PMID- 16875884
OWN - NLM
STAT- MEDLINE
DCOM- 20070228
LR  - 20071115
IS  - 1551-7144 (Print)
IS  - 1551-7144 (Linking)
VI  - 27
IP  - 6
DP  - 2006 Dec
TI  - Respiratory adverse event profiles in cystic fibrosis placebo subjects in short- 
      and long-term inhaled therapy trials.
PG  - 561-70
AB  - The frequency and nature of adverse events (AEs) are important safety endpoints 
      in clinical trials of therapies for cystic fibrosis (CF) subjects, yet published 
      tables of background AE rates in the CF population are not readily available. Our 
      objective in this study was to produce tables of respiratory AE rates for placebo 
      subjects (pediatric and adult) for inhaled therapy trials in CF subjects. 
      Respiratory AE rates in inhaled therapy trials were computed by combining data on 
      placebo subjects from early-phase dosing studies and middle/late-phase studies, 
      where placebo consisted of 4 or 5 mL of inhaled saline solution. AE rates were 
      computed as number of events divided by number of placebo-subject days of 
      observation, and 95% confidence intervals were computed based on a Poisson model. 
      AEs were categorized as both broad (e.g., respiratory, reactive airway disease) 
      and specific (e.g., cough, chest tightness, hemoptysis). In short-term studies, 
      respiratory AE rates (95% confidence interval) were 1.1(0.7, 1.6)/person-week and 
      1.0(0.7, 1.4)/person-week in pediatric and adult subjects, respectively. In 
      long-term studies, respiratory AE rates were 1.7(1.6, 1.8)/person-month and 
      2.2(2.1, 2.3)/person-month in pediatric and adult subjects, respectively. 
      Stepwise Poisson models were fit to determine if baseline covariates were 
      important in predicting AE rates. Forced expiratory volume in one second (FEV(1)) 
      percent of predicted and age in short-term studies, and FEV(1) percent predicted 
      and gender in long-term studies were statistically important in predicting 
      respiratory AE rates. Although these variables were statistically significant, 
      the models' predictive abilities were low, with adjusted R(2)'s of 0.06 and 0.12 
      in the short- and long-term studies, respectively. Combining placebo-subject AE 
      data recorded from multiple CF clinical trials yields better estimates of true 
      rates of occurrence in the CF population. The tables published from this study 
      can be used to assist those charged with safety monitoring in CF clinical trials.
FAU - Sucharew, Heidi
AU  - Sucharew H
AD  - CF Therapeutics Development Network Coordinating Center, Seattle, WA, United 
      States.
FAU - Goss, Christopher H
AU  - Goss CH
FAU - Millard, Steven P
AU  - Millard SP
FAU - Ramsey, Bonnie W
AU  - Ramsey BW
CN  - Cystic Fibrosis Therapeutics Development Network
LA  - eng
GR  - M01-RR00037/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060609
PL  - United States
TA  - Contemp Clin Trials
JT  - Contemporary clinical trials
JID - 101242342
RN  - 0 (Placebos)
SB  - IM
MH  - Administration, Inhalation
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Clinical Trials Data Monitoring Committees
MH  - Cystic Fibrosis/*drug therapy
MH  - Female
MH  - Forced Expiratory Volume
MH  - Humans
MH  - Long-Term Care
MH  - Male
MH  - Placebos/*adverse effects
MH  - Randomized Controlled Trials as Topic/*adverse effects
MH  - Respiratory Tract Diseases/diagnosis/*etiology
MH  - Risk
MH  - Sample Size
MH  - United States
EDAT- 2006/08/01 09:00
MHDA- 2007/03/01 09:00
CRDT- 2006/08/01 09:00
PHST- 2005/12/19 00:00 [received]
PHST- 2006/04/10 00:00 [revised]
PHST- 2006/06/02 00:00 [accepted]
PHST- 2006/08/01 09:00 [pubmed]
PHST- 2007/03/01 09:00 [medline]
PHST- 2006/08/01 09:00 [entrez]
AID - S1551-7144(06)00069-3 [pii]
AID - 10.1016/j.cct.2006.06.001 [doi]
PST - ppublish
SO  - Contemp Clin Trials. 2006 Dec;27(6):561-70. doi: 10.1016/j.cct.2006.06.001. Epub 
      2006 Jun 9.