A METHODOLOGICAL ASSESSMENT OF DIURNAL VARIABILITY OF PEAK FLOW AS A BASIS FOR COMPARING DIFFERENT INHALED STEROID FORMULATIONS

Background: A ''survival'' model offers certain ethical and practical advantages over alternative experimental designs if used to compare an tiasthmatic inhaled steroid formulations. The model requires an object ive daily measure of therapeutic effect (e.g., peak expiratory flow ra te, which may be expressed as the lower of two daily measurements (LPF ) or as diurnal variability (DVPF). The relative efficiency of these t wo measures is unknown. Objective: This study was conducted to determi ne the relative efficiency of LPF and DVPF. Methods: We analyzed data from a placebo-controlled comparison of an active inhaled formulation of budesonide versus an inactive oral formulation. The primary outcome measure in this design is the number of days from the time the test t reatments start until a statistically significant deterioration occurs from an optimal asthma control value established at baseline. Results : DVPF proved less sensitive than LPF; that is, fewer patients relapse d during the 8-week trial period: 32 versus 41, respectively. Also, th e median interval until relapse was longer: 24 versus 9 days. With LPF , inhaled budesonide proved more effective than placebo or oral budeso nide (p = 0.03), whereas DVPF failed to discriminate among the test tr eatments (p = 0.38). LPF correlated with all three symptom indices (p greater than or equal to 0.003) and two of three spirometric indices m easured concomitantly (p less than or equal to 0.04). DVPF did not cor relate with any index (p greater than or equal to 0.10). Conclusion: I n this experimental model, LPF proved more sensitive and valid than DV PF as an indicator of differences in antiasthmatic potency between two inhaled steroid formulations.