Translation of clinical trial documentation: protocols and informed consent

In recent years Georgia has become an active base for international clinical trials: sponsors and contract research organisations (CROs) conduct multicentre trials here, and Georgian clinics and investigators join international projects. Every such trial begins with a package of documents that must be submitted to the ethics committee and the regulator in Georgian. The translation of clinical trial documentation is the stage of this process where one inexact wording delays the project by weeks, and an unclear translation of the informed consent calls the patient's rights and the validity of the trial into question.

What documents make up a clinical trial package

• The trial protocol and its amendments: trial design, objectives, inclusion and exclusion criteria, visit schedule
• The informed consent form (ICF) and the patient information sheet, including parental consent and the minor's assent in paediatric trials
• The investigator's brochure (IB): a summary of the preclinical and clinical data on the investigational product
• Patient diaries and questionnaires: quality of life scales, symptom diaries, PRO instruments
• Case report forms (CRF) and the instructions for completing them
• Safety reports: serious adverse event (SAE) reports, SUSAR notifications, DSUR
• Correspondence with the ethics committee and the regulator, opinions, approvals
• Clinical trial agreements (CTA) between the sponsor, the CRO and the research site
• Patient recruitment materials: advertisements, brochures, telephone scripts

The informed consent form: precision and clarity at the same time

The informed consent form is the most sensitive document of a clinical trial, because it is the only one the patient reads and signs themselves. The Declaration of Helsinki and the ICH-GCP guideline require that the patient understands exactly the purpose of the trial, the procedures, risks, benefits, alternatives and the right to withdraw from the trial at any time.

The translation challenge is twofold. On the one hand, the medical content must be identical to the English original, because the sponsor and the ethics committee compare the translation with the original. On the other hand, the text must be written in such Georgian that a person without a medical education understands it without additional explanation. That is why two people work on the ICF translation: a medical translator, who ensures the accuracy of the content, and an editor, who checks the readability of the text. "Randomisation", "placebo" and "double-blind" must be conveyed in the Georgian ICF with exactly the explanation the original provides, no more and no less.

The ethics committee often returns a package precisely because of the ICF translation: overly technical language, a risk description omitted from the original or an unclear wording about the right to withdraw from the trial. Our translations are checked against these criteria in advance.

Protocol translation: terminological consistency

A trial protocol is often a 100-200 page document in which the same term is repeated hundreds of times. If "primary endpoint" is rendered one way in one place and another way elsewhere, the document loses credibility for the investigator and the monitor. That is why we begin work on a protocol by creating a terminology base, which is agreed with the sponsor and then used identically in every accompanying document (ICF, CRF, diaries, amendments).

The highest-risk blocks are:

• the inclusion and exclusion criteria, where one "and" or "or" decides the patient's enrolment
• the dosing scheme, dose modification and discontinuation rules
• the classification of adverse events (AE, SAE, SUSAR) and their severity grade according to CTCAE
• the visit schedule and the permitted time windows
• the statistical analysis section, where the terminology must match the biostatistical standard

Patient questionnaires and linguistic validation

Quality of life and symptom questionnaires (PRO instruments) are not translated by ordinary translation. The questionnaire authors and sponsors require the international methodology of linguistic validation:

• two independent forward translations
• creation of an agreed version (reconciliation)
• back translation by a translator who has not seen the original
• comparison of the back translation with the original and correction of discrepancies
• cognitive debriefing with patients, which checks that the questions are understood the same way
• a translation certificate confirming every stage of the process

We carry out this process in full and provide the sponsor with the documentation of each stage.

Regulatory and ethical requirements in Georgia

To start a clinical trial in Georgia a positive opinion of the ethics committee and a permit from the regulatory agency are needed. Both bodies require the patient-facing documents (ICF, information sheet, diaries, recruitment materials) in Georgian, while for the protocol and the investigator's brochure they often accept the English version accompanied by a Georgian summary. We know which document is required in which format and prepare the package so that the submission goes through the first time. Where needed we certify the translation with the agency's seal or notarize it, which some sponsors require under their internal procedures.

Version control and confidentiality

Clinical trial documents are alive: the protocol goes through amendments, and the ICF is approved as a new version after every change. We keep the version numbering and dates identical to the original, and in the case of an amendment we translate only the changed fragment and leave the rest of the text unchanged, so that the ethics committee can compare easily.

The data on the investigational product are the sponsor's trade secret, and patient data are a special category of personal data. Every translator and editor works under an NDA, files are transferred over an encrypted channel, and where needed a data processing agreement (DPA) is signed with the sponsor.

Frequently asked questions