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NCT Number: NCT06140823

Prospective Validation of Liver Cancer Risk Computation (LIRIC) Models

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.

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This study is active but is not currently recruiting participants.

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Key information

Age range

40 year–100 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Liver Risk Computation Model (LIRIC)

Other

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

Liver Risk Computation Model (LIRIC)_cirrhosis

Other

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

Liver Risk Computation Model (LIRIC)_no_cirrhosis

Other

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

Primary outcomes

  1. 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.

  2. 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.

  3. 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

Secondary outcomes

  1. 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.

  2. 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

Sponsors and collaborators

Lead sponsor

Beth Israel Deaconess Medical Center

Other

Collaborators

  • Massachusetts Institute of Technology
  • TriNetX, LLC

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Nov 20, 2023
Registry last updated
Apr 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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