants. 

Although the FDA’s draft guidance defines DCTs as clinical trials in which some or all of the trial-related activities occur offsite, most DCTs use something of a hybrid model: Participants are given the option of using telehealth services or local HCPs for certain scheduled visits and tests. 

This necessitates a larger number of stakeholders, including study teams and offsite team members, HCPs, or medical facilities close to participants. In addition to challenges related to ensuring compliance and data privacy in these settings, clear communication is of the essence. This is important not only for seamless execution but also to ensure participant safety, data quality, and patient engagement.

Patient Engagement and Plain Language

Patient engagement is critical for any clinical trial’s success but crucial for DCTs. Participants need to be provided with clear, concise information about the trial in plain language that is easy to understand. If trial participants comprehensively understand what the trial is about and what is expected of them, they are more likely to adhere to the protocol, remain engaged, and provide accurate information, which is essential for data integrity.

Communication is Key

Effective communication is crucial in ensuring the successful execution of a DCT. In a traditional setting, investigators and patients interact face-to-face. In contrast, in a DCT, they may never meet in person, making it significantly more difficult to establish a rapport and build relationships. This challenge is only increased when participants speak a different language. Cultural differences and language barriers can further impede trust and lead to misunderstandings and errors. 

Implementing a strategic communication plan that includes translation, localization, and other language services is essential to overcome these issues.

The Role of Translation

To run a decentralized trial involving non-English speakers, several documents require translation. These could include, but are not limited to:

1. 1. Protocols
   2. ICFs
   3. Patient Information Materials (brochures, presentations, video scripts, subtitles, etc.)
   4. Case Report Forms
   5. Investigator’s Brochure
   6. Data Privacy Documents
   7. Referral and Recruitment Letters
   8. Recruitment Posters
   9. Instructions for Use (if devices are used)

Which materials need to be translated may vary depending on factors such as local regulations, the product being investigated, the specific requirements of the study, and the country or countries involved. 

Generally speaking, both the FDA and EU authorities require professional translation of all patient-facing materials into a language the participant understands. The EU-CTR further stipulates that translations be provided in the respective country’s official language (or languages).

This can prove more complex than it sounds: some EU countries have multiple official languages, and language variants such as US and UK English must be considered. For instance, a document translated into French for use in France would require adaptation for French-speaking participants in Belgium, Switzerland, or Canada. Also, consider that, especially given immigrant and refugee populations, some participants may speak another language altogether, for instance, a Turkish speaker living in Germany or a speaker of Haitian Creole speaker in the US. 

To ensure compliance, data quality, and a superior patient experience, a high level of expertise and attention to detail are necessary in the translation process. These services are best provided by experienced translators, editors, and proofreaders who are subject matter experts and attuned to the target audience’s culture.

Finding and selecting these professionals is an added challenge. This is where experienced, specialized language service providers (LSPs) with the necessary resources, skills, and subject matter expertise come in. They can help quickly put together the right team and ensure that all materials are provided on time and in the necessary quality for the seamless rollout of a DCT. 

Minutiae that Matter

Translations, as per regulations, must be consistent. This means that apart from the skill, expertise, and cultural competence of the translator, resources such as terminology databases and translation memory software must be developed and well-managed. Consider a scenario, for instance, where a trial has adult and pediatric participants who speak a language that uses formal and informal forms of address, such as German or French. In these languages, the formal form of address is often used for adults, whereas the informal is used for children. While large parts of your informed consent and assent forms may be identical in English, these documents must be adapted – and the translation memories properly managed – to avoid mixing the forms of address and potentially alienating participants and undermining trust. On a larger scale, this could significantly impact recruitment efforts.

The Importance of Subject Matter Experts

Those outside the translation and localization space often assume that anyone who speaks a language must be able to translate. In fact, having an excellent command of two languages is only the first prerequisite for translation. Translators need to fully understand all the implications of what they are translating and have a good knowledge of the appropriate vocabulary. Subject matter experts are absolutely essential.

Digital Health Technologies and Localization

Software localization refers to the process of adapting the content and user interface – the entire digital user experience (UX) – of apps and software to suit a specific region’s language and cultural norms. DCTs have increased the reliance on Digital Health Technologies, making software localization essential to effective communication and data collection. This also includes aspects such as units of measurement, address, number, time and date formatting, holidays, and societal expectations. 

For example, if you were to instruct a clinical trial participant in the US to enter their temperature in degrees Celsius, this could cause confusion and frustration that could impact data quality and participant retention. Listing dates in a format different from your target user’s expectations can lead to missed appointments.

Localization also addresses issues such as how content is displayed on a screen. For instance, not all languages read from left to right, so design adjustments may be required. Significant text expansion can be expected in some languages, such as when translating from English into German. This can be challenging, especially on small screens like smartphones or tablets often used in DCTs. Expert translators with deep experience in software localization can help circumnavigate these issues. 

A Word about AI

You may be thinking: Why would I need human translators when generative AI is fast, reliable, (almost) free, and accurate? Why indeed?

While generative AI technology can be immensely beneficial, privacy concerns are an issue. In addition, LLM-based AI can come with consistency issues that impair communication and negatively impact compliance.

Most importantly, as powerful as these tools are, they cannot empathize with participants and make crucial cultural and linguistic decisions based on these insights. Consider, for instance, the simple matter of how to address someone: Should you use the formal or the informal form of address? First or last name? What about pronouns and gendered language in more or less conservative cultures? Details such as these, which may seem insignificant to a non-expert, can strongly impact recruitment, engagement, and retention. 

In translating from one language to another, we have to remember there is rarely an exact 1-1 match for a term or a turn of phrase that is not only correct but also the best choice in every situation.

Lastly, participant-entered data is not infrequently fraught with typos, non-standard grammar, and unusual or regional phrases. When the source content does not neatly fit into patterns, AI tools can often produce wildly inaccurate renderings. In these situations, a skilled human translator with the required expertise can help ensure an error-free rendering and, by extension, regulatory compliance and the validity of your data.

Conclusion

Decentralization in clinical research is an innovative approach with many benefits. However, DCTs also come with a set of unique challenges, including communication and language barriers. It is essential to develop effective communication strategies to ensure patient engagement and regulatory compliance.

When planning a DCT, developing a comprehensive communication plan that spans the entire research timeline is helpful. This plan should be developed early and revised as needed. An LSP such as Vistatec, who has experience in DCTs and understands the nuances of multilingual communication and regulatory requirements, can help. For assistance with developing and executing communication, translation, and localization strategies to ensure the successful execution of an upcoming DCT, contact us or see www.vistatec.com