The results of this study indicate that national and linguistic (country) variations in patient responses to the MDASI are small relative to individual patient-related factors. Analysis of MDASI symptom and interference ratings from cancer patients in five countries—the United States, China, Japan, Russia, and Korea—revealed that the variance of the random effects for country was between 20% and 50% of the intersubject variance. These results give some reassurance that symptom data obtained using various language versions of the MDASI, and possibly patient-reported symptom data from other measures, can be pooled to analyze multinational clinical research.
Previous studies have begun to address cross-cultural equivalence in patient-reported health-related quality-of-life measures. Although progress has been made toward identifying the arenas in which equivalency should be established, few studies have been designed to test assertions about cultural applicability. Such studies have noted that adapting a PRO measure for cross-cultural use requires a careful accounting for the differential impact of culture on results (19
) and the establishment of conceptual equivalency (7
). Confirmation of an adapted measure's psychometric validity and reliability is insufficient evidence of its suitability for use across cultures (20
). A few studies of cross-cultural comparison have examined the dimensional structure of certain PRO instruments (21
) but not within the cancer population. Other studies conducted in patients with cancer examined multidimensional scaling for cancer pain (23
) and the use of differential item functioning for the European Organisation for Research and Treatment of Cancer 30-item quality-of-life questionnaire (24
) and FACT–Breast (25
) but did not examine the magnitude of effects of language translation and culture/nationality on how people respond to these measures. Thus, additional investigation in internationally coordinated projects is needed to provide sufficient evidence of measurement equivalence for various language versions of major health-related quality-of-life measures (26
). Findings of cross-cultural equivalency would support the international application of clinical guidelines for symptom management because such guidelines are often based on symptom ratings.
In this study, we compared variations in MDASI scores attributable to linguistic and cultural variations with inherent intersubject variations in patient responses. In the interpretation of retrospective data collected from a single nationality, the results from our analyses suggest that the magnitude of various cultural or linguistic backgrounds is likely to be only one-fourth to one-half of the interpatient variation of MDASI symptom reports obtained from an otherwise homogeneous population.
In future studies that use PROs, this type of probit analysis method would allow investigators to estimate the impact on symptom reports of patient or clinical variables, such as sex or ECOG PS, thus making it possible to determine whether the effects of such variables are sufficiently important to be included in subsequent data analyses. For example, in this study, the average difference between symptom reports of patients with poor performance status (ECOG PS = 2–4) and patients with good performance status (ECOG PS = 0–1) was larger than the country effect for most symptoms. We note that it is common practice to collapse ECOG status into poor and good categories when analyzing PRO data; our analyses thus suggest that ignoring the language effects associated with the administration of the MDASI instrument is likely to have a smaller effect on study conclusions than collapsing ECOG categories in this way. We also found small but statistically significant effects for sex across samples, with women reporting more severe fatigue, sadness, sleep disturbance, and distress. Again, these differences were small compared with overall individual patient variability.
A finding of a statistically significant country effect in cross-national and cross-cultural studies affecting symptom report data might derive from several sources. First, a poor translation from the original linguistic version could compromise the instruments’ comparability (27
). Although there is no empirical evidence in favor of one specific method of translation of a PRO tool, we used an internally consistent procedure for translating all versions of the MDASI (28
). In addition, in contrast to the more abstract concepts assessed in most quality-of-life measures, the MDASI assesses only symptoms; it uses single words or simple phrases for its items and a straightforward 0 to 10 numeric rating scale, making the translation of MDASI items relatively simple and the establishment of equivalency less challenging. In this study, we demonstrated that the more severe symptoms—fatigue, disturbed sleep, distress, and pain—are less subject to nation and linguistic effects, as evidenced by the small effect of country on these symptom items.
Symptom management practice is known to vary from country to country (29
), as well as from one treatment site to another within a country (30
). It is thus not unreasonable to expect that symptoms might be more severe in countries and sites with less aggressive symptom management. With the current models, we did not take into account differences in symptom management practice between countries as a fixed-effect factor. However, the consistency in this study in the most severe symptoms reported by patients, regardless of the characteristics from each sample, as well as the consistency in patients with poor ECOG PS reporting more severe symptoms, indicates that the MDASI functioned similarly across language versions in characterizing symptom burden. In addition, the very small effect of country on pain ratings from this study also supports our procedures, given that one would expect much greater cross-national variation in pain control (ie, variations in practice of prescribing opioids, which are the World Health Organization's recommended standard for management of severe cancer pain) (31
) than in fatigue management (because of lack of widely used therapeutic methods to control fatigue).
The study had several limitations. First, the effect of country was confounded with the effect of the individual sample site because only one to three treatment centers were sampled in each country. This could prevent a full examination of patient cultural differences within the same language from country to country. Second, although we expect that language differences in symptom reporting will be even smaller with more homogeneous samples, this expectation needs to be tested empirically. The current analysis used pooled data from heterogeneous samples and did identify one MDASI interference item—relations with others—that was affected by country. Additional research is needed, and caution is warranted when interpreting the meaning of “relations with others” in international MDASI data. Third, we were not able to use cancer stage as a covariate in the modeling because data from one country for this variable were missing. However, the similarity in the percentage of patients with metastasis indicates a comparable disease status across all samples.
In conclusion, this analysis suggests that once psychometrically sound translations of the MDASI have been established, various language versions can be used to gather symptom severity and interference ratings that can be interpreted in a similar way across patient nationalities. The generalizability is meaningful for interpreting the results across various cultural and language groups and provides greater utility in symptom assessment for oncology practice, clinical trials, and clinical research—not only among the diversity of patients in the United States but also for patients with cancer in other parts of the world.