33 7.1.10 Unanticipated Problem.......................................... ................................................ 33 NCI-IRB Reporting and Clini cal Director (CD) Reporting......... ................................. 33 7.2.1 NCI-IRB and NCI CD Expedited Reporting of Unanticipated Problem s and Deaths 33 7.2.2 NCI-IRB Requirements for PI Reporting at Continuing Review ..... ........................ 33 7.2.3 NCI-IRB Reporting of IND Safety Reports........................ ...................................... 34 IND Sponsor Reporting Criteria ................................................................................... 34 7.3.1 Reporting Pregnancy................................................................................................. 34 Institutional Biosafety Committee (IBC) Reporting Criteria........................................ 35 7.4.1 Serious Adverse Event Reports to IBC........................... .......................................... 35 7.4.2 Annual Reports to IBC.............................................................................................. 35 Data and Safety Monitoring Plan................................ .................................................. 36 7.5.1 Principal Investigator/Research Team ........................... ........................................... 36 7.5.2 Sponsor Monitoring Plan ........................................ .................................................. 36 8 STATISTICAL CONSIDERATIONS .................................... ...................................... 37 Statistical Hypothesis.................................................................................................... 37 8.1.1 Primary Efficacy Endpoint ...................................... ................................................. 37 8.1.2 Secondary Efficacy Endpoint ................................................................................... 37 Sample Size Determination........................................................................................... 37 Population for Analyses................................................................................................ 38 Statistical Analyses ....................................................................................................... 38 8.4.1 General Approach ............................................... ...................................................... 38 8.4.2 Analysis of the Primary Endpoints ........................................................................... 38 8.4.3 Analysis of the Secondary Endpoint(s).......................... ........................................... 38 8.4.4 Safety Analyses................................................ .........................................................