Making it real!

Antoine Regnault1, Catherine Acquadro2, Ana Bayles3, Benoit Arnould4
1Research Director, Patient-Centered Outcomes, Mapi HEOR and Strategic Market Access
2Scientific Advisor, Mapi Linguistic Validation
3Operations Director, Mapi Linguistic Validation
4Senior Director, Patient-Centered Outcomes, Mapi HEOR and Strategic Market Access

Nothing ever becomes real till it is experienced – John Keats
The globalization of clinical research has fostered the need of patient-centered outcomes measures adapted for use in a multicultural context. In international multicenter studies, many efforts have been made to control the variability of biomarker measures (e.g., calibration and centralization) but not so much for patient-centered outcomes. Yet these are very likely to be culturally sensitive, and measuring them across different cultures certainly raises many questions. Beyond the theoretical question of the very possibility of a culture-free measurement of concepts in the health outcome field (i.e., debate between the relativist and absolutist or universalist positions of cross-cultural research),1 the question of how this can be achieved led to the development of theoretical models of cross-cultural measurement. Over more than two decades, Mapi has continuously strived to translate these theoretical models of cross-cultural measurement into practice and implement operational approaches that allow patient-centered outcomes to be assessed across different cultures in a scientifically valid way.

Mapi has been leading the development of the linguistic validation process, which allows new language versions of a measure to be obtained from an original master version (generally in English), using a standardized and rigorous method. Mapi has not only been a methodological leader for the linguistic validation process, and setting the rules,2-3 but has also significantly driven the implementation of the approach and its dissemination in the outcome research community for more than two decades. This has been achieved by steering early large international initiatives of linguistic validation, such as the International Quality of Life (IQOLA) project4,5 that aimed to translate and validate the SF-36 Health Survey for international use, and participating actively to international workgroups on the question (ISOQOL Translation and Cultural Adaptation Special Interest Group; ISPOR linguistic validation task force) but also by raising awareness of all stakeholders on the critical importance of the question by continuous pedagogical efforts. For example, many of the widely used and striking examples that demonstrate the importance, and challenges, of proper linguistic validation comes from Mapi’s experience (for example, how to translate “Are you able to cut your meat?” in India; or “do you have difficulties in shoveling snow?” in Egypt).
In addition, Mapi contributed to the regulatory efforts towards better cross-cultural outcome measurement in clinical trials by presenting to the U.S Food and Drug Administration and the PRO Consortium a checklist of criteria to evaluate linguistic validation processes (i.e., the Translation Evidence Tracking Tool).6

Mapi is still at the forefront of the research on linguistic validation methods and cultural adaptation of outcome measures. In the last decade, we have developed Translatability Assessment (TA) to evaluate the extent to which a PRO measure can be meaningfully translated into another language.7 The goal of a TA is to identify translation difficulties and thus suggest (a) changing the original wording of the item in the source language or (b) retaining the original wording in the source language and providing alternative wording on which potential translations in the target language may be based before embarking on the translation process in all the relevant languages that are to be used in the clinical trials. In a recent retrospective study,8 we have shown that TA confirmed problematic issues in items previously identified as having poor content validity or poor measurement performance. Also, Mapi has developed innovative cultural adaptation approaches for challenging and uncommon measurement situations such as adaptation of neurocognitive scales, which can involve the cultural adaptation of images, sounds, or stories.9-11
Cultural aspects should also be considered when it comes to developing a new patient-centered outcome measure. In this respect, simultaneous development has been recommended for the equivalence across cultures of concepts to be measured, as well as the way they are measured, to be optimized.12,13 In simultaneous development, major cultural issues in concepts and constructs measured are addressed before item development; items are developed simultaneously in several languages based on common, culturally relevant concepts and on patient wording in the different languages; and thorough cognitive debriefing testing is performed in the different languages. Simultaneous development is a powerful approach to avoid cultural standardization by providing an equal voice to each culture/language, but it obviously raises many practical challenges, in particular due to the need for multi-local fieldwork and international consolidation. Mapi has developed a pragmatic process that allows these challenges to be addressed efficiently. In this approach, the multicultural reality is taken into account at all stages: definition of the target population, development of study material (interview guides, codebooks), patient recruitment, interviews, data analysis, item generation, and questionnaire testing.

Finally, cross-cultural issues also arise when data are collected with patient-centered outcome measures within multinational studies. In particular, in this situation, evidence supporting the cross-cultural equivalence of patient-centered outcomes measures can be generated using quantitative analyses. Cross-cultural equivalence of patient-centered outcome measures is a complex concept and the most complete model describing it is likely the Universalist model of equivalence.14 It includes six different types of equivalence (Conceptual, Item, Semantic, Operational, Measurement, and Functional Equivalences) which cover comprehensively all aspects pertaining to cross-cultural equivalence.

Mapi developed an integrated approach that allows this model to be operationalized using quantitative methods such as measurement invariance and differential item functioning.15 This pragmatic approach was developed to be versatile enough to be adapted to any patient-centered outcome (symptoms, HRQoL, functioning, etc.), type of research study (observational study, clinical trial, etc.) or cultural context (regional, multi-regional, or global). Demonstrating cross-cultural equivalence with this approach warrants the legitimacy of using the measure in the different cultures, and therefore, in the context of multinational clinical trials, consolidates the analyses of data pooled from the different cultures.

Over the years, Mapi has continuously been developing methods allowing better measurement in multicultural studies. These efforts were particularly directed to enhance measurement in multinational clinical trials, in which any source of variability, including culture, can dramatically jeopardize the demonstration of a true treatment benefit for the patients. In this respect, a lot has been achieved, but, clearly, a lot remains to be done.

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