Replication of the INSPIRE 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 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
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Replication of the INSPIRE Trial in Healthcare Claims Data

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Tiotropium
* Drug: salmeterol-fluticasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 40-80 years [0,0] days Diagnosis of COPD [all available data, 0] days Clinical history of at least 1 COPD exacerbation [all available data, -43] days Exclusion Criteria: COPD exacerbation [-42, 0] days Asthma, eczema, atopic dermatitis, allergic rhinitis [-180, 0] days Known respiratory disorder other than COPD e.g. pulmonary fibrosis or interstitial lung disease (ILD), sarcoidosis, lymphangioleiomyomatosis, primary/pulmonary tuberculosis, cystic fibrosis, pulmonary hypertension/other pulmonary heart disease, lung/pulmonary malignancies, alpha-1 antitrypsin deficiency, pneumoconioses and other lung diseases due to external agents [all available data, 0] days Narrow angle glaucoma or prostatic hyperplasia or obstruction of the neck of the bladder [-180, 0] days At least one 30-day supply prescription claims for oral alfuzosin, doxazosin, tamsulosin, silodosin, finasteride 5 mg, dutasteride [-180,0] days Lung transplant or lung volume reduction surgery (LVRS) [all available data, 0] days Daily long term oxygen therapy (LTOT) [all available data, 0] days Beta-blockers (except eye drops) [-180, 0] days Evidence of alcohol, drug or solvent abuse [-180, 0] days Use of salmeterol, tiotropium and fluticasone containing inhaler use [-180, 0] days

Ages Eligible for Study
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Minimum Age: 40 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 |
| --- | --- |
| Tiotropium<br>Reference group | Drug: Tiotropium<br>* Tiotropium dispensing claim is used as the reference group.<br>|
| Salmeterol/Fluticasone<br>Exposure group | Drug: salmeterol-fluticasone<br>* Salmeterol/Fluticasone 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 |
| --- | --- | --- |
| Healthcare utilization exacerbation rate per year | Claims-based algorithm: healthcare utilization exacerbation rate per year | Through study completion or censoring, up to 193 days |