Prospective Validation of Liver Cancer Risk Computation (LIRIC) Models

April 17, 2026 updated by: Limor Appelbaum, Beth Israel Deaconess Medical Center

Prospective Validation of Liver Cancer Risk Computation (LIRIC) Models on Multicenter EHR Data

The goal of this prospective observational cohort study is to validate previously developed Hepatocellular Carcinoma (HCC) risk prediction algorithms, the Liver Risk Computation (LIRIC) models, which are based on electronic health records.

The main questions it aims to answer are:

  • Will our retrospectively developed general population LIRIC models, developed on routine EHR data, perform similarly when prospectively validated, and reliably and accurately predict HCC in real-time?
  • What is the average time from model deployment and risk prediction, to the date of HCC development and what is the stage of HCC at diagnosis?

The risk model will be deployed on data from individuals eligible for the study. Each individual will be assigned a risk score and tracked over time to assess the model's discriminatory performance and calibration.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The investigators will conduct a prospective observational cohort study, separately deploying three separate LIRIC models (the general population, cirrhosis, and no_cirrhosis models) on retrospective de-identified EHR data of 44 HCOs in the USA, using the TriNetX federated network platform. LIRIC will generate a risk score for each individual. All risk-stratified individuals will be prospectively, electronically followed for up to 3-years to assess the primary end-point of HCC development. At the end of this period, model discrimination will be assessed, using the following metrics: AUROC, sensitivity, specificity, PPV/NPV. Risk scores generated by the model will be divided into quantiles. For each quantile, the investigators will evaluate the following: number of individuals in each quantile, number of HCC cases, PPV, NNS, SIR. Model calibration will be used for assessing the accuracy of estimates, based on the estimated to observed number of events. The model will dynamically re-evaluate all individual data every 6 months, re-classifying individuals (as needed).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6000000

Contacts and Locations

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

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Beth Israel Deaconess Medical Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The cohort will be selected from 44 eligible HCOs comprised of community hospitals, outpatient clinics and academic medical centers from across the US.

Description

The investigators will utilize the following criteria for all 3 models:

Inclusion criteria:

  • Male and females age ≥40 years from all US HCOs available on the platform
  • at least at least 2 clinical encounters to the HCO, within the last year, before the study start date

Exclusion Criteria:

  • Personal history of HCC or current HCC (ICD-9: 155.0; ICD-10: C22.0)
  • Age below 40. The same dataset will be utilized for the non-cirrhosis validation, with exclusion of all cases with cirrhosis (ICD-9: 571.2, 571.5; ICD-10: K70, K70.3, K70.30, K70.31, K74, K74.0, K74.6, K74.60, K74.69). For the cirrhosis validation, the investigators will include only patients with the above cirrhosis codes.

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
prospective general population cohort
Males and females age >= 40 years, without a personal history of HCC or current HCC and at least two clinical visits to their HCO, within the last year, before the study start date.
Other: Liver Risk Computation Model (LIRIC)
A neural network model (LIRIC-NN) and a logistic regression model (LIRIC-LR) that use routinely collected EHR data to stratify individuals into HCC risk groups for the general population
Prospective cirrhosis population cohort
Males and females age >= 40 years, with liver cirrhosis and without a personal history of HCC or current HCC, that have at least two clinical visits to their HCO, within the last year, before the study start date.
Other: Liver Risk Computation Model (LIRIC)_cirrhosis
A neural network model (LIRIC-NN) and a logistic regression model (LIRIC-LR) that use routinely collected EHR data to stratify individuals into HCC risk groups for the population with liver cirrhosis
Prospective no_cirrhosis population cohort
Males and females age >= 40 years, without a personal history of HCC or current HCC and without a diagnosis of liver cirrhosis, that have at least two clinical visits to their HCO, within the last year, before the study start date.
Other: Liver Risk Computation Model (LIRIC)_no_cirrhosis
neural network model (LIRIC-NN) and a logistic regression model (LIRIC-LR) that use routinely collected EHR data to stratify individuals into HCC risk groups for the population without liver cirrhosis

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Area under the receiver operating characteristic curve (AUROC) of LIRIC for all groups stratified
Time Frame: 6 months from index date, at 1 year, 2 years and 3 years
To assess the discriminatory performance of LIRIC for prospective identification of high-risk individuals for HCC development. ROCs and AUROC numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location.
6 months from index date, at 1 year, 2 years and 3 years
Calibration of LIRIC for all groups stratified
Time Frame: 6 months from index date, at 1 year, 2 years and 3 years
To assess how well the risk prediction by LIRIC aligns with observed risk without recalibration. Calibration plots will be created for the whole population and groups stratified by age, sex, race, and geographical location.
6 months from index date, at 1 year, 2 years and 3 years
Performance metrics for LIRIC model risk quantiles
Time Frame: 6 months from index date, at 1 year, 2 years and 3 years
To evaluate the sensitivity, specificity, number of individuals/number of HCC cases, PPV, NNS in each predicted risk quantile for multiple risk thresholds
6 months from index date, at 1 year, 2 years and 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Timing of incident HCC occurrence
Time Frame: 6 months from index date, at 1 year, 2 years and 3 years
To evaluate how long in advance before HCC occurrence should be expected for LIRIC models to make high-risk predictions based on different thresholds for high-risk. Distribution plots of the date of HCC incidence for multiple risk thresholds will be created.
6 months from index date, at 1 year, 2 years and 3 years
Tumor stage at HCC diagnosis
Time Frame: 6 months from index date, at 1 year, 2 years and 3 years
TNM staging at HCC diagnosis
6 months from index date, at 1 year, 2 years and 3 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beth Israel Deaconess Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Massachusetts Institute of Technology
TriNetX, LLC

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 15, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 20, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Nov2023Trial

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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