The Asian project for collaborative derivation of reference intervals: (1) strategy and major results of standardized analytes

Abstract

Background : A multicenter study conducted in Southeast Asia to derive reference intervals (RIs) for 72 commonly measured analytes (general chemistry, inflammatory markers, hormones, etc.) featured centralized measurement to clearly detect regionality in test results. The results of 31 standardized analytes are reported, with the remaining analytes presented in the next report. Method : The study included 63 clinical laboratories from South Korea, China, Vietnam, Malaysia, Indonesia, and seven areas in Japan. A total of 3541 healthy individuals aged 20 -65 years (Japan 2082, others 1459) were recruited mostly from hospital workers using a well-defined common protocol. All serum specimens were transported to Tokyo at − 80 ° C and collectively measured using reagents from four manufacturers. Three-level nested ANOVA was used to quantitate variation (SD) of test results due to region, sex, and age. A ratio of SD for a given factor over residual SD (representing net between-individual variations) (SDR) exceeding 0.3 was considered significant. Traceability of RIs was ensured by recalibration using value-assigned reference materials. RIs were derived parametrically. Results : SDRs for sex and age were significant for 19 and 16 analytes, respectively. Regional difference was significant for 11 analytes, including high density lipoprotein (HDL)-cholesterol and inflammatory markers. However, when the data were limited to those from Japan, regionality was not observed in any of the analytes. Accordingly, RIs were derived with or without partition by sex and region. Conclusions : RIs applicable to a wide area in Asia were established for the majority of analytes with traceability to reference measuring systems, whereas regional partitioning was required for RIs of the other analytes.

The Asian project for collaborative derivation of reference intervals: (2) results of non-standardized analytes and transference of reference intervals to the participating laboratories on the basis of cross-comparison of test results

“…The framework of the Asian multicenter study was described in the companion paper, Part 1 of this article [ 1 ]. In brief, 48 laboratories from 14 cities distributed widely from the north to the south of Japan, and 15 laboratories in nine cities outside Japan (Seoul, Beijing, Taipei, Tainan, Hong Kong, Macau, Ho Chi Minh City, Kuala Lumpur, and Jakarta) took part in the study.…”

“…The Asian multicenter study conducted in 2009 was unique in that it also attempted to derive common RIs for non-standardized analytes, such as protein hormones and tumor markers, most of which were measured by immunoassays [ 1 ]. The key strategy was to centralize measurement by transporting all serum specimens in a deep-frozen state to central laboratories located in Japan.…”

Progress and impact of enzyme measurement standardization

“…The introduction of enzyme reference measurement systems to provide traceable patient results have therefore been followed by the definition of traceable reference intervals to provide more congruent and effective information to clinicians. In particular, traceable reference intervals have been established for AST, ALT, γGT, LDH, CK, alkaline phosphatase (ALP), and AMY first in Caucasian adults and afterwards in Asian individuals [17,18,[22][23][24][25][26]. Table 1 reports a synopsis of traceable reference intervals for enzymes obtained in European and Asian subjects.…”

Multicenter reference intervals studies: a promising perspective for the future?

“…In the first study [ 9 ] the authors determined RIs for 72 analytes traceable to a reference system. As in their previous study [ 11 ] they limited the component of inter-laboratory variability by centralizing analyzes of deep-frozen sera of volunteers from 63 participating laboratories (in Japan and South-East Asia) in a single laboratory in Japan.…”

“…The analytical quality of the data represents the second major strength of the first study [ 9 ]. The verification of the traceability to a reference system ensures that RIs may be used by another laboratory using a similar traceable method.…”