Accessible Requires Authentication Published by De Gruyter August 19, 2015

An epidemiology-based model as a tool to monitor the outbreak of inappropriateness in tumor marker requests: a national scale study

Massimo Gion, Lucia Peloso, Chiara Trevisiol, Elisa Squarcina, Marco Zappa and Aline S.C. Fabricio


Background: Evaluation of appropriateness of laboratory tests on the basis of individual requests remains a serious problem as the clinical question is usually not reported with the test order. This study explored the comparison of the rate of tumor marker orders with cancer prevalence as a putative indicator of inappropriateness.

Methods: Tumor marker orders (2011 and 2012) were obtained from the Ministry of Health and cancer prevalence from the Italian Association of Cancer Registries. The rate of tumor marker orders was matched with demographic data and tumor prevalence and examined by using the confidence interval approach. Region-to-region and year-to-year variations were also examined. Focus was placed on CEA, CA125, CA19.9 and CA15.3.

Results:Tumor markers ordered in Italy were 13,207,289 in 2012 (221.3/1000 individuals). Given an estimated prevalence of 2,243,953 cancer cases, 7.04 tumor markers appear to be requested for each prevalent case of epithelial cancer per year. The rate of requests of CEA, CA125, CA19.9 and CA15.3 (in aggregate 5,834,167 requests in 2012, 44.2% of total) from the first and the last ranked region (96 and 244/1000 individuals) are significantly different (p<0.01). Region-to-region differences do not correspond to any known variation of prevalence in the different regions.

Conclusions: The developed approach provides a proxy indicator of inappropriateness showing that tumor markers are overused in Italy and their ordering pattern is not related to tumor prevalence. The model is suitable to be validated in other laboratory tests used in diseases whose prevalence is known.

Corresponding author: Dr. Massimo Gion, Regional Center for Biomarkers, Department of Clinical Pathology and Transfusion Medicine, Ospedale Civile – Azienda ULSS 12 Veneziana, Campo SS. Giovanni e Paolo, 6777 – 30122 Venezia, Italy, Phone: +39 041 5294260, Fax: +39 041 5294910, E-mail:


We wish to thank the Ministry of Health, New National Health IT System (Direzione generale della digitazione, del sistema informativo sanitario e della statistica – Elaborazione a cura dell’Ufficio III – NSIS, flusso di specialistica ambulatoriale – Art. 50 della legge n.326/2009) for allowing us to use the requested biomarker data. We would like to thank the Interregional Biomarkers Working Group – IBWG instituted by the Health Commission of the Italian Permanent Conference for relations between state, regions and autonomous provinces of Trento and Bolzano (Gruppo Tecnico Interregionale “Miglioramento della Pratica Clinica per l’Utilizzo dei Biomarcatori in Oncologia”, Commissione Salute – Conferenza Permanente per i rapporti tra Stato, Regioni e Province Autonome di Trento e Bolzano). In particular, we would like to thank the IBWG members for their important contributions in discussing rough preliminary data: Antonino Iaria (Regional Representative for Calabria); Vincenzo Montesarchio (Regional Representative for Campania); Tommaso Trenti (Regional Representative for Emilia-Romagna); Laura Conti (Regional Representative for Lazio); Luigina Bonelli, and Gabriella Paoli (Regional Representatives for Liguria); Mario Cassani (Regional Representative for Lombardia); Lucia Di Furia (Regional Representative for Marche); Emiliano Aroasio (Regional Representative for Piemonte); Mario Brandi (Regional Representative for Puglia); Marcello Ciaccio, and Antonio Russo (Regional Representatives for Sicilia); Gianni Amunni (Regional Representative for Toscana); Emanuela Toffalori (Representative for Autonomous Province of Trento); Basilio Ubaldo Passamonti (Regional Representative for Umbria); Claudio Pilerci, and Francesca Russo (Regional Representatives for Veneto); Annarosa Del Mistro (Istituto Oncologico Veneto IOV – IRCCS, Veneto Region); Massimo Gion (Coordinator); Aline S.C. Fabricio, and Chiara Trevisiol (Scientific Secretariat of the Regional Center for Biomarkers); and Ornella Scattolin (Organizing Secretariat of the Regional Center for Biomarkers). We would also like to thank Candice Fulgenzi for editorial assistance in the manuscript preparation.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: None declared.


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Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2015-0329) offers supplementary material, available to authorized users.

Received: 2015-4-8
Accepted: 2015-7-15
Published Online: 2015-8-19
Published in Print: 2016-3-1

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