In antiemetic research, the primary endpoints of emesis, nausea and rescue medication use are patient-reported. As such, linguistically valid translations of measures to collect these endpoints are needed to pool data across countries. In a Phase III study of a new antiemetic, aprepitant, for the prevention of chemotherapy-induced nausea and vomiting (CINV), patients recorded emetic episodes, rescue medications and nausea ratings in a 5-day diary. Patients also reported the impact of CINV on their daily lives using the Functional Living Index-Emesis (FLIE). A complete linguistic validation of the diary and FLIE was undertaken in 22 languages prior to their use in the multi-national trials primarily in Europe, North America and Latin America. An internationally recognized procedure for linguistic validation used the following steps: forward and backward translations, review by cancer experts, comprehension test with patients and harmonization across languages. The original developer of each instrument was consulted to clarify problematic concepts. The process identified several areas where literal translation of the English expressions were not conceptually equivalent or relevant in the target languages. In some languages, terms for "dry heaves" or "retch" do not exist so a phrase or entire sentence was used instead. The question "How much nausea have you had?" was adapted for languages where the question was interpreted to reflect intensity or frequency but not both concepts as in English. For the FLIE, some questions had to be modified from a literal translation in order to maintain conceptual equivalence or modified to include tasks relevant to both males and females. In summary, linguistic validation of patient-reported endpoints is important for collecting clinical trial data that will be pooled across different sites. The rigorous process by which the emesis diary, nausea rating scale and FLIE were translated resulted in linguistically valid measures appropriate for use in the Phase III clinical trials of aprepitant.
