68 7.3 NIH Required Data and Safety Monitoring Plan ........................................................... 69 8 SPONSOR PROTOCOL/SAFETY REPORTING ............................................................... 70 8.1 Definitions ...................................................................................................................... 70 8.2 Assessment of Safety Events .......................................................................................... 71 8.3 Reporting of Serious Adverse Events ............................................................................ 72 8.4 Waiver of expedited reporting to CCR .......................................................................... 72 8.5 Safety Reporting Criteria to the Pharmaceutical Collaborators ..................................... 72 8.6 Reporting Pregnancy ...................................................................................................... 72 8.7 Regulatory Reporting for Studies Conducted Under CCR-Sponsored IND .................. 73 8.8 Sponsor Protocol Deviation Reporting .......................................................................... 73 9 CLINICAL MONITORING PLAN ...................................................................................... 74 10 STATISTICAL CONSIDERATIONS .................................................................................. 74 10.1 Statistical Hypothesis ................................................................................................. 74 10.2 Sample Size Determination ........................................................................................ 75 10.3 Populations for Analyses ............................................................................................ 76 10.4 Statistical Analyses ..................................................................................................... 76 11 COLLABORATIVE AGREEMENTS ................................................................................. 78 11.1 Cooperative Research and Development Agreement (CRADA) ............................... 78 12 HUMAN SUBJECTS PROTECTIONS ............................................................................... 78 12.1 Rationale For Subject Selection ................................................................................. 78 12.2 Participation of Children ............................................................................................ 78 12.3 Participation of Subjects Unable to Give Consent ..................................................... 78 12.4 Risks/Benefit Assessment ........................................................................................... 79 12.5 Consent Process and Documentation ......................................................................... 80 13 REGULATORY AND OPERATIONAL CONSIDERATIONS ......................................... 82 13.1 Study Discontinuation and Closure ............................................................................ 82 13.2 Quality Assurance and Quality Control ...................................................................... 82 13.3 Conflict of Interest Policy ........................................................................................... 82 13.4 Confidentiality and Privacy ........................................................................................