RENEB Inter-Laboratory comparison 2017: limits and pitfalls of ILCs

Abstract

Purpose: In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance. Materials and methods: Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min À1 , and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose. Results: This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Zand U-tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model.

RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay

“…Similar to recent RENEB ILCs ( 17, 18, 23 ), heterogeneity was observed with regard to the calibration curves used by the participants. This strongly suggests that each laboratory should use its own calibration curve and regularly perform intra-laboratory quality checks to ensure if the scoring does still agree with the used calibration curve, especially when there are changes in the staff of the laboratory.…”

“…One recent publication from Saudi-Arabia compared dose effect curves based on a 320 kVp X-ray source between 10 adult donors and suggested that the differences between individuals can be neglected ( 49 ). Moreover, several exercises performed with variable donors have shown that doses can be successfully recovered based on the DCA ( 17, 18, 41, 50, 51 ). Nevertheless, it cannot be fully excluded that individual variations contributed to the observed bias.…”

“…Regular quality-controlled inter-laboratory comparisons (ILCs) are important to allow the comparison of laboratories performance and to identify needs to optimize international networking and the workflows of the participants for preparedness to future RN events. ILCs simulating various real-life exposure situations are regularly performed in the frame of RENEB to validate and improve the procedures of the participants for various assays (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”

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“…In biodosimetry, many exercises of different sizes have been organized (Beinke et al, 2013;Rothkamm et al, 2013;Wilkins et al, 2015;Oestreicher et al, 2017;Pan et al, 2019;Port et al, 2019;Endesfelder et al, 2021;Gregoire et al, 2021). One such exercise was recently carried out by RENEB in partnership with EURADOS Working Group 10.…”

RENEB Inter-Laboratory Comparison 2021: The Cytokinesis-Block Micronucleus Assay

“…Within the RENEB network, regular inter-laboratory comparison exercises have been organized for harmonization and training as well as to maintain the preparedness for large-scale emergency situations, using a broad variety of biodosimetric assays (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”