Reference Intervals With Indirect Methods in Italy (REFIND-IT)

February 19, 2026 updated by: Centro di Riferimento Oncologico - Aviano

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.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

1000000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Desio, Italy
        • Not yet recruiting
        • Ospedale di Desio, ASST Brianza
        • Contact:
        • Principal Investigator:
          • Domenico Tripodi
        • Principal Investigator:
          • Rosanna Falbo
      • La Spezia, Italy
        • Not yet recruiting
        • ASL5 Spezzino, La Spezia
        • Contact:
        • Principal Investigator:
          • Concetta Tomasello
        • Principal Investigator:
          • Paolo Bucchioni
      • Milan, Italy
        • Not yet recruiting
        • ASST Grande Ospedale Metropolitano Niguarda, Milano
        • Contact:
        • Principal Investigator:
          • Elvira Inglese
      • Treviso, Italy
        • Not yet recruiting
        • Azienda ULSS 2 Marca Trevigiana
        • Contact:
        • Principal Investigator:
          • Lorena Zardo
        • Principal Investigator:
          • Antonino Antico
    • Altamura
      • Altamura, Altamura, Italy
        • Not yet recruiting
        • ASL Bari, Ospedale della Murgia, Altamura
        • Contact:
        • Principal Investigator:
          • Paola Nardiello
        • Principal Investigator:
          • Diana Fuzio
    • Ancona
      • Ancona, Ancona, Italy
        • Not yet recruiting
        • Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona
        • Contact:
        • Principal Investigator:
          • Alessio Mancini
    • Arezzo
      • Arezzo, Arezzo, Italy
        • Not yet recruiting
        • Azienda USL Toscana Sud Est, Arezzo
        • Contact:
        • Principal Investigator:
          • Maria Lorubbio
        • Principal Investigator:
          • Agostino Ognibene
    • Belluno
      • Belluno, Belluno, Italy
        • Not yet recruiting
        • Azienda ULSS 1 Dolomiti
        • Contact:
        • Principal Investigator:
          • Claudio De Seta
        • Principal Investigator:
          • Paola Centa
    • Firenze
      • Florence, Firenze, Italy
        • Not yet recruiting
        • Azienda Ospedaliero-Universitaria Careggi, Firenze
        • Contact:
        • Principal Investigator:
          • Luisa Lanzilao
    • Milano
      • Milan, Milano, Italy
        • Not yet recruiting
        • IRCCS Istituto Clinico Humanitas, Milano
        • Contact:
        • Principal Investigator:
          • Giorgio Da Rin
        • Principal Investigator:
          • Francesca Panvini
      • Milan, Milano, Italy
        • Not yet recruiting
        • IRCCS Ospedale San Raffaele, Milano
        • Contact:
        • Principal Investigator:
          • Anna Carobene
        • Principal Investigator:
          • Massimo Locatelli
    • Modena
      • Modena, Modena, Italy
        • Not yet recruiting
        • Azienda Ospedaliero-Universitaria di Modena
        • Contact:
        • Principal Investigator:
          • Tommaso Pirotti
        • Principal Investigator:
          • Tommaso Fasano
    • Monza
      • Monza, Monza, Italy
        • Not yet recruiting
        • Bianalisi Carate Brianza, Monza e Brianza
        • Contact:
        • Principal Investigator:
          • Michela Cuccorese
        • Principal Investigator:
          • Tommaso Trenti
    • Novara
      • Novara, Novara, Italy
        • Not yet recruiting
        • Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
        • Contact:
        • Principal Investigator:
          • Sara Sacchetti
        • Principal Investigator:
          • Roberta Rolla
    • Padova
      • Padua, Padova, Italy
        • Not yet recruiting
        • Azienda Ospedale Universita Padova
        • Contact:
        • Principal Investigator:
          • Andrea Padoan
        • Principal Investigator:
          • Paola Galozzi
    • Palermo
      • Palermo, Palermo, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria Policlinico 'Paolo Giaccone' di Palermo
        • Contact:
        • Principal Investigator:
          • Luisa Agnello
        • Principal Investigator:
          • Marcello Ciaccio
    • Pordenone
      • Aviano, Pordenone, Italy, 33081
        • Recruiting
        • Centro di Riferimento Oncolgico -IRCCS
        • Contact:
        • Principal Investigator:
          • Fabio Del Ben
      • Pordenone, Pordenone, Italy
        • Not yet recruiting
        • Azienda Sanitaria Friuli Occidentale, Ospedale di Pordenone
        • Contact:
        • Principal Investigator:
          • Paolo Doretto
    • Siena
      • Siena, Siena, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria Senese,
        • Contact:
        • Principal Investigator:
          • Marcello Fiorini
        • Principal Investigator:
          • Roberto Guerranti
    • Trieste
      • Trieste, Trieste, Italy
        • Not yet recruiting
        • Azienda Sanitaria Universitaria Giuliano Isontina
        • Contact:
        • Principal Investigator:
          • Paola Pradella
    • Udine
      • Udine, Udine, Italy
        • Not yet recruiting
        • Azienda Sanitaria Universitaria Friuli Centrale, Ospedale di Udine
        • Contact:
        • Principal Investigator:
          • Francesco Curcio
        • Principal Investigator:
          • Riccardo Lucis
    • Venezia
      • Mestre, Venezia, Italy
        • Not yet recruiting
        • AULSS 3 Serenissima, Ospedale di Mestre
        • Contact:
        • Principal Investigator:
          • Mara Seguso
    • Verona
      • Verona, Verona, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria Integrata di Verona
        • Contact:
        • Principal Investigator:
          • Giovanni Poli
    • Vicenza
      • Vicenza, Vicenza, Italy
        • Not yet recruiting
        • AULSS 8 Berica, Ospedale S. Bortolo di Vicenza
        • Contact:
        • Principal Investigator:
          • Alessandra Brocca

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

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.

Description

Inclusion Criteria:

  • no one

Exclusion Criteria:

  • no one

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Define indirect reference intervals for complete blood count (CBC) parameters by analyzing large-scale retrospective routine laboratory data.
Time Frame: up to 3 years
up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess regional differences by comparing results across 10 Italian regions.
Time Frame: up to 3 years
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
Time Frame: up to 3 years
up to 3 years
Evaluate inter-instrument variations by considering results obtained from different analytical platforms.
Time Frame: up to 3 years
Statistical heterogeneity will be assessed using Cochran's Q test, and I squared index
up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centro di Riferimento Oncologico - Aviano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2025

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

February 19, 2026

First Submitted That Met QC Criteria

February 19, 2026

First Posted (Actual)

February 25, 2026

Study Record Updates

Last Update Posted (Actual)

February 25, 2026

Last Update Submitted That Met QC Criteria

February 19, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

  • CRO-2025-025

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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