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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Canagliflozin
* Drug: DPP4 inhibitor
* Drug: Liraglutide
* Drug: Saxagliptin
* Drug: 2nd generation Sulfonylurea


Participation Criteria
=================
Eligibility Criteria
-----------------
The Eligibility Criteria for CANVAS, LEADER and SAVOR-TIMI are replicated Please see the Criteria for each under: CANVAS: https://clinicaltrials.gov/ct2/show/NCT03936010 LEADER: https://clinicaltrials.gov/ct2/show/NCT03936049 SAVOR-TIMI: https://clinicaltrials.gov/ct2/show/NCT03936023
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clinical Trial, Emulation, Epidemiology, Type 2 Diabetes, Regulatory, Real World Evidence, Real World Data