Guidelines for Conducting

Clinical Trials in India

Dr Arun Bhatt MD (Med) FICP (Ind)
Member, Faculty of Pharmaceutical
Medicine
President
ClinInvent Research Pvt Ltd

Challenges for Pharmaceutical

Medicine Personnel

Sophisticated products
Alternative medicine
New public health threats
International commerce
Consumer awareness
Information technology
Regulatory activism
Global ethics
Media pressure

Kerala Controversy: Inquiry

Commissions Findings
Trial at RCC started without approval from Drugs
Controller
No clearance from Health Ministry for
collaboration with a foreign Institute
Banned drug smuggled by the Johns Hopkins
scientist
Patients signed informed consent in language
other than their native language
Neither ICH-GCP nor the ICMR guidelines for
biomedical research on human subjects followed
Clinical trials suspended at RCC for 6 months

Critical Path of a Clinical Trial

Planning
Protocol CRF
Regulatory and
Ethical Approval
Trial Documents Materials
Select
Investigators
Initial Visits
Site Assessments
Patient Recruitment
Periodic Monitoring

Data
Entry
*START

Study
Termination
Data
Statistical
Clean-up
Analysis

Final
Report
*END

Pharmaceutical Medicine
Personnel - The Knowledge Gap

Science Policies
International
Regulations
local /
international

Regulations
local

Industry

Company
policy local /
international

Academia

Institute
Regulations

Clinical Trial : Conduct and Plan

Good
Fast
Cheap
Choose any two

Guidelines for Clinical Trials

1996
2000
2001
2003
2003

:
:
:
:
:

ICH Guidelines
ICMR guidelines
Indian GCP guidelines
Revision of BE guidelines
Revision of Schedule Y

Applicability of Guidelines
ICH (in USA)

GCP (India)

Legal Position :

Guidance

Guideline Law

Scope :

Clinical trials for

regulatory
submission

All biomedical
research at all
stages of drug
development

Structure
ICH E6
Glossary
Principles
IRB/IEC
Investigator
Sponsor
Protocol
Investigators Brochure
Essential Documents

Indian GCP
Definitions
Pre-requisites
Responsibilities
Records & Data
Quality Assurance
Statistics
Special Concerns
Appendices

Ethical Principles of Indian GCP

Essentiality
Voluntariness, Informed consent and
community agreement
Non-exploitation
Privacy and confidentiality
Precaution & risk minimisation
Professional competence

Ethical Principles of Indian GCP

Accountability and transparency
Maximisation of the public interest and
Distributive justice
Institutional arrangements
Public domain
Totality of responsibility
Compliance

Indian and ICH-GCP :

Significant Differences

Investigator
Ethics Committee
Informed Consent
Compensation
Data Records

Investigator
Qualifications as prescribed by MCI
Sign on a copy of the protocol and SOPs
Sign and forward the data (CRFs, results
and interpretations, analyses and reports)
of the study from his / her centre to the
sponsor and the ethics committee

Ethics Committee

Details of composition
Quorum - minimum of 5 members
Decision making process
Can order discontinuation of trial if the
goals are achieved or unequivocal results
obtained
Records to be retained for at least 5 years
after completion / termination of study

Informed Consent
Ensure freedom of consent for vulnerable
groups and members of group with a
hierarchical structure
Right to prevent use of biological samples
Free treatment of research-related injury
Possible current and future use of
biological material
Risk of discovery of biologically sensitive
information
Publication plan

Compensation
All payments, reimbursements and medical
services for subjects to be approved by IEC
Liability of involved parties (investigator, sponsor
/ manufacturers, institutions) etc to be clearly
agreed and stated before initiation of study
Sponsor (company, government, institution) to
agree to provide compensation for any serious
physical or mental injury or to provide insurance
coverage

Compensation
Research subjects who suffer physical injury in a
trial entitled to financial / other assistance to
compensate them equitably for any temporary or
permanent impairment or disability subject to
confirmation from IEC
In case of death, their dependents entitled to
material compensation
When a subject is withdrawn from research for
medical reasons related to the study, he should
get benefit of full participation

Data Records
Sponsor to retain records for a period of 5
years after completion of study or
submission of data

Revised Schedule Y : Clinical Trials

Definition of Phases I IV
Concurrent Phase II-III
Central lab and trial samples
Flexibility in data requirements for new
drugs for life threatening / serious
conditions or disease of relevance to India
Classification of Fixed Dose Combinations
for clinical studies

Phase IV Studies
Same scientific and ethical standards as applied
in pre-marketing studies
Outside the purview of the ethical however, the
adverse reactions induced by drugs, if any,
should be brought to the notice of the EC
In post-marketing stage, clinical trials designed to
explore new indications, new methods of
administration or new combinations, etc.
considered as trials for new pharmaceutical
products

Special Populations

Children
Pregnant or nursing women
Socio-economically disadvantaged
Mentally challenged
Students, Subordinates, Employees
Army personnel
Prisoners

Clinical Trials in Children

EC for paediatric trials to include
members knowledgeable about paediatric,
ethical, clinical and psychosocial issues
Mature minors and adolescents to sign an
assent form

Ethics Committee
EC approval of protocol / informed
consent form (ICF) and notification to
DCGI prior to initiation
EC approval for sites without EC
EC approval of protocol amendments and
notification to DCGI
Composition of EC

Schedule Y:
Commitments by Investigator
Study not to begin until EC / DCGI
approval
Adherence to protocol
Personal supervision
Ensure requirements of IC and EC review
Report of ADE to sponsor
Understanding of investigators brochure
Maintenance of records and availability for
audits / sponsor inspection / EC and DCGI

Commitments by Investigator
Ensure that all associates, colleagues and
employees suitably qualified and
experienced and aware of their obligations
Cooperation in audits
Report to EC promptly about changes and
unanticipated problems
Confidentiality of data and patients
Compliance with all other obligations of
clinical investigators

Responsibility of Sponsor
Quality assurance to ensure compliance
to GCP guidelines of CDSCO
Submission of status report at prescribed
periodicity; reasons for premature
termination to be communicated
Serious adverse event to be
communicated promptly (within 14
calendar days) to DCGI and other
investigators

Checklists and Formats

Content of Protocol
Structure and content of report
Undertaking by investigator
Checklist of contents for ICF
Format of EC approval, ICF

Special Research Areas

Vaccines
Contraceptives
Herbal
Surgical procedures / Medical devices
Diagnostic agents radioactive material
Genetics
Epidemiology
National priorities
Biotechnology

Herbal Research
Approach as per DCGI guidelines for
Herbal remedies for use in Allopathic
system
Extract by method different from
Ayurvedic text
Indication different from Ayurvedic text
Isolated chemical compound
Plant not described in Ayurvedic text

Herbal Research
Toxicity studies (4-6 weeks toxicity) study in 2
species of animals) needed for phase 2 trials, if
reports suggesting toxicity or trial use for more
than 3 months, or before Phase 3 trial
Preparation of plants and herbal remedies as per
the literature and GMP norms with
standardization and identification of markers
Ethical guidelines (patient information, informed
consent, protection of vulnerable populations etc)
for biomedical research should be followed.
Ayurvedic, Siddha or Unani physician as a coinvestigator

Bioequivalence Guidelines
Organization premises and facilities
Protocol and study design for conventional
Release dosage forms and extended release
dosage forms
Methodology for conduct of study
Analytical methodology and validation
In-vitro dissolution
Statistical evaluation
Documentation
In-vitro in-vivo correlation
Adverse drug reaction
Good laboratory practice

 By three methods we may learn wisdom:

first, by reflection, which is noblest;
second, by imitation, which is easiest;
and
third by experience, which is the
bitterest.
Confucius