## long half-life and large variability [Regulatives / Guidelines]

Dear all,

I would appreciate the forum members thoughts on the following situation.

In short:
• pretty long half-life (i.e. replicate designs are out of scope)
• huge total variablity (i.e. within + between variability)
• total variability is expected to be explained to some degree by some covariates (i.e. including these covariates in the model is expected to lead to a feasable study size)
My interpretation of regulatoy guidelines: adding additional fixed effect factors to the factors mentioned in the guidelines is typically considered as not acceptable by regulators.

best regards & looking forward to some ideas to potentially address this situation

martin