Ignite Creation Date:
2025-12-24 @ 1:30 PM
Ignite Modification Date:
2025-12-30 @ 3:36 PM
Study NCT ID:
NCT06675695
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-11-25
First Post:
2024-11-01
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Emulation of the FLAURA (NCT02296125) Trial Using Specialty Oncology Electronic Health Records Databases
Sponsor:
Brigham and Women's Hospital
Organization:
Study Overview
Official Title:
Emulation of the FLAURA (NCT02296125) Trial Using Specialty Oncology Electronic Health Records Databases
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Investigators are building an empirical evidence base for real world data through large-scale emulation 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:
Randomized controlled trials (RCTs) are generally regarded as the gold-standard of evidence for establishing efficacy of medical products. However, real-world data (RWD) are increasingly used to complement evidence coming from RCTs. Yet, to have confidence in the accuracy of RWD studies of oncology products and their outcomes, investigators need to know which questions can be validly answered, with which non-interventional study designs and analysis methods, given the data that is available. Building on a process based on the RCT DUPLICATE initiative, the trial emulation discussed in this protocol is part of the expansion project EmulatioN of Comparative Oncology trials with Real-world Evidence (ENCORE) which is specific to oncology and aims to emulate 12 randomized oncology RCTs using multiple EHR data sources.
The purpose of this protocol is to describe the emulation of the FLAURA trial in a study conducted using specialty oncology electronic health record data. FLAURA was a Phase III, double-blind, randomised study assessing the efficacy and safety of AZD9291 (= osimertinib, 80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib \[250 mg orally, once daily\] or erlotinib \[150 mg orally, once daily\]) in patients with locally advanced or metastatic EGFR sensitizing mutation (EGFRm+) Non-small Cell Lung Cancer (NSCLC) who are treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
The database study designed to emulate FLAURA trial will be a new-user active comparative study, where we will compare the effect of osimertinib versus SoC on overall survival among patients with locally advanced or metastatic EGFRm+ NSCLC who are treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) extension project ENCORE, being conducted at the Brigham and Women's Hospital, Harvard Medical School. It is intended to emulate, as closely as is possible in specialty oncology electronic health records data, the trial listed below/above. Although many features of the trial cannot be directly emulated using secondary healthcare data, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not emulable 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 data for emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.
The purpose of this protocol is to describe the emulation of the FLAURA trial in a study conducted using specialty oncology electronic health record data. FLAURA was a Phase III, double-blind, randomised study assessing the efficacy and safety of AZD9291 (= osimertinib, 80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib \[250 mg orally, once daily\] or erlotinib \[150 mg orally, once daily\]) in patients with locally advanced or metastatic EGFR sensitizing mutation (EGFRm+) Non-small Cell Lung Cancer (NSCLC) who are treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
The database study designed to emulate FLAURA trial will be a new-user active comparative study, where we will compare the effect of osimertinib versus SoC on overall survival among patients with locally advanced or metastatic EGFRm+ NSCLC who are treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) extension project ENCORE, being conducted at the Brigham and Women's Hospital, Harvard Medical School. It is intended to emulate, as closely as is possible in specialty oncology electronic health records data, the trial listed below/above. Although many features of the trial cannot be directly emulated using secondary healthcare data, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not emulable 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 data for emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: