All Times EDT
Keywords: rare disease, external control, real world data, patient reported outcome
In recent years, drug sponsors have been increasingly interested in developing drugs for small populations of patients diagnosed with rare diseases or pediatric disorders. Although randomized clinical trials with concurrent control are the gold standard for assessing drug efficacy, this type of trials with parallel arms is usually not feasible in the face of ethical concern or limited sample size. Alternatively, the use of either single arm or hybrid concurrent control (e.g., historical control or information based on natural history data from registries, literature, or the real-world data) may be a viable option for assessing the efficacy of new drugs or biologics.
It may be appealing to use innovative designs to gain efficiency, but there are accompanying challenges such as data comparability and statistical analyses addressing confounding effects and missing observations. Another concern is how to properly specify clinical meaningful endpoints in advance for patient reported outcomes commonly needed for rare disease trials. In this presentation, I will discuss main issues and challenges encountered in rare disease and pediatric clinical trials. I will share case examples and my research on how to maintain the standard with some flexibility using rigorous statistical methods.