Post Hoc Analysis Combining This Study and Our Previous Study
Our previous study also randomized patients with irreversible CAL to guide theophylline therapy by n of 1 trials or standard practice. However, that study was limited to patients taking theophylline at the time of recruitment into the study, making them most comparable to prior-theophylline-use patients in the present study, and follow-up went only to 6 months. Therefore, we combined prior-theophyl-line-use patients in the present study with patients from our previous study (N = 61) and assessed their responses over 6 months. In this case, theophylline use was significantly higher at 6 months among standard practice patients (21/29 [72%]) than among n of 1 trial patients (13/32 [41%]): a 32% difference (standard practice minus n of 1 trial) and 95% CLs on the difference (9%, 56%). This difference was not associated with significant between-group changes from baseline to 6 months in the CRQ Physical Function score (point estimate in difference [n of 1 trial minus standard practice], 0.3; 95% CLs, -3.2, 3.9), CRQ Emotional Function score (point estimate in difference, 0.5; 95% CLs, -3.7, 4.6), or 6-min walk (point estimate in difference, -17 m; 95% CLs, -44, 11 m).
Discussion
When determining therapy in single patients, the objectivity of n of 1 trials makes them an appealing alternative to the standard approach of open, before-after trials. Despite this, n of 1 trials are rarely used, for two reasons. First, they make extra demands of patients and physicians there buying antibiotics online. Second, randomized studies have not shown that n of 1 trials improve clinical outcomes over standard practice. The present study is the largest such randomized study to date and did not confirm our main hypothesis that prescribing theophylline to patients with irreversible CAL by n of 1 trials improved quality of life and exercise capacity compared to standard practice. Therefore, we cannot recommend routine use of n of 1 trials to guide decisions about theophylline treatment for this problem.