definiens: means any serious and unanticipated adverse clinical experience associated with the use of a device . as defined under 21 C.F.R. § 812.3 Add a new Article 3.3 as follows : 3.3 Protocol Modification . The Study shall be done in strict accordance with the Protocol and no changes in the finalized Protocol will be made unless mutually agreed upon in writing by both Parties . In the event that the appropriate Institutional Review Board ( IRB ) requires changes in the Protocol or the Informed Consent Form, both Parties agree to modify the Protocol and/or Informed Consent Form as appropriate . Clinical protocols for each study within the scope of the CRADA Research Plan will be developed by the PHS CRADA PI . Each clinical protocol will describe in detail the research to be conducted intramurally or extramurally . Each clinical protocol developed by PHS CRADA PI will be forwarded to Collaborator for review and comment approximately four ( 4 ) weeks before it is reviewed by the I RB . Comments from Collaborator received by the NCI PI before the IRB meeting will be discussed by the IRB . will be given due consideration . and will be incorporated into the protocol . absent good cause