1. Natasa Rajicic, ScD July 31, 2019
Database lock to Data Safety Monitoring Board Meeting – More than a click of a button?
- Adaptive Design IA Example-
Natasa Rajicic, ScD
July 31, 2019

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3. DMC REPORTS ARE NOT STUDY REPORTS
1. Title page
2. Synopsis
3. Table of contents for the clinical study report
4. List of abbreviations and definition of terms
5. Ethics
6. Investigators and study administrative structure
7. Introduction
8. Study objectives
9. Investigational plan including Statistical Method
10. Study patients
11. Efficacy evaluation
12. Safety evaluation
13. Discussion and overall conclusions
14. Tables, Figures and Graphs Referred to but not included in the text
15. References
16. Appendices
Appendix Protocol and any protocol amendments
Appendix Sample CRF (unique pages only)
Appendix List of IECs/IRBs, information for volunteers, consent forms
Appendix List and description of investigators and other important staff, including brief (1-page) CVs
Appendix Signatures of the Principal Investigator and Sponsor’s medical officer
Appendix List of subjects receiving IMP from specific batches, if more than one batch was used
Appendix Randomisation scheme and codes Appendix Audit certificates (if applicable)
Appendix Documentation of statistical methods
Appendix Documentation of inter-lab standardisation methods (if applicable)
Appendix Publications based on the study (if applicable)
Appendix Important publications referenced in the report (if applicable
DMC REPORTS ARE NOT STUDY REPORTS
JSM2019
natasa rajicic, ScD

4. DMC Reports Need to be COMPREHENSIVE COMPREHENSIBLE
Include all potentially relevant information so that the DMC has full access to what it needs to monitor the trial
Comprehensiveness not done on the expense of comprehensibility
Reports should be carefully and intuitively organized, easily readable
Therapeutic Innovation & Regulatory Science, 2017
JSM2019
natasa rajicic, ScD

5. Top Down Report Structure
High-level overview
Detailed summaries + Figures +
Summary Tables
Listings+
lengthy Tables
Consider adding Executive Summary
Aim at presenting data in similar formats eg. across all lab components, across all AE summaries, etc.
Helps the DMC review many analyses quickly
Put the lengthy tables and listings in Appendices – include references and make them easily accessible from the main text
JSM2019
natasa rajicic, ScD

6. Interim Analysis Decision Tree
JSM2019
natasa rajicic, ScD

7. Interim Analysis Process Flow
START
Cytel to validate primary analyses and unblinding
CROy to generate all unblinded ADaMs
p-value <
p-value <
CROy to generate outputs incl. primary endpt analysis
Cytel to conduct SSR based on CP/PP in East and provide output to CROy
CROy to prepare IA report for DMC /w support from Cytel
CROy share primary endpt ADaMs w/ Cytel
CROy and Cytel unblinded stats participated in DMC
JSM2019
natasa rajicic, ScD

8. references
Buhr, et al. Reports to Independent Data Monitoring Committees: An Appeal for Clarity, Completeness, and Comprehensibility. Therapeutic Innovation & Regulatory Science, 2017
ICH Harmonized Tripartite Guideline (E3). STRUCTURE AND CONTENT OF CLINICAL STUDY REPORTS. 1995
JSM2019
natasa rajicic, ScD

9.
31-Jul-2019
JSM 2019 DMC Panel