Study objectives: 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
Design: We analyzed the operating
characteristics of 66 surrogate markers of treatment failure using a
receiver operating characteristic (ROC) curve analysis.
Participants: Information regarding FEV1,
symptoms, β2-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 FEV1 from baseline).
Measurements and results: None of the measures
had an acceptable ability to discriminate subjects with a ≥ 20% fall
in FEV1 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
Conclusions: Studies that seek to detect
treatment failure defined by a significant fall in FEV1
should not use such individual surrogate measures to estimate disease