Replication of the GRADE 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 GRADE Diabetes Trial in Healthcare Claims Data

Conditions
-----------------
Diabetes

Intervention / Treatment
-----------------
* Drug: Sitagliptin
* Drug: Glimepiride


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age greater or equal than 30: days [0,0] Diagnosis of Type 2 Diabetes: days [- All Data, 0] 2+ recorded HbA1c levels: days [-365,0] Metformin use: days [-30, 0] Exclusion Criteria: Type 1 or Secondary DM: days [-All Data, 0] Previous organ transplant: days [-All Data, 0] HIV/AIDS: days [-All Data, 0] History of bariatric surgery: days [-All Data, 0] Congestive heart failure: days [-All Data, 0] NYHA >=3: days [-All Data, 0] Pancreatitis: days [-All Data, 0] Medullary thyroid cancer/MEN-2: days [-All Data, 0] History of MI: days [-365, 0] Stroke: days [-365, 0] Coronary Revascularization: days [-365, 0] PTCA/Stenting/CABG: days [-365, 0] Trans myocardial revascularization: days [-365, 0] Carotid bypass: days [-365, 0] Cerebrovascular revascularization: days [-365, 0] PVD: days [-365, 0] CCI >=10: days [-365, 0] History of cancer, other than non-melanoma skin cancer: days [-1,825, 0] Treatment of metformin more than 10 years: days [-3,650, 0] Treatment with any diabetes drug other than metformin; PCOS; symptomatic hyperglycemia; pregnancy; gestational diabetes: days [-180, 0] History of hemolytic anemia; history of severe liver disease; current alcoholism; chronic transfusion requirement; ESRD: days [-180, 0] Oral, IV, or IM cortisone, hydrocortisone, prednisone, methylprednisone, or dexamethasone: days [-90, 0] Treatment with atypical antipsychotics, language barriers, nursing home, or missing age or gender: days {-180, 0] Hospitalization with length of stay >3 days: days [-30, 0]

Ages Eligible for Study
-----------------
Minimum Age: 30 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 |
| --- | --- |
| Sitagliptin<br>Reference group | Drug: Sitagliptin<br>* Sitagliptin dispensing claim is used as the reference<br>|
| Glimepiride<br>Exposure group | Drug: Glimepiride<br>* Glimepiride dispensing claim is used as the reference<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time until failure to maintain metabolic control | Lab based algorithm: time until failure to maintain metabolic control (HbA1c level >= 7.0% or 53 mmol/mol) | Through censoring or study completion, up to 765 days after cohort entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time until a severe hypoglycemic episode | Claims based algorithm: time until a severe hypoglycemic episode | Through censoring or study completion, up to 765 day after cohort entry | 
| HbA1C change from baseline | Lab based algorithm: HbA1C change from baseline | Through censoring or study completion, up to 765 days after cohort entry |