Prospective Validation Of An EHR-based Pancreatic Cancer Risk Model

Study Overview

Prospective Validation of an EHR-based Pancreatic Cancer Risk Model

The goal of this prospective observational cohort study is to validate a previously developed pancreatic cancer risk prediction algorith (the PRISM model) using electronic health records from the general population. The main questions it aims to answer are: * Will a pancreatic cancer risk model, developed on routine EHR data, reliably and accurately predict pancreatic cancer in real-time? * What is the average time from model deployment and risk prediction, to the date of pancreatic cancer development and what is the stage of pancreatic cancer 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.

To prospectively validate, implement in real-time, and assess performance of an EHR- based PDAC risk-prediction model. To test the hypothesis that our model will reliably predict PDAC in a real-time clinical setting, we will conduct a multi-center prospective cohort study, deploying the PDAC risk model within the TriNetX federated network database, and will take the following steps: i) generate a risk prediction score for each individual under the care of 44 health care organizations (HCOs) in the USA ii) follow all individuals for up to 3 years to assess the primary end-point of PDAC development. The following metrics will be used to test the discriminative performance and calibration of the EHR-based PDAC risk model in predicting incident PDAC, at the end of the 3-year period: 1. AUROC, sensitivity, specificity, PPV/NPV for assessing discrimination 2. Calibration: for assessing the accuracy of estimates, based on the estimated to observed number of events

Pancreatic Adenocarcinoma
Predictive Cancer Model

OTHER: Pancreatic Cancer Risk Model (PRISM)

2023Trial

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2023-07-17	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-11-06
First Submitted that Met QC Criteria 2023-08-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-11-07
First Posted (ACTUAL) 2023-08-02	Results First Posted N/A	Last Verified 2024-11

Study Plan

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

Design Details

Primary Purpose:
N/A

Allocation:
N/A

Interventional Model:
N/A

Masking:
N/A

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
: prospective general opulation cohort Males and females age >= 40 years, without a personal history of PDAC or current PDAC, with at least 2 clinical encounters to the HCO within the year prior to the study start date.	OTHER: Pancreatic Cancer Risk Model (PRISM) A neural network model (PrismNN) and a logistic regression model (PrismLR) that use routinely collected EHR data to stratify individuals from the general population into PDAC risk groups

Participant Group/Arm

Intervention/Treatment

: prospective general opulation cohort

Males and females age >= 40 years, without a personal history of PDAC or current PDAC, with at least 2 clinical encounters to the HCO within the year prior to the study start date.

OTHER: Pancreatic Cancer Risk Model (PRISM)

A neural network model (PrismNN) and a logistic regression model (PrismLR) that use routinely collected EHR data to stratify individuals from the general population into PDAC risk groups

Primary Outcome Measures	Measure Description	Time Frame
Area under the receiver operating characteristic curve (AUROC) of PRISM for all groups stratified	To assess the discriminatory performance of PRISM for prospective identification of high-risk individuals for PDAC 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
Area under the receiver operating characteristic curve (AUROC) of PRISM for all groups stratified	To assess the discriminatory performance of PRISM for prospective identification of high-risk individuals for PDAC development. ROCs and AUROC numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location.	at 1 year
Area under the receiver operating characteristic curve (AUROC) of PRISM for all groups stratified	To assess the discriminatory performance of PRISM for prospective identification of high-risk individuals for PDAC development. ROCs and AUROC numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location.	at 2 years
Area under the receiver operating characteristic curve (AUROC) of PRISM for all groups stratified	To assess the discriminatory performance of PRISM for prospective identification of high-risk individuals for PDAC development. ROCs and AUROC numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location.	at 3 years
Calibration of PRISM for all groups stratified	To access how well the risk prediction by PRISM 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
Calibration of PRISM for all groups stratified	To access how well the risk prediction by PRISM 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.	at 1 year
Calibration of PRISM for all groups stratified	To access how well the risk prediction by PRISM 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.	at 2 years
Calibration of PRISM for all groups stratified	To access how well the risk prediction by PRISM 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.	at 3 years
PRISM performance metrics of high-risk group for direct screening	To evaluate sensitivity, specificity, PPV, and SIR for patients identified as high-risk by PRISM. Numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location. Risk threshold determined based on Standardized Incidence Ratio of 5 or greater. The absolute one-year risk thresholds are 0.1834% for PrismNN and 0.2048% risk for PrismLR. SIR 5 or greater was chosen because it is comparable to the current screening inclusion threshold for individuals with an inherited predisposition.	6 months from index date
PRISM performance metrics of high-risk group for direct screening	To evaluate sensitivity, specificity, PPV, and SIR for patients identified as high-risk by PRISM. Numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location. Risk threshold determined based on Standardized Incidence Ratio of 5 or greater. The absolute one-year risk thresholds are 0.1834% for PrismNN and 0.2048% risk for PrismLR. SIR 5 or greater was chosen because it is comparable to the current screening inclusion threshold for individuals with an inherited predisposition.	at 1 year
PRISM performance metrics of high-risk group for direct screening	To evaluate sensitivity, specificity, PPV, and SIR for patients identified as high-risk by PRISM. Numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location. Risk threshold determined based on Standardized Incidence Ratio of 5 or greater. The absolute one-year risk thresholds are 0.1834% for PrismNN and 0.2048% risk for PrismLR. SIR 5 or greater was chosen because it is comparable to the current screening inclusion threshold for individuals with an inherited predisposition.	at 2 years
PRISM performance metrics of high-risk group for direct screening	To evaluate sensitivity, specificity, PPV, and SIR for patients identified as high-risk by PRISM. Numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location. Risk threshold determined based on Standardized Incidence Ratio of 5 or greater. The absolute one-year risk thresholds are 0.1834% for PrismNN and 0.2048% risk for PrismLR. SIR 5 or greater was chosen because it is comparable to the current screening inclusion threshold for individuals with an inherited predisposition.	at 3 years
PRISM performance metrics of medium-risk group for biomarker testing	To evaluate sensitivity, specificity, PPV, and SIR for patients identified as medium-risk by PRISM. Numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location. Risk threshold determined by specificity 85%, with sensitivity around 46%. The absolute one-year risk thresholds are 0.0574% for PrismNN and 0.0564% for PrismLR. Prism operates as a tiered system for identifying individuals in need of screening with this lower risk threshold.	6 months from index date
PRISM performance metrics of medium-risk group for biomarker testing	To evaluate sensitivity, specificity, PPV, and SIR for patients identified as medium-risk by PRISM. Numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location. Risk threshold determined by specificity 85%, with sensitivity around 46%. The absolute one-year risk thresholds are 0.0574% for PrismNN and 0.0564% for PrismLR. Prism operates as a tiered system for identifying individuals in need of screening with this lower risk threshold.	at 1 year
PRISM performance metrics of medium-risk group for biomarker testing	To evaluate sensitivity, specificity, PPV, and SIR for patients identified as medium-risk by PRISM. Numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location. Risk threshold determined by specificity 85%, with sensitivity around 46%. The absolute one-year risk thresholds are 0.0574% for PrismNN and 0.0564% for PrismLR. Prism operates as a tiered system for identifying individuals in need of screening with this lower risk threshold.	at 2 years
PRISM performance metrics of medium-risk group for biomarker testing	To evaluate sensitivity, specificity, PPV, and SIR for patients identified as medium-risk by PRISM. Numbers will be calculated for the whole population and groups stratified by age, sex, race, and geographical location. Risk threshold determined by specificity 85%, with sensitivity around 46%. The absolute one-year risk thresholds are 0.0574% for PrismNN and 0.0564% for PrismLR. Prism operates as a tiered system for identifying individuals in need of screening with this lower risk threshold.	at 3 years

Secondary Outcome Measures	Measure Description	Time Frame
Timing of incident PDAC occurrence	To evaluate how long in advance before PDAC occurrence should be expected for PRISM models to make high-risk predictions. Distribution plots of the date of PDAC incidence for high/medium-risk groups (defined in Outcome 3 and Outcome 4) will be created.	6 months from index date
Timing of incident PDAC occurrence	To evaluate how long in advance before PDAC occurrence should be expected for PRISM models to make high-risk predictions. Distribution plots of the date of PDAC incidence for high/medium-risk groups (defined in Outcome 3 and Outcome 4) will be created.	at 1 year
Timing of incident PDAC occurrence	To evaluate how long in advance before PDAC occurrence should be expected for PRISM models to make high-risk predictions. Distribution plots of the date of PDAC incidence for high/medium-risk groups (defined in Outcome 3 and Outcome 4) will be created.	at 2 years
Timing of incident PDAC occurrence	To evaluate how long in advance before PDAC occurrence should be expected for PRISM models to make high-risk predictions. Distribution plots of the date of PDAC incidence for high/medium-risk groups (defined in Outcome 3 and Outcome 4) will be created.	at 3 years
Tumor stage at PDAC diagnosis	stage at diagnosis per tumor registry/pathology report	6 months from index date
Tumor stage at PDAC diagnosis	stage at diagnosis per tumor registry/pathology report	at 1 year
Tumor stage at PDAC diagnosis	stage at diagnosis per tumor registry/pathology report	at 2 years
Tumor stage at PDAC diagnosis	stage at diagnosis per tumor registry/pathology report	at 3 years

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
40 Years

Accepts Healthy Volunteers:
1

Male and females age >= 40 years from 44 US HCOs from the TriNetX platform
at least 2 clinical encounters to the HCO, within the last year, before the study start date

Personal history of PDAC or current PDAC
Age below 40

Collaborators and Investigators

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

Massachusetts Institute of Technology
TriNetX, LLC

Investigators

PRINCIPAL_INVESTIGATOR: Limor Appelbaum, MD, Beth Israel Deaconess Medical Center

Publications

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