The utility of peak flow, symptom scores, and beta-agonist use as outcome measures in asthma clinical research

Study objectives: Several methods of utilizing peak expiratory flow (PEF) a nd other markers of disease activity have been suggested as useful in the m anagement of asthma. It remains unclear, however, as to which surrogate mar kers of disease status are discriminative indicators of treatment failure, suitable for use in clinical trials. Design: We analyzed the operating characteristics of 66 surrogate markers o f treatment failure using a receiver operating characteristic (ROC) curve a nalysis. Participants: Information regarding FEV1, symptoms, beta (2)-agonist use, a nd PEF was available from 313 subjects previously enrolled in two Asthma Cl inical Research Network trials, in which 71 treatment failures occurred (de fined by a 20% fall in FEV1 from baseline). Interventions: None, Measurements and results: None of the measures had an acceptable ability to discriminate subjects,vith a greater than or equal to 20% fall in FEV1 fro m those without, regardless of the duration of the period of analysis or th e criteria for test positivity employed. Areas under the ROC curves generat ed ranged from 0.51 to 0.79, but none were statistically superior. Sensitiv ity and specificity combinations mere generally poor at all cutoff values; true-positive rates could not be raised without unacceptably elevating fals e-positive rates concurrently. Conclusions: Studies that seek to detect treatment failure defined by a sig nificant fall in FEV1 should not use such individual surrogate measures to estimate disease severity.