Trial Designs to Demonstrate Cost-Benefit Claims for Antiulcer Drugs

Abstract

Clinical trials of long-term maintenance therapy for ulcer disease were undertaken with the goal of demonstrating prevention of ulcer recurrence. Modeling of the recurrence and healing process with its high frequency of asymptomatic ulcers demonstrates that trials with infrequent scheduled endoscopies are inadequate to demonstrate prevention. The design of future trials should be based on specification of the goals of therapy.

The design process will then entail:

1. 1.

defining alternate diagnostic-therapeutic strategies

2.

specifying costs for elements in these approaches

3.

defining a model for the relevant elements of the disease process and the effects of treatment, and

4.

using parameter estimates in simulations to assess the adequacy of a proposed design

Different goals or different models for the disease process will suggest different trial designs. Very simple models can provide considerable insight and spreadsheet programs can assist with modeling calculations. The process is discussed in detail for designs directed at reduction of symptomatic recurrences and for designs directed at reduction of complications.