Prediction of the PRONOUNCE Prostate Cancer Trial in Healthcare Claims Data

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Degarelix; Drug: Leuprolide

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 14417

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Subjects were selected on the basis of having at least one diagnosis code indicating prostate cancer, male sex, and a history of artherosclerotic cardiovascular disease. In contrast to the the PRONOUNCE RCT trial, patients cannot be required to have had established tumor staging information, angiography-verified stenosis/occlusion of vessels, and a lack of planned cardiac surgery at the time of treatment initiation due to poor capture of this information administrative data. All patients were required to have continuous enrollment for 365 days prior to cohort entry to ensure incident use of the study drugs.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Degarelix; Reference group	Drug: Degarelix; Degarelix dispensing claim is used as the reference group.
Leuprolide; Exposure group	Drug: Leuprolide; Leuprolide dispensing claim is used as the exposure group.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Shirley Wang, PhD, ScM, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2019
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 18, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: 2018P002966-DUP-PRONOUNCE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No