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Abstract:
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Patient recruitment is challenging in rare disease trials. To save time and resources, an inferential seamless phase II/III clinical trial design is considered for a clinical trial in a rare disease area. In particular, two doses compared to a placebo control are evaluated at phase II. Based on the results of a phase II intermediate endpoint, additional patients may be enrolled into the two doses and control, one selected dose and control or none of the three treatment arms at stage II. All patients including those of unselected dose(s) will be followed for the measurements of the phase III primary and secondary endpoints and incorporated in the final analysis. Under a reasonable condition, the type I error rate will be controlled at the nominal level if the same nominal level is applied for testing a dose effect based on either only the data of patients of stage I or data of patients of stages I and II combined. A graphical testing procedure is used for multiplicity adjustments. Simulations are carried out under different parameter configurations to compare the performances of various approaches. The trial example is further used to illustrate the applications of the methods.
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