dr bhatt -gcp-jj-mar05

8/9/2019 Dr Bhatt -GCP-JJ-Mar05

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ICH-GCP and Indian GCP Guidelines

Dr Arun Bhatt MD (Med) FICP (Ind)

Member, Faculty of PharmaceuticalMedicine

President

ClinInvent Research Pvt Ltd


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Structure of Presentation

Definition Evolution and Needs Principles and Content Responsibilities

Sponsor

Investigator Ethics committee

Processes Documentation Informed consent Monitoring Audits

Implementation


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Guidelines for Clinical Trials

1996 : ICH Guidelines

2000 : ICMR guidelines

2001 : Indian GCP guidelines 2005 : Amendment to Schedule Y


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ICH GCP : Definition

A standard for the design, conduct,

performance, monitoring, auditing,

recording, analyses, and reporting of clinicaltrials, that provides assurance that the data and

reported results are credible and accurate, and

that the rights, integrity and confidentiality

of trial subjects are protected


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Life must be lived forwards,but can only be

understood backwards

Soren Kierkegaard


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Need for GCP

Tuskegee syphilis trials - 1930s

German prisoner's trials - 1940s

Harvard fraud - 1980s

California investigator - 1999

Johns Hopkins - 2001

Kerala controversy - 2001

Letrozole lapses - 2004


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A Doctors Drug Trials Turn into Fraud(NY Times May 17 1999)

For Dr Fiddes was conducting research fraud of

audacious proportions, cutting corners and

inventing data to keep the money flowing from drug

industry. Fictitious patients were enrolled in studies.Blood pressure readings were fabricated. Bodily

fluids that met certain lab values were kept on hand

in the office refrigerator, ready to be substituted for

the urine or blood of patients who did not qualify for

the studies.


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Kerala Controversy:

Inquiry Commissions Findings

Trial at RCC started without approval from DrugsController

No clearance from Health Ministry for collaborationwith a foreign Institute

Banned drug smuggled by the Johns Hopkinsscientist

Patients signed informed consent in language otherthan their native language

Neither ICH-GCP nor the ICMR guidelines forbiomedical research on human subjects followed

Clinical trials suspended at RCC for 6 months


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Nuremberg Code 1947

Voluntary consent

Anticipate scientific

benefits

Benefits outweigh risks

Animal experiments first

Avoid suffering

No intentional death ordisability

Protection from harm

Subject free to stop

Qualified investigators

Investigator will stop ifharm occurs


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Duty of physician to protect the life, health, privacy anddignity of the human subject

Review of proposed research by independent ethics

committee Medical research involving human subjects only by

scientifically qualified persons and under the supervisionof a clinically competent medical person

Physician to obtain the subjects freely-given consent,

preferably in writing

Stress on publication of results - negative or positive

Declaration of Helsinki 1964 - 2000

World Medical Association


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ICH

International Conference on Harmonization

Primary participants

USA, European Union, Japan

Regulatory and industry representatives

Observers

Canada, Australia, Nordic countries

Others

WHO as facilitator

IFPMA as secretariat


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ICH Topics

Q - Quality

S- Safety

E - Efficacy

E6 : GCP

M - Multidisciplinary


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Principles of GCP

Ethical principles - Declaration of Helsinki, GCP &regulatory requirements

Benefits vs. Risks

Safety of subjects vs. interest of science / society

Adequacy of non-clinical & clinical information Clinical trials scientifically sound & described in clear,

detailed protocol

Compliance with protocol that has received priorapproval of EC / IRB

Medical care responsibility of qualified physician /dentist


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Principles of GCP

Each individual involved in trial qualified byeducation, training and experience

Informed consent freely given

Information recorded, handled, stored for accuratereporting, information and verification

Protection of subjects confidentiality

Investigational products manufactured, stored andhandled as per GMP

Systems with procedures for quality assurance


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Indian GCP Guidelines

Evolved with consideration of WHO, ICH, USFDA ,European GCP and Ethical Guidelines of Biomedical

Research on Human Subjects of ICMR

Should be followed for carrying out biomedicalresearch in India at all stages of drug development,whether prior or subsequent to product registration in

India


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Ethical Principles of Indian GCP

Essentiality

Voluntariness, Informed consent and

community agreement

Non-exploitation

Privacy and confidentiality

Precaution & risk minimisation

Professional competence


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Ethical Principles of Indian GCP

Accountability and transparency

Maximisation of the public interest and

Distributive justice

Institutional arrangements

Public domain

Totality of responsibility

Compliance


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Structure

ICH E6

Glossary

Principles

IRB/IECInvestigator

Sponsor

Protocol

Investigators BrochureEssential Documents

Indian GCP

Definitions

Pre-requisites

ResponsibilitiesRecords & Data

Quality Assurance

Statistics

Special ConcernsAppendices


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Critical Path of a Clinical TrialPlanning

Protocol CRF

Regulatory andEthical Approval

Trial Documents Materials

SelectInvestigators

Initial Visits

Patient Recruitment

Periodic Monitoring

Data Data Statistical FinalEntry Clean-up Analysis Report

Site Assessments

StudyTermination

*START *END


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Definition of Clinical Trial

Clinical trial means a systematic study of new

drug(s) in human subject(s) to generate data for

discovering and / or verifying the clinical,

pharmacological (including pharmacodynamic

and pharmacokinetic) and /or adverse effects

with the objective of determining safety and / or

efficacy of the new drug.


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Clinical Trial : Participants

Chefs to design protocols

Lovers clinical investigators

Organisers project managers

Mechanics computer people

Policemen monitors / ethics

committee / regulators


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Heaven Hell

Chefs French British

Lovers Italians Swiss

Organizers Swiss Italians

Mechanics Germans French

Policemen British German


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Sponsor Responsibilities

Study design

Select sites

Regulatory

Study managementInformation

Clinical trial supplies

AE reporting

Monitoring

QC & QA

Termination

Study Report

DE & DM

Documentation

Communication

GCP


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Investigator Responsibilities

Monitoring / Audit

Regulatory compliance

Ethics approval

Informed consent

InvestigatorSafety reporting

Investigationalproduct

Medical careStaff supervision

Records Reports


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Investigator =

Protective Physician

+

Responsible Researcher


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Ethics Committee

Composition

Quorum

SOPs

Assessment of investigator competence

Review of documents

Decision making process

Reporting of adverse events Continuing review


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Informed Consent

Essential elements

Prior approval by EC

Responsibility of investigator

Process of explanation and documentation


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Documentation

If it is not written,If it is not written,

it did not happen!it did not happen!

Do what you write

Write what you do.


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Monitoring

Verification of

Protection of rights and well-being of trial subjects

Accuracy, completeness of data confirmed with

source documents

Conduct of trial as per

Approved / amended valid protocol

Good Clinical PracticeRegulatory requirements


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Audit

A systematic and independent examination of

trial-related activities and documents to

determine whether the evaluated trial-related activities

were conducted, and the data were recorded, analyzedand accurately reported, according to the protocol,

sponsors SOP, GCP and the applicable regulatory

requirement(s)


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Indian GCP : Special Populations

Children

Pregnant or nursing women

Socio-economically disadvantaged

Mentally challenged

Students, Subordinates, Employees

Army personnel

Prisoners


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Indian GCP : Special Research Areas

Vaccines

Contraceptives

Herbal

Surgical procedures / Medical devices

Diagnostic agents radioactive material


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Performance

Attitude

Knowledge Skills

GCP Implementation

What to Why to How to

Want to


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GCP - A Shared Responsibility

Sponsor

InvestigatorRegulatory Authority

Ethics Committee