The impact of FDA regulatory activities on incident dispensing of LABA-containing medication: 2005–2011

ABSTRACT

Objective: Evidence of safety issues associated with long-acting beta₂-agonist (LABA) treatment has led to multiple regulatory activities by the U.S. Food and Drug Administration (FDA) on this class of medications. This study describes the impact of the regulatory activities on incident LABA-containing medication dispensing. Methods: A monthly rolling cohort of asthma patients who were eligible to initiate a LABA-containing product was created in the Mini-Sentinel Distributed Database between January 2005 and June 2011. Cohorts of individuals who initiated LABA were examined for the changes in the proportions of single-ingredient to fixed-dose inhaled corticosteroid (ICS)-LABA initiators, appropriate initiation of LABA-containing products, and use of controller medications. The impact of the 2005 and 2010 FDA regulatory activities associated with LABA-containing products was measured using interrupted time series with segmented regression. Results: LABA-containing product initiation was declining prior to the 2005 regulatory activities and continued to decline over the study period, accompanied by increased initiation of fixed dose ICS-LABA among LABA initiators. While the 2010 regulatory activities had no immediate impact on the proportion of LABA initiation in patients with prior controller medication dispensing and/or poor asthma control, there was an increasing positive trend toward LABA initiation in the appropriate patient population after the regulatory activities. Conclusion: The 2005 and 2010 FDA regulatory activities likely had an impact on communicating the safety concerns of LABA products. However, the impact cannot be viewed independent of scientific publications, guidelines for asthma treatment and other regulatory activities.

KEYWORDS:

• Asthma
• long-acting beta₂-agonist
• drug safety
• sentinel
• U.S. FDA

Abbreviations

CI	=	confidence interval
DSC	=	Drug Safety Communication
FDA	=	U.S. Food and Drug Administration
ICD-9-CM	=	International Classification of Diseases, 9th Revision, Clinical Modification
ICS	=	inhaled corticosteroid
ITS	=	interrupted time-series
LABA	=	long-acting beta2-agonist
NAEPP	=	National Asthma Education and Prevention Program
SI-LABA	=	single-ingredient LABA
SMART	=	Salmeterol Multicenter Asthma Research Trial

Acknowledgements

The authors would like to thank Marsha Reichman, PhD and Monika Houstoun, PharmD from the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, for their scientific and administrative support. The authors would like to thank Mini-Sentinel collaborators included Data and Academic Partners that provided access to health care data and ongoing scientific, technical, methodological, and organizational expertise.

Declaration of interest

The following authors were employees of the FDA and have had no potential conflicts of interest to disclose when the work had been performed, Drs. Zhou, Y Wu, Levenson, Seymour, and Iyasu. The content is solely the responsibility of the authors and does not necessarily represent the official views of FDA.

Funding

Drs. Butler, Toh, and Baker were supported by the FDA through the Department of Health and Human Resources contract HHSF223200910006I (Mini-Sentinel Initiative). During the time of this work, Drs. Butler, A Wu, and P Wu, were also supported by Grant 1R01HS019669 for the Population-Based Effectiveness in Asthma and Lung Diseases (PEAL) Network. In addition, Drs. P Wu and A Wu are also funded by Grant 1R01HS022093 for the ‘Real-World Patient Responsiveness & Safety Of Long-Acting Beta Agonists in Asthma’ study.