I have reviewed protocols that were masterpieces of scientific precision yet utterly impractical to implement. I have seen others that were operationally elegant but scientifically incoherent. And I have encountered too many that achieved neither virtue, cobbled together under time pressure with insufficient attention to the details that matter. Each failure mode produces its own characteristic problems: enrollment struggles, protocol deviations, unreliable data, and sometimes harm to participants who deserved better.

Principle 8 of ICH E6(R3) addresses protocol requirements directly. It establishes that the protocol must be clear, scientifically sound, and operationally feasible. These are not alternative criteria; all three must be satisfied. A protocol that is scientifically brilliant but impossible to follow is not a good protocol. Neither is one that sites can execute perfectly but that asks the wrong scientific questions.

I have reviewed protocols that were masterpieces of scientific precision yet utterly impractical to implement. I have seen others that were operationally elegant but scientifically incoherent. And I have encountered too many that achieved neither virtue, cobbled together under time pressure with insufficient attention to the details that matter. Each failure mode produces its own characteristic problems: enrollment struggles, protocol deviations, unreliable data, and sometimes harm to participants who deserved better.

Principle 8 of ICH E6(R3) addresses protocol requirements directly. It establishes that the protocol must be clear, scientifically sound, and operationally feasible. These are not alternative criteria; all three must be satisfied. A protocol that is scientifically brilliant but impossible to follow is not a good protocol. Neither is one that sites can execute perfectly but that asks the wrong scientific questions.