- Hypothesis-testing substudy. These studies have a specific hypothesis that can be tested with at most 6 participants per arm. If additional participants are required, the Principal Investigator (PI) and Protocol Review Committee (PIRC) will decide together whether to continue the hypothesis-testing substudy with more participants without an amendment, or to file an amendment or new protocol. A memo requesting a review of a hypothesis-testing substudy for possible additional enrollment will be sent to PIRC and its statistical reviewer.