Data and safety monitoring committees in clinical trials /

Data and safety monitoring committees in clinical trials /

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Bibliographic Details
Author / Creator:Herson, Jay.
Imprint:Boca Raton, FL : Chapman & Hall/CRC, c2009.
Description:xviii, 173 p. : ill. ; 25 cm.
Language:English
Series:Chapman & Hall/CRC biostatistics series ; 30
Subject:Drugs -- Testing -- Evaluation.
Drugs -- Testing -- Statistical methods -- Evaluation.
Clinical Trials Data Monitoring Committees -- organization & administration.
Clinical Trials as Topic -- standards.
Data Collection.
Drug Industry -- standards.
Research Design.
Safety Management.
Format: Print Book
URL for this record:http://pi.lib.uchicago.edu/1001/cat/bib/7733614
Hidden Bibliographic Details
ISBN:9781420070378 (hardcover : alk. paper)
1420070371 (hardcover : alk. paper)
Notes:Includes bibliographical references (p. 155-166) and index.
Table of Contents:
  • Preface
  • 1. Introduction
  • 1.1. What Is a Data Monitoring Committee (DMC)?
  • 1.2. Some Definitions
  • 1.3. DMC in Federal Government-Sponsored Clinical Trials versus Pharmaceutical Industry Clinical Trials
  • 1.4. Stewardship
  • 1.5. Some Recent History
  • 1.5.1. Development of DMCs in the Pharmaceutical Industry
  • 1.5.2. Guidances-FDA, NIH, and ICH
  • 1.5.3. Other Vehicles for Patient Protection
  • 1.6. DMC's Place in the Drug Development Cycle
  • 1.6.1. Phases of Drug Development
  • 1.6.2. Limitations of a Clinical Program for Revealing Safety Issues
  • 1.6.3. Postmarket Safety Actions
  • 1.6.4. Role of DMCs in Exploratory and Confirmatory Trials
  • 1.6.5. Investigator-Sponsored Trials
  • 1.6.6. Open Label Extension Studies
  • 1.7. Pharmaceutical Industry Demographics
  • 1.7.1. Size of Companies
  • 1.7.2. Public versus Private Companies
  • 1.8. Conclusion
  • DMCounselor
  • 2. Organization of a Safety Monitoring Program for a Confirmatory Trial
  • 2.1. Members of the Safety Monitoring Team
  • 2.1.1. The Sponsor
  • 2.1.2. Data Monitoring Committee
  • 2.1.3. Data Analysis Center
  • 2.1.4. Institutional Review Board
  • 2.1.5. Scope of DMC Authority
  • 2.2. How Is a DMC Created?
  • 2.3. Membership
  • 2.3.1. Physicians
  • 2.3.2. Biostatisticians
  • 2.3.3. How Many Members Are Needed?
  • 2.3.4. Ad Hoc Consultants
  • 2.3.5. Ubiquitous DMC Members
  • 2.3.6. Disclosure of DMC Membership
  • 2.3.7. Multiple Sponsorship
  • 2.3.8. From Where Are DMC Members Recruited?
  • 2.4. Term
  • 2.5. Conflicts of Interest
  • 2.6. Compensation
  • 2.7. Liability and Indemnification
  • 2.8. Sponsor DMC Relationship
  • 2.9. Interdisciplinary Training
  • 2.10. Conclusion
  • DMCounselor
  • 3. Meetings
  • 3.1. DMC Charter
  • 3.2. Types of Meetings
  • 3.2.1. Orientation or Organizational Meeting
  • 3.2.2. Data Review
  • 3.2.3. Ad Hoc
  • 3.3. Orientation Meeting
  • 3.3.1. Chair for Orientation Meeting
  • 3.3.2. Introduction of the Safety Monitoring Team
  • 3.3.3. Appointment of DMC Secretary
  • 3.3.4. Presentation of DMC Charter
  • 3.3.5. Masking Policy
  • 3.3.6. Investigator Brochure
  • 3.3.7. Protocol
  • 3.3.8. Informed Consent
  • 3.3.9. Data Flow
  • 3.3.10. Useful Software
  • 3.3.11. Review of Integrated Summary of Safety
  • 3.3.12. Policy on Review of Publications and Package Insert
  • 3.3.13. Formats for Tables, Listings, and Graphs
  • 3.3.14. Schedule First Data Review Meeting
  • 3.4. Data Review Meetings
  • 3.4.1. Attendance
  • 3.4.2. Open Session
  • 3.4.2.1. Study Progress
  • 3.4.2.2. Data Quality
  • 3.4.2.3. Update on Pending Action Items
  • 3.4.2.4. Questions for the DMC
  • 3.4.2.5. Sample Agenda for Open Session
  • 3.4.3. Closed Session
  • 3.4.4. Scheduling of Next Meeting
  • 3.4.5. Minutes
  • 3.5. Ad Hoc Meetings
  • 3.6. Conclusion
  • DMCounselor
  • 4. Clinical Issues
  • 4.1. Goals of Safety Analysis
  • 4.2. Definitions
  • 4.2.1. Adverse Event
  • 4.2.2. Serious Adverse Event
  • 4.2.3. Serious Adverse Event Reporting Requirements
  • 4.3. Safety Data
  • 4.3.1. Pharmacovigilence Group
  • 4.3.2. Case Report Forms
  • 4.3.3. Adverse Event Dictionary
  • 4.3.4. Adverse Event Severity
  • 4.3.5. SAE Narratives
  • 4.3.6. Titration to Dose
  • 4.4. Deaths
  • 4.5. Impact of Multinational Trials
  • 4.5.1. Cultural Issues
  • 4.5.2. Political Issues
  • 4.5.3. Medical/Surgical Practices Issues
  • 4.6. Conclusion
  • DMCounselor
  • 5. Statistical Issues
  • 5.1. Goals of Statistical Analysis
  • 5.2. Useful Data Displays
  • 5.2.1. Enrollment by Center
  • 5.2.2. Graph of Cumulative Patient Enrollment by Month
  • 5.2.3. Graph of Cumulative Patient Exposure to Study Drug
  • 5.2.4. Treatment Emergent Adverse Events
  • 5.2.4.1. Classification
  • 5.2.4.2. An Example
  • 5.2.4.3. Incidence Calculation
  • 5.2.4.4. Incidence and Exposure Time Calculation
  • 5.2.4.5. Kaplan-Meier Time to First Occurrence
  • 5.2.4.6. Incidence at a Time Point after Treatment Start-Landmark Estimate
  • 5.2.4.7. Other Ways of Looking at Incidence
  • 5.2.5. Laboratory Data
  • 5.3. Analysis Methods-Frequentist
  • 5.3.1. What Is Frequentist Analysis?
  • 5.3.2. Hypothesis Tests
  • 5.3.3. Confidence Intervals
  • 5.3.3.1. Incidence
  • 5.3.3.2. Rate per 100 Patient Years
  • 5.3.3.3. Odds Ratio
  • 5.3.3.4. Poisson Rate Ratio
  • 5.3.3.5. Inference with Kaplan-Meier Landmark Estimates of Incidence
  • 5.3.4. Data Analysis without Statistics
  • 5.4. Power
  • 5.5. Multiplicity
  • 5.6. Analysis Methods-Likelihood
  • 5.7. Analysis Methods-Bayesian
  • 5.8. Conclusion
  • DMCounselor
  • 6. Bias and Pitfalls
  • 6.1. What Is Bias?
  • 6.2. Sources of Bias
  • 6.3. Knowledge of Treatment Assignment
  • 6.3.1. By Sponsor Staff
  • 6.3.2. By the DMC
  • 6.4. Reporting Bias
  • 6.4.1. Investigator Level
  • 6.4.1.1. Knowledge of Treatment Assignment
  • 6.4.1.2. Incomplete Follow-Up
  • 6.4.1.3. Spontaneous versus Solicited Adverse Event Collection
  • 6.4.2. Analysis Level
  • 6.4.2.1. Early Termination Due to Efficacy
  • 6.4.2.2. Granularity Bias
  • 6.5. Competing Risks
  • 6.6. Conclusion
  • DMCounselor
  • 7. Data Monitoring Committee Decisions
  • 7.1. Types of DMC Decisions
  • 7.2. Decision-Making Environment
  • 7.3. Risk versus Benefit Analyses
  • 7.4. When a Safety Issue Arises
  • 7.4.1. Unmasking
  • 7.4.2. "Dear Investigator" Letter
  • 7.4.3. Modification of Informed Consent
  • 7.4.4. Protocol Modification
  • 7.4.5. Trial Termination
  • 7.4.6. Unmasking the Sponsor
  • 7.5. Information beyond the Present Trial
  • 7.6. Meta-Analysis
  • 7.7. Final Meeting
  • 7.8. Special Problems with Infant Pharma Companies
  • 7.9. Conclusion
  • DMCounselor
  • 8. Emerging Issues
  • 8.1. Introduction
  • 8.2. Issues in Technology
  • 8.2.1. Adaptive Designs
  • 8.2.1.1. Dropping a Dose or Treatment Group
  • 8.2.1.2. Adaptive Assignment to Treatment Group
  • 8.2.1.3. Changing Objectives: Superiority to Noninferiority
  • 8.2.1.4. Seamless Transition: Phase II to Phase III
  • 8.2.1.5. Change in Effect Size of Interest
  • 8.2.1.6. Further Thoughts on Adaptive Designs
  • 8.2.2. Real-Time SAE Reporting via the Internet
  • 8.2.3. Causal Inference
  • 8.2.4. Biomarkers
  • 8.2.5. Exciting Times Ahead
  • 8.3. Issues Due to Maturing of DMC Processes and Evolution of the Pharmaceutical Industry
  • 8.3.1. Training of DMC Members
  • 8.3.2. Cost Control
  • 8.3.3. DMC Audit
  • 8.3.4. Internal Safety Review Committee
  • 8.3.5. Mergers and Licensing
  • 8.3.6. Journal Policies Regarding Independent Review
  • 8.4. Resignation from a DMC
  • 8.5. Conclusion
  • DMCounselor
  • Appendix
  • Glossary
  • List of Abbreviations
  • References
  • Index
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