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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 239990

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, 43183
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Type 2 diabetes mellitus (T2DM) adult patients enrolled in the two claims databases and are eligible to be included according to the inclusion and exclusion criteria of each of the three investigated clinical trial studies: CANVAS, LEADER and SAVOR-TIMI.

All subjects meeting the inclusion and exclusion criteria will be assessed. Remaining sample size will be dependent on the number of matched subjects in each cohort using the two data sources combined.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	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

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]

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• CANVAS
• LEADER
• SAVOR-TIMI

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2020
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: April 6, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 25, 2023

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; Epidemiology; Clinical Trial; Real World Evidence; Real World Data; Regulatory; Emulation
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Liraglutide; Dipeptidyl-Peptidase IV Inhibitors; Canagliflozin; Saxagliptin
• Other Study ID Numbers: D1843R00345

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: from 05 December 2022
• IPD Sharing Access Criteria: Protocol and SAP details along with programming code to be supplied upon request via mail.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No