The Four Main Considerations For Translation Of Clinical Trial Protocols

A clinical trial protocol (CTP) can be regarded as a written agreement between the investigator, the participants and the scientific community. The protocol describes the objectives, design, methods, statistical aspects and organisation of a trial. Since clinical trial protocols are specialised, highly technical, complex documents, they call for an accurate, clear and unambiguous style of translation. The language of CTPs is a blend of medical, technical and administrative jargon and there is often an intermingling of terminology from multiple fields of medicine and laboratory practices that are unique to each individual trial. This is distinctly different from other documents that get translated in clinical trials like the informed consent documents and other patient-facing documents. These need translations that are within the comprehension of 6^th to 8^th graders as per the Institutional Review Boards (IRB) in the USA. Also, CTPs are supposed to be self-contained and has no need to refer to any other document or points of reference that should be taken into account while translating.

Inaccurate and poor translations can have very serious consequences. It may negatively impact the health of the participants, the outcome of the trial, revenue and the credibility of the trials. It can be extremely serious in terms of human lives, and economic revenues. It may cause emotional and physical damage, waste time and result in misconduct of the trial. In order to ensure that the quality of translations meet acceptable standards, we need to take into account the following:

Regulatory considerations: Clinical trials are, more often than not, a global affair these days. Consequently, translation of trial documentation are mandatory as per regulations. These regulations are stringent and vary from country to country. Depending on the country where it is being conducted, clinical trials are governed by the regulatory body that has jurisdiction in that country. For example, in the European Union one must comply with the regulations set by the European Medicines Agency and its Committee for Human Medicinal Products besides other local regulations. In China, the regulatory body is the State Food and Drug Administration. In Japan it is the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency. In the USA it is the United States Food and Drug Administration. In India the national regulatory body is the Central Drugs Standard Control Organization. This body has authority over the Drugs Controller General of India who is the final regulatory authority for clinical trials in India. In most cases, regulatory bodies and ethics committees make it compulsory for documents in local language to be submitted for review and approval. In the European Union, Commission Directive 2005/28/EC of 8th April 2005 came into force and set out detailed guidelines for good clinical practice. All clinical trials are carried out as per the Declaration of Helsinki. To provide a uniform standard and to maintain quality, safety, efficacy, and regulatory obligations to protect public health, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), takes into consideration the Good Clinical Practice now in vogue in the United States, Japan, the European Union, Canada, Australia and the World Health Organization.

Quality considerations: Language is “as critical as patient screening or any other trial preparatory component”. However, translations of clinical trial documents have often been found to be of poor quality. The possible reasons for this may be that translations are not given as much priority as they should be given which results in less than adequate time being allotted to it. It may also be because this genre of translations calls for a combination of professional translation skills, medical knowledge, knowledge of different regulations that govern clinical trials, and technological acumen to communicate and access data efficiently from various storage sources worldwide and to work with different software and tools in varied online and offline technological environments, which is not often found. Another possible reason may be that not enough attention is given to the needs of the readers of the translated documents. There are many known cases of translations where the source has been significantly modified leading to confusion necessitating reference to the main English documentation.

The common errors in translations found are inconsistencies in translating terminologies, inaccuracies and omissions. The failure to see the importance of a robust review process and the implementation of the same is the reason why we see such poor quality in the translated versions of clinical trial documentation. The International Society for Pharmacoeconomics and Outcomes Research provides a ten step approach to ensure quality for this specialized genre of translation which are preparation, forward translation, reconciliation, back translation, back translation review, harmonisation, cognitive debriefing, review of cognitive debriefing results and finalisation, proofreading and final report. Unfortunately, not all of these steps are always implemented into the review process due to the lack of time that would be needed to execute them to their fullest extent.

Technological considerations:  As clinical trials are now global affairs, technology plays an important role in enhancing data accessibility, assisting in data processing, promoting flexible workflow and improving strong regulatory compliance, and consequently generating a higher quality of data. In geographically distributed multisite clinical trials, different software and tools are used at different locations to collect and capture data, different web portal technologies are used to share information and communicate between clinical partners and regulators. New document formats defined by regulatory bodies like the ICH, for example the Structured Product Labelling (SPL) or the Electronic Common Technical Document (eCTD), call for efficient document management application software. Different data collection modalities are used at different sites like digital pens, tablets, touch screens and other hand-held devices and these calls for considering ways to handle issues regarding their adaptation for different geographies within a particular study. Since more often than not, the personnel involved in a study feel comfortable in their native language, all software graphical user interfaces, documentation, and eLearning materials should be localised in order to enhance compliance and the quality of clinical data and to ensure device effectiveness in patient reporting.

The translation arena has seen some major changes in its environment owing to the advent of the cloud technology. Different aspects of translation including its business end has found a convenient solution thanks to the cloud technology which provides a collaborative work environment across geographical boundaries bringing together divergent skillsets to work on a particular study. Issues related to translation, its review, audit are implemented into the translation process workflow with regulations compliance checks in place through sign-off tools. Clients of translation companies can now assign jobs; upload files, check work progress, and provide updates, through a secure cloud based web portal. The same portal also assists the translation company to assign jobs, track progress and assess quality, review jobs and provide feedback to individual translators of on-going projects within a particular study without losing time in any of the operational areas while maintaining quality. And all of this happens within a secure environment with minimal chances of data loss.

Cultural considerations: In a clinical trial spanning countries cultural considerations play an important role. They need to be taken into consideration and accommodated otherwise we run the risk of the trial being negatively impacted. Varying cultural values may impact the relationships amongst investigators, subjects and regulatory bodies. For the success of global trials the important cultural factors that need to be considered are the following:

i.                     Standard therapies available for the condition being investigated.

ii.                   Patient’s acceptance of “experimental” therapies.

iii.                  Patient’s and his/her family’s attitude towards mental illness.

iv.                 Attitude towards sensitive topics such as sex and habits.

v.                   Attitude towards responding towards limited efficacy of some therapies.

vi.                 The extent of education of the site population.

vii.                How the investigator presents the study to the participants.

viii.              Attitude towards ethics and willingness to follow instructions.

This list is by no means exhaustive and will vary from country to country. Various measures are adopted to overcome these cultural barriers. Appointing or contracting cultural experts, conducting orientation programs for staff from foreign sites are some common approaches used frequently to bridge the cultural barriers. For translations of study documentation, it is imperative that preference be given to native speakers of the country where the trial is being conducted.

In conclusion, we may sum up by saying that accurate translation of clinical trial protocols are an essential part of the study itself, not simply as a regulatory obligation, but also as a practical means to an end. The complete understanding of clinical trial documentation is essential and it makes sense to make them available to all involved parties in a language they are most familiar with. To overcome cultural and linguistic barriers, globalisation and localisation techniques along with translation resources need to be considered and planned from the early stages of planning the trial. The rapid proliferation of information technology has brought about a welcome change to the environment of clinical trials and how they are conducted. They have provided an almost seamless environment for translating trial documentation across all corners of the world and ensuring quality of the work and compliance with regulations. However, it also calls for translators who can combine translation skills, medical acumen and technological knowledge and adaptability to be able to fit into this fast changing information technology driven translation environment.