A multicenter, randomized phase III study of bortezomib and ...

HOVON 104 AL AMYLOIDOSIS Clinical trial protocol version 7, 27 November 2012
12 SAFETY ......................................................................................................................................................34
12.1 Definitions..........................................................................................................................................34
12.2 Adverse event ...................................................................................................................................35
12.2.1 Reporting of adverse events...............................................................................................35
12.2.2 Follow up of adverse events...............................................................................................36
12.3 Serious Adverse Events....................................................................................................................36
12.3.1 Reporting of serious adverse events ..................................................................................36
12.3.2 Causality assessment of Serious Adverse Events .............................................................37
12.3.3 Follow up of Serious Adverse Events.................................................................................37
12.3.4 Processing of serious adverse event reports .....................................................................37
12.4 Reporting Suspected Unexpected Serious Adverse Reactions........................................................38
12.5 Pregnancies ......................................................................................................................................38
12.6 Reporting of safety issues.................................................................................................................39
12.7 Annual safety report ..........................................................................................................................39
12.8 Data Safety and Monitoring Board....................................................................................................39
13 ENDPOINTS................................................................................................................................................40
13.1 Primary endpoint ...............................................................................................................................40
13.2 Secondary endpoints ........................................................................................................................41
14 STATISTICAL CONSIDERATIONS ...........................................................................................................41
14.1 Patient numbers and power considerations......................................................................................41
14.2 Statistical analysis.............................................................................................................................41
14.2.1 Efficacy analysis .................................................................................................................42
14.2.2 Toxicity analysis..................................................................................................................42
14.2.3 Additional analyses.............................................................................................................42
14.2.4 Statistical analysis plan (optional) ......................................................................................42
14.3 Interim analysis .................................................................................................................................43
14.4 Stopping rules ...................................................................................................................................43
15 REGISTRATION AND RANDOMIZATION.................................................................................................44
15.1 Regulatory Documentation................................................................................................................44
15.2 Registration and Randomization.......................................................................................................44
16 DATA COLLECTION AND QUALITY ASSURANCE ................................................................................45
16.1 Case Report Forms...........................................................................................................................45
16.2 Data quality assurance......................................................................................................................46
16.3 Monitoring..........................................................................................................................................46
16.4 Audits and inspections ......................................................................................................................47
17 ETHICS .......................................................................................................................................................47
17.1 Accredited ethics committee or Institutional Review Board..............................................................47
17.2 Ethical conduct of the study ..............................................................................................................47
17.3 Patient information and consent .......................................................................................................47
17.4 Benefits and risks assessment. ........................................................................................................48
17.5 Trial insurance...................................................................................................................................48
18 ADMINISTRATIVE ASPECTS AND PUBLICATION .................................................................................49
18.1 Handling and storage of data and documents ..................................................................................49
18.1.1 Patient confidentiality..........................................................................................................49
18.1.2 Filing of essential documents .............................................................................................49
18.1.3 Record retention .................................................................................................................49
18.1.4 Storage of samples.............................................................................................................50
18.2 Amendments .....................................................................................................................................50
18.3 Annual progress report......................................................................................................................50
18.4 End of study report............................................................................................................................50
18.5 Publication policy ..............................................................................................................................51
19 GLOSSARY OF ABBREVIATIONS ...........................................................................................................53
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