P13 Global test for heterogenous patient population in rare disease clinical trials

In drug development, multiple efficacy endpoints may be used to assess diseases with multiple clinical manifestations. A drug may affect multiple disease aspects or outcomes. Usually, we are not sure which aspect is more likely to show a drug effect before conducting the trial. Many statistical methods, including the global test, have been used to evaluate the treatment effects on multiple endpoints. For rare diseases with small to very small patient populations, there are more challenges to analyze the data. The patient population often has heterogeneous clinical presentation. Different participants may benefit from the drug in different disease aspects. The drug that shows strong effect in endpoint 1 may have no or small effect in endpoint 2 for the same participant. However, for a different participant, the same drug may have the reversed effect (i.e., strong effect in endpoint 2, but no or small effect in endpoint 1). While all the endpoints are important to the rare disease patient population. To overcome such challenges of heterogeneous drug effect on different endpoints, we proposed several stratified global test methods, which are natural extensions of the existing global test approaches, including the O'Brien's ordinary lease squares (OLS) method and multi-domain responder index (MDRI) method. These proposed methods deal with the heterogeneous patient population and the small sample size in rare disease. Simulations of hypothetical trials are conducted to compare the type I error and power between the existing and proposed methods.

Pediatric, Small Population, Rare Disease

ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop 2024