Table of contents for Manual of drug safety and pharmacovigilance / Barton L. Cobert.

Bibliographic record and links to related information available from the Library of Congress catalog.

Note: Contents data are machine generated based on pre-publication provided by the publisher. Contents may have variations from the printed book or be incomplete or contain other coding.


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Chapter 1. The Theory & Definitions of Drug Safety (Pharmacovigilance)
The Theory
		Adverse event
		Adverse reaction
		Serious Adverse Event (SAE) and Serious Adverse Reaction (SAR):
		Suspected Adverse Drug Reaction (SADR)
		Serious, Unexpected Adverse Drug Reaction (SUSAR)
Serious, Expected Adverse Drug Reaction (SESAR)
Unexpected
Expected
The Practice
Chapter 2. Clinical Trials, CROs, Phases I-IV, Investigator Initiated Trials
The Theory
		Phase I
		Phase II
		Phase III
		Phase IV
		Investigator-Initiated Trials (IITs) or Studies (IISs)
The Practice
FAQs
Chapter 3. Spontaneous, post-marketed AEs. 
Background
The Theory
The Practice
Chapter 4. The Theory of Drug Safety (Pharmacovigilance)
	Background
	The Theory
		The US Regulations & Guidances
		The European Union directives, regulations and guidances
	The Practice
	FAQs
Chapter 5. AEs with new chemical entities, generics, excipients and placebos
	Background
The Theory
		Generics
		Excipients
		Placebo
		Other manufacturers¿ AEs
	The Practice	
		Placebo
		Excipients
		Generics
	FAQs
Chapter 6. Acute and Chronic (Late Occurring) AEs, AEs that disappear (Bendectine ¿), Diethylstilbesterol (DES)
	Background
	The Theory
	The Practice
		Adriamycin
		Gene Therapy
		Anti-Retroviral Drugs
		Diethylstilbesterol (DES)
			Delayed Onset of Malignancy (Long Latency)
			Actions Taken
	Bendectin¿: A False Alert
			Return to the Market in Canada
			The Future
	FAQ
Chapter 7. The Mathematics of AEs.
	
	Background
		Weber Effect 
		Secular Effects	
	The Theory
	The Practice
Chapter 8. Organizations: The Food and Drug Administration (FDA). MedWatch
	Background
	The Theory
		CDER
		Risk Management
		MedWatch
			FDA Safety Databases
			Drugs
			Biologics
		CBER
		What is Expected from Drug Companies by FDA
			Clinical Trials - AEs reported to the IND
			Marketed drugs - AEs reported to the NDA
What is Expected from Consumers & Health Care Professionals by the FDA
Product Safety News
	The Practice
	FAQ
Chapter 9. Organizations: European Medicines Evaluation Agency
	Background
	The Theory
		EudraVigilance
		Risk Management
		Qualified Person
	The Practice
	FAQ
Chapter 10. Where data resides.
	Background
	The Theory
	The Practice
		US Food and Drug Administration
		The Uppsala Monitoring Centre (UMC)
Chapter 11 Signals and signaling in the context of Risk Management
	Background
	The Theory
		The Signal
		Signal Generation
		Increase Frequency
		Data Mining
		Signal Work-up
The FDA Guidance on Good Pharmacovigilance Practices of 3/05
Investigating a Signal
Interpreting a Signal
	The Practice
	FAQ
Chapter 12. Data privacy and sharing. 
	Background
	The Theory
		HIPAA
		The European Union Privacy Directive
	The Practice
Chapter 13. The roles of academia, companies, government health authorities, non-governmental organizations (NGOs), consumer groups and gadflies in the world of pharmacovigilance
	Background
	The Theory
	The Practice
	FAQ
Chapter 14. Risk: What is it? Risk management and assessment
	Background
	The Theory
	The Practice
Chapter 15. FDA¿s Premarketing Risk Assessment Guidance of March 2005.
	Background
	The Theory and The Practice
		Pre-marketing Risk Assessment
			Size of the Safety Database 
			Long-term controlled safety trials 
			Diversity
			Exploring Dose Effects
			Drug Interactions
			Comparative Safety Data
			Special Circumstances
			¿Large Simple Safety Studies¿ (LSSS)
			Medication Errors
			Assessing safety during product development
			Biologic products may require additional testing
			Data Analysis and Interpretation
			Describing AEs to identify signals (Coding)
			Coding Accuracy
			Coding Analysis
			Analyzing temporal and other associations
			Analyzing dose effect
			Data Pooling
			Rigorous ascertainment of reasons for withdrawals from studies
			Long term follow- up
			Important Aspects of Data Presentation
Chapter 16. FDA¿s Development and Use of Risk Minimization Action Plans. Guidance of March 2005.
	Background
	The Theory and The Practice
		Planning in designing a Risk MAP 
Goals
			Objectives
			Tools
				Targeted education and outreach
				Reminder systems
				Performance-linked access systems
		When to Develop a RiskMAP
		Mechanisms available to FDA to minimize risks 
		Assessing the Effectiveness of the Tools and the Plan
		Evaluating Effectiveness of the RiskMAP
		FDA Assessment and publication of RiskMAP results
	The Practice
Chapter 17. FDA¿s Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment Guidance of March 2005.
	
Background
	The Theory and The Practice
		Identifying Signals: Good Reporting Practice
		Developing a Case Series
		Data Mining 
		Safety signals that may warrant further investigation
		Reporting rates vs incidence rates
		Epidemiologic Studies
		Pharmacoepidemiologic Studies
		Registries
		Surveys
		Interpreting signals
		Developing a Pharmacovigilance Plan
Chapter 18. Epidemiology and Pharmacoepidemiology. What are they? What are their limitations and advantages?
	
	The Theory and The Practice
		Case Report
		Aggregate Reports
		Randomized Clinical Trial (RCT)
		Case-Control Study
		Cohort study
		Nested case-control study
		Confidence interval
Chapter 19. Product Quality Issues
	Background
	The Theory
	The Practice
Chapter 20. Pregnancy, lactation and AEs. AEs in pregnant partners of males taking a drug. Pregnancy registries. The Swedish Pregnancy Registry
	Background
	The Theory
		FDA Pregnancy Categories (Table 20.1)
		FDA Guidance for Industry ¿ 2002
		Regulatory Reporting Requirements
		Lactation
		AEs in pregnant partners of males taking a drug
	The Practice
	FAQs
Chapter 21. Children, the elderly and other special groups
	Background
	The Theory
		Children
		The Elderly
			The ICH & FDA Guideline
			FDA Guideline & Rule
	The Practice
		Children
		The Elderly
		Other Special Groups
			Women
			African-Americans
Chapter 22. Drug Interactions and Polypharmacy
	Background
	The Practice
Chapter 23. Drug labeling, warnings, etc. Physicians¿ Desk Reference (PDR) and equivalents. Differences from country to country. 
	Background and Theory
	The Practice
Chapter 24. Regulations, directives, guidances, law and practice in the EU and US. CIOMS and ICH documents. What is written down and what is traditional practice. 
	Background and Theory
		United States
		European Union
	The Practice
Chapter 25. CIOMS & CIOMS Reports 
Council for International Organizations of Medical Sciences (CIOMS)
CIOMS I (1990) International Reporting of Adverse Drug Reactions
CIOMS II (1992) International Reporting of Periodic Drug-Safety Update Summaries
CIOMS III (1995 & 1998/9) Guidelines for Preparing Core Clinical-Safety Information on Drugs (1995) - Including New Proposals for Investigator's Brochures (1998/9).
CIOMS IV (1998) Benefit-Risk Balance for Marketed Drugs: Evaluating Safety Signals
CIOMS V (2001) Current Challenges in Pharmacovigilance: Pragmatic Approaches
		CIOMS VI (2005) Management of Safety Information from Clinical Trials
		CIOMS VII (Ongoing) Developmental Safety Update Report (DSUR)
Chapter 26. ICH Reports 
International Conference on Harmonization (ICH)
Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A)
		Definitions
What should be reported to regulatory authorities as expedited reports?
Reporting Time Frames
			Minimum Criteria for Reporting
			Managing Blinded Cases
			Other Issues
Data Elements for Transmission of Individual Case Safety Reports (E2B) and Message Specification Technical Details (M2)
	The E2B (¿medical¿) documents
	The M2 (Informatics) Documents
Periodic Safety Update Reports (PSURs) for Marketed Drugs (E2C)
Periodic Safety Update Reports for Marketed Drugs (Addendum to E2C)
Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting E2D
Pharmacovigilance Planning E2E
Chapter 27. Pharmaceutical Companies
	Big and Somewhat Big Pharma
		Generic Companies
		Mid and Small Size Pharma
		Clinical or Contract Research Organizations (CROs)
Chapter 28. Universities and Academic and Non-Academic Medical Centers
	Discovery & Licensing
	Clinical Research Units/Centers (CRUs/CRCs)
	Other Divisions Running Studies
Training Medical Students, Pharmacists, Nurses, Epidemiologists and other Health Care Professionals
	Ethics Committees/Institutional Review Boards (IRBs)
	Data (Safety) Monitoring Committees (DSMC or DMC)
	Consultation to the Industry
	Reporting Adverse Events that Occur in the Hospital
Chapter 29. Organization & structure of a typical safety department
	
	The Standard Units/Functions
	Management
	Triage Group
	Case Assessment & Prioritization
	Data Entry Group
	Case Processing Group
	Medical Case Review
	Transmission Unit
	Regulatory Unit
	Legal Unit
	Signaling/Pharmacovigilance/Pharmacoepidemiology/Medical Affairs Unit
	Aggregate Report Preparation
	Labeling Review & Update for Safety
	Archive/File Room
	Information Technology/Informatics Liaison
	SOP Creation & Maintenance
	Training
	Quality Assurance/Control
Adverse Event Exchange Agreement Function: creation & maintenance
Literature Review
Data Dictionary Maintenance
Coding Unit
Planning & Project Management/Operations
Liaison to External Organizations: CIOMS, ICH, PhRMA etc.
Chapter 30. Business partners and AE exchange agreements
	Hubs vs Direct Party to Party Exchange
	Timing & Documents Exchanged
Chapter 31. Computers, Informatics, Validation, Data Entry. E2B
	Database Needs and Functions
	Information Technology (IT)/Informatics Support
	Privacy
	Data Entry Strategy
	E2B
Chapter 32. SOPs, guidelines, etc.
	Version Control, Numbering, Updating, Training
	Quality
Working with Business Partners
SOPs for Drug Safety
Chapter 33. Training
	Drug Safety
	Other Groups
	Typical Curriculum for a New Hire in Drug Safety
		Organizational Structure & Site Information
		Computer/Forms/Electronic & Print Resources
		What is pharmacovigilance?
		Corporate & Drug Safety SOPs 
		MedDRA and other dictionaries
		Safety Database
		Workflow
		Signaling and Pharmacovigilance
Chapter 34. The Safety department¿s role in clinical research, marketing and sales, labeling, regulatory, due diligence and legal issues
Clinical Research
Marketing and Sales
Labeling
Legal
Regulatory Affairs
Quality and Compliance
New Business Due Diligence Reviews
Manufacturing (complaints)
Chapter 35. AE volume, quality and medical records
	Quality and Completeness
	Medical Records & Archiving
Chapter 36. How an AE is handled in the company from start to finish
	Mission and Goals
	Arrival of AEs from Various Sources
	Call Centers
	AE Triage (Case Assessment)
	Data Entry
	Data Review and Quality Checks
	Medical Review
	Case Closure/Completion
	Distribution & Submission
	Tracking and Metrics
	Timing
	Special Situations
		Database Lock
		Investigator Notification
		15 Calendar Days and Day 0 vs Day 1
Chapter 37. Seriousness, expectedness and causality
	
	Seriousness
	Expectedness (Labeledness)
	Causality (Relatedness)
	Casualty Reporting Recommendations
		US FDA
		European Union
	CIOMS 1
		Assessment of Casualty
	Others
	Algorithms
	Global Introspection
	Over The Counter (OTC) Drugs
Chapter 38. Coding of AEs: MedDRA® & coding conventions. Conventions and arbitrary usage. Drug dictionaries & drug naming problems. When a drug has a different name in different countries.
	Browsers
	Coding
	Drug Codes
		Multiple Names
		Name Changes
	WHO Drug Dictionary
	EudraVigilance Medicinal Product Dictionary
Chapter 39. IND Reports: 7 and 15 day reports. IND annual reports
	
	Investigational New Drug Application (IND) Reports
		Expedited IND reports (Alert Reports, 7 and 15 day IND Reports) 
		IND Annual Reports
		Other Clinical Trial (IND) Reporting Issues
			Blinding and Unblinding 7 and 15 day alert reports
			SAE reporting after the end of the of the trial
		When to start collecting SAEs in trials
Chapter 40. NDA Reports: 15 day alert reports. 
	Feeder Groups
	Literature and Publications
	MedWatch to Manufacturer Program: Reports received from FDA
	Reports received from the FDA via the Freedom of Information Act (FOI)
	Collection of Reports
Parent-child/fetus reports
	Follow-up
	Instructions on filling out the MedWatch form 
Chapter 41. NDA Reports: Periodic Reports 
	NDA Periodic Reports
Post-Marketing Period Report
Section 1: Narrative summary and analysis 
		Section 2: Narrative discussion of actions taken 
		Section 3: Index line listing 
		Section 4: FDA Form 3500As or VAERS forms 
	Other Reports
		Distribution reports
		Annual Reports
Chapter 42. The Tome. FDAs proposed 2003 regulations 
	Definitions
	IND Safety Reports
	Post-Marketing Reporting
	Exedited Reports
	Contractors and Sharded Manufacturers
Prescription Drugs Marketed without an Approved Application
	SADRs from Class Action Lawsuits
	Blood Products
	Post-Marketing Periodic Safety Reports
	Semiannual Reports
Old Drugs (BEFORE 1/1/98): Traditional NDA Periodic Reports now called TPSRs
	New Drugs (AFTER 1/1/98): PSURs
	Interim Periodic Safety Reports
	Forms
Record Keeping
	ANDAs
	Annual Report
	In Vivo Bioavailability and Bioequivalence Studies
Chapter 43. Periodic Safety Update Reports (PSURs) 
Chapter 44. Business Partners and Exchange of Safety Data. Due Diligence. 
	Why a written safety exchange agreement is needed
	Telling the Safety Department about a New Contract
	The Generic or Boilerplate or Template Agreement
	Developing a Safety Agreement with the Safety Department
	The Safety Agreement Database
	The Safety Agreement Contents
		The Regulatory Status
		The Regulatory Responsibilities
		Regulatory Documents
		Health Authority Queries and Requests
		Regulatory Submissions
Investigator and IRB/Ethics Committee Notifications. Blinding and Unblinding
		Databases
		Definitions
		Data and mechanisms of data exchange
		Signaling and Safety Reviews
		Other Issues
		Appendices
Chapter 45. Audits and Inspections
	FDA Inspections
	EMEA Inspections
	Internal Inspections
	Company Inspection Procedures
Chapter 46. Ethical issues. Conflicts of Interest. 
	Some of the dynamics at play in regard to drug safety and companies
Some of the dynamics at play in regard to drug safety and health agencies
Some of the dynamics at play in regard to drug safety and academia and (non-academic health care facilities)
Some of the dynamics at play in regard to drug safety and consumer groups, disease groups and websites
Some of the dynamics at play in regard to drug safety with regard to television and the media
Some of the dynamics at play in regard to drug safety and lawyers/litigation
Chapter 47. Some Real-World Safety Issues and Controversies: FIAU
Chapter 48. Some Real World Safety Examples and Issues ¿ Fen-Phen
Chapter 49 Some Real World Safety Examples and Issues ¿ Nomifensine
Chapter 50. Some Real World Safety Examples and Issues ¿ Vioxx®, Dr. Graham et al

Library of Congress Subject Headings for this publication:

Drugs -- Side effects -- Handbooks, manuals, etc.
Pharmacoepidemiology -- Handbooks, manuals, etc.
Pharmaceutical Preparations -- adverse effects.
Product Surveillance, Postmarketing.
Drug Toxicity.
Pharmacoepidemiology.
Risk Management.