The utility of peak flow, symptom scores, and beta-agonist use as outcome measures in asthma clinical research.
OBJECTIVE
Several methods of utilizing peak expiratory flow (PEF) and other markers of disease activity have been suggested as useful in the management of asthma. It remains unclear, however, as to which surrogate markers of disease status are discriminative indicators of treatment failure, suitable for use in clinical trials.


METHODS
We analyzed the operating characteristics of 66 surrogate markers of treatment failure using a receiver operating characteristic (ROC) curve analysis.


METHODS
Information regarding FEV(1), symptoms, beta(2)-agonist use, and PEF was available from 313 subjects previously enrolled in two Asthma Clinical Research Network trials, in which 71 treatment failures occurred (defined by a 20% fall in FEV(1) from baseline).


METHODS
None.


RESULTS
None of the measures had an acceptable ability to discriminate subjects with a > or % fall in FEV(1) from those without, regardless of the duration of the period of analysis or the criteria for test positivity employed. Areas under the ROC curves generated ranged from 0.51 to 0.79, but none were statistically superior. Sensitivity and specificity combinations were generally poor at all cutoff values; true-positive rates could not be raised without unacceptably elevating false-positive rates concurrently.


CONCLUSIONS
Studies that seek to detect treatment failure defined by a significant fall in FEV(1) should not use such individual surrogate measures to estimate disease severity.
Leone
F T
FT
Thomas Jefferson University, Philadelphia, PA, USA. frank.leone@mail.tju.edu
Mauger
E A
EA
Peters
S P
SP
Chinchilli
V M
VM
Fish
J E
JE
Boushey
H A
HA
Cherniack
R M
RM
Drazen
J M
JM
Fahy
J V
JV
Ford
J
J
Israel
E
E
Lazarus
S C
SC
Lemanske
R F
RF
Martin
R J
RJ
McGeady
S J
SJ
Sorkness
C
C
Szefler
S J
SJ
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000627:therapeutic use*; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D005189:False Positive Reactions; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D012372:ROC Curve; D015656:Respiratory Mechanics; D012680:Sensitivity and Specificity; D017211:Treatment Failure; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D000420:Albuterol