We hypothesized that the use of n of 1 trials to guide theophylline therapy in a group of patients with CAL would lead to a better outcome than that a group in which theophylline use was guided by open therapeutic trials. This improvement would result from more reliable identification of those patients who do, and do not, benefit from the drug. Randomization, blinding, and multiple crossovers would limit false conclusions that theophylline is effective by controlling for the placebo effect, patient and physician expectations, and regression to the mean; multiple crossovers would also limit false conclusions that theophylline is not effective by controlling for temporal variation in the underlying course of the patients’ CAL. To the extent that the biases of open trials appear weighted toward false conclusions of efficacy, we also predicted that n of 1 trials would result in less overall theophylline use than standard practice.
In a previous randomized study of theophylline use for irreversible CAL guided by n of 1 trials vs standard practice, we found that n of 1 trials significantly reduced theophylline use over 6 months.
However, improved quality of life and exercise capacity among n of 1 trial patients was not seen, possibly because of the small sample size. We report a larger study with follow-up to 1 year that tested two a priori hypotheses. Our primary hypothesis was that patients with irreversible CAL who were given theophylline guided by n of 1 trials would have better quality of life and exercise capacity than patients treated according to standard practice further my canadian pharmacy online. Our secondary hypothesis was that n of 1 trials would result in less theophylline use than standard practice. We also report the results of a post hoc analysis in which patients from this and our previous study were combined.
Materials and Methods
Protocol
Our rationale for studying theophylline for irreversible CAL was twofold: (1) prescription of theophylline for CAL meets the prerequisites for n of 1 trials (CAL is chronic and relatively stable, the action of theophylline starts and ends within several days, and the efficacy of theophylline in a specific patient with CAL is often in doubt); and (2) successful n of 1 trials of theophylline for CAL have been reported. Approval by institutional review boards was obtained, and all patients provided informed consent.