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
Study Type
OBSERVATIONAL
Enrollment
6,134,060
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
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: at 3 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: at 3 years
Tumor stage at PDAC diagnosis
stage at diagnosis per tumor registry/pathology report
Time frame: 6 months from index date
Tumor stage at PDAC diagnosis
stage at diagnosis per tumor registry/pathology report
Time frame: at 1 year
Tumor stage at PDAC diagnosis
stage at diagnosis per tumor registry/pathology report
Time frame: at 2 years
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Tumor stage at PDAC diagnosis
stage at diagnosis per tumor registry/pathology report
Time frame: at 3 years