"Good samples make good assays" – the problem of sourcing clinical samples for a standardization project.

摘要

Clinical samples are the cornerstone in all aspects related to in vitro diagnostic testing. They are particularly valuable in the process of establishing/validating metrological traceability, because they eliminate commutability issues potentially associated with artificial calibrators. Therefore, they are essential for IFCC standardization projects. However, sourcing clinical specimens is particularly challenging. It mostly turns out that only dedicated supply sources can accommodate the varying specifications within reasonable timelines. Here we describe the torturous experience in this regard of the IFCC Working Group for Standardization of Thyroid Function tests (since transformed into a Committee). We always focused on obtaining high quality samples in sufficient volume to serve all project participants. We applied a step-up approach: in phase I, we used high volume (200 mL of plasma/serum) single donations from apparently healthy individuals, and switched in phase II and III to medium-sized volume clinical samples (15 – 30 mL) from well-defined patient categories. In the first two phases we observed for some assays a sample-related discrepant analytical performance for total/free triiodothyronine and thyroid stimulating hormone (TSH), whereas in phase III we faced a severe delay in obtaining the relevant panels for free thyroxine (FT4) and TSH (n = 90 and n = 100, respectively). Additional experiments only allowed us to exclude hypothesized causes of the observations. We believe that there would be merit in a collaborative effort by chairholders of similar projects to establish a sample procurement infrastructure based on a solid relationship with commercial supply sources with the support of a significant number of committed clinicians.