This book offers a wide-ranging description and analysis of recent developments and current trends in health policy with regard to cancer drug safety. The book opens with an overview of pharmacovigilance for cancer blockbuster drugs, covering both general considerations and efforts to develop a structured framework for the identification and reporting of adverse drug reactions (ADRs). A number of important examples of serious ADRs to hematology and oncology drugs are then reviewed, with evaluation of the lessons learned and the policy implications of the ensuing legal cases and their settlements. Further, the difficulty of reporting such blockbuster side effects in the medical literature is explored in an empirical study. Significant advances have been achieved in analytic methods for the identification of ADRs, and here there is a particular focus on the value of optimal discriminant analysis. Finally, the impacts on pharmacovigilance and drug safety of the huge fines paid under the U.S. False Claims Act relating to the defrauding of governmental programs also receive careful attention – these fines are playing an important role in changing the landscape for pharmaceutical safety.
Author(s): Charles Bennett, Courtney Lubaczewski, Bartlett Witherspoon
Series: Cancer Treatment and Research, 184
Publisher: Springer
Year: 2022
Language: English
Pages: 170
City: Cham
Preface
Contents
Editors and Contributors
1 Fluoroquinolone-Associated Disability and Other Fluoroquinolone-Associated Serious Adverse Events: Unexpected Toxicities Have Emerged in Recent Years
1.1 Introduction
1.1.1 FQ Adverse Event Drug Label Warnings
1.1.2 FQ Drug Label Changes (See Table 1.1 for Levofloxacin Label Changes)
1.1.3 FDA Reports of FQ Adverse Events
1.1.4 November 5, 2015, FDA Advisory Committee Meeting Identifies FQAD
1.1.5 November 5, 2015, FDA Advisory Committee Votes
1.1.6 Boxwell FDA FQ Data Compared with Social Media FQ Reports
1.1.7 Gender
1.1.8 Specific FQs
1.1.9 Duration of FQAD
1.1.10 FQAD: Reasons for Which FQ was Prescribed
1.1.11 FQAD Specific Events
1.1.12 Possible Mechanism of FQ Toxicities
1.1.13 Another Possible Pathophysiologic Mechanism: Matrix Metalloproteinase Toxicity
1.1.14 FQ-Associated Peripheral Neuropathy
1.1.15 Levaquin Clinical Trials Completed Prior to FDA Approval in 1997
1.1.16 2001 FDA FQ Review
1.1.17 2003 FDA FQ Review
1.1.18 2008 FDA Pediatric Levofloxacin Review
1.1.19 2010 Pfizer Report
1.1.20 2011 Levaquin Postmarketing Review
1.1.21 2013 FDA Review
1.1.22 2014—Present Media Reports Regarding FQs
1.1.23 2014 FDA Advisory Committee Comments
1.1.24 2014 FDA Dear Healthcare Professional Letters
1.1.25 2014 Citizen Petition
1.1.26 2014 Meeting with U.S. Senate Health Committee
1.1.27 2015 Meeting with FDA
1.1.28 2015 FQ Case Studies
1.1.29 2015 FDA Advisory Committee Meeting
1.1.30 2015 FDA Listening Session
1.1.31 2016 FQ Neuropsychiatric Study
1.1.32 2016 FQ Label Updates
1.1.33 2016 FDA Response to Citizen Petition
1.1.34 2018 FQ Nature Article
1.1.35 2019 Citizen Petition
1.1.36 2019 FQ Neuropsychiatric Toxicity Study
1.2 Discussion
1.3 Conclusions
1.3.1 Recommendations
1.3.2 Significance of This FQ Study
1.4 REMS Request
References
2 Biosimilar Epoetin in the United States: A View from the Southern Network on Adverse Reactions
2.1 Introduction
2.1.1 Regulatory Approval for Epoetin Biosimilar in the United States
2.1.2 Chemistry, Manufacturing, and Controls
2.1.3 Biological Activity
2.1.4 Pharmacology/Toxicology
2.1.5 Immunogenicity
2.1.6 Clinical Pharmacology
2.1.7 Clinical Efficacy and Safety
2.1.8 Risk Evaluation and Mitigations Strategy (REMS)
2.1.9 Extrapolation
2.1.10 Findings of the Oncology Drug Advisory Committee (ODAC) of the FDA
2.1.11 Patents and Litigation
2.1.12 Naming and Labeling
2.1.13 Interchangeability
2.1.14 Substitution
2.1.15 Pharmacovigilance and Immunogenicity
2.1.16 Lessons from the European Union (EU) Countries
2.1.17 Lessons from Japan
2.2 Conclusions
References
3 Policing of Drug Safety Information Dissemination Under the False Claims Act
3.1 Introduction
3.1.1 The Settlement
3.1.2 Lessons Learned and Legal Precedent
3.1.3 Future of Policing Drug Safety Efforts
3.2 Conclusion
References
4 Translating Research into Health Policy: The Citizen Petition Experience with the Food and Drug Administration
4.1 Introduction
4.1.1 The Citizen Petitions
4.2 Conclusions
4.2.1 Policy Implications
References
5 Systemic Barriers and Potential Concerns from Reporting Serious Adverse Drug Reactions
5.1 Introduction
5.2 Findings of Litigation Risks
5.2.1 Fear of Being Included in a Lawsuit Against the Manufacturer
5.2.2 Fear of Being Sued for Libel
5.2.3 Fear of Personally Being Sued for Malpractice
5.2.4 Fear of Physician Partners Being Sued for Malpractice
5.3 Professional Retaliation
5.3.1 Fear of Exclusion from Cooperative Industry-Sponsored Clinical Trials
5.3.2 Fear of Jeopardizing Existing Academic Collaborations
5.3.3 Fear of Being Excluded from a Pharmaceutical Corporation’s Speaker’s Bureau
5.4 Regulatory Considerations
5.4.1 Concern that no Response from the FDA Was Likely
5.4.2 Concern that no Response from the FDA Was Needed
5.5 Discussion
References
6 Was There Something Rotten in Denmark: Nephrogenic System Fibrosis Cases Occurring in Copenhagen
6.1 Introduction
6.1.1 European Actions
6.1.2 Actions of the Manufacturer of Gadodiamide
6.2 Basic Science Considerations
6.3 Explanations for the Danish Findings
6.4 International Considerations
6.5 Summary
References
7 Rituximab-Associated Progressive Multifocal Leukoencephalopathy: A Twenty-Year Update
7.1 Introduction
7.2 Methods
7.3 Results
7.4 Case Series
7.4.1 Periodic Safety Update Report, Global Safety Database, EudraViglinance Database, and FAERS Database
7.5 Epidemiologic Studies
7.5.1 PML-Related Safety Notifications from Market Authorization Holders for Rituximab in the US and Europe
7.6 Discussion
References
8 Maximum Accuracy Machine Learning Statistical Analysis—A Novel Approach
8.1 Introduction
8.1.1 Data Analysis in Practice
8.1.2 Logistic Regression (MELR) Analysis
8.1.3 Using ODA to Maximize the Accuracy of the MELR Model
8.1.4 Novometric CTA Models Explicitly Maximizing ESS
8.2 Conclusion
References
9 Investigating Severe Adverse Reactions: Examples of the ANTICIPATE Methodology at Work
9.1 Introduction
9.1.1 The Toxicities
9.1.2 HX575-Associated PRCA
9.1.3 Gadodiamide-Induced Nephrogenic Systemic Fibrosis
9.1.4 Peginesatide-Associated Anaphylaxis
9.2 The ANTICIPATE Evaluation
9.2.1 Signal Detection
9.3 sADR Data Analysis
9.3.1 Root Cause Analyses/Toxicity Eradication
9.4 Conclusion
References
10 Consequences to Patients, Clinicians, and Manufacturers When Very Serious Adverse Drug Reactions Are Identified (1997–2019): A Qualitative Analysis from the Southern Network on Adverse Reactions (SONAR)
10.1 Introduction
10.2 Methods
10.3 Results
10.4 Clinical and Economic Impact
10.5 Harms to Clinicians
10.6 Harms to Manufacturers, Actions by Regulatory Agencies, Financial Payments, and Attempts to Discredit Physicians
10.7 Discussion
References
11 Moderna, Pfizer-BioNTech, and Johnson & Johnson/Janssen Post-Covid Vaccine Hematological Adverse Events Including Cerebral Venous Sinus Thrombosis (CVST), Thrombotic Thrombocytopenia (VITT), Blood Clots, Increased Vaginal/Menstrual Bleeding and/or Miscarriage, Stillbirth Delivery, or Premature Birth
11.1 Introduction
11.1.1 Study Implementation
11.2 Methods
11.3 Results
11.3.1 Blood Clot Related Events
11.3.2 Vaginal/Menstrual Bleeding AEs
11.3.3 Miscarriage, Stillbirth Delivery, or Premature Birth AEs
11.4 Conclusions
12 Investigating Novel Genetic Markers for Fluoroquinolone Associated Disorders
12.1 Introduction
12.1.1 Timeline of Events
12.1.2 Background of CYP2D6
12.2 Conclusion
References
Index
