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Prospective Validation of an EHR-based Pancreatic Cancer Risk Model

Active, not recruiting
Conditions
Pancreatic Adenocarcinoma
Predictive Cancer Model
Interventions
Other: Pancreatic Cancer Risk Model (PRISM)
Registration Number
NCT05973331
Lead Sponsor
Beth Israel Deaconess Medical Center
Brief Summary

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.

Detailed Description

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

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
6134060
Inclusion Criteria
  • 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
Exclusion Criteria
  • Personal history of PDAC or current PDAC
  • Age below 40

Notes on sampling method: no sampling was performed. All eligible individuals are included in this study.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
prospective general opulation cohortPancreatic Cancer Risk Model (PRISM)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.
Primary Outcome Measures
NameTimeMethod
Area under the receiver operating characteristic curve (AUROC) of PRISM for all groups stratifiedat 3 years

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.

Calibration of PRISM for all groups stratifiedat 3 years

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.

PRISM performance metrics of high-risk group for direct screeningat 3 years

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.

PRISM performance metrics of medium-risk group for biomarker testingat 3 years

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.

Secondary Outcome Measures
NameTimeMethod
Timing of incident PDAC occurrenceat 3 years

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.

Tumor stage at PDAC diagnosisat 3 years

stage at diagnosis per tumor registry/pathology report

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

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