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Reference intervals are an essential tool for the clinical interpretation of laboratory test results. Traditionally, these interval are determined using samples from healthy individuals, a process that is resource-intensive, time-consuming, and require the active recruitment of healthy volunteers.
In recent years, due to the increasing availability of electronic health record (EHR) databases and the growing number of laboratory tests, it is possible to determine the reference intervals indirectly. This approach relies on the analysis of routine data acquired in clinical laboratories, eliminating the need for active recruiting healthy subjects and significantly reducing costs. Moreover, the method has the potential to eliminate the selection bias of an ultra-healthy population typical of the direct methods. The indirect methods for determining reference intervals have evolved from simple strategies of isolating the healthy population using sample metadata, to sophisticated statistical models that effectively distinguish normal from pathological distributions. One of the advanced techniques, RefineR, has reached an excellent combination of accuracy, robustness, and computational efficiency, outperforming previous methods. It has been implemented as an open-source R package, facilitating its application in real-world settings.
In recognition of these advantages, the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine), through its Committee on Reference Intervals and Decision Limits (C-RIDL), has promoted the adoption of indirect methods for determining reference intervals, highlighting the advantages of this strategy, including greater speed, lower costs, and the absence of a need to recruit healthy donors.
Furthermore, a recent study has highlighted age-related physiological variations in hemoglobin levels in elderly population. This underscores the need for defining age-specific reference intervals which are currently absent from most laboratory reports, potentially impacting diagnostic accuracy.
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| Measure | Description | Time Frame |
|---|---|---|
| Define indirect reference intervals for complete blood count (CBC) parameters by analyzing large-scale retrospective routine laboratory data. | up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Assess regional differences by comparing results across 10 Italian regions. | Statistical heterogeneity will be assessed using Cochran's Q test, and I squared index | up to 3 years |
| Establish age- and sex-specific reference intervals |
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Inclusion Criteria:
Exclusion Criteria:
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The study population consists of all patients undergoing routine laboratory testing during the year 2024 at the participating centers.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fabio Del Ben | Contact | 0434659101 | fabio.delben@cro.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ASL Bari, Ospedale della Murgia, Altamura | Not yet recruiting | Altamura | Altamura | Italy |
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| up to 3 years |
| Evaluate inter-instrument variations by considering results obtained from different analytical platforms. | Statistical heterogeneity will be assessed using Cochran's Q test, and I squared index | up to 3 years |
| Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona | Not yet recruiting | Ancona | Ancona | Italy |
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| Azienda USL Toscana Sud Est, Arezzo | Not yet recruiting | Arezzo | Arezzo | Italy |
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| Azienda ULSS 1 Dolomiti | Not yet recruiting | Belluno | Belluno | Italy |
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| Azienda Ospedaliero-Universitaria Careggi, Firenze | Not yet recruiting | Florence | Firenze | Italy |
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| IRCCS Istituto Clinico Humanitas, Milano | Not yet recruiting | Milan | Milano | Italy |
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| IRCCS Ospedale San Raffaele, Milano | Not yet recruiting | Milan | Milano | Italy |
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| Azienda Ospedaliero-Universitaria di Modena | Not yet recruiting | Modena | Modena | Italy |
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| Bianalisi Carate Brianza, Monza e Brianza | Not yet recruiting | Monza | Monza | Italy |
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| Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara | Not yet recruiting | Novara | Novara | Italy |
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| Azienda Ospedale Università Padova | Not yet recruiting | Padova | Padova | Italy |
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| Azienda Ospedaliera Universitaria Policlinico 'Paolo Giaccone' di Palermo | Not yet recruiting | Palermo | Palermo | Italy |
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| Centro di Riferimento Oncolgico -IRCCS | Recruiting | Aviano | Pordenone | 33081 | Italy |
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| Azienda Sanitaria Friuli Occidentale, Ospedale di Pordenone | Not yet recruiting | Pordenone | Pordenone | Italy |
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| Azienda Ospedaliera Universitaria Senese, | Not yet recruiting | Siena | Siena | Italy |
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| Azienda Sanitaria Universitaria Giuliano Isontina | Not yet recruiting | Trieste | Trieste | Italy |
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| Azienda Sanitaria Universitaria Friuli Centrale, Ospedale di Udine | Not yet recruiting | Udine | Udine | Italy |
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| AULSS 3 Serenissima, Ospedale di Mestre | Not yet recruiting | Mestre | Venezia | Italy |
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| Azienda Ospedaliera Universitaria Integrata di Verona | Not yet recruiting | Verona | Verona | Italy |
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| AULSS 8 Berica, Ospedale S. Bortolo di Vicenza | Not yet recruiting | Vicenza | Vicenza | Italy |
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| Ospedale di Desio, ASST Brianza | Not yet recruiting | Desio | Italy |
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| ASL5 Spezzino, La Spezia | Not yet recruiting | La Spezia | Italy |
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| ASST Grande Ospedale Metropolitano Niguarda, Milano | Not yet recruiting | Milan | Italy |
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| Azienda ULSS 2 Marca Trevigiana | Not yet recruiting | Treviso | Italy |
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