Assessing the usefulness of outcomes measured in a cystic fibrosis treatment trial.
Forced expiratory volume in 1s (FEV(1)) is the usual primary outcome variable in clinical trials in cystic fibrosis (CF). Usually, several secondary outcomes are also measured. We assessed which secondary outcomes are likely to give additional clinically useful information about treatment effects, in order to inform the design of future studies. The study was performed as part of a trial comparing daily rhDNase with alternate day rhDNase and hypertonic saline in CF. The primary outcome was FEV(1). Secondary outcomes were forced vital capacity (FVC), forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75)), number of pulmonary exacerbations, weight gain, quality of life (QOL), and exercise tolerance. The usefulness of each secondary outcome was investigated by assessing if the change in that outcome over the treatment period could be predicted from the primary outcome. Change in FEV(1) correlated with changes in FVC (r(2)=0.76, P=0.001), FEF(25-75) (r(2)=0.64, P=0.001), weight (r(2)=0.08, P=0.001), and change in oxygen saturation with exercise (r(2)=0.08, P=0.001). However, it did not correlate with changes in visual analogue score (VAS) with exercise, QOL, nor with the occurrence of pulmonary exacerbations. Only the outcomes QOL and VAS with exercise actually provided additional information to FEV(1) in this study.
Suri
Ranjan
R
Respiratory Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, UK. surir@gosh.nhs.uk
Metcalfe
Chris
C
Wallis
Colin
C
Bush
Andrew
A
D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005080:Exercise Test / Q000379:methods; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008450:Maximal Midexpiratory Flow Rate / Q000502:physiology; D011446:Prospective Studies; D011788:Quality of Life; D012141:Respiratory Tract Infections / Q000150:complications; D016896:Treatment Outcome; D014797:Vital Capacity / Q000502:physiology; D015430:Weight Gain / Q000502:physiology
C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I