Regulatory Considerations for Paper COA Translations | What You Need to Know
Collecting data for a global clinical trial on paper COAs or managing a mixed-mode study that combines both paper and electronic formats means satisfying multiple regulatory bodies before a single patient enrolls. None of these entities operate on the same timeline or answer to each other.
While paper instruments might seem more flexible to deploy because they don’t require electronic implementation, there are still process considerations based on the instrument’s intended end use in the trial, as well as copyright holder requirements. Translation and linguistic validation follow a documented, sequential methodology that takes months and represent a critical milestone in study start-up, regulatory submissions, and readying materials for first patient in (FPI) dates.
Most of the frameworks that govern this process are guidance rather than legal requirements. However, regulators use them as benchmarks when reviewing submissions, particularly for new drug applications (NDAs), and many sponsors treat them as mandatory. The exception is copyright licensing, which is a legal requirement where applicable.
If your study uses electronic instruments, the submission process can be more daunting given the lengthier timelines and additional electronic materials involved. Our companion blog on eCOA regulatory submissions explains this in more detail.
Proactive Study Planning
Translation and linguistic validation for paper COAs take a minimum of 8 to 12 weeks on average, which is often longer than sponsors typically anticipate when building a study timeline. The full COA linguistic validation process includes concept definition, dual forward translation, reconciliation, back translation, resolution, cognitive debriefing or clinician review (depending on the type of COA), and a final report documenting every decision made along the way. As one phase of the broader COA development process, each step is completed sequentially, so adding resources won’t shorten the timeline while maintaining scientific rigor. For multinational studies, your language service provider (LSP) manages this process across all required languages simultaneously while ensuring harmonization among them.
The ideal time to engage your LSP is during protocol development, when the list of study countries is taking shape and the instruments are being selected. Waiting until the protocol is finalized means the translation process is already behind the study timeline before it even begins.
If translations already exist for a language in scope, they may not automatically meet current ISPOR or FDA standards and could require additional work before they can be considered linguistically validated.
Regulatory Guidance for Paper COA Translation
These bodies don't oversee the same stages of the translation process, nor do they ask for the same documentation. Some set guidelines for how submissions are structured. Others define how the translation should be done.
IRB and Ethics Committee
Ethics committee and IRB submissions typically include patient-facing materials, such as COAs. While specific requirements vary by country, the expectation that COAs be included is generally consistent across regions.
ICH E6 Good Clinical Practice
ICH E6 establishes the international standard for good clinical practice in trials involving human subjects. It doesn't prescribe how COA translation should be done, but it requires that participants understand what is being asked of them and that every step of the process is fully documented for verification. A translation produced without a documented process creates a compliance gap under GCP regardless of its quality.
ISPOR Good Practices for PRO Translation
ISPOR, the International Society for Pharmacoeconomics and Outcomes Research, established good practice guidelines for PRO translation that have become the closest thing the industry has to a universal methodology standard. Before these guidelines were published, there was no consistent framework for translating these instruments. Today, regulators use them to evaluate sponsor methodology during the review process.
FDA PRO Guidance for Industry
The FDA's 2009 PRO guidance sets out what the agency expects when patient-reported outcomes are used to support a labeling claim in clinical outcome assessment submissions. For translation, it reinforces the ISPOR standard: the agency expects sponsors to demonstrate that their instruments were translated using a documented, validated process and that conceptual equivalence was maintained across languages. Like ISPOR, this is guidance rather than regulation, but it functions as the benchmark reviewers apply when evaluating PRO data.
These bodies don’t operate on the same schedule or coordinate with each other. However, you can satisfy all of them by producing a translation to ISPOR standards, documenting it to GCP requirements, and clearing the copyright before work begins.
Conceptual Equivalence in COA Translation
COA translations require more than linguistic accuracy because conceptual equivalence demands that the instrument measure the same thing across every language in the study. When a translation uses the dictionary definition of a term instead of accounting for the clinical intent behind it, patients in different countries are no longer answering the same question, even if the translation is technically correct in a literal manner. Pooling that data as if they were equivalent introduces an error into the study results.
ISPOR's methodology includes cognitive debriefing to help prevent this issue for patient- and observer-reported outcomes. Before the instrument is used in a study, a small group of respondents in the target country tests the translation to verify that it elicits the clinical response it was designed to capture. This step helps ensure conceptual validity and equivalence between the target language and the source.
Copyright and Instrument Licensing
Many established COA instruments are protected by copyright, and the rights holder has to authorize translation before any work begins. Unlike the regulatory frameworks covered above, this is a legal requirement, and proceeding without authorization exposes the sponsor to liability regardless of how well the translation was executed.
Copyright holders review translation requests on their own timeline and may require approval of the methodology or the translated output before authorizing use. That review is outside the sponsor's control, which means licensing has to be initiated before translation begins, not alongside it.
For instruments that will also be deployed electronically, a separate license is typically required for the digital version. Sometimes this is held by a different entity than the one that controls the paper rights.
Planning Your COA Translation Strategy
Paper COA translation involves licensing, methodology, and regulatory submissions that may not align with one another or with the overall study schedule. Sponsors with experience in this area know that licensing must be underway before translation can begin, that existing translations may not meet current standards, and that the methodology regulators expect is more rigorous than standard document translation.
TransPerfect's COA Solutions practice has extensive experience working with copyright holders and instrument developers, along with the linguistic validation expertise to manage the entire process, from licensing through the final report. Contact us to speak with a COA expert about your study's translation and licensing needs.