Prediction of the PRONOUNCE Prostate Cancer Trial in Healthcare Claims Data

Study Overview
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Brief Summary
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Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Detailed Description
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This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Official Title
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Prediction of the PRONOUNCE Prostate Cancer Trial in Healthcare Claims Data

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Degarelix
* Drug: Leuprolide


Participation Criteria
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Eligibility Criteria
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Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions. Eligible cohort entry dates: The degarelix indication for treatment of prostate cancer was approved by the FDA on Dec 24, 2008. Leuprolide was initially approved for the same indication prior to Dec 24, 2008. IBM MarketScan: Dec 24, 2008 - December 31, 2018 (end of available data) Optum CDM: Dec 24, 2008 - June 30, 2020 (end of available data) CMS Diabetes: Dec 24, 2008 - Dec 31, 2017 (end of available data) Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate Pre-existing ASCVD (confirmed diagnosis, documented) according to a least 1 of the following criteria: Previous MI >= 30 days before randomization Previous revascularization procedure >= 30 days before randomization Coronary artery: stent placement/balloon angioplasty or coronary artery bypass graft surgery Carotid artery: stent placement/balloon angioplasty or endarterectomy surgery Iliac, femoral, popliteal arteries: stent placement/balloon angioplasty or vascular bypass surgery Exclusion Criteria: Treatment naivety (ADT) Previous or current hormonal management of prostate cancer including surgical castration, any hormonal manipulation, or any previous neoadjuvant/adjuvant hormonal therapy, unless treatment was terminated more than 12 months prior to enrollment Uncontrolled Type 1 or Type 2 diabetes mellitus Uncontrolled hypertension A history of congenital long QT syndrome or risk factors for Torsade de pointes ventricular arrhythmias MI; stroke; or coronary, carotid, or peripheral artery revascularization
Sexes Eligible for Study
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Male

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Degarelix<br>Reference group | Drug: Degarelix<br>* Degarelix dispensing claim is used as the reference group.<br>|
| Leuprolide<br>Exposure group | Drug: Leuprolide<br>* Leuprolide dispensing claim is used as the exposure group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiovascular Events (MACE) | Composite of all-cause mortality, nonfatal MI, and nonfatal stroke | Through study completion (earliest of 336 days or censoring) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-Cause Mortality | Component of MACE | Through study completion (earliest of 336 days or censoring) | 
| Nonfatal MI | Component of MACE | Through study completion (earliest of 336 days or censoring) | 
| Nonfatal Stroke | Component of MACE | Through study completion (earliest of 336 days or censoring) |