Significance. The comparative effectiveness of long-acting beta agonists (LABA) in asthma management withother controller medicines has not been established. Although LABA monotherapy increases the risk of seriousadverse events (AEs) and is recommended to be used in combination with inhaled corticosteroids (ICS), thesafety of combination therapy is not known. Also not known, and clinically important to understand, is how, whyand to whom LABAs and/or combination therapy are associated with increased risk of serious AEs.
Specific Aims. To address the comparative effectiveness and safety concerns of the combination therapy(ICS + LABA), as well as to understand the profile of those who experience AE, and the profile of those whobenefit most from the combination therapy, we will (1) determine the effectiveness of LABA-containingtherapies in comparison with other available controller regimens in persistent asthma disease management; (2)determine if LABA-containing therapies are associated with an increased risk of asthma-related serious AEsand all-cause mortality; and (3) determine the characteristics of patients who clinically respond to, or have AEsattributable to, LABA-containing therapies.Research Design.
In Aim 1, we will conduct a population based cohort study of subjects with persistentasthma. The effect of LABA-containing therapies in the real-world setting will be measured and compared withother asthma controller therapies on asthma control and exacerbation prevention from 1998-2010. This periodallows for the study of LABAs during use of LABA monotherapy, and during a period prior to AE recognitionand the FDA black box warning. The study will be done in diverse populations of nearly 664,000 asthmaticswhich we have assembled, including a state Medicaid population, four HMO research populations, and aDepartment of Defense population.
In Aim 2, we will conduct a nested case-control study to evaluate the risk ofserious asthma-related AEs with the use of LABA-containing therapies. Asthma-related and all-cause deathwill be studied separately.
In Aim 3, patient characteristics associated with both response to, and serious AEsrelated to, LABA-containing therapies will be assessed, including patient demographics, disease severity,underlying asthma control, medication utilization patterns, adherence, and definable asthma phenotypes usingmultivariable regression modeling. For each aim, various subgroup analyses, sensitivity analyses andsimulation studies will be performed to provide robust results and to evaluate the accuracy of the estimates.Impact. This project is of critical importance as it addresses comparative effectiveness and safety concerns inasthma pharmacotherapy. It will inform and empower physicians, patients, and healthcare policy makersproviding timely knowledge in how, when, and to whom to provide or avoid LABA containing therapies. Suchknowledge will have widespread public health impact in asthma disease management.

Public Health Relevance

This will be the first project to develop patient-specific therapeutic choices in asthma control by considering two very important issues related to a class of asthma medications called long acting beta agonists (LABAs). The first is how well these medications work for patients with asthma in clinical practice and second is the recognized safety concerns related to these medications. This study will permit physicians and patients to make treatment decisions based upon the patient-specific benefit-risk assessments of LABAs.

Agency
National Institute of Health (NIH)
Institute
Agency for Healthcare Research and Quality (AHRQ)
Type
Research Project (R01)
Project #
6R01HS022093-02
Application #
9294369
Study Section
Health Care Quality and Effectiveness Research (HQER)
Program Officer
Basu, Jayasree
Project Start
2013-09-30
Project End
2017-09-29
Budget Start
2016-04-30
Budget End
2017-09-29
Support Year
2
Fiscal Year
2013
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232
Turi, Kedir N; Gebretsadik, Tebeb; Lee, Rees L et al. (2018) Seasonal patterns of Asthma medication fills among diverse populations of the United States. J Asthma 55:764-770
Stone, Cosby; Gebretsadik, Tebeb; Lee, Rees L et al. (2018) Trends in health care utilization for asthma exacerbations among diverse populations with asthma in the United States. J Allergy Clin Immunol Pract 6:295-297.e5
Yu, Chang; Zelterman, Daniel (2017) A general approximation to quantiles. Commun Stat Theory Methods 46:9834-9841
Yu, Chang; Zelterman, Daniel (2017) A parametric model to estimate the proportion from true null using a distribution for p-values. Comput Stat Data Anal 114:105-118
Jackson, Daniel J; Hartert, Tina V; Martinez, Fernando D et al. (2014) Asthma: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc 11 Suppl 3:S139-45