Benchmark surveillance tests for diagnosing disease progression (biopsies, endoscopies, etc.) in early-stage chronic non-communicable disease patients (e.g., cancer, lung diseases) are usually invasive. For detecting progression timely, over their lifetime, patients undergo numerous invasive tests planned in a fixed one-size-fits-all manner (e.g., biannually). We present personalized test schedules based on progression-risk, that aim to optimize the number of tests (burden) and time delay in detecting progression (shorter is beneficial) better than fixed schedules. Our motivation comes from the problem of scheduling biopsies in prostate cancer surveillance studies.

Using joint models for time-to-event and longitudinal data, we consolidate patients’ longitudinal data (e.g., biomarkers) and results of previous tests, into individualized future cumulative-risk of progression. We then create personalized schedules by planning tests on future visits where the predicted cumulative-risk is above a particular threshold (e.g., 5% risk). This schedule is updated on each follow-up with newly gathered data. To find the optimal risk threshold, we minimize a utility function of the expected number of tests (burden) and expected time delay in detecting progression (shorter is beneficial) for different thresholds. We estimate these two quantities in a patient-specific manner for following any schedule by utilizing the predicted risk profile of the patient. Patients/doctors can employ these quantities to compare various personalized and fixed schedules objectively. Last, we implement our methodology in a web-application for prostate cancer patients.

Additional Metadata
Keywords Personalized Schedules, Joint Models, Longitudinal data analysis, survival analysis, Prostate Cancer
Promotor D. Rizopoulos (Dimitris) , E.W. Steyerberg (Ewout)
Publisher Erasmus University Rotterdam
Sponsor The research described in this thesis was supported by Nederlandse Organisatie voor Wetenschappelijk Onderzoek VIDI grant nr. 016.146.301, and Erasmus University Medical Center funding
Persistent URL hdl.handle.net/1765/129280
Note For copyright reasons there is a partial embargo for this dissertation
Organisation Department of Biostatistics
Citation
Tomer, A. (2020, September 16). Personalized Schedules for Invasive Diagnostic Tests: With Applications in Surveillance of Chronic Non-Communicable Diseases. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/129280