Good Clinical Practice - KSR

By Ayurmitra Dr KSR Prasad

1. Good Clinical Practice (GCP)
Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)

2. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Introduction
•Clinical Research and Practice looks similar with
variation
–Research require to work in a stipulated frame work
–Where in the practice is patient oriented /beneficial
–The research do not require any clinical experience
and it starts with a research question
–but clinical practice do require clinical experience and
regularity
–To prevent undo practices in Clinical research and
practice
“Good Clinical Practice”is brought out
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3. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Clinical Research
•Research is –
–A search for knowledge with Systematic
investigation to establish facts in scientific
manner
•Clinical Research is –
–Fact establishment in a clinic /hospital
dependingon direct observation of patients
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4. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
What is Clinical trial
•A clinical trial is a prospectiveevaluating
the effect and value of intervention (s) in
human beings underpre-specified
conditions
•A controlled clinical trial is a clinical trial
comparingan intervention group against
controls
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5. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Good Clinical Practice
Good Clinical Practice (GCP) is defined as –
A ‘standardfor the design, conduct,
performance, monitoring, auditing,
recording, analyses and reporting of
clinical trials that provides assurance that
-the dataand reported results are
credibleand accurate, and that
-the rights, integrity and confidentiality
of trial subjectsare protected’
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6. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
GCP principles summary (1)
•Patient
–Rights, safety & well beingof subjects prevail over
interests of science and society
–Individuals involved in trial should be qualifiedby
education, training and experience to perform his/her
tasks
•Data
–
Information recorded, handled and storedto allow
accurate reporting, interpretation and verification and confidentiality of subjects’ records
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7. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
GCP principles summary (2)
•Study
–Trials shall be scientifically sound and guided by
ethicalprinciples in all their aspects
–Necessary procedures to secure the qualityof every
aspect of the trial shall be complied with
–Available non- clinical and clinical information shall be
adequateto support the trial
–Conductedaccording to Helsinki Declaration (1996)
–Protocolshall provide inclusion and exclusion criteria,
monitoring and publication policy
–Investigator/sponsor shall considerall relevant
guidance
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8. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI
Ethical Principles for Medical Research Involving Human Subjects
•Adopted by the 18th WMA
General Assembly Helsinki,
Finland, June 1964and
amended by the
•29th WMA General Assembly,
Tokyo, Japan, October 1975
•35th WMA General Assembly,
Venice, Italy, October 1983
•41st WMA General Assembly,
Hong Kong, September 1989
•48th WMA General Assembly,
Somerset West, Republic of
South Africa, October 1996
•52nd WMA General Assembly,
Edinburgh, Scotland, October
2000
•Note of Clarification on
Paragraph 29 added by the
WMA General Assembly,
Washington 2002
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9. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Declaration of Helsinki
•Basic Principles
–Concern for the interests of the subjects must always
prevail over the interests of science and society.
–Research must conform to accepted scientific principles;
design appropriate and clear in experimental protocol.
–Research must be conducted by qualified persons.
–Research must have importance proportionate to inherent
risk (risks acceptable given the benefits to individuals)
–Safeguard subjects’ integrity & privacy.
–Present results accurately in publications
–Inform subjects of their right to withdraw. Obtain true
informed consent from the subject or legal guardian.
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41
st
World Medical Assembly, Hong Kong, September 1989.

10. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
41
st
World Medical Assembly, Hong Kong, September 1989.
•Medical Research Combined with Clinical Care
(Clinical Research)
–In the treatment of the sick person, the physician must be free to
use a new diagnostic and therapeutic measure
–The potential benefits, hazards and discomfort of a new method
should be weighed against the advantages of the best current
diagnostic and therapeutic methods
–In any medical study, every patient should be assured
–The physician can combine medical research with professional
care
–If the physician considers it essential not to obtain informed
consent, the specific reasons for this
–proposal should be stated in the experimental protocol for
transmission to the independent committee (I.2).
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11. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
41
st
World Medical Assembly, Hong Kong, September 1989.
•Non-Therapeutic Biomedical Research
Involving Human Subjects (Non-Clinical
Biomedical Research)
–it is the duty of the physician to remain the protector
of the life and health of that person, on whom
biomedical research is being carried out.
–The subjects should be volunteers --either healthy
persons, or patients for whom the experimental
design is not related to the patient's illness.
–The investigator or the investigating team should
discontinue the research, if in his/her or their
judgment it may, if continued, be harmful to the
individual.
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12. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Note of Clarification on Paragraph 29 added by the
WMA General Assembly, Washington 2002 on
Placebo controlled trial
•Extreme care must be taken in making use of a placebo
controlled trial and that in general this methodology
should only be used in the absence of existing proven
therapy. However, a placebo-controlled trial may be
ethically acceptable, even if proven therapy is available,
under the following circumstances:
–Where for compelling and scientifically sound methodological
reasons its use is necessary to determine the efficacy or safety
of a prophylactic, diagnostic or therapeutic method; or
–Where a prophylactic, diagnostic or therapeutic method is being
investigated for a minor condition and the patients who receive
placebo will not be subject to any additional risk of serious or
irreversible harm.
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13. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
GCP compliance
•Who must comply with GCP?
–All individuals involved in any aspect of the trial must be suitably
‘qualified’ to be able to comply with GCP.
–Sponsors/CIs are responsible for ensuring that all staff are able
to comply with GCP.
•ICH GCP section 5.18.3 allows individual researchers to
assess the needs of their trial and apply GCP
appropriately
‘central monitoring in conjunction with procedures such as
investigators’ training and meetings and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP.’
(On-site monitoring not
compulsory)
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14. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
What counts as qualified?
According to GCP each individual involved in
conducting a trial ‘shall be qualified by
education, training, and experience to perform
his or her respective task (s)’
(GCP –principle 8)
•Education
•Training
•Experience
There is no GCP ‘qualification’
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15. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
GCP qualifications
•Education
–Cliniciansmust be clinically qualified
–Statisticiansmust be qualified
–Managersmust be appropriately educated
•Training
–Employer induction courses
–Industry courses
–E-learning (Institute of Clinical Research)
–Private courses(usually run by freelance consultant)
–Host institution courses
–Trial specific workshops
–Investigators meetings
•Experience
–Discovering what is required
–Doing the job(sometimes wrongly)
–Cascading information and knowledge through teams/units
–Conversationto other trial makers
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16. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Approvals and permissions
•Ethics committee approval
•Clinical Trials Authorisation
•R & D permission
•Sponsor approval
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17. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Informed consent
•Following the second world war and the Nuremberg trials,
the Nuremberg Codeand Declaration of Helsinkiwas
agreed worldwide as a charter to protect people/patients
against human experimentation
–Up until 1995 USA, Japan and Europe worked to different
standards in the conduct of clinical trials
–1995 ICH-GCP was implemented –a global standard
–2001 EU Directive set out regulations for clinical trials of medicines
conducted within the EU
–2004 (May) the UK implemented the Directive and the UK
Regulations became law
Informed consent – personal autonomy
‘…a competent individual should have the right to determine
those discretionary risks he/she is willing to accept for
whatever benefits he/she perceives may result.’
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18. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Consent procedures
•Given freely
•Face to face
•Telephone
•Watch
•Listen
•Learn
•What works well?
•Share
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19. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Good Clinical Practice (E6)
•The GCP document describes the
responsibilitiesand expectationsof all
participants in the conduct of clinical trials,
including investigators, monitors and sponsors.
•GCP covers the aspects of monitoring, reporting
and archiving of clinical trials and incorporating
addenda on the essential documents and on the
investigators broacherwhich had been agreed
earlier through consent process.
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20. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP) 19

21. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP) 20

22. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP) 21

23. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
•Phase 1
–First use in humans (healthy or ill)
–Physiological observations (pre-clinical status)
–Tolerance of different dosages
–Finding optimal dose- relationship
–Interactions with other treatments
–Pre-finding of clinical indication
•Phase 2
–Dose-relationship in patients
–Treatment efficacy compared to an other method or
substance
–Tolerance proof of dose (s)
–Physiological observations of phase I results
–Interactions with other treatments
–Real finding of indication
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24. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
•Phase 3
–Treatment efficacy compared to another method or
substance
–Give reasons for effect (power, number of cases)
–Tolerance proof of dose (s)
–Physiological observations of phase I&II results
–Interactions with other treatments
–Confirmation interactions to be registered
•Phase 4
–Additional findings under conditions of daily use
–Periodic safety update to keep marketing
authorization (Vigoxx©, Lipoxx©)
–Impressions about new indication (s)
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25. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Designs of study
•Randomized clinical trial
•Parallel group design
•Crossover design
•Multi center studies (trials)
•Active control trial
–Superiority trial (new advances)
–Equivalence or non inferiority trial (safety
purpose)
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26. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Principles of Research
•Randomization principle
•Blindness principle
–Single / Double
•Placebo principle
•
Intent to treat principle
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27. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP) 26

28. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Follow-
•CONSORT checklist
•Show proper reporting effects
–Acknowledgements
–
Statistics
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29. Dr. K. Shiva Rama Prasad, at http://www.technoayurveda.com/
Good Clinical Practice (GCP)
Acknowledgements
•GCP -J. Hedderich -Institut für Medizinische
Informatik und Statistik
•UKTMN
•MRC GUIDELINES FOR GOOD CLINICAL
PRACTICE IN CLINICAL TRIALS, March 1998,
Medical Research Council, 20, Park Crescent,
London, W1N 4AL
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