Abstract
Rationale: The conducting of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures. Objectives: To evaluate safety, feasibility, and ability to detect abnormalities in lung function of serial pulmonary function tests (PFTs) in infants with CF. Methods:Multicenter observational study using a commercial device, rigorous training, ongoing quality control, and over-reading of data by an independent panel. Raised volume rapid thoracoabdominal compression technique and plethysmography were performed at enrollment and at 6 and 12 months, with an additional 1-month reproducibility visit. Measurements and Main Results: A total of 342 procedures were performed in 100 infants with CF at 10 centers. FRC measurements were acceptable at a higher proportion of study visits (89%) than raised volume (72%) or fractional lung volume (68%) measurements. Average Z scores for many parameters differed significantly from historical control values. Mean (95% confidence interval) Z scores were: -0.52 (-0.78 to -0.25) for forced expiratory flow at 75% (FEF75) for FVC; 1.92 (1.39-2.45) for FRC; 1.22 (0.68-1.76) for residual volume; 0.87 (0.60-1.13) for FRC/total lung capacity; and 0.66 (0.27-1.06) for residual volume/total lung capacity. For future multicenter clinical trials using infant PFTs as primary endpoints, minimum detectable treatment effects are presented for several sample sizes. Conclusions: In this 10-center study, key PFT measures were significantly different in infants with CF than in historical control subjects. However, infant PFTs do not yet appear ready as primary efficacy endpoints for multicenter clinical trials, particularly at inexperienced sites, based on acceptability rates, variability, and potentially large sample sizes required to detect reasonable treatment effects.
| Original language | English |
|---|---|
| Pages (from-to) | 1387-1397 |
| Number of pages | 11 |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 182 |
| Issue number | 11 |
| DOIs | |
| State | Published - Dec 1 2010 |
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Keywords
- FEV
- Forced expiratory flow rates
- Longitudinal studies
- Outcome assessment
- Plethysmography
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
Cite this
Multicenter evaluation of infant lung function tests as cystic fibrosis clinical trial endpoints. / Davis, Stephanie D.; Rosenfeld, Margaret; Kerby, Gwendolyn S.; Brumback, Lyndia; Kloster, Margaret H.; Acton, James D.; Colin, Andrew; Conrad, Carol K.; Hart, Meeghan A.; Hiatt, Peter W.; Mogayzel, Peter J.; Johnson, Robin C.; Wilcox, Stephanie L.; Castile, Robert G.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 182, No. 11, 01.12.2010, p. 1387-1397.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Multicenter evaluation of infant lung function tests as cystic fibrosis clinical trial endpoints
AU - Davis, Stephanie D.
AU - Rosenfeld, Margaret
AU - Kerby, Gwendolyn S.
AU - Brumback, Lyndia
AU - Kloster, Margaret H.
AU - Acton, James D.
AU - Colin, Andrew
AU - Conrad, Carol K.
AU - Hart, Meeghan A.
AU - Hiatt, Peter W.
AU - Mogayzel, Peter J.
AU - Johnson, Robin C.
AU - Wilcox, Stephanie L.
AU - Castile, Robert G.
PY - 2010/12/1
Y1 - 2010/12/1
N2 - Rationale: The conducting of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures. Objectives: To evaluate safety, feasibility, and ability to detect abnormalities in lung function of serial pulmonary function tests (PFTs) in infants with CF. Methods:Multicenter observational study using a commercial device, rigorous training, ongoing quality control, and over-reading of data by an independent panel. Raised volume rapid thoracoabdominal compression technique and plethysmography were performed at enrollment and at 6 and 12 months, with an additional 1-month reproducibility visit. Measurements and Main Results: A total of 342 procedures were performed in 100 infants with CF at 10 centers. FRC measurements were acceptable at a higher proportion of study visits (89%) than raised volume (72%) or fractional lung volume (68%) measurements. Average Z scores for many parameters differed significantly from historical control values. Mean (95% confidence interval) Z scores were: -0.52 (-0.78 to -0.25) for forced expiratory flow at 75% (FEF75) for FVC; 1.92 (1.39-2.45) for FRC; 1.22 (0.68-1.76) for residual volume; 0.87 (0.60-1.13) for FRC/total lung capacity; and 0.66 (0.27-1.06) for residual volume/total lung capacity. For future multicenter clinical trials using infant PFTs as primary endpoints, minimum detectable treatment effects are presented for several sample sizes. Conclusions: In this 10-center study, key PFT measures were significantly different in infants with CF than in historical control subjects. However, infant PFTs do not yet appear ready as primary efficacy endpoints for multicenter clinical trials, particularly at inexperienced sites, based on acceptability rates, variability, and potentially large sample sizes required to detect reasonable treatment effects.
AB - Rationale: The conducting of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures. Objectives: To evaluate safety, feasibility, and ability to detect abnormalities in lung function of serial pulmonary function tests (PFTs) in infants with CF. Methods:Multicenter observational study using a commercial device, rigorous training, ongoing quality control, and over-reading of data by an independent panel. Raised volume rapid thoracoabdominal compression technique and plethysmography were performed at enrollment and at 6 and 12 months, with an additional 1-month reproducibility visit. Measurements and Main Results: A total of 342 procedures were performed in 100 infants with CF at 10 centers. FRC measurements were acceptable at a higher proportion of study visits (89%) than raised volume (72%) or fractional lung volume (68%) measurements. Average Z scores for many parameters differed significantly from historical control values. Mean (95% confidence interval) Z scores were: -0.52 (-0.78 to -0.25) for forced expiratory flow at 75% (FEF75) for FVC; 1.92 (1.39-2.45) for FRC; 1.22 (0.68-1.76) for residual volume; 0.87 (0.60-1.13) for FRC/total lung capacity; and 0.66 (0.27-1.06) for residual volume/total lung capacity. For future multicenter clinical trials using infant PFTs as primary endpoints, minimum detectable treatment effects are presented for several sample sizes. Conclusions: In this 10-center study, key PFT measures were significantly different in infants with CF than in historical control subjects. However, infant PFTs do not yet appear ready as primary efficacy endpoints for multicenter clinical trials, particularly at inexperienced sites, based on acceptability rates, variability, and potentially large sample sizes required to detect reasonable treatment effects.
KW - FEV
KW - Forced expiratory flow rates
KW - Longitudinal studies
KW - Outcome assessment
KW - Plethysmography
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UR - http://www.scopus.com/inward/citedby.url?scp=78649838472&partnerID=8YFLogxK
U2 - 10.1164/rccm.200908-1236OC
DO - 10.1164/rccm.200908-1236OC
M3 - Article
C2 - 20622043
AN - SCOPUS:78649838472
VL - 182
SP - 1387
EP - 1397
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 11
ER -