Should a single centre for the assay of biochemical markers of nutritional status be mandatory in multicentric trials?

Abstract

Clinical trials to identify patients at risk and to assess new therapeutic agents in the nutritional field are often single-site. The principal advantage of mounting a multicentric trial is that patient accrual is much quicker. Albumin, transthyretin, and C-reactive protein are frequently used biochemical markers of nutritional and inflammation status. However, the different techniques, reagents, and calibrators used to measure these markers introduce wide variations in values among laboratories. This study was carried out as part of a prospective multicentric study in chronic respiratory disease patients to evaluate variability and comparability of results among laboratories for these biochemical markers, and to determine whether centralization is necessary. Thirty enrolled laboratories provided their own range of reference values for those proteins a nd were then requested to process two control samples C1 and C2 blind. The results showed a broad dispersion of values for albumin and transthyretin. In 7% of laboratories, results of albumin for C2 (mean, all techniques: 39.1±3 g/l) were <35 g/l, the threshold value indicating a potential risk of malnutrition. When only laboratories using immunonephelemetry were considered, the results were satisfactory (CV<10% for all proteins). Given the possible incorrect classification of patients at risk, measurement should be made per site only if all participants use an immunonephelometric method. Otherwise, a centralizing assay of these biological markers should be considered.