Harmonizing RCT-Duplicate Emulations In A Real World Replication Program (HARRP)

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT06099067

Collaborator

(none)

239,990

Enrollment

Location

39.5

Actual Duration (Months)

6072.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Replication of three clinical trial emulations CANVAS, LEADER, and SAVOR TIMI that form part of the RCT-Duplicate initiative, sponsored by the FDA and delivered by the Brigham and Women's Hospital and Harvard Medical School. AstraZeneca will use the Instant Health Data platform PANALGOS (IHD) for the analyses.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Canagliflozin Drug: DPP4 inhibitor Drug: Liraglutide Drug: Saxagliptin Drug: 2nd generation Sulfonylurea

Detailed Description

RCT-duplicate (RCT-D) is an initiative led by the Brigham and Women's Hospital and Harvard Medical School, that selected 30 clinical trials as part of an empirical experiment where these trials would be emulated using RWD. AstraZeneca will replicate three emulations CANVAS, LEADER, and SAVOR TIMI from among the 30 plus clinical trials analyzed in RCT-D. These clinical trials assess type 2 diabetes mellitus drugs. The replications will be conducted on the Instant Health Data PANALGOS (IHD) platform to assess these studies in two claims databases Optum and IBM Watson Market Scan. The aim is to recreate these three emulations to investigate the reproducibility of the emulations, increase transparency and better understand the process of trial emulations; and where possible, contribute with potential improvements to the RCT-D framework.

Study Design

Study Type:

Observational

Actual Enrollment :

239990 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Harmonizing RCT-Duplicate Emulations: A Real World Replication Program Analyzing Three Clinical Trials, CANVAS, LEADER, and SAVOR TIMI in Type 2 Diabetes Mellitus

Actual Study Start Date :

May 15, 2020

Actual Primary Completion Date :

Aug 31, 2023

Actual Study Completion Date :

Aug 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
CANVAS Canagliflozin CANVAS expousre Group	Drug: Canagliflozin Canagliflozin dispensing claim is used as the exposure drug in CANVAS replication
CANVAS DPP4i CANVAS reference Group	Drug: DPP4 inhibitor DPP4 inhibitor dispensing claim is used as the reference drug in CANVAS and LEADER replications
LEADER Liraglutide LEADER exposure Group	Drug: Liraglutide Liraglutide dispensing claim is used as the Exposure drug in LEADER replication
LEADER DPP4i LEADER reference Group	Drug: DPP4 inhibitor DPP4 inhibitor dispensing claim is used as the reference drug in CANVAS and LEADER replications
SAVOR-TIMI Saxagliptin SAVOR-TIMI exposure Group	Drug: Saxagliptin Saxagliptin dispensing claim is used as the Exposure drug in SAVOR-TIMI replication
SAVOR-TIMI 2nd generation Sulfonylurea SAVOR-TIMI reference Group	Drug: 2nd generation Sulfonylurea 2nd generation Sulfonylurea dispensing claim is used as the Exposure drug in SAVOR-TIMI replication

Outcome Measures

Primary Outcome Measures

3-point MACE [Follow up begins the day after drug initiation for the three investigated studies [a median of 134-167 days]]
3-point MACE: Relative hazard of composite outcome of Stroke, MI, and Mortality