1. OVERVIEW OF CLINICAL RESEARCH: ITS PRINCIPLES, PROCESSES, AND REGULATORY ENVIRONMENT
- Background of the Clinical Research Process
- Overview of Clinical Trials
- The Role of the Food and Drug Administration in Clinical Trials
- Obtaining FDA Approval for a Proposed New Drug
- New Biologicals
- Investigational and New Medical Devices
- Informed Consent
- Privacy and Confidentiality of Research Records and Information
- Conflicts of Interest in Clinical Research
- Reimbursement Issues Related to Clinical Trials
- Anti-Kickback Fraud and Abuse Implications of Clinical Trials
- Intellectual Property Issues in Clinical Research
- Protecting Research Materials, Research Results, and Inventions: A University Perspective
- International Regulation and Global Ethics in Clinical Research
2. HUMAN SUBJECT PROTECTIONS IN CLINICAL RESEARCH
- Historical Overview of Human Subject Protection in Clinical Research
- FDA Human Subject Protection Regulations and Their Distinctions from HHS Regulations
- Detailed Analysis of the Common Rule and OHRP Regulations for the Protection of Human Subjects
- Additional Protections for Vulnerable Populations
- Detailed Analysis of FDA Regulations for the Protection of Human Subjects
- Compliance with Human Subject Protection Regulations
- Guidance on Human Subject Protections
- Exhibit 2-1 Registering an IRB and Obtaining an FWA: What to do in What Order
3. INFORMED CONSENT IN FEDERALLY REGULATED RESEARCH
- The Federal Requirements for Consent in Clinical Research
- Federal Documentation Requirements for Consent in Clinical Research
- Special Populations Recognized in Federal Clinical Research Regulations on Consent
- Clinical Trials Consent Provisions and the FDA
- State Laws on Consent in Clinical Research
- The Effect of Regulatory Guidance on Consent in Clinical Research
- Consent Litigation and Clinical Research
- Emerging Issues in Clinical Research and Consent
- Avoiding Consent Litigation in Clinical Research
4. INSTITUTIONAL REVIEW BOARDS: THEIR ROLE AND RESPONSIBILITIES IN CLINICAL RESEARCH PROGRAMS
- The History of the IRB System
- Regulatory Structure of IRBs—OHRP
- Registration of IRBs—OHRP
- Criteria for Approval of Research—OHRP
- Conduct of IRB Review—OHRP
- Unanticipated Problems, Adverse Event Reporting, and Protocol Deviation/Violation—OHRP
- FDA-Specific IRB Regulations
- Criteria for IRB Approval of Research—FDA
- Adverse Event Reporting—FDA
- Registration of IRBs—FDA
- Registration of Clinical Trials—FDA
- Alternative (Independent) IRBs
- Data Monitoring Committees
- Protection of Vulnerable Human Subjects
- Legal and Ethical Challenges Facing IRBs
- Lessons Learned from the Johns Hopkins Experience
- Exhibit 4-1 Data Elements for Interventional Trials
- Exhibit 4-2 Quick Guide to Facilitated Review
5. OVERVIEW OF FEDERAL GRANTS ADMINISTRATION
- What Are Federal Grants?
- Sources of Law and Policy for Federal Grants
- Overview of Key Provisions of the Uniform Guidance
6. ADMINISTRATION OF NIH-SUPPORTED CLINICAL RESEARCH
- Select Pre-Award Requirements
- Select Post-Award Requirements
- After-Award Requirements
- Administrative Requirements for State, Local, and Tribal Governments
- NIH Monitoring, Enforcement, and Disputes
7. KEY GRANTS MANAGEMENT AND ACCOUNTING ISSUES
- Financial Management Overview
- Internal Controls
- Allowable Costs
- Budget or Project Changes
- New Issues in NIH Grants Management
8. CONFLICT OF INTEREST RULES FOR FEDERALLY REGULATED CLINICAL RESEARCH
- The Impact of Conflict of Interests: Gelsinger and Vioxx
- Defining the Terms and Players
- Institutional Interests: The Bayh-Dole Act
- Conflict of Interest Regulations and Guidelines
- Enforcement: The Federal False Claims Act
- Conclusion: Practically Speaking
- Exhibit 8-1. Checklist to Avoid Conflict of Interest in Clinical Studies
9. MISCONDUCT IN CLINICAL RESEARCH
- The Role of the Office of Research Integrity
- The Definition of Research Misconduct
- The 2005 Final Rule
- Role of Journal Editors and Peer Reviewers in Detecting and Preventing Research Misconduct
- Proving a Finding of Research Misconduct
- Selected Research Misconduct Case Summaries
- Exhibit 9-1 Research Misconduct Policy Checklist
- Exhibit 9-2 Sample Research Misconduct Policy
- Exhibit 9-3 Sample Research Integrity Officer’s Responsibilities Policy
10. A PRACTICAL GUIDE TO GOOD CLINICAL PRACTICE STANDARDS
- Good Clinical Practices Are Born
- The Core of the Consolidated GCP Guidance
- GCP Risk Areas
- The Basics of Good Clinical Practices
- Selected Areas of Compliance Risk
- Developing a Plan for Improving Compliance with GCPs
- Exhibit 10-1 Clinical Trial Documentation Checklist
- Exhibit 10-2 GCP Checklist: Assessing the Health of Your Institution
11. KEY CONCEPTS IN REIMBURSEMENT FOR CLINICAL TRIALS
- Medical Research Issues Relevant for Reimbursement Considerations
- Reimbursement Rules
- Enforcement Activities
12. BEST PRACTICES AND LEGAL PRINCIPLES IN CLINICAL RESEARCH COMPLIANCE
- Key Steps for Effective Compliance
- Developing an Educational and Training Program
- Assisting Research Personnel in Responding to and Coordinating Internal or Independent Auditors with Compliance Reviews and Monitoring Activities
- Continual Assessment of Training Programs
- Identification and Assessment of Risks
- Independent Monitoring of Clinical Research Billing
- Draft Compliance Program Guidance for Recipients of Public Health Research Awards
- Legal Issues Associated with Clinical Research Billing
- Exhibit 12-1 Clinical Research Compliance Education Matrix
- Exhibit 12-2 Clinical Research Billing Compliance Checklist
- Exhibit 12-3 Clinical Research Billing Monitoring Protocol Instructions
- Exhibit 12-4 Action Item Grid for Supplemental Compliance Program Guidance for Hospitals
13. INTELLECTUAL PROPERTY ISSUES AND DATA EXCLUSIVITY IN CLINICAL RESEARCH
- Exemption from Patent Infringement During Clinical Trials
- Non-Patent Market Exclusivity
- Hatch-Waxman Patent-Based Exclusivity: Orange Book Listings
- Patent Reform Gives New Tools to Challenge Patents
- Biosimilars
- Patent Term Extensions for Regulatory Delay
- Disclosure of Clinical Data
14. PROTECTING RESEARCH MATERIALS, RESEARCH RESULTS, AND INVENTIONS: A UNIVERSITY’S PERSPECTIVE
- Conditions of Patentability, Payment, and Commercialization
- Confidentiality Agreements
- Material Transfer Agreements for a Non-profit Institution
- Useful Resources
- Exhibit 14-1. Sample Confidentiality Agreements
- Exhibit 14-2. Simple Letter Agreement (Standardized MTA)
- Exhibit 14-3. Uniform Biological Material Transfer Agreement
- Exhibit 14-4. Sample Invention-Report Disclosure Form
- Exhibit 14-5. Sample License Agreement: Biological Materials for Licensee’s Internal Use
15. RESEARCH PRIVACY ANDSECURITY
- Federal Privacy Rules
- State Privacy and Mandatory Disclosure Laws
- Electronic Records and Signatures
- Information Security and Human Research
- Exhibit 15-1 HIPAA Authorization Exceptions for Research
- Exhibit 15-2 Sample Data Use Agreement
- Exhibit 15-3 Compliance Checklist for 21 C.F.R. Part 11: FDA Electronic Signature Mandates
16. INTERNATIONAL REGULATION AND GLOBAL ETHICS IN CLINICAL RESEARCH
- U.S. Federal Standards for Research in Foreign Countries
- International Standards for Human Subject Protections and Clinical Research Ethics
- Beyond Regulations: Ethics in Cross-Cultural Contexts
- Concluding Considerations: Cultural Competence and Social Projection
17. GDPR COMPLIANCE CONSIDERATIONS
- Overview of GDPR Compliance
- Status and Implementation
- Personal Data and Processing
- Territorial Scope of Application
- Enforcement and Fines
- Obligations for Controllers and Processors
- Rights of Data Subjects
- Transfer of Personal Data
Glossary
Table of Cases
Index
