Replication of the SEPRA Diabetes Trial in Healthcare Claims Data

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Replication of the SEPRA Diabetes Trial in Healthcare Claims Data

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)


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| New use of semaglutide injection<br>Exposure group | Drug: New use of semaglutide injection<br>* New use of semaglutide injection dispensing claim is used as the exposure.<br>|
| New initiation of standard of care<br>(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)<br>* 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.<br>|

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 |