Sample size regulatory issues

This document has set down some initial thoughts from a regulatory point of view about the issues involved in allowing the design of a clinical trial to be adapted as the trial progresses. Modification of the sample size based on blinded data and stopping for overwhelming efficacy or futility are forms of adaptation that are already well accepted, but this Reflection Paper considers other possibilities that are more controversial. 

Regulatory issues around PAT drying operations are usually uncomplicated, because in most cases, the regulatory specifications for solvent and water content apply only to the final composite sample of the milled material. Similar to the previous two applications, the PAT drier check data are thus usually treated for information only. In essence, the PAT data do not carry any regulatory entanglements and can be thought of as a sophisticated alarm that lets the operator know when the batch is ready to be unloaded, or when to take the official in-process control (IPC) drier check sample to the lab. The particle size information referred to earlier can also be regarded in the same way. 

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