Designing a clinical trial to demonstrate prevention of ulcer recurrence: Modelling simulation approaches

Abstract

We describe a Markov chain model for the ulcer recurrence and healing process, review the available literature to obtain appropriate parameter estimates, and use this model to evaluate alternative clinical trial designs. We focus on designs aimed at supporting recurrence prevention claims for a duodenal ulcer maintenance treatment. Our results show that a trial with endoscopies scheduled only at four month intervals is inadequate to support recurrence prevention claims; discrimination between the null and alternative hypotheses is impossible because of the size and direction of expected biases in observed recurrences. Our results suggest that endoscopy intervals should be at most four weeks to establish a claim of ulcer prevention.