Clinical Usefulness of n-of-1 Randomized Controlled Trials in Patients with Nonreversible Chronic Airflow Limitation

To determine if n-of-1 randomized controlled trials (n-of-1 RCT) are useful in the care of patients with nonreversible chronic airflow limitation (CAL). Individual trials had a double-blind, randomized, multiple crossover design. Patients with CAL were recruited from several respirology practices. For each individual trial the main outcome measure was a symptom questionnaire; peak flow measurements were used as a secondary measure. Physicians' plans of management (before and after trials) and confidence in the plans were determined. The proportion of trials that provided a definite clinical or statistical answer was established. Patients were followed, and long-term adherence to decisions based on n-of-1 RCT was examined. A total of 26 n-of-1 RCT in patients with CAL were attempted; 18 of these (69%) were completed. After 17 (94%) of the completed trials clinicians expressed a high degree of confidence in their management plans, confidence that was not, in any case, present before the trial. After 8 n-of-1 RCT (44% of all completed, or 31% of all trials) clinicians decided to stop the drug, which would otherwise have been continued indefinitely. In all 17 of the clinically definite n-of-1 RCT, the management decision that followed the trial was still being adhered to 40 months (on average) after completion of the trial. The results support the feasibility and usefulness of n-of-1 RCT in respirology practice.