Reference Intervals With Indirect Methods in Italy

NCT07433777 | Recruiting

• 1 other identifier: CRO-2025-025
• Study Type: observational
• Target: 1,000,000
• Locations: 1 country
• Sites: 24

Brief Summary

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.

Conditions

Reference Intervals

Outcome Measures

Primary Outcomes (1)

• Define indirect reference intervals for complete blood count (CBC) parameters by analyzing large-scale retrospective routine laboratory data.

  up to 3 years

Secondary Outcomes (3)

• Assess regional differences by comparing results across 10 Italian regions.

  up to 3 years

• Establish age- and sex-specific reference intervals

  up to 3 years

• Evaluate inter-instrument variations by considering results obtained from different analytical platforms.

  up to 3 years

Eligibility Criteria

• Age: 0 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of all patients undergoing routine laboratory testing during the year 2024 at the participating centers.

You may qualify if:

• no one

You may not qualify if:

• no one

Sponsors & Collaborators

• Centro di Riferimento Oncologico - Aviano: lead

Study Sites (24)

ASL Bari, Ospedale della Murgia, Altamura

Altamura, Altamura, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona

Ancona, Ancona, Italy

NOT YET RECRUITING

Azienda USL Toscana Sud Est, Arezzo

Arezzo, Arezzo, Italy

NOT YET RECRUITING

Azienda ULSS 1 Dolomiti

Belluno, Belluno, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Careggi, Firenze

Florence, Firenze, Italy

NOT YET RECRUITING

IRCCS Istituto Clinico Humanitas, Milano

Milan, Milano, Italy

NOT YET RECRUITING

IRCCS Ospedale San Raffaele, Milano

Milan, Milano, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria di Modena

Modena, Modena, Italy

NOT YET RECRUITING

Bianalisi Carate Brianza, Monza e Brianza

Monza, Monza, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara

Novara, Novara, Italy

NOT YET RECRUITING

Azienda Ospedale Università Padova

Padua, Padova, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Policlinico 'Paolo Giaccone' di Palermo

Palermo, Palermo, Italy

NOT YET RECRUITING

Centro di Riferimento Oncolgico -IRCCS

Aviano, Pordenone, 33081, Italy

RECRUITING

Azienda Sanitaria Friuli Occidentale, Ospedale di Pordenone

Pordenone, Pordenone, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Senese,

Siena, Siena, Italy

NOT YET RECRUITING

Azienda Sanitaria Universitaria Giuliano Isontina

Trieste, Trieste, Italy

NOT YET RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale, Ospedale di Udine

Udine, Udine, Italy

NOT YET RECRUITING

AULSS 3 Serenissima, Ospedale di Mestre

Mestre, Venezia, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, Verona, Italy

NOT YET RECRUITING

AULSS 8 Berica, Ospedale S. Bortolo di Vicenza

Vicenza, Vicenza, Italy

NOT YET RECRUITING

Ospedale di Desio, ASST Brianza

Desio, Italy

NOT YET RECRUITING

ASL5 Spezzino, La Spezia

La Spezia, Italy

NOT YET RECRUITING

ASST Grande Ospedale Metropolitano Niguarda, Milano

Milan, Italy

NOT YET RECRUITING

Azienda ULSS 2 Marca Trevigiana

Treviso, Italy

NOT YET RECRUITING

Central Study Contacts

Fabio Del Ben

CONTACT

0434659101; fabio.delben@cro.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2026
• First Posted: February 25, 2026
• Study Start: October 8, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

IT (24)