33 4.4.9 DTH Reaction ....................................................................... 34 4.5 Discontinuation of Protocol-Specified Therapy ................................... 34 4.6 Subject Discontinuation ....................................................................... 35 4.7 Study Discontinuation ......................................................................... 36 4.8 Statistical Methods .............................................................................. 36 4.8.1 Analysis of the Conduct of the Study .................................... 36 4.8.2 Analysis of Treatment Group Comparability ......................... 37 4.8.3 Efficacy Analysis .................................................................. 37 4.8.4 Safety Analysis ..................................................................... 39 4.8.5 Planned Analyses ................................................................. 40 4.8.6 Missing Data ......................................................................... 41 4.8.7 Determination of Sample Size ……………………………….. 41 4.9 Data Quality Assurance ...................................................................... 42 5. REPORTING OF ADVERSE EVENTS ........................................................... 42 5.1 Adverse Event and Reporting Definitions ........................................... 42 5.2 Reporting of Serious Adverse Events Associated with this Study ....... 43 5.2.1 MedWatch 3500A Reporting Guidelines .............................. 44 5.3 Reporting Requirements for IND Holders ............................................ 45 6. INVESTIGATOR REQUIREMENTS ............................................................... 46 6.1 Study Initiation ..................................................................................... 46 6.2 Study Completion ................................................................................ 46 6.3 Informed Consent ................................................................................ 46 6.4 Institutional Review Board or Ethics Committee Approval .................. 46 6.5 Study Monitoring Requirements .......................................................... 48 6.6 Data Collection .................................................................................... 48 6.7 Study Medication Accountability ......................................................... 49 6.8 Disclosure of Data ............................................................................... 49 6.9 Retention of Records .......................................................................... 49 6.10 Publications ......................................................................................... 49 6.11 Changes to the Protocol ......................................................................