Theophylline for Irreversible Chronic Airflow Limitation: DiscussionWe doubt that biased assessment of quality of life and exercise capacity explains our negative result. Personnel ascertaining these measures were masked to treatment- group allocation. We also suspect that the isolated finding of a higher CRQ Emotional Function score at 6 months among n of 1 trial patients within the No Prior Theophylline Use subgroup reflected chance. Thus, other reasons for our negative finding, beyond the main explanation that n of 1 trials are not effective in this setting, should be considered.
First, the question of inadequate statistical power can be addressed by comparing the observed 95% CLs for the between-group differences (n of 1 trial minus standard patients) in within-group changes over time (12 months minus baseline) in the primary outcomes to their corresponding minimal important differences. Given the respective CLs and minimal important differences for the CRQ Physical Function score (-8.2, 2.5; 4.5), the CRQ Emotional Function score (-4.7, 5.7; 5.5), and the 6-min walk (-26, 42 m; 30 m),- it remains possible, but unlikely, that clinically important effects in favor of n of 1 trials were missed. Asthma inhalers Reading here A second possible reason for our negative result is that theophylline is not effective for irreversible CAL through 1 year. This question has not been answered in existing randomized, placebo-controlled trials because no studies have assessed theophylline’s effect beyond 2 months. If the drug’s impact on patient well-being is not maintained in the longer term, then our study could not have been expected to show a difference.
A third possible reason for the negative result was that the n of 1 trials were conducted suboptimally. Nearly one half (16/34) of the n of 1 trials were based on two or less pairs of active and placebo treatments, including four patients in whom only one course of either active or placebo treatment was received. Because the experimental unit in an n of 1 trial is a treatment period, the power to detect differences between two therapies depends directly on the number of treatment periods. Thus, n of 1 trials having very few treatment periods are unlikely to detect weak treatment effects.