gms | German Medical Science

Introduction: Completing an international multicenter trial involves the successful negotiation of many challenges. One review of the literature found that the issues which most arose in studies on international multisite trials were human rights, informed consent, patient recruitment, and data collection [1]. Other researchers see the challenges of internationally conducted studies as also encompassing increased study complexity, standardization of protocols and procedures, the potential for increased costs, and communication difficulties due to language barriers [2]. To this can also be added openness to change, the remote nature of site set-up and coordination, differences in cultural norms and perceptions, and differences in healthcare structures [3].

These are all factors with the potential to influence the success of a study. Multicultural issues are increasing because clinical trials are increasingly conducted in more diverse locations. A review of 150 articles published in 1995, and another 150 articles published in 2005 in the New England Journal of Medicine, the Lancet, and the Journal of the American Medical Association, found that the number of countries outside of the US where trials are being conducted had more than doubled within a decade [4]. However, all of the extra work associated with multicenter trials is generally worth it because although studies may take longer to get started, they tend to finish earlier [2], [4].

It is important to state from the outset that all cultural observations in this abstract are not stereotypes but generalizations which may or may not apply to someone from a particular culture or to a particular situation [5]. It is also important to keep in mind that we all have our own cultural background and baggage which may bias observations or interpretations of culture [6], [7].

We will now examine one specific issue which arises from clinical studies conducted in different cultural settings. Multicultural use of outcome measurements. The two main issues in using outcome measures in international multicenter trials are measuring the same data at each site (i.e. the same variable) and obtaining the same data (i.e. overcoming infrastructural and environmental barriers to collect the necessary data) [8].

Although many outcome measurement instruments are freely available online, their use in clinical studies conducted among different cultures may be anything other than simple. Take Japan for example. Japanese people may sit on the floor for cultural reasons leading to a higher level of incidence of knee osteoarthritis than in other populations [9]. A question on difficulties related to sitting will have a different meaning in Tokyo compared to Tennessee. Similarly, how should someone who eats using chopsticks answer the question relating to the difficulty of eating with a knife/fork in the Michigan Hand Outcome Questionnaire [10]? Indeed, activities which are not done by patients have been identified as a weakness of this particular outcome measure [11].

Validating outcome measurements is a difficult but necessary task. It may be the case in international multicenter trials that instruments are not available in the local language of one or more of the clinics. This means either forgoing this element of the study in those clinics or developing a local language version. However, the problems of using these instruments to clinically assess patient progress may well extend beyond simple translation. Other researchers note the need to cross-culturally adapt outcome measurements developed elsewhere. For example, a team in the Netherlands translated and cross-culturally adapted the PROMIS physical function item bank to the Dutch language. Since Dutch streets are irregularly shaped, unlike in the US, the question, "Are you able to walk a block on flat ground?" was changed to "Can you walk 150 meters on flat ground?" to make it more understandable to Dutch people [12].

The pain element of an outcomes measure may differ from culture to culture. Filipino [13], Japanese [8], and Irish patients [5] have a tendency to minimize expressions of pain compared to other patient groups. A lack of knowledge of these cultural issues on the part of the treating physician may have unintended yet serious consequences [5].

Patient-reported outcomes can be a confounding factor if they have been translated but not undergone a process of cross-cultural adaptation and testing. This involves forward and back translating as well as synthesis and expert review [14]. The importance of scrupulously checking translations and back translations in multicultural studies has been previously noted [3].

Our research organization has experience in the cross-cultural adaptation of outcome measures as part of our studies. However, each time we have to do so it takes up valuable time. It also means that clinics where the new version of the outcome measure is required are unable to begin recruitment until the rigorous validation process (including testing) has been completed. Outcome instruments intended for use in a study should be carefully chosen, with their availability in local languages also checked before the protocol and site selection are finalized.

Conclusions: The literature we reviewed along with our real-life experience indicates that organizations engaged in multicenter, international studies should be aware that a "one size fits all" approach to clinical research is simply not possible. CROs cannot expect to 'fly in' to countries and replicate their own work processes and so on without some adaptions to suit the culture they are operating in. Equally, there is also no "one size fits all" solution to the problems posed by multicenter and multicultural challenges.

A myriad of possible barriers to success exist, from the easily identifiable to the more intractable problems. We would also like to repeat the caveat that the opinions contained here reflect our organization's experience from conducting clinical research in over 40 different countries and may not reflect the experience of others.

In closing, just as we say in Evidence-Based Medicine that evidence cannot make the decision for you, it can only guide you, the cultural problems faced in international clinical research cannot be solved by generalizations, but have to be tackled on an individual basis as every case is different.