RANDOMIZED STUDY OF N-OF-1 TRIALS VERSUS STANDARD PRACTICE

Objective-To compare outcomes between groups of patients with irrevers ible chronic airflow limitation given theophylline by n of 1 trials or standard practice. Design-Randomised controlled study of n of 1 trial s versus standard practice. Setting-Tertiary care centre outpatient de partment. Subjects-31 patients with irreversible chronic airflow limit ation who were unsure that theophylline was helpful after an open tria l. Interventions-n Of 1 trials (single patient randomised multiple cro ssover comparisons of theophylline against placebo) followed published guidelines. For standard practice patients theophylline was stopped a nd 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 out come measures-Exercise capacity as measured by six minute walking dist ance, quality of life as measured by the chronic respiratory disease q uestionnaire at baseline and six months after randomisation, and propo rtions of patients taking theophylline at six months. Results-26 patie nts 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 diff erences in exercise capacity or quality of life. Conclusions-n Of 1 tr ials led to less theophylline use without adverse effects on exercise capacity or quality of life in patients with irreversible chronic airf low limitation, These data directly support the presence of a clinical ly important bias towards unnecessary treatment during open prescripti on of theophylline for irreversible chronic airflow limitation. Confir mation in a larger study and similar studies for other problems approp riate for n of 1 trials are needed before widespread use of n of 1 tri als can be advocated in routine clinical practice.