Replication of the INSPIRE 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: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Tiotropium; Drug: salmeterol-fluticasone

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): 98278

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: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will involve a new user, parallel group, propensity score matched retrospective cohort study design comparing tiotropium to salmeterol. The patients will be required to have continuous enrollment during baseline period of 180 days before initiation of SFC or tiotropium inhalers (cohort entry date).

Description

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

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
Tiotropium; Reference group	Drug: Tiotropium; Tiotropium dispensing claim is used as the reference group.
Salmeterol/Fluticasone; Exposure group	Drug: salmeterol-fluticasone; Salmeterol/Fluticasone dispensing claim is used as the exposure group.

What is the study measuring?

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

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): September 22, 2020
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: December 16, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 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: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Sympathomimetics; Fluticasone; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Tiotropium Bromide
• Other Study ID Numbers: 2018P002966-DUP-INSPIRE

Drug and device information, study documents

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