Global clinical trials: be aware of the pitfalls
Though there are many benefits to conducting clinical trials in countries outside the US and Europe, there are also cultural and linguistic challenges to consider.
The globalisation of clinical studies is now well-established, particularly from the therapeutic exploratory stage of research onwards. Many factors draw drug developers to global, often emerging, markets. These include greater diversity and availability of patient populations, lower costs relative to the US and Europe and a looser regulatory framework, to name a few. However some stumbling blocks remain in global clinical development, particularly in large phase II/III trials. This article looks at some of the location-specific challenges that arise during study start-up.
The most fundamental challenge in taking a clinical trial global is linguistic; it is not simply a question of ensuring that the correct language is used for patient information, though this is worth double-checking in countries such as India, where the 2001 census recognised 30 languages with over a million native speakers and the 2011 census recognised a total of 1,635 languages.
The tone and register of documentation must also be appropriate. For example, an Informed Consent Form should be aimed at a reading level of approximately age 13, to ensure that the patient has understood the study and the procedures and treatment to which he/she is consenting. An Investigator's Brochure, meanwhile, is a highly technical document intended to be read by medical professionals and the register of both the original document and the translated versions should reflect this.
The ability of global study teams to communicate with local sites and regulatory agencies is crucial, and a good line of communication is indispensable if study timelines are to be met and the study is to be conducted effectively. This means that swift solutions must be in place for translating requests for clarification and responses to questions from regulatory agencies, often within a very short time-frame.
Study managers often find that version control and consistency of terminology is not maintained by their language service providers, such that a disease name may be translated differently across different documents or even within the same document, or a study title may be inconsistently rendered across different study documents. This can have huge financial impacts, particularly where study titles have already been submitted for insurance.
Partnering with a global language service provider which has highly developed translation productivity and quality assurance tools should mitigate the risks associated with these linguistic challenges.
Levels of literacy must also be considered. Areas of low literacy may impede investigators in the process of obtaining informed consent. There are different methods, such as video and audio, and electronic informed consent is certainly on the rise as an alternative to hard copy documentation (and as part of a general move towards electronic trial management).
Culture and infrastructure
The infrastructure at local site level varies considerably by geography; many regions of Africa, for example, have inadequate health infrastructure to deal with requirements (as the ongoing Ebola outbreak has reminded us), and this must be considered in light of the increased likelihood of protocol deviations as a result of differing health infrastructures and/or standards of care.
In Argentina three-quarters of clinical trial sites are located in Buenos Aires due to the highly developed healthcare infrastructure and availability of patients and investigators.
"Brazil, for example, is widely considered to have the lengthiest regulatory approval timelines in Latin America"
In addition to healthcare infrastructure the regulatory environment must also be considered. While moves have been made to harmonise global regulatory frameworks, there is still a great deal of work to be done to streamline regulatory requirements so that they are not only effective but also efficient. Furthermore, some countries have more complex and lengthy regulatory approval processes than others. Brazil, for example, is widely considered to have the lengthiest regulatory approval timelines in Latin America. This has an impact on planning and study milestones. The rules around import and export of Investigational Medicinal Products (IMPs) and their distribution also differ significantly by locale and must be taken into account.
The conduct of global clinical studies requires knowledge of, and sensitivity to, cultural norms in the study locations; for example, the relationship between doctors and patients in Japan, where patients are deferential and trust the word of their physician, should be taken into account. While this can be advantageous from a patient recruitment and retention perspective, it requires the sponsor to be engaged with the investigators and local physicians, as well as the local community.
In parts of Africa, meanwhile, the notion of individual informed consent does not quite match the traditional Western model, and the community plays a much more active role.
Cultural awareness training and global partners with local presence and knowledge of in-country customs are indispensable tools in the clinical development process, but protocol design must also take into account the ongoing globalisation of clinical research, and account for at least breathing space for differences of language, culture and infrastructure.
About the author:
Chris McCourt is a global consultant in SDL's Life Sciences Solutions division.
SDL is a top three provider of language, technology and business intelligence solutions to international pharmaceutical and medical device companies and contract research organisations.
Chris can be reached on firstname.lastname@example.org or +44 (0)7715 798981
For more information on SDL's portfolio of Life Sciences Solutions please visit http://www.sdl.com/solutions/industry/life-sciences/
Have your say: What hurdles have you had to overcome in running non-US or EU-based trials?