List of Abbreviations.
1. Challenges to the Design of Clinical Study.
Development of Clinical SOPs.
Selection of Study Patients, Investigators, and Study Sites.
Definition of Enrolled Subjects in a Clinical Study.
Definition of the Investigational Device System.
Research Contract Challenges.
Review of Literature.
Challenges to the Design of the Study Protocol, Statistical Analysis Plan (SAP), and Selection of Study Endpoints.
Masking or Blinding.
Primary and Secondary Outcomes.
Selection of Study Endpoints.
Differences between the Primary Endpoint in FDA and CE Mark Studies.
SAP and Study Endpoints.
Components of the SAP for Clinical Trials.
Roles and Responsibilities of the Clinical Personnel in Completing the Study Protocol.
Changing the Primary Outcome during the Conduct of the Study.
Definition of Primary and Secondary Endpoints.
Combined "Composite" Endpoints.
Reducing the Study’s Sample Size.
Statistical Terms to Define Endpoint Measurements.
Reporting Results of Clinical Trials.
Superiority and Equivalence Trials.
Challenges to ICF.
2. Challenges to Managing the Study.
Enhancing Patient Enrollment by Relaxation of Study Criteria.
Compliance with the Study Protocol.
Challenges Associated with Data Accuracy and Completeness.
Criteria for Using Meta-Analysis Studies.
Who Should have Access to Clinical Trial Records.
Managing Study Data and Quality Assurance.
Missing Data Analysis.
Examination of Data across Study Sites.
Challenges to Adverse Event Reporting.
Adverse Event Coding Systems.
Protocol Deviation Report.
Adverse Event Reporting in Final Study Clinical Report.
Difference between the US and EU Definitions and Reporting of Adverse Events.
Adverse Event Reporting Challenges.
Minimization of Bias in Clinical Trials.
3. Selection of Historic Controls.
Types of Control Group in Medical Device Clinical Trials.
Purpose of Control Group.
Use of Placebo Control.
Advantages of Randomized Control Clinical Trials.
Disadvantages of Randomized Control Clinical Trials.
Commonly Used Pivotal Designs.
Definition of Historic Control.
Objective Performance Criteria (OPC).
Examples of Clinical Studies with Historic Controls.
LACI Clinical Study.
Left Ventricular Assist Devices.
Summary of Clinical Studies.
Summary of Recommendations for Historic Control.
4. Fraud and Misconduct in Clinical Trials.
Fraud and Misconduct in Clinical Trials.
Warning Signs of Fraud.
Tips for Detecting Serious Misconduct.
False Claims Act.
Policy on Handling Complaints of Misconduct.
Reporting Research Misconduct.
Bioresearch Monitoring Information System (BMIS).
5. Challenges to the Regulation of Medical Device.
Determination of 510(K) Devices.
510(K) "Substantial Equivalence Decision Making Process".
Determination of Nonsignificant Risk Devices (NSR).
Similarities and Differences between Medical Device and Drug Regulations in Clinical Trials.
Definitions of Drugs and Devices.
Investigator-Initiated Clinical Trials.
6. Challenges of Global Clinical Studies and the CE Mark Process.
Global Trial Considerations.
Global Harmonization Task Force Challenges.
FDA Recommendations on Acceptance of Foreign Clinical Sites.
Operational Tips on Conductance of Global Clinical Trials.
CE Mark Process and Challenges.
International Standard ISO 14155.
Differences between FDA and CE Mark Clinical Trials.
Challenges to CE Mark Studies.
7. Challenging FDA PMA Cases.
PMA P970029 (TMR 2000 Holmium Laser System).
PMA P040012 Carotid Stenting for Treating Carotid Disease.
Historic Control Assumptions.
Use of Angiographic Late Loss as Primary Endpoint in Drug-Eluting Stent PMA P070015 (Xience V DES).
8. Bioethics in Clinical Research.
Bioethical Challenges in Clinical Studies.
Good Clinical Practice for the Investigator.
WHO Principles of GCP.
Guidelines and Ethical Principles.
IRB Review Process.
Glossary of Clinical, CE Mark, and Statistical Terms.