title: The utility of peak flow, symptom scores, and beta-agonist use as outcome measures in asthma clinical research.
abstract: 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.
authors: Thomas Jefferson University, Philadelphia, PA, USA. frank.leone@mail.tju.edu
authors: F T
authors: FT
authors: Leone
authors: E A
authors: EA
authors: Mauger
authors: S P
authors: SP
authors: Peters
authors: V M
authors: VM
authors: Chinchilli
authors: J E
authors: JE
authors: Fish
authors: H A
authors: HA
authors: Boushey
authors: R M
authors: RM
authors: Cherniack
authors: J M
authors: JM
authors: Drazen
authors: J V
authors: JV
authors: Fahy
authors: J
authors: J
authors: Ford
authors: E
authors: E
authors: Israel
authors: S C
authors: SC
authors: Lazarus
authors: R F
authors: RF
authors: Lemanske
authors: R J
authors: RJ
authors: Martin
authors: S J
authors: SJ
authors: McGeady
authors: C
authors: C
authors: Sorkness
authors: S J
authors: SJ
authors: Szefler
mesh_terms: 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
chemical_list: D000318:Adrenergic beta-Agonists; D000420:Albuterol