Over 25 years of experience have taught TJC Global, a translation company situated in the heart of Oxford, that the importance of translation in clinical trials is often overlooked. This article briefly summarizes the need for accurate, lucid and reliable clinical trial documents at every step in the research and development of a new drug, and explores the role translation has in ensuring that this is preserved.
The Requirements of Clinical Trial Documents
The preparation of original PRO (patient reported outcome), ICF (informed consent form) and other clinical trial questionnaires, forms and documents is universally acknowledged to be a meticulous process, a process in which mistakes simply cannot be tolerated – inaccurate or poorly worded documents jeopardise the informed consent and well-being of those individuals taking part in the trials, and more fundamentally have the potential to invalidate the results of the trial itself.
Aside from these obvious implications, the research data gathered by clinical trials must be scrutinized by an independent authority; any miscommunication incurred by the original trial documents is liable to render that part of the research data unusable.
If we briefly consider the implications that this has for the profit margins of the companies undertaking such research, the importance of faithful translation of precisely written documents at every stage of the research phase becomes yet more startlingly obvious: put succinctly, if a portion of research data becomes unusable, a delay will almost certainly ensue.
Of course, delays erode profit margins in any business; within pharmaceutical businesses, however, their effects are magnified. Figures such as the $820 billion forecast for pharmaceutical sales in 2009 belie the sensitivity and exposure to loss that afflict those undertaking original research and development of products: estimations for the cost of developing an innovative, approved drug vary wildly and are likely to have increased considerably in recent years, but they are frequently in excess of $1 billion.
The 20 year patent protection period is another figure which masks the true size of the margins involved: typically, a company will be left with less than 10 years in which to earn back the research and development costs before the market is available for generic knock-offs to exploit. Accepting 8 years as a representative time-frame in which the approximated $1 billion costs may be recouped, and allowing for the drug to do nothing more than break even, the true cost of the delays encountered incurred in the trial is sobering – every day the trial is delayed incurs a loss of revenue in excess of $342,000.
Problems of Translation and the Role of the Translator
These social, scientific and economic considerations underpin the process by which original clinical trial questionnaires, forms and documents are created; they account for the unique degree of precision that is required.
The need for this precision to be preserved in the translation of these documents is implicitly recognised and addressed by the stringent guidelines that accompany the process of translation – for example, organisations from Rotterdam (EuroQol) to Boston (IQOLA) publish guidelines governing the translation of trial questionnaires. This process typically involves a team of translators, working independently, who are then individually and collectively evaluated before a ‘reconciled’ translation is produced. The subsequent multiple, independent back-translation of this provides a means of comparing the translation with the original; it provides an indication of the level of dynamic equivalence between the two.
With an increase in the number of clinical trials taking place in EECs, Asia, Latin America and Africa, the role of translation has never been so crucial, and the challenges have never been so prominent. Yet, translation is not a word for word exchange, striving to keep notions of formal equivalence or faithfulness; rather, it is a complex and varied process of adaptation, always aiming for this dynamic equivalence.
This dynamic equivalence ensures that the new text bears the meaning conveyed in the original language, whilst retaining the syntactical, grammatical and idiomatic qualities of the new language. Etymologically, the Latin root for translation, ‘a transporting’ or ‘bringing across’ of information further illustrates the redundancy of the ignorant view that translation is merely an equational, mathematical process.
Cultural sensitivity, for example, becomes key when we consider that the idea of willing consent is primary to the ethical obligations of a trial, as stated in the Nuremberg Code and the Declaration of Helsinki: in some cultures it is customary for male members of the family or community leaders to take decisions on behalf of women, children or other community members.
This poses multiple problems to the notion of informed consent which must be addressed – participants must not only be aware of all potential risks or adverse effects, but also that they are able to withdraw at any point during the trial. The wording of the form must be culturally sensitive; even the fact that a written form must be used at all becomes problematic in cultures with low literacy levels, where it may be more appropriate for witnessed, verbal consent to be used instead.
There might be additional problems in the complexity and technicality of the wording which need to be addressed before the subjects can be fully aware of the purpose and processes of the trial – for example, many languages simply do not have corresponding words for terms such as ‘placebo’, and the very concept of a ‘placebo’ does not exist in some cultures. Ultimately, it is the responsibility of the translator to ensure that the subject has fully comprehended the document.
However, the role of the translator is not restricted to the reception of trial documents: it is equally as vital that subjects are able to communicate any issues, especially those which may act as contradictions for the drug being tested, to those running the trial. Patients will not have full knowledge of technical medical terminology; only accurate translations, borne out of a familiarity with the idioms of a culture and its language, can avoid potentially harmful and dangerous consequences, maintaining the requisite efficiency and effectiveness of the trial.
The extraordinary demands placed upon any trial document, and the need for these demands to be met in multiple media and languages, emphasises the necessity of finding skilled and experienced native speakers. Only then can a translation be produced which reliably withstands the cultural, linguistic and technical demands placed upon a document by those who will use it, from trial subject to chief executive of the medical research council.
Time-consuming mistakes and misunderstandings in translation are simply not an option. This is where companies such as TJC Global come in: with a wide and experienced team of specialist translators and interpreters, we offer a service which, without exception, meets the dual requirements of accuracy and efficiency as stipulated by our clients.
Our situation in the heart of Oxford, one of the country’s chief seats of learning and research, is critical to the service that we offer: it has allowed us to build an extensive network of links with pharmaceutical and biomedical companies; it places us directly alongside, among others, important research centres such as the Weatherall Institute of Molecular Medicine, the Sir William Dunn School of Pathology, the Medawar Building for Pathogen Research, the Wellcome Trust Centre for Human Genetics, the Nuffield Department of Medicine (containing the Clinical Trials Service Unit and Epidemiological Studies Unit, two world renowned research units), and the John Radcliffe Hospital.
There is increasing recognition that it is no longer practical for manufacturers to undertake their own clinical trials; the objective and impartial role of an academic group – such as those based in Oxford, close to TJC Global – is invaluable to pharmaceutical companies in ensuring the credibility of the trials and the negotiation of stringent regulatory conditions. Translation is often the last step in this process, and yet is seldom given the consideration that it requires.
As experienced translators of all the vital documents in a clinical trials – from CRFs, ICFs and PROs to information leaflets for trial subjects – as well as papers publishing trial results and patents and marketing materials associated with the release of a drug, TJC Global frequently employs specialist translators with expertise in relevant pharmaceutical fields. All of our translators are native speakers of the target language who fully understand and are able to create the dynamic equivalence so critical to the ‘bringing across’ of meaning from an original document into one for reception in either the developing or developed worlds.
Our experience and location have afforded us an excellent understanding of the demands placed upon a translation in the field of clinical research and development, and the services that we offer reflect this at every step. The implications of an inaccurate or inefficient translation are too serious to ignore.