Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec;10(6):453-9.
doi: 10.1016/j.jcf.2011.07.003. Epub 2011 Jul 30.

Design and powering of cystic fibrosis clinical trials using pulmonary exacerbation as an efficacy endpoint

D R Vandevanter  1 , A Yegin, W J Morgan, S J Millar, D J Pasta, M W Konstan
Affiliations

Design and powering of cystic fibrosis clinical trials using pulmonary exacerbation as an efficacy endpoint

D R Vandevanter et al. J Cyst Fibros. 2011 Dec.

Abstract

Background: Reduction in pulmonary exacerbations is an important efficacy endpoint for CF clinical studies. Powering exacerbation endpoints requires estimation of the future exacerbation incidence in CF study populations, but rates differ across the population.

Methods: We have estimated exacerbation rates for Epidemiologic Study of CF subpopulations stratified by age, FEV(1)% predicted, sex, weight-for-age percentile, respiratory signs and symptoms, and history of exacerbation and bacterial culture. Sample sizes required to attain 80% power to detect exacerbation reductions of 20% to 80% in 1:1 randomized studies of 3 to 12 month duration were determined. Exacerbation treatments with "any" antibiotic (new oral quinolone, new inhaled antibiotic, or intravenous (IV) antibiotic) and with IV antibiotics were studied.

Results: At all ages, decreased FEV(1), female sex, exacerbation history, and Pseudomonas aeruginosa culture history were associated with increased treatment for exacerbation.

Conclusions: These data should assist investigators in the design of future CF exacerbation studies.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Effects of Treatment Definition and Duration of Observation on Sample Sizes Required to Detect a Given Treatment Effect in a Randomized Controlled Study
Sample sizes per arm required to assure 80% power to detect reductions in exacerbation treatment (as hazard ratios) in 1:1 randomized studies of 3 month (clear lines), 6 month (light gray lines), 9 month (dark gray lines), or 12 month (black lines) durations. Results for exacerbation treatment defined as administration of “any” antibiotics are shown as solid lines and those for treatment defined as administration of IV antibiotics are shown as dashed lines.
Figure 2
Figure 2. Sample Sizes Required per Study Arm to Retain 80% Power to Detect a 40% Reduction in Risk of Treatment for Exacerbation as a Function of Lung Disease Stage and Study Duration
Panel A: Sample sizes required to detect a reduction in treatment with “any” antibiotics. Panel B: Sample sizes required to detect a reduction in treatment with IV antibiotics. Note that the scale of the vertical axis of panel B is twice the magnitude of that of panel A.
See this image and copyright information in PMC

References

    1. Ratjen F, Döring G. Cystic fibrosis. Lancet. 2003;361:681–9. REVIEW. - PubMed
    1. Goss CH, Burns JL. Exacerbations in cystic fibrosis. 1: Epidemiology and pathogenesis. Thorax. 2007;62:360–7. REVIEW. - PMC - PubMed
    1. Ramsey BW. Management of pulmonary disease in patients with cystic fibrosis. N Engl J Med. 1996;335:179–88. Review. - PubMed
    1. Clinical Practice Guidelines for Cystic Fibrosis. Cystic Fibrosis Foundation; Bethesda, MD: 1997.
    1. Ferkol T, Rosenfeld M, Milla CE. Cystic fibrosis pulmonary exacerbations. J Pediatr. 2006;148:259–64. - PubMed