Guidelines for clinical trials

1. GCP
Guidelines
Dr. Nilesh Siddhawar,
JR1, Dept. of Pharmacology,
VNGMC, Yavatmal

2. Contents-
 Introduction
 Historical Background
 Principles of Guidelines
 Ethics Committee
 Informed Consent Process
 Responsibilities of Sponsor, Monitor & Investigator
 Guidelines For Special Concern
 Conclusion

3. Good Clinical Practice is a set of
guidelines which encompasses the
design, conduct, termination, audit,
analysis, reporting and documentation of
the studies involving human subjects
Clinical
Trials or
Studies
Designing
Conducting
Monitoring
Recording
Analysis
Reporting

4. Historical Background
 Nuremberg Code, 1946
 Kefauver Amendments, 1962
 Declaration of Helsinki, 1964
 Belmont Report, 1979

5. Nuremberg Code(1946)
German Physicians conducted medical experiments on prisoners of war
without their consent .
Most of the participants of these experiments died or were permanently
crippled.

6. • In December 9, 1946 - American military
tribunal opened criminal proceedings against
23 leading German physicians
• The Nuremberg Code was established in 1948,
stating that "The voluntary consent of the
human participant is absolutely essential,"
• Nuremberg Code was the first international
document which advocated voluntary
participation and informed consent.

7. Kefauver Amendments(1960)
• 6000-12000 children had congenital anomalies d/t
maternal use of Thalidomide.
• 1962 US Senate hearings Kefauver Amendments
passed into law - For the first time, drug
manufacturers were required to prove to the FDA
the effectiveness of their products before marketing
them

8. Declaration Of Helsinki
• Adopted by the 18th WMA general assembly Helsinki, Finland, June 1964.
It has since undergone seven revisions (the most recent at the general
assembly in October 2013) .
• A statement of ethical principles to provide guidance to physicians and
other participants in medical research involving human subjects.
• The Declaration specifically addressed clinical research, reflecting changes
in medical practice from the term 'Human Experimentation' used in the
Nuremberg Code

9. • The US Public Health Services conducted a
Syphilis Study on 600 low income African-
American individuals
• Stopped in 1972
• led to the 1979 Belmont Report and the
establishment of OHRP.
Tuskegee Syphilis Study- 1932 to 1972

10. A comprehensive representation of the development of GCP
can be found in a literature review of …..
Declaration of
Helsinki
The common rule
The Belmont
report
World Health Organisation
Guidelines for GCP
International
Conference on
Harmonization
FDA GCP

11. The Principles Of GCP
1. Follow ethical principles according to Declaration of Helsinki
2. Essentiality
3. Voluntariness, informed consent and community agreement
4. Non-exploitation
5. Privacy and confidentiality
6. Precaution and risk minimisation
7. Professional competence

12. 8. Accountability and transparency
9. The maximisation of the public interest and of distributive justice
10. Institutional arrangements
11. Public domain
12. Totality of responsibility
13. Compliance

13. Ethics Committee
Responsibilities
1. To protect the dignity, rights and well being of research participants.
2. To ensure that universal ethical values and international scientific
standards are followed.
1. To assist in the development and the education of a research community
responsive to local health care requirements

14. Composition
1. Chairperson
2. 1-2 basic medical scientists (preferably one pharmacologists).
3. 1-2 clinicians from various Institutes
4. One legal expert or retired judge
5. One social scientist / representative of non-governmental voluntary agency
6. One philosopher / ethicist
7. One lay person from the community
8. Member Secretary

15. 1. The researcher should submit an appropriate application to the IEC along
with the study protocol.
2. The IEC should be able to provide complete and adequate review of the
research proposals submitted to them.
3. All documentation and communication of an IEC are to be dated, filed and
preserved according to written procedures. Strict confidentiality is to be
maintained.

16. Informed Consent Process
1. The expected duration participation
2. The benefits as an outcome of research
3. Any alternative procedures or courses of treatment that might be as
advantageous to the subject as the procedure or treatment to which
she/he is being subjected;
4. Any foreseeable risk or discomfort to the resulting from participation
in the study.
5. Right to prevent use of his/her biological sample (DNA, cell-line,
etc.)

17. 7. Confidentiality of records
8. Free treatment for research related injury .
9. Compensation of subjects for disability or death resulting from such
injury.
10.Freedom of individual to participate and to withdraw from research any
time without penalty or loss of benefits.
11.The identity of the research teams and contact persons with address
and phone numbers.

18. Compensation for Participation
1. Subjects may be paid for the inconvenience and time present, and
should be reimbursed for expenses incurred.
2. Payments should not be large or the medical services extensive.
3. All payments should be approved by the IEC.
4. When a subject is withdrawn from research for medical reasons
related to the study the subject should get the benefit for full
participation

19. Selection of Special Groups As Research Subject
Pregnant or nursing women :
1. Trials that are designed to protect or advance the health of
pregnant or nursing women or foetuses.
2. The justification of participation would benefit subject from
investigations, drugs, vaccines or other agents that promise
therapeutic or preventive benefits.
3. Research related to termination of pregnancy.
4. Research related to pre-natal diagnostic techniques

20. Children-
1. The study in children should always be carried out after the phase III clinical
trials in adults.
2. Research should be conducted in settings in which the child and parent can
obtain adequate medical and psychological support.
3. The child's refusal to participate in research must always be respected unless
there is no medically acceptable alternative to the therapy provided
4. The assent of the child should be obtained to the extent of the child's
capabilities.

21. Responsibilities Of Sponsor
1. Selection the investigator / institutions.
2. The sponsor should establish detailed standard operating
procedures (sop’s).
3. Allocation of duties and responsibilities.
4. Make arrangements for safe and secure custody of all study
related documents and material.
5. Compensation for participation.
6. Confirmation of review by the ethics committee.

22. 7. Sponsor is responsible for providing the Investigator with an
Investigator’s Brochure.
8. Supply, storage and handling of Pharmaceutical Products.
9. The Sponsor should expedite the reporting to all concerned of all
serious or unexpected adverse drug reactions.
10. Sponsor should perform an audit as a part of QA system
11.In case of foreign sponsor it shall appoint a local representative
or CRO to fulfil the appropriate local responsibilities.

23. The Monitor:
• The monitor should have adequate medical,
pharmaceutical and / or scientific qualifications and clinical
trial experience.
• He is a principal communication link between the sponsor
and the investigator and is appointed by the sponsor.

24. Responsibilities
• Verification of investigator(s) qualifications, expertise and the
resources to carry out the study.
• Verification of institutional facilities like laboratories, equipment,
staff, storage space etc.
• Assessments of the protocol compliance and data handling .
• He should assist the investigator in reporting the data and
results of the study to the sponsor.

25. Investigator
 Should have qualifications prescribed by MCI.
 Should be thoroughly familiar with the safety, efficacy and
appropriate use of the investigational product .
 Responsible for all study related medical decisions.
 Investigator has the primary responsibility for investigational
products accountability at the study site.
 Responsible for ensuring the unbiased selection of an adequate
number of suitable subjects

26. Record keeping and data handling
• All steps involved in data management should be documented .
• For electronic data processing only authorised person should
be allowed to enter or modify the data in the computer.
• If trial data are entered directly into the computer to ensure
validation there must be a signed and dated printout and
backup records.
• The sponsor ensure electronic data processing system verified
for completeness, accuracy, reliability and validation.

27. Quality Assurance
• The Sponsor is responsible quality assurance that the Study is
performed and the data is generated, recorded and reported in
compliance with the Protocol, GCP.
• Documented Standard Operating Procedures are a prerequisite
for quality assurance.

28. SPECIAL CONCERNS
1. Guidelines for vaccine trials-
• Conducted by trained investigator in institute with facility
of laboratory evaluation for seroconversion.
• Active or live-attenuated vaccine > risk of producing
infection. The subjects should be informed.
• For all the recombinant vaccines/products - guidelines
issued by the Dept. of Biotechnology should be strictly
followed.

29. 2. Guidelines for Clinical Trials of Contraceptives
• When implant is used for contraception, follow up for removal of the implant should
be done.
• Children born due to failure of contraceptives under study should be followed up for
any abnormalities .

30. Guidelines for Clinical trials with surgical
procedures/ medical devices
• Safety data of the medical device in animals should be obtained.
• Phase I of drug trial is not necessary for trial on devices
• Patient information sheet should contain information about procedures
to be adopted if the patient decides to withdraw from the trial.

31. Guidelines for Clinical trials for Diagnostic Agents
- Use of Radio-active Materials and X- Rays
• Research should be performed on patients undergoing the
procedures for diagnostic or therapeutic purposes.
• Safety measures should be taken to protect research subjects
• The protocol should make provisions for detecting pregnancies
• Non-radioactive diagnostic agents are considered as drugs and
the same guidelines should be followed

32. Guidelines for Clinical trials
of Herbal Remedies and
Medicinal Plants
• Same guidelines applied for herbal medicines as well.
• Herbal remedies currently in use or mentioned in traditional system of
medicine- No neccessity to undertake phase I studies
• Such clinical trials be carried out only when a competent Ayurvedic,
Siddha or Unani physician is a co-investigator

33. Conclusion
• GCP Guidelines safeguard the rights and safety of trial subjects
• It also guides clinicians for proper conduction of research.
• It ensures accuracy, legibility and acceptability of outcome of
research.
• GCP is amalgamation of science and practical wisdom gained by
personal experiences.