Once-daily versus twice-daily dosing of theophylline. A decision analysis approach to evaluating theophylline blood levels and compliance

The question of whether to prescribe once-daily or twice-daily theophylline was investigated using decision-analysis techniques with sensitivity procedures. While the relative efficacies of the two theophylline preparations have been examined in a number of studies, previous efforts have not assessed the impact of compliance on therapeutic effectiveness. When a blood theophylline level of 10 to 20 micrograms is taken to constitute the therapeutic range, twice-daily has been shown to yield 15% greater efficacy than once-daily dosing. However, results of the present investigation suggest that a drop in compliance greater than 4 to 14%, associated with once- versus twice-daily dosing, would be sufficient to obliterate the apparent advantage of the twice-daily preparation. The existing empirical evidence suggests that selecting twice-daily over once-daily dosing will incur a drop in compliance that is substantially greater than 14%. Consequently, when the impact of compliance is incorporated into a decision analysis, once-daily dosing is favored over twice-daily dosing for most patients. The decision will favor twice-daily theophylline only in the unusual case in which continuity of contact with a given patient provides strong evidence that he/she is more than 80% likely to comply with the twice-daily regimen. Decision analyses applied to this topic would benefit greatly from better studies of compliance in asthmatic patients and more careful correlations of symptoms with varying medication usage.