title: The feasibility of using multiple databases to study rare outcomes: the potential effect of long-acting beta agonists with inhaled corticosteroid therapy on asthma mortality.
abstract: OBJECTIVE
  Long-acting beta agonists (LABAs) when used without concomitant inhaled corticosteroids (ICS) increase the risk of asthma-related deaths, but the effect on asthma-related death of LABA used in combination with ICS therapy is unknown. To address this question, we explored the feasibility of conducting an observational study using multiple US health care data sources.
  
  
  METHODS
  Retrospective cohort study to evaluate the likelihood of getting an upper 95% confidence limit ≤1.4 for the asthma mortality rate ratio and ≤0.40 per 10 000 person-years for the mortality rate difference, assuming no effect of new use of combined LABA + ICS (versus non-LABA maintenance therapy) on asthma mortality. Ten research institutions executed centrally distributed analytic code based on a standard protocol using an extracted (2000-2010) persistent asthma cohort (asthma diagnosis and ≥4 asthma medications in 12 months). Pooled results were analyzed by the coordinating center. Asthma deaths were ascertained by linkage with the National Death Index.
  
  
  RESULTS
  In a cohort of 994 627 persistent asthma patients (2.4 million person-years; 278 asthma deaths), probabilities of the upper 95% confidence limit for effect estimates being less than targeted values, assuming a null relation, were about 0.05. Modifications in cohort and exposure definitions increased exposed person-time and outcome events, but study size remained insufficient to attain study goals.
  
  
  CONCLUSIONS
  Even with 10 data sources and a 10-year study period, the rarity of asthma deaths among patients using certain medications made it infeasible to study the association between combined LABA + ICS and asthma mortality with our targeted level of study precision. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: RTI Health Solutions, Waltham, MA, USA.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Johannes
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: McQuay
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Midkiff
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Calingaert
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Andrews
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Tennis
authors.affiliation: Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Brown
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
authors.affiliation: GlaxoSmithKline, Durham, NC, USA.
authors.forename: Rachael L
authors.initials: RL
authors.lastname: DiSantostefano
authors.affiliation: RTI Health Solutions, Durham, NC, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rothman
authors.affiliation: Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Til
authors.initials: T
authors.lastname: Stürmer
authors.affiliation: HealthCore Inc., Wilmington, DE, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lanes
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Kourtney J
authors.initials: KJ
authors.lastname: Davis
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D016001:Confidence Intervals; D016208:Databases, Factual / Q000706:statistics & numerical data; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D006801:Humans; D012107:Research Design; D012189:Retrospective Studies; D013997:Time Factors; D014481:United States
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations
keywords: asthma mortality; distributed network; feasibility; long-acting beta agonist; pharmacoepidemiology; postmarketing evaluation