“We shouldn’t use an adaptive design, our sample size is too small.”
Most clinical trial planners have heard this line of reasoning so often it has come to be taken as true. Never mind the fact that the first product to receive FDA approval using an adaptive sample size re-estimation design, was for a genetic condition affecting fewer than two thousand children worldwide .
The PROCYSBI trial was for nephropathic custinosis, a condition which attacks the body’s ability to process proteins, glucose and electrolytes, leading to muscular and pulmonary difficulties. It was also Raptor Pharma’s first Phase 3 study.
The trial is instructive for anyone planning a trial with a small sample size. A sample size of 20, re-estimated to 40, managed to stretch PROCYSBI’s orphan drug status by nearly two years. A strategic vision which streamlined trial analysis with data management, was able to save the company an additional 20% of expected development costs.
Like many companies sponsoring a smaller trial, Raptor had not planned to use a sample size re-estimation initially. Rather, it decided to change its trial design after receiving an FDA special protocol assessment asking for demonstration of non-inferiority. It had already conducted six studies by this time, and was hoping to submit as soon as possible to maintain its orphan drug status.