Clinical research translation affects almost every global study. Understanding the translation process and the planning required can help keep your study on track.
Clinical trial statistics can be surprising. We frequently write about different aspects of the growing complexity of global clinical trials. Despite the added complications of conducting a study internationally, a review of urologic oncology trials actually found that single-center trials and trials with exclusively U.S. sites were among those most likely to fail.1
Several sources estimate a roughly 20 percent failure rate for cancer-related trials in general due to poor participant accrual.1, 2 Analyses of clinical trial failure rates suggest that multinational, multicenter trials with higher enrollment goals fail less frequently than other trials.1 Additionally, some advantages of global clinical trials include:
- Faster approval in the locales where the investigational product was tested
- Cost savings from faster recruitment and some areas have lower expenses
- Geographically diverse trial sites help ensure the investigational product is safe and works the same way in differing ethnic groups5
So, there is every reason to conduct trials internationally.
Global clinical trials
Conducting a trial internationally is not always in the original planning, and low initial enrollment can ultimately force a study to expand into additional countries. This comes at a huge cost by necessitating protocol amendments and the reallocation of funds away from planned tests and toward document translation. This is not uncommon.
For a real-world example, a study on ischemic heart failure initially planned exclusively for the U.S. and Canada was later forced to expand internationally due to poor recruitment. The costs associated with this unplanned expansion wound up diverting funds away from imaging studies, thus weakening the overall strength of the study.3
An international scope calls for translated materials and document translation to never be an afterthought. It is a key component of the project’s design, especially when patient centricity is one of the values embedded in the conceptual planning of the trial.
The importance of planning document management at the earliest stages of clinical study design cannot be overstated. This is integral to the subsequent success of a clinical trial. A 2018 review conducted by David B. Fogel highlighted factors associated with clinical trial failure, including “problems with patient recruitment, enrollment, and retention.”3 The review also points to a study of U.K. clinical trials (P. Bower et al.) indicating that “only 31% met enrollment goals.” It has also been claimed (Campbell et al.) that a third of publicly funded trials “required a time extension because they failed to meet initial recruitment goals.”
Where to start?
Clear writing
The sheer volume of documents needed for clinical trials is immense, ranging from complex protocols to simply worded participant thank-you cards. Whether we are talking about participant satisfaction questionnaires or informed consent forms that must pass legal and regulatory muster, information management becomes all the more complex when a trial is to be conducted across multiple languages. In this case, document translation is key to the success of the clinical trial.
Before even a single word of clinical trial materials is translated, it is important to bear in mind that the initial patient-facing materials of the clinical study should be written in plain language to communicate effectively. Using the principles of plain language fosters clear and understandable communication with increased comprehension and engagement for all literacy and educational levels. According to plainlanguage.gov, plain language is communicating in a way the audience can understand the first time they read or hear it.
Using plain and straightforward language is also important when writing materials that will be translated. Avoiding idioms, slang, colloquial phrases, abbreviations, and acronyms makes the text easier to translate. These documents set up the source documents for future translation steps.
Even some participants who decide to enroll in a study suggested to them by their doctor, dutifully sign an ICF, and go on to complete the clinical trial may later admit that they had not fully understood the ICF presented to them for the trial. Testing has shown that patient comprehension of clinical trial details is generally just as good when a simplified ICF is used.3, 4 You can surmise that nothing is sacrificed by the thoughtful simplification of patient-facing materials. Details do not have to get lost in the weeds of overly technical language.
Clinical trial translators
Because clinical trial materials are aligned with a protocol that has received regulatory approval, errors in translation can change the meaning of important content in study documents. This can cause protocol violations. Therefore, professional translators for clinical research need to have an excellent command of the language and they also need to have a medical/scientific background to understand medical terminology and the protocol. It is also important that they know local lingo so the participant materials are relevant and friendly to participants.
The clinical research translation process
The translation process includes an initial translation of a document. For example, a patient recruitment flyer is translated into the participant’s target language. This forward translation undergoes an editing and quality assurance check. Translation memory (TM) software may be used to streamline the entire process and produce consistent results across multiple teams and projects by leveraging existing, tried-and-true translation knowledge. No need to reinvent the wheel. After the quality assurance check, the document is then sent to the client for review, preferably by the in-country managers.
Sometimes, based on the type of document and sponsor requirements, a back-translation is made of the translated text from the target language back into English. This produces an English-language document that can be checked side-by-side against the original source text. The back translation is typically a blinded one. This means it is produced by a translator with no access to the original source document. Afterward, a comparative review of these documents can turn up deviations that need to be addressed.
Documents such as patient-reported outcomes (PROs) usually go through a rigorous linguistic validation process. This involves more than one forward and backward translation from independent translators. The reconciled version of the translated document is forward and back-translated, reviewed, and then tested on a panel of patients living in the target country. Based on feedback from the panel, the document is edited before delivery to the client. This is to ensure data, like PROs, maintain the validity of the data collected across multiple languages.
The design stage
Next is the design stage, and the formatting, called desktop publishing (DTP). Dealing with multiple languages that use different alphabets, characters, and text writing direction (left-to-right, right-to-left) can make DTP challenging. When the original design is done for clinical trial materials, allowances for text expansion and contraction must be planned for. Text expansion and contraction is a phenomenon related to differences in the number of words languages may employ to express the same idea. A sentence in one language can be shorter or much longer in another language.
To understand the importance of considering foreign language expansion/contraction, think of the carefully sized text box you may have on the front page of your informational brochure, where it neatly holds the clinical study name within its margins. You don’t want the foreign language version to have letters awkwardly sticking out of the box on either side, do you? Unless planning for DTP formatting is included as part of the process, such a thing can easily happen with translated text expansion. The size of the material, the amount of text, and the design itself must allow for this expansion.
Clinical research translation management
One of the great challenges with clinical research translations (some might call it a nightmare) is managing the translation process. Part of this process is keeping track of the document versions at every stage. A robust quality management system is highly important and valuable to navigate necessary changes in documents when protocol amendments take place.
Conclusion
The translation of clinical trial materials is a paramount task, but a necessary one that is crucial to participant recruitment and the overall outcome of a clinical trial. Performed with efficiency and done well, the effort will enhance recruitment and retention, helping to ensure trial success.
The Imperial Advantage
Many sponsors and CROs rely on several vendors for the different processes needed to create, design, and translate study materials. Imperial’s single workstream model streamlines these interlocking processes to integrate not only the clinical research translation processes outlined above but also the DTP design/layout considerations and a translation management system certified to ISO 9001:2015 by Intertek. Imperial has everything necessary to produce print-ready materials in all the languages required for your clinical trial.
Product realization from design to translation to delivery, within a single organization and tied to a robust quality management system, is key to the success of a clinical trial. Contact us for more information on how Imperial can help with your clinical trial translation needs.
Sources:
- Stensland KD, McBride RB, Latif A, Wisnivesky J, Hendricks R, Roper N, et al. Adult cancer clinical trials that fail to complete: an epidemic? J Natl Cancer Inst2014;106 10.1093/jnci/dju229.
- Khunger M, Rakshit S, Hernandez AV, Pasupuleti V, Glass K, Galsky MD, et al. Premature Clinical Trial Discontinuation in the Era of Immune Checkpoint Inhibitors. Oncologist2018;23:1494–9. 10.1634/theoncologist.2018-0003.
- Fogel David B. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review Contemporary Clinical Trials Communications September 2018, Vol. 11, pp. 156-164. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092479/
- Davis, Terry C., et al. “Informed consent for clinical trials: a comparative study of standard versus simplified forms.” JNCI: Journal of the National Cancer Institute90.9 (1998): 668-674.
- Lang T, Siribaddana S. Clinical Trials Have Gone Global: Is This a Good Thing? PLoS Medicine2012 Jun; 9(6): e1001228. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373653/
