Randomised study of n of 1 trials versus standard practice

Abstract

Objective: To compare outcomes between groups of patients with irreversible chronic airflow limitation given theophylline by n of 1 trials or standard practice.

Design: Randomised controlled study of n of 1 trials versus standard practice.

Setting: Tertiary care center outpatient department.

Subjects: 31 patients with irreversible chronic airflow limitation who were unsure that theophylline was helpful after an open trial.

Interventions: n Of 1 trials (single patient randomised multiple crossover comparisons of theophylline against placebo) followed published guidelines. For standard practice patients theophylline was stopped and resumed if their dyspnoea worsened; if their dyspnoea then improved theophylline was continued. For both groups a decision to continue or stop the drug was made within three months of randomisation.

Main outcome measures: Exercise capacity as measured by six minute walking distance, quality of life as measured by the chronic respiratory disease questionnaire at baseline and six months after randomisation, and proportions of patients taking theophylline at six months.

Results: 26 patients completed follow up. 47% fewer n of 1 trial patients than standard practice patients were taking theophylline at six months (5/14 versus 10/12; 95% confidence interval of difference 14% to 80%) without differences in exercise capacity or quality of life.

Conclusions: n Of 1 trials led to less theophylline use without adverse effects on exercise capacity or quality of life in patients with irreversible chronic airflow limitation. These data directly support the presence of a clinically important bias towards unnecessary treatment during open prescription of theophylline for irreversible chronic airflow limitation. Confirmation in a larger study and similar studies for other problems appropriate for n of 1 trials are needed before widespread use of n of 1 trials can be advocated in routine clinical practice.