Presentation: Good Clinical Practice 101: An Introduction

(This presentation is also available in video format with captioning and PDF printer-friendly format.)

Presented by: Lester “Jao” Lacorte, MD

Medical Officer – Commissioner’s Fellow
Division of Bioresearch Monitoring
Office of Compliance
Center for Devices and Radiological Health

Objectives:

• Define Good Clinical Practice (GCP)
• Outline the goals of GCP
• Provide a historical perspective on GCP
• Outline FDA regulations relating to GCP in medical device research

What is Good Clinical Practice (GCP)?

• GCP is defined as a standard for the design, conduct, performance, monitoring, auditing, recording, analysis and reporting of clinical trials or studies

Additional terms defined:

• Clinical Investigation
• Clinical Investigator
• Human Subject
• Institutional Review Board

Why is GCP important?

• GCP compliance provides public assurance that the rights, safety and well-being of human subjects involved in research are protected

What are the goals of GCP?

• To protect the rights, safety and welfare of humans participating in research
• To assure the quality, reliability and integrity of data collected
• To provide standards and guidelines for the conduct of clinical research
• Good Clinical Practice = Ethics + Quality Data

What are the foundations for the ethical conduct of clinical research?

• The Nuremberg Code (1947)
• The Declaration of Helsinki (1964)
• The Belmont Report (1979)
• International Conference on Harmonisation (ICH-GCP)
• International Standards Organization 14155
• Code of Federal Regulations

GCP: A Historical Perspective

• Nuremberg Code (1947)
  • Voluntary participation
  • Informed Consent
  • Minimization of risk
• Declaration of Helsinki (1964)
  • Well-being of subject takes precedence
  • Respect for persons
  • Protection of subjects health and rights
  • Special protection for vulnerable populations
• Belmont Report Ethical Principles (1979)
  • Respect for Persons
    • Informed consent
    • Protection of vulnerable populations
  • Beneficence
    • Non-malfeasance
  • Justice
    • Fairness

The International Conference on Harmonisation (ICH-GCP)

• GCP is an international quality standard that is provided by the International Conference on Harmonisation (ICH)
• Goals: Harmonize technical procedures and standards; improve quality; speed time to market
• In 1997, the FDA endorsed the GCP Guidelines developed by ICH
• ICH guidelines have been adopted into law in several countries, but used as guidance for the FDA in the form of GCP

What are the 13 principles of ICH-GCP?

• Ethics:
  1. Ethical conduct of clinical trials
  2. Benefits justify risks
  3. Rights, safety, and well-being of subjects prevail
• Protocol and science:
  4. Nonclinical and clinical information supports the trial
  5. Compliance with a scientifically sound, detailed protocol
• Responsibilities:
  6. IRB/IEC approval prior to initiation
  7. Medical care/decisions by qualified physician
  8. Each individual is qualified (education, training, experience) to perform his/her tasks
• Informed Consent:
  9. Freely given from every subject prior to participation
• Data quality and integrity:
  10. Accurate reporting, interpretation, and verification
  11. Protects confidentiality of records
• Investigational Products
  12. Conform to GMP’s and used per protocol
• Quality Control/Quality Assurance
  13. Systems with procedures to ensure quality of every aspect of the trial

A Comparison

DECLARATION OF HELSINKI:

• Ethical principles
  e.g. ethical and scientific
• Focus: Physicians in research
• World Medical Assembly- International medical societies
• Guidance with broad recommendations

ICH-GCP:

• Broader principles e.g. ethical, scientific & operational for designing, conducting, reporting & recording trials
• Focus: Drug sponsors, investigators & IRB
• Representatives from industry and public health
• Guidance document but has the effect of law when put into Regulation

International Standards Organization

• ISO 14155: Clinical Investigation of Medical Devices for Human Subjects
  • Assists sponsors, monitors, and clinical investigators in the design and conduct of device clinical investigations
  • Assists regulatory bodies and ethics committees in their roles of reviewing clinical investigational plans

What constitutes Good Clinical Practice in device research?

• IRB-approved protocol
• Valid Informed Consent
• Monitoring Plan
• Adverse Device Effect Reporting [Adverse Event (AE) or Serious Adverse Event (SAE)]
• Proper documentation
• Valid data collection/reporting procedures

Who is responsible for GCP compliance?

• Sponsors
• Clinical Investigators (CIs)
• Independent Ethics Committees (IECs)
  • Institutional Review Boards (IRBs)
• Contract Research Organizations (CROs)
• Research nurses
• Clinical Research Coordinators (CRCs)
• Clinical Research Associates (CRAs)
• Medical monitors
• Data entry personnel
• Others

How does FDA implement GCP?

• 21 CFR 11 – Electronic Records & Signatures
• 21 CFR 50 – Protection of Human Subjects
• 21 CFR 54 – Financial Disclosure
• 21 CFR 56 – Institutional Review Boards
• 21 CFR 812 – Investigational Device Exemptions
• 21 CFR 814 – Premarket Approval of Medical Devices

Summary:

• Defined Good Clinical Practice (GCP)
• Outlined the goals of GCP
• Presented a historical perspective on GCP
• Outlined FDA regulations relating to GCP in medical device research

For further information:

• FDA Good Clinical Practice Regulations & ICH Guidance