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Review
. 2022 Feb 10;60(4):494-504.
doi: 10.1515/cclm-2021-0725. Print 2022 Mar 28.

Critical review and meta-analysis of biological variation estimates for tumor markers

Fernando Marques-Garcia  1   2 , Beatriz Boned  2   3 , Elisabet González-Lao  2   4 , Federica Braga  5 , Anna Carobene  6 , Abdurrahman Coskun  7 , Jorge Díaz-Garzón  2   8 , Pilar Fernández-Calle  2   8 , Maria Carmen Perich  2 , Margarida Simon  2   9 , Niels Jonker  10 , Berna Aslan  11 , William Alexander Bartlett  12 , Sverre Sandberg  13   14   15 , Aasne K Aarsand  13   14 ; European Federation of Clinical Chemistry and Laboratory Medicine Working Group on Biological Variation and Task Group for the Biological Variation Database
Affiliations
Free article
Review

Critical review and meta-analysis of biological variation estimates for tumor markers

Fernando Marques-Garcia et al. Clin Chem Lab Med. .
Free article

Abstract

Objectives: Biological variation data (BV) can be used for different applications, but this depends on the availability of robust and relevant BV data. In this study, we aimed to summarize and appraise BV studies for tumor markers, to examine the influence of study population characteristics and concentrations on BV estimates and to discuss the applicability of BV data for tumor markers in clinical practice.

Methods: Studies reporting BV data for tumor markers related to gastrointestinal, prostate, breast, ovarian, haematological, lung, and dermatological cancers were identified by a systematic literature search. Relevant studies were evaluated by the Biological Variation Data Critical Appraisal Checklist (BIVAC) and meta-analyses were performed for BIVAC compliant studies to deliver global estimates of within-subject (CVI) and between-subject (CVG) BV with 95% CI.

Results: The systematic review identified 49 studies delivering results for 22 tumor markers; four papers received BIVAC grade A, 3 B, 27 C and 15 D. Out of these, 29 CVI and 29 CVG estimates met the criteria to be included in the meta-analysis. Robust data are lacking to conclude on the relationship between BV and different disease states and tumor marker concentrations.

Conclusions: This review identifies a lack of high-quality BV studies for many tumor markers and a need for delivery of BIVAC compliant studies, including in different disease states and tumor marker concentrations. As of yet, the state-of-the-art may still be the most appropriate model to establish analytical performance specifications for the majority of tumor markers.

Keywords: biological variation; critical review; meta-analysis; tumor marker.

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References

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