Clinical trial NCT06140823: Prospective Validation of Liver Cancer Risk Computation (LIRIC) Models
Official title: Prospective Validation of Liver Cancer Risk Computation (LIRIC) Models on Multicenter EHR Data
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Predictive Cancer Model
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Massachusetts Institute of Technology
name: TriNetX, LLC
First posted: 2023-11-20
Enrollment: 6000000
Sex: ALL
Minimum age (years): 40
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Area under the receiver operating characteristic curve (AUROC) of LIRIC for all groups stratified
timeFrame: 6 months from index date, at 1 year, 2 years and 3 years
measure: Calibration of LIRIC for all groups stratified
timeFrame: 6 months from index date, at 1 year, 2 years and 3 years
measure: Performance metrics for LIRIC model risk quantiles
timeFrame: 6 months from index date, at 1 year, 2 years and 3 years
Secondary outcomes:
measure: Timing of incident HCC occurrence
timeFrame: 6 months from index date, at 1 year, 2 years and 3 years
measure: Tumor stage at HCC diagnosis
timeFrame: 6 months from index date, at 1 year, 2 years and 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
References: