Reproducibility of a symptom response to omeprazole therapy in functional dyspepsia evaluated by a random-starting-day trial design

Abstract

Background: Satisfactory treatment options for functional dyspepsia are lacking. Single subject trial designs may identify subgroups of patients with a uniform response to therapy. Aim: To test reproducibility of response in a new random-starting-day trial design developed to identify acid-related symptoms in functional dyspepsia. Methods: One hundred and nineteen patients with functional dyspepsia completed a 12-day, double-blind random-starting-day trial with an initial placebo run-in followed by switch to omeprazole on a randomized and blinded day (between days 5 and 9) with active treatment continuing for the rest of the trial. Response was defined as a sustained ≥50% reduction of a daily symptom-score within 3 days of active treatment. Fifty-nine patients repeated the random-starting-day trial at relapse of symptoms. Results: After exclusion of placebo responders, 14% (15 of 106) were classified as responders in the first and 20% (10 of 50) in the subsequent random-starting-day trial series. Sixty-eight per cent (40 of 59) of the patients reproduced their initial response with a chance-corrected agreement of 0.29. Comparing response patterns using different symptom rating-scales showed good correlation (kappa 0.60). Conclusion: Reproducibility of response in a random-starting-day trial was imperfect, mainly because of the low response rates and strict response criteria. Lack of symptom stability impairs the value of the random-starting-day trial and only patients with frequent and stable symptoms should be evaluated in this design.