TY - JOUR
T1 - Design and powering of cystic fibrosis clinical trials using pulmonary exacerbation as an efficacy endpoint
AU - VanDevanter, D. R.
AU - Yegin, A.
AU - Morgan, W. J.
AU - Millar, S. J.
AU - Pasta, D. J.
AU - Konstan, M. W.
N1 - Funding Information:
Donald VanDevanter, Wayne Morgan, and Michael Konstan have received honoraria from Genentech, Inc., for serving as members of the Scientific Advisory Group for the Epidemiologic Study of Cystic Fibrosis (ESCF), and have served as consultants to Genentech. No compensation was provided to these authors in exchange for production of this manuscript. Stefanie Millar and David Pasta are employees of ICON Clinical Research. ICON Clinical Research was paid by Genentech for providing biostatistical services for this study. Ashley Yegin is currently an employee of Genentech. This study is sponsored by Genentech, Inc.
PY - 2011/12
Y1 - 2011/12
N2 - 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, FEV1% 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 12month 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 FEV1, 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.
AB - 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, FEV1% 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 12month 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 FEV1, 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.
KW - Pulmonary exacerbation
KW - Sample size
KW - Study design
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U2 - 10.1016/j.jcf.2011.07.003
DO - 10.1016/j.jcf.2011.07.003
M3 - Article
C2 - 21803665
AN - SCOPUS:81255206186
VL - 10
SP - 453
EP - 459
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
SN - 1569-1993
IS - 6
ER -