An essential phase of every drug development cycle is the clinical trial. As part of the clinical trial process, it is vital to collect data from trial participants to determine how their abilities, functioning or feelings are influenced during the study. This is accomplished using tools called clinical outcome assessments (COAs).
Before your product can hit the market, you must guarantee that the results of your COAs are valid and comparable worldwide. This is critically important; inaccurate translations of medical questionnaires can lead to copyright infringement and the retraction of permission for use by the copyright holders. Other potential problems include rejection by ethics committees, rejection of submissions by regulatory authorities, patient misunderstanding and unreliable data.
Linguistic validation is the solution to the translation challenges COAs present. The linguistic validation process is designed to ensure the COA translations are linguistically accurate and culturally and conceptually equivalent to the source instrument so that trial sponsors can capture the patient’s response as accurately as possible. It consists of forward translation, back- translation, reconciliation and cognitive interviewing.
To ensure a high level of precision, the translation process requires a reiterative procedure that typically includes:
- Translation and review by at least three translators, a project coordinator or project manager, a survey research analyst and a client, developer, or copyright holder (if applicable)
- Testing and validation of the translation through cognitive debriefing interviews with either native-speaking subjects or patients (depending on the patient population addressed in the clinical trial and the nature of the questionnaire)
Implementing linguistic validation is a requirement for pharmaceutical and medical device companies seeking approval of their products. Because of the critical importance of an exacting linguistic validation process and the impact the process has on clinical studies, public health regulatory bodies are diligent in their oversight, issuing recommendations and guidance to ensure that translation, cultural adaptation assessment and linguistic validation follow good practice methodology.
In 2005, the European Medicines Agency (EMA) issued a reflection paper on the use of patient-reported outcome (PRO) questionnaires in clinical trials. In 2009, the US Food and Drug Administration (FDA) issued a paper on PRO guidance.
Both the EMA and FDA have said they expect study sponsors to demonstrate that content validity and other measurement properties are adequately similar across all translated versions used in a clinical trial, and they expect to see evidence of the patient perspective when approvals are sought for new drug applications.
In June of 2022, the FDA released new guidance on the selection of COAs for use in clinical trials. The FDA recommends that linguistic validation (along with translation and cultural adaptation assessment) be conducted early in the COA selection and development process, and that “one approach is to describe in detail the process of language translation and/or cultural adaptation (including cognitive interviews) to support the quality of the resulting translation and/or adaptation.”
According to the FDA guidance, “A robust process of translation and/or cultural adaptation increases confidence that all trial participants, regardless of their language and/or cultural backgrounds, understand the measure’s instructions, items or tasks, and response options similarly.”
Our approach to linguistic validation
Governing authorities, patients, and the general public require and deserve medical products that have been through rigorous testing to ensure effectiveness and safety. And as shown, linguistic validation is a necessary and critical step in this development process.
RWS has mastered the complex and demanding practice of linguistic validation. Our linguistic validation process is modeled on the FDA’s guidance document and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) good practice guidelines. Our process includes the following key steps:
- Concept elaboration
- Dual forward translation
- Back translation
- Survey research analyst review
- Developer review
- Clinician review
- Client subsidiary review
- Recruitment of patients
- Cognitive debriefing of patients
- Data analysis and proofreading
- Validation reports and certifications
During harmonization, an RWS survey research analyst analyzes the source file and creates a concept elaboration guide. The guide breaks down each item of the questionnaire and explains wording that might have multiple interpretations or could be difficult to replicate in other languages.
The source English questionnaire is given to two independent RWS linguists, who separately create a target version of the questionnaire. They then reconcile the two versions of the translation and create a harmonized translation.
Next comes review, which first consists of a blinded linguist at RWS translating the harmonized version back to English. Our quality specialist and survey research analyst teams review the back translation and discuss issues or potential differences among the original English and the back translation.
Finally, we conduct cognitive debriefing with a sample group of patients from the target therapeutic area. During one-on-one interviews, the patients review the translation and provide their feedback. The linguists and the RWS project teams evaluate the feedback and implement solutions to the issues encountered. After the questionnaire is proofread and undergoes a quality control check, the translation is officially linguistically validated and RWS provides the certificate of translation.
As you have seen, linguistic validation of clinical outcome assessments is more than just a simple translation. It is a rigorous process that addresses the need for accurate translations while also helping prevent several potentially challenging difficulties that can accompany the use of COAs in clinical trials. These problems include problematic licensing and developer interactions, complications regarding the coordination of multiple parties, and migration delays and quality issues during electronic migration when the COAs will be administered electronically (eCOAs).
Finding the right partner
The RWS strategic approach is to manage and coordinate all the parties involved in the linguistic validation process. Our team is designed to address and solve your COA problems through a dedicated account team, end-to-end process management and eCOA process development.
You need a language partner to guide you through this process and industry thought leaders to help you choose the best instrument for your study.
RWS is the partner you need. Our expertise includes industry-renowned survey research analysts, an eCOA solutions team, the Linguistic Validation Center of Excellence for Quality, specialization in large and complex projects and more.
The RWS linguistic validation procedures exceed all industry standards. We are the market leader in linguistic validation and have been specializing in linguistic validation since 2002.
To ensure a successful product, linguistic validation must be done right. Contact us to learn more about how our team can help you.