Replication of the SEPRA Diabetes 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: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: New use of semaglutide injection; Drug: New initiation of "standard of care" (SGL2i, 2nd generation SU, DPP-4i and GLP-1 RA except for semaglutide inj or oral)

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): 2316

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: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 diabetes who have previously been treated with metformin.

Description

Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.

All patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of semaglutide or standard of care (SGL2i, 2nd generation SU, DPP-4i and GLP-1 RA except for semaglutide inj or oral) (cohort entry).

Eligible cohort entry dates:

Market availability of semaglutide/standard of care in the US started on December 6th, 2017:

• For Optum: December 6, 2017 - June 30, 2021 (end of data availability)

Inclusion Criteria:

• Age >= 18
• Type 2 diabetes mellitus diagnosis
• Use of metformin
• At least 2 HbA1c records within the prior 280 days
• At least 1 HbA1c record >= 7% within the prior 90 days

Exclusion Criteria:

• Missing age or gender
• Use of any other anti-diabetes medications
• Any insulin use
• Pregnancy
• Multiple Endocrine Neoplasia syndrome type 2
• CKD stage 5, ESRD, dialysis, or renal transplant
• Nursing home admission

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
New use of semaglutide injection; Exposure group	Drug: New use of semaglutide injection; New use of semaglutide injection dispensing claim is used as the exposure.
New initiation of "standard of care"; (SGL2i, 2nd generation SU, DPP-4i and GLP-1 RA except for semaglutide inj or oral) Reference group	Drug: New initiation of "standard of care" (SGL2i, 2nd generation SU, DPP-4i and GLP-1 RA except for semaglutide inj or oral); New initiation of "standard of care" (SGL2i, 2nd generation SU, DPP-4i and GLP-1 RA except for semaglutide inj or oral) dispensing claim is used as the reference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term glycemic control defined as proportion of patients who will achieve an HbA1c of less than 7.0% (53.0 mmol/mol)	Number of subjects	At year 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Change in HbA1c from baseline at 365 days after drug initiation.	At 1 year
Number of hypoglycemic episodes leading to an inpatient admission or emergency room encounter.		At 1 year

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): July 1, 2021
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 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: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 2018P002966-DUP-SEPRA

Drug and device information, study documents

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