Replication of the LEAD-2 Diabetes Trial in Healthcare Claims Data

Study Overview
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Brief Summary
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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
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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 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 through 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
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Replication of the LEAD-2 Diabetes Trial in Healthcare Claims Data

Conditions
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Diabetes

Intervention / Treatment
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* Drug: Glimepiride
* Drug: Liraglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Type 2 Diabetes mellitus [0,0] days 3 or more recorded HbA1c values [-365, 0] days At least two dispensing claims for metformin [-180,0] days 1 or more recorded HbA1c values [-90,0] days Age between 18-80 [0,0] days Exclusion Criteria: Cancer, malignant neoplasm, or MEN2 [-1,825,0] days Use of other anti-diabetic medications [-180,0] days Cirrhosis or Hepatic decompensation [-180,0] days Viral hepatitis B or C [-180,0] days Stage 5 CKD, ESRD, dialysis or renal transplant [-180,0] days MI or HF [-180,0] days Treatment with Anti-VEGFi or Photocoagulation [-180,0] days Hypertensive crisis or uncontrolled hypertension [-180,0] days Two diagnoses of hypoglycemia [-180,0] days Alcohol/drug abuse/dependence [-180,0] days Dementia and brain damages or non-compliance [-180,0] days Pregnancy [-180,0] days Type 1 DM, DKA, or other metabolic acidosis [-180,0] days Systemic corticosteroids [-90,0] days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Glimepiride<br>Reference Group | Drug: Glimepiride<br>* Glimepiride dispensing claim is used as the reference group.<br>|
| Liraglutide<br>Exposure group | Drug: Liraglutide<br>* Liraglutide dispensing claim is used as the exposure group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Hazard of change in HbA1c from baseline to 26 weeks of treatment (end of follow-up) | Claims-based algorithm: relative hazard of change in HbA1c from baseline to 26 weeks of treatment (end of follow-up) | 26-week follow-up window with a median follow-up time of 99 [84, 148] days |