48 9.1.1 Medical Cover ...................................................................................................................... 48 9.2 Adverse event definitions ..................................................................................................... 48 9.2.1 Adverse event ...................................................................................................................... 48 9.2.2 Serious adverse events ....................................................................................................... 48 9.2.3 Suspected, unexpected, serious adverse reactions ............................................................ 49 9.2.4 Determining adverse event causality .................................................................................. 49 9.2.5 Expectedness ...................................................................................................................... 50 9.3 Collection of safety information ............................................................................................ 50 9.3.1 Screening failures ................................................................................................................ 50 9.3.2 Patients who consent to HLA screening .............................................................................. 50 9.3.3 Eligible patients ................................................................................................................... 50 9.3.4 Follow -up of AEs and SAEs ................................................................................................ 50 9.3.5 Other safety information of interest ..................................................................................... 50 9.4 Reporting of SAEs to the Sponsor Pharmacovigilance Department .................................... 51 9.4.1 Events exempt from being reported as SAEs to the Pharmacovigilance Department ........ 51 9.5 Recording of adverse events and serious adverse events in eCRFs .................................. 51 9.6 Urgent safety measures ....................................................................................................... 52 9.7 Pregnancy ............................................................................................................................ 52 9.8 Protocol specific grading: Injection Site Reactions .............................................................. 54 10 ASSESSMENT OF EFFICACY ........................................................................................... 55 10.1 Timing and type of tumour assessments ............................................................................. 55 10.2 Tumour response ................................................................................................................. 55 10.2.1 Recording of response in the eCRF ................................................................................ 55 11 PATIENT WITHDRAWAL BEFORE COMPLETION OF TREATMENT SCHEDULE ..... 56 12 DEFINING THE END OF TRIAL ......................................................................................... 57 13 DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ............................................ 58 13.1 Interim analysis .................................................................................................................... 58 13.2 Final analysis ....................................................................................................................... 58 13.3 Presentation of data ............................................................................................................. 58 13.4 Safety ................................................................................................................................... 58 13.5 Pharmacodynamics .............................................................................................................. 59 13.6 Tumour response ................................................................................................................. 59 14 ADMINISTRATION ............................................................................................................. 60 14.1 Protocol deviations and amendments .................................................................................. 60 14.2 Serious breach of Good Clinical Practice ............................................................................ 60 14.3 Completion of the electronic case report form ..................................................................... 60 14.4 Trial performance, monitoring, auditing and inspection ....................................................... 61 14.5 Source document verification ............................................................................................... 61 14.6 Clinical study report .............................................................................................................. 61 14.7 Record retention ................................................................................................................... 62 14.8 Ethical considerations .......................................................................................................... 62 14.9 Indemnity .............................................................................................................................. 62 14.10 Publication policy and press releases .................................................................................. 62 14.11 Guidance for disruption to trial conduct ............................................................................... 63 15 REFERENCES ....................................................................................................................