Good Clinical Practice

Presented by: Dr Nilamjyoti Medhi

PGT, Dept of Pharmacology

Moderator: Dr Rituparna P Ray

Associate Professor

Objectives

What is GCP

The history of Good Clinical Practices

Guidelines for GCP

Basic principles

Definition

A standard for the Design AuditingRecording ConductAnalyses PerformanceReporting Monitoring of clinical trials that provide assurance that the data and the reported results are CREDIBLE, ACCURATE and that the RIGHTS, INTEGRITY and CONFIDENTIALITY of trial subjects are protected.

The history…

– Public disasters, serious fraud and abuse of human rights.

– Trials of War criminals --Nuremberg code 1949

– Thalidomide -- Declaration of Helsinki 1964

– Belmont report 1978

– ICH 1990

How ICH started..

– 1st conf. in 1990 in Brussels

– 3 regions participated EU / United States / Japan

– Representatives from Industry/ Academia/ Ministry of health.

– WHO, EFTA and Canada observers

– Reduce duplication

– Efficiency , registration for new pharmaceuticals

ICH resulted in...

Many guidelines made

– Most important- ICH GCP guidelines

– Evolved in several steps

– Consolidated guideline ICH E6 Sept 1997

Role of ICH

– Safeguard public health

– Assure consumer protection standards

– Facilitate availability of safe and effective products

– Eliminate inconsistent standards internationally

– Facilitate mutual acceptance of data from clinical trials

ICH GCP guideline..

8 sections

Sections..

1. Glossary

2. Principles of Good Clinical Practice

3. Requirements for IRB/IEC

4. Responsibilities of the investigator

5. Responsibilities of the sponsor

6. Requirements for clinical trial protocol and protocol amendments

7. Responsibility of the sponsor in the development of investigator’s brochure

8. Essential documents.

1. Glossary

62 points Common language for investigators/sponsors/ethics

committees

1. Adverse Drug Reaction (ADR)

2. Audit

3. Case Report Form (CRF)

4. Contract Research Organization (CRO)

5. Independent Ethics Committee (IEC)

2. GCP Principles…

1. The ethical principles

2. Risk and benefits.

3. The rights, safety, and well-being

4. Supportive data

5. Protocol

6. Ethical clearance.

7. Subject care

8. Qualified staff

GCP Principles…

9. Informed consent

10.Data

11. Confidentiality

12. Investigational Product

13.Quality of procedures.

3. Requirements for IRB/IEC

– Responsibilities

– Composition, Functions and Operations

– Procedures

– Records

4. Responsibilities of the investigator

Investigator's Qualifications and Agreements Adequate Resources Medical Care of Trial Subjects Communication with IRB/IEC Compliance with Protocol Investigational Product(s) Randomization Procedures and Unblinding Informed Consent of Trial Subjects

5. Responsibilities of the sponsor

Quality Assurance and Quality Control Contract Research Organization (CRO) Medical Expertise Trial Design Trial Management, Data Handling, and Record Keeping Investigator Selection Allocation of Responsibilities

6. Clinical trial protocol and protocol amendment(s)

General Information Background Information Trial Objectives and Purpose Trial Design Selection and Withdrawal of Subjects Treatment of Subjects Assessment of Efficacy Assessment of Safety

7. Investigator’s brochure

Introduction General Considerations Contents of the Investigator’s Brochure

8. Essential documents..

Before the Clinical Phase of the Trial Commences During the Clinical Conduct of the Trial After Completion or Termination of the Trial

Indian GCP guidelines..

– Released in Dec 2001(Developed by CDSCO and endorsed by DCGI)

– Has Revised Schedule Y (Jan 2005) addressed discrepancies?

Issues in Developing Countries

– The informed consent process

– Economic Vulnerability

– Patient doctor relationship

– Education level

STAKEHOLDERS & THEIR RELATIONSHIPS

SUBJECT

REGULATORY AUTHORITY

SPONSORETHICS

COMMITTEEINVESTIGATOR

Declaration of Helsinki - 1964

– Developed to guide physicians in biochemical research involving human subjects

– Requires:

o All physicians to conform to accepted scientific principles

o A research protocol to be reviewed by an independent committee

o Research performed by “clinically competent person”

o Objective proportional to risk

o Rights of patients protected

o Participants to be fully informed, and to consent to take part

Cont…

– 1962 US FDA IND Guidelines

– 1964 Declaration of Helsinki

– 1968 Committee on Safety of Medicines, UK

– 1978 GCP, US FDA

– 1991 GCP, Europe

– 1996 ICH GCP

– 1997 ICH GCP Guideline

Nuremberg code 1949..

– Nuremberg, Germany

– October 1946–April 1949 – trial of the World War II

– Nuremberg Military Tribunals

– Control Council Law No. 10

code 1949..

1. The voluntary consent of the human subject is absolutely essential.

2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.

3. The experiment should be so designed and based on the results of animal experimentation

4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.

5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur.

code 1949..

6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment

7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.

8. The experiment should be conducted only by scientifically qualified persons

9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end

10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage

Belmont report 1978...

Cont...

5. Clinical trials should be scientifically sound, and described in a clear, detailed protocol.

6 A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favorable opinion

7 The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist

8 Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective tasks

9 Freely given informed consent should be obtained from every subject prior to clinical trial participation

Cont...

10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification

11. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements

12. Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol

13. Systems with procedures that assure the quality of every aspect of the trial should be implemented

Role of GCP

– Good clinical practice (GCP) is an international ethical & scientific standard for conducting clinical trials that involve the participation of human subjects

– Compliance with this standard provides public assurance that the rights, safety & well-being of trial subjects are protected, which is consistent with the principles outlined in the declaration of Helsinki

– GCP also ensures the credibility of clinical trial data.