Reference IntervalsREFIND-ITNCT07433777
Reference Intervals With Indirect Methods in Italy
An observational study of Reference Intervals, run by Centro di Riferimento Oncologico - Aviano at 24 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Reference Intervals
- How many people
- 1,000,000 participants
- Where
- 24 sitesItaly
- Study dates
- 8 Oct 2025to 1 Jun 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 100 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: The study population consists of all patients undergoing routine laboratory testing during the year 2024 at the participating centers.
Who may be able to join
- no one
Who cannot join
- no one
Trial locations and contacts
24 sites in 1 country. Contact the study team or a site near you to ask about taking part.
24 sites in 1 country
Italy24 sites, 24 recruiting
- Not yet recruiting
ASL Bari, Ospedale della Murgia, Altamura
Altamura, Altamura
Diana Fuzio, diana.fuzio@asl.bari.it
Paola Nardiello
- Not yet recruiting
Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona
Ancona, Ancona
Alessio Mancini, alessio.mancini@sanita.marche.it
Alessio Mancini
- Not yet recruiting
Azienda USL Toscana Sud Est, Arezzo
Arezzo, Arezzo
Agostino Ognibene, agostino.ognibene@uslsudest.toscana.it
Maria Lorubbio
- Recruiting
Centro di Riferimento Oncolgico -IRCCS
Aviano, Pordenone, 33081
Fabio Del Ben, 0434659101, fabio.delben@cro.it
Fabio Del Ben
- Not yet recruiting
Azienda ULSS 1 Dolomiti
Belluno, Belluno
Claudio De Seta, claudio.deseta@aulss1.veneto.it
Claudio De Seta
- Not yet recruiting
Ospedale di Desio, ASST Brianza
Desio
Rosanna Falbo, rosanna.falbo@asst-brianza.it
Domenico Tripodi
- Not yet recruiting
Azienda Ospedaliero-Universitaria Careggi, Firenze
Florence, Firenze
Luisa Lanzilao, lanzilaol@aou-careggi.toscana.it
Luisa Lanzilao
- Not yet recruiting
ASL5 Spezzino, La Spezia
La Spezia
Paolo Bucchioni, paolo.bucchioni@asl5.liguria.it
Concetta Tomasello
- Not yet recruiting
AULSS 3 Serenissima, Ospedale di Mestre
Mestre, Venezia
Mara Seguso, mara.seguso@aulss3.veneto.it
Mara Seguso
- Not yet recruiting
IRCCS Istituto Clinico Humanitas, Milano
Milan, Milano
Francesca Panvini, francesca.panvini@humanitas.it
Giorgio Da Rin
- Not yet recruiting
IRCCS Ospedale San Raffaele, Milano
Milan, Milano
Anna Carobene, carobene.anna@hsr.it
Anna Carobene
- Not yet recruiting
ASST Grande Ospedale Metropolitano Niguarda, Milano
Milan
Elvira Inglese, elvira.inglese@gmail.com
Elvira Inglese
- Not yet recruiting
Azienda Ospedaliero-Universitaria di Modena
Modena, Modena
Tommaso Fasano, t.fasano@ausl.mo.it
Tommaso Pirotti
- Not yet recruiting
Bianalisi Carate Brianza, Monza e Brianza
Monza, Monza
Tommaso Trenti, tommaso.trenti@gmail.com
Michela Cuccorese
- Not yet recruiting
Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
Novara, Novara
Roberta Rolla, roberta.rolla@med.uniupo.it
Sara Sacchetti
- Not yet recruiting
Azienda Ospedale Università Padova
Padova, Padova
Paola Galozzi, paola.galozzi@unipd.it
Andrea Padoan
- Not yet recruiting
Azienda Ospedaliera Universitaria Policlinico 'Paolo Giaccone' di Palermo
Palermo, Palermo
Marcello Ciaccio, marcello.ciaccio@unipa.it
Luisa Agnello
- Not yet recruiting
Azienda Sanitaria Friuli Occidentale, Ospedale di Pordenone
Pordenone, Pordenone
Paolo Doretto, paolo.doretto@asfo.sanita.fvg
Paolo Doretto
- Not yet recruiting
Azienda Ospedaliera Universitaria Senese,
Siena, Siena
Roberto Guerranti, guerranti@unisi.it
Marcello Fiorini
- Not yet recruiting
Azienda ULSS 2 Marca Trevigiana
Treviso
Antonio Antico, antonio.antico@aulss2.veneto.it
Lorena Zardo
- Not yet recruiting
Azienda Sanitaria Universitaria Giuliano Isontina
Trieste, Trieste
Paola Pradella, paola.pradella@asugi.sanita.fvg.it
Paola Pradella
- Not yet recruiting
Azienda Sanitaria Universitaria Friuli Centrale, Ospedale di Udine
Udine, Udine
Riccardo Lucis, lucis.riccardo@spes.uniud.it
Francesco Curcio
- Not yet recruiting
Azienda Ospedaliera Universitaria Integrata di Verona
Verona, Verona
Giovanni Poli, giovanni.poli@aovr.veneto.it
Giovanni Poli
- Not yet recruiting
AULSS 8 Berica, Ospedale S. Bortolo di Vicenza
Vicenza, Vicenza
Alessandra Brocca, alessandra.brocca@aulss8.veneto.it
Alessandra Brocca
About this study
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.
Read more
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
What is being measured
The primary outcome is the main question the study is designed to answer.
Define indirect reference intervals for complete blood count (CBC) parameters by analyzing large-scale retrospective routine laboratory data.
Measured: up to 3 years
Secondary outcomes (3)
Assess regional differences by comparing results across 10 Italian regions.
Statistical heterogeneity will be assessed using Cochran's Q test, and I squared index
Measured: up to 3 years
Establish age- and sex-specific reference intervals
Measured: 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
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2026
- Study start8 Oct 2025
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Reference IntervalsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,000,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro di Riferimento Oncologico - Aviano
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07433777
- Sponsor's protocol ID
- CRO-2025-025
- Acronym
- REFIND-IT
- Status last verified
- Feb 2026
- First submitted
- 19 Feb 2026
- Last updated
- 25 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reference Intervals With Indirect Methods in Italy
- ClinicalTrials.gov ID
- NCT07433777
- Acronym / sponsor ID
- REFIND-IT / CRO-2025-025
- Conditions
- Reference Intervals
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000,000 participants (estimated)
- Lead sponsor
- Centro di Riferimento Oncologico - AvianoUniversity, hospital or other
- Study start
- 8 Oct 2025 (actual)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 25 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 0 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population consists of all patients undergoing routine laboratory testing during the year 2024 at the participating centers.
Key inclusion criteria (1 listed)
- no one
Key exclusion criteria (1 listed)
- no one
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Define indirect reference intervals for complete blood count (CBC) parameters by analyzing large-scale retrospective routine laboratory data.
Time frame: up to 3 years
3 secondary outcomes
Assess regional differences by comparing results across 10 Italian regions.
Time frame: up to 3 years
Establish age- and sex-specific reference intervals
Time frame: up to 3 years
Evaluate inter-instrument variations by considering results obtained from different analytical platforms.
Time frame: up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
Related trials for Reference Intervals
RecruitingObservational study
Trans and Non-binary Prostate-Specific Antigen Reference Interval Determination Study
Prostate CA
RecruitingObservational study
Generating Intervals of Reference FFor Early Life Brain Biomarkers.
Reference Intervals, Biomarker in Early Diagnosis
Active, not recruiting
Reference Measurements of the Neuronal Integration Window and Anatomical and Functional MRI (Magnetic Resonance Imaging)
Neuropsychiatric Disorders
RecruitingObservational study
Establishment and Clinical Application of Reference Intervals of Salivary Cortisol
Healthy Adult, Cushing Syndrome
RecruitingObservational study
Iron Status of Non-anemic Pregnant Women in First Trimester
Iron Deficiency (Without Anemia), Reference Values
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Reference Intervals, run by Centro di Riferimento Oncologico - Aviano at 24 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fabio Del Ben (0434659101, fabio.delben@cro.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Define indirect reference intervals for complete blood count (CBC) parameters by analyzing large-scale retrospective routine laboratory data. (time frame: up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026.