Quality-of-life assessment in comparative therapeutic trials and causal structure considerations in peripheral occlusive arterial disease

When considering the use of quality of life as a primary end-point in phase III to IV comparative trials, the trial designer generally faces some unresolved questions. These include: How does one explain that some dimensions [quality-of-life (QOL) instruments usually have more than I dimension] are directly influenced by the studied treatments whereas others are not? How can one interpret conflicting results between conventional clinical measurements and QOL measurements, when the relationships between conventional clinical measurement and quality of life are not known? In this paper, we consider the use of Structural Equation Modelling (SEM) as a methodological alternative to answer these problems. As an example, we analyse the internal causal structure of the Claudication Scale (CLAU-S), a specific QOL 5-dimensional instrument for peripheral occlusive arterial disease. In applying SEM to different studies and different types of calculation, we suggest that CLAU-S is based on a stable, simple and comprehensive QOL model, is compatible with the general International Classification of Impairments, Disabilities and Handicaps (ICIDH) classification, is coherent and complementary with clinical data measurements and, using differences in a prospective study, considerably improves specificity. We suggest that SEM can help in QOL scale validation, in providing a unified scheme of the inter-relationships between internal dimensions and with external variables, in particular, clinical measurements.