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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 ®ulatory 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