“Good samples make good assays” – the problem of sourcing clinical samples for a standardization project

Abstract

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.

Perspective and priorities for improvement of parathyroid hormone (PTH) measurement – A view from the IFCC Working Group for PTH

“…Sourcing appropriate clinical specimens is critically important for commutability and other studies to establish or validate metrological traceability, as has been highlighted in a recent article which describes difficulties encountered in a similar thyroid hormone standardisation project [27]. The IFCC Working Group for PTH is therefore carefully considering how best to avoid such pitfalls when developing specifications for the planned reference panel, taking heed also of recommendations from the systematic review [24].…”

Harmonization in laboratory medicine: the complete picture

“…For example, the identification of pre-analytical errors may only be possible because measurements have become more accurate and specific as a result of standardizing the actual measurements. This in turn creates the need to obtain higher quality samples to sustain further standardization projects [ 73 ].…”

Harmonization of Serum Thyroid-Stimulating Hormone Measurements Paves the Way for the Adoption of a More Uniform Reference Interval

“…Although a reference measurement procedure existed for free thyroxine, we considered this option for TSH unlikely and developed a pragmatic approach to harmonization rather than standardization (17,18). To circumvent the often encountered commutability issues in establishing calibration traceability of IVD assays, it was a premise for C-STFT that harmonization should be done from a multi-assay method comparison study with a panel of native and clinically relevant samples (19)(20)(21). We developed a robust factor analysis method for estimation of the harmonization targets and demonstrated the equivalence of the approach to standardization to a reference measurement procedure (22,23).…”