Design and powering of cystic fibrosis clinical trials using rate of FEV(1) decline as an efficacy endpoint.
BACKGROUND
Rate of lung function decline (RLFD) (as FEV(1) percent predicted/yr) is a robust measure of CF therapeutic efficacy rarely used as a study endpoint, in part due to uncertainty of sample size requirements.


METHODS
Sample size requirements for 1:1 randomizations to detect RLFD treatment effects from 20% to 80% were assessed in Epidemiologic Study of CF (ESCF) patients. Effects of measuring FEV(1) 1-4 times per year in studies of 1- to 4-year durations were assessed in 399 patients age ≥ 6 years with FEV(1) ≥ 70%. Impacts of inclusion/exclusion based on risk factors in 2369 ESCF patients were assessed over 1.5 years using semi-annual FEV(1) measures.


RESULTS
Increasing study duration and exclusion of lower risk patients (e.g., no P. aeruginosa infection) both substantially reduced requirements.


CONCLUSIONS
CF RLFD studies of 1.5 years in duration appear feasible provided that investigators account for the beneficial effects of subject inclusion/exclusion based on risk factors in power estimates.
Konstan
M W
MW
Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Wagener
J S
JS
Yegin
A
A
Millar
S J
SJ
Pasta
D J
DJ
VanDevanter
D R
DR
D000293:Adolescent; D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology*; D005240:Feasibility Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008875:Middle Aged; D010560:Personnel Selection; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult