ICH-GCP

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 HISTORY OF MEDICINES

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 SMALL POX

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 CHOLERA

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 TODAY……….

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 Some of these wonder
drugs have

a dark past
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 BECAUSE…..

THEY WERE DEVELOPED

UNETHICALLY

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 The Tuskegee Syphilis Study

1932-1972

 600 low-income African-American males

 400 infected with syphilis
 Monitored for 40 years
The study continues until 1972 with participants
denied treatment
 As many as 100 died of syphilis during the study (Allen, 1978)
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* Tuskegee Syphilis Study Legacy Committee Final Report of May 20, 1996
 WHAT WENT WRONG ?

 Is syphillis confined to Black population ?

 Even though a proven cure (penicillin) became available in

the1950s, the study continues until 1972 with participants
denied treatment
 Throughout the forty years of the study it was periodically
reviewed by U.S. Health Service officials
 The study was stopped only after its existence was leaked to
the public and it became a political embarrassment
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* Tuskegee Syphilis Study Legacy Committee Final Report of May 20, 1996
 The horrors of World War II

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• German Nazi Doctors
• Horrifying research on
prisoners

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 Nazi Prisoner Research During World
War II

 Objectives of various trials:

 Effect of cold, heat, chemicals on men, women and
children
 “Time to death” testing in response to stressors in
healthy “volunteers”
 Organ transplant experiments on healthy
“volunteers”
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 Nazi Prisoner Research During World
War II

 Any information given (some?) is irrelevant

because prisoners were forced to participate

 Outcome:

 23 German scientists taken to court, 7

acquitted, 9 imprisoned, 7 given death sentence

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 ONLY GERMANY ?

AMERICA AND BRITAIN ALSO

!!!!!!!!!!!

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President Franklin Roosevelt created an Office of Scientific
Research and Development to combat diseases such as
dysentery, influenza and malaria
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 ONLY GERMANY ?

 World war II

 Dysentery, Malaria and Influenza – Diseases affecting soldiers

 Dysentery vaccine was tried in orphans and mentally retarded

individuals marginal groups such as asylum inmates and

prisoners

 Malaria drug – introduced malaria in psychotic patients

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 THALIDOMIDE TRAIL

o 1945-66
o Pregnant women- Thalidomide
o ? ? To prevent miscarriages
o FDA head – disapproved d/t unsatisfactory results
o Over 2,00000 women consumed it as a routine
therapy
o Result …………..
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 THALIDOMIDE TRIAL

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 WHAT WENT WRONG ?

 Drug was not approved by the USFDA

 Women were not knowing that they were

taking a trial drug

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 WHAT MORE

 Article by Henry Beecher that appeared in the June 16, 1966

issue of the New England Journal of Medicine

 22 examples of unethical research

 Classical example- Mentally retarded children at a state school

were infected with hepatitis virus

 Clinical trials were done on marginal members of society such

as the poor, developmentally disabled and senile

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 Still today ?

 Unfortunately YES
 Sep 1999, 18 yr old research participant died at

the University of Pennsylvania

 The participant and his father had not been told

enough about the risks of the procedure

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 WHAT THESE EXAMPLES TELL US

 Marginalized population

 No information provided about the trial

 No voluntary participation

 No safety assessment

 No ethical way

 Human being treated worse than animals

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 The need for the field of
bioethics

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 EVOLUTION OF BIOETHICS

 Every unethical trial was a lesson to learn

 Every lesson concluded a way to control unethical

practices
 Every attempt to improve the control over unethical

practices gave birth to what we call today as

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 Biomedical Research in Humans

 The Nuremberg Code, 1947

 The Declaration of Helsinki, 1964 (2000)

 The Belmont Report, 1979

 ICH GCP, 1997

 ICMR Guidelines, 2000

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 The Nuremberg Code

After the war, many of these doctors were tried at

the Nuremberg for their crimes.
The International community was shocked by the
revelations of their research
As a result of the trial, the Nuremberg Code was
created in 1948

One of the earliest international document

Addressed informed consent for the 1st time

12/10/06 Adopted by United Nations in 1948

 The Nuremberg Code

 A set of 10 principles on research involving humans

 Developed after the horrors of Nazi experiments on

humans became public

 Published in 1947

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 The Nuremberg Code

 The voluntary consent of the human subject is

absolutely essential

 Person must have legal capacity to consent

 Should have “sufficient knowledge and comprehension” to

make an “understanding and enlightened decision”

 Must be able to exercise “free power of choice”

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 Nuremberg code

After the war and creation of the Nuremberg code,

many American medical researches still felt the same

and continued with unethical medical research

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 Amendment to the Food, Drug and
Cosmetic Act

 Passed by Congress

 Result of Thalidomide scandal

 Doctors to tell patients if they were taking a trial drug

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 The Declaration of Helsinki

 Developed from the Nuremberg Code

 Made by physicians

 Published by the World Medical Association

 A statement of ethical principles on research

involving humans
 First adopted at Helsinki in 1964

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 The Declaration of Helsinki

 Subjects must be

 Volunteers
 Informed participants

 Consent be obtained, preferably in writing

 If subject in a dependent relationship with the

physician, consent be obtained by an independent
physician
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 The Declaration of Helsinki

 Consent from legally acceptable representative

required if subject:
 Minor
 Incapable of giving consent
 Physical or mental disability

 If subject is a minor, assent be taken, where

possible
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 The Declaration of Helsinki

 When consent not possible prior to participation in

research
 Approved by the “review committee”
 Consent must be obtained as soon as possible
from the subject or a legally acceptable
representative

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 The Belmont Report

 Developed by a commission set up in the US in the

aftermath of the Tuskeegee Study becoming public

 Published in 1979

 Ethical principles and guidelines for protecting

humans in clinical research

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 The Belmont Report

 Identifies three elements of the process

of ICF
 Information
 Comprehension
 Voluntariness

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 The Belmont Report

 Information

 All information be provided

 Conditions under which information provided also

important (rapid/ disorganized manner?)

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 The Belmont Report

 Comprehension
 Adapt presentation of information to subject’s capacities
 Investigators must ascertain comprehension
 Special provisions – immaturity, mental disability

 Voluntariness
 There must be no coercion or undue influence

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THE PROCESS IS DYNAMIC…..

YOU HAVE GUIDELINES….

STILL MALPRACTICE…..

ADD CORRECTIONS/ AMMENDMENTS

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 WHAT WE FOLLOW TODAY..

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 What is ICH ?

What is GCP ?

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 Hundreds of nations…
 Too many guidelines…
 Which is the best ?
 If I want to submit a study for more than one country
should I do it too many times as per different
guidelines ?
 Why not to have a common set of guidelines which
is acceptable to most of the countries ?
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 1990

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Group of representatives from industry and regulatory agencies
 ROUND TABLE CONFERENCE
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 GOALS OF

1) Set international standards for the quality, safety, and

efficacy of new drugs

2) Reduce duplicate testing around the globe

3) Increase cost efficiency through better use of

resources
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 GOALS OF

4) minimize delays in drug development.

5) The overarching goal was to increase "mutual

acceptance of clinical data by regulatory authorities in

these jurisdictions."
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 ICH-GCP

Initially published in three separate parts

 Guideline for the Investigator's Brochure

 Guideline for Essential Documents for the Conduct

of a Clinical Study and

 Guideline on Good Clinical Practice

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To increase usability, the final versions of these three
parts were brought together as the consolidated
guideline.

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 ICMR Guidelines

 Participation must be voluntary

 Participants must be “fully apprised of the research”
 The investigator must obtain informed consent
 Responsibilities and information that must be provided
 Assent be obtained, where possible, for minors
 Requirement for consent can be waived by an ethics
committee if risk is minimal (e.g. collecting data from
subjects’ records)
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 ICMR Guidelines

 Ethical guidelines for research involving humans

 “Ethical Guidelines for Biomedical Research on Human

Subjects”

 Published by the Indian Council of Medical Research

in 2000
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