GOOD CLINICAL PRACTICE

Introduction
• Good clinical practice (GCP) is a set of internationally-recognised ethical and
scientific quality requirements that must be followed when designing,
conducting, recording and reporting clinical trials involving human subjects.

• GCP provides assurance that the data and reported results are credible and
accurate, and that the rights, integrity and confidentiality of trial subjects
are respected and protected. 
 International Conferences on
Harmonisation (ICH)
• GCP  is an international quality standard that
is provided by International Committee on
Harmonisation (ICH).

• ICH is an international body that defines

standards which governments can adopt as
regulations for clinical trials involving human
subjects.
 Historical background of ICH-GCP
• Health research ethics as a discipline has developed as a
result of scandals and tragedies.

• Codes, regulations and guidelines were developed from

public debates or in response or anticipation of human
abuses.
Historical background of health research ethics
 1. World war II: Nazi Germany
• Dr. Josef Mengele was a Nazi camp doctor
• Nicknamed “the angel of death”
• Performed murderous and torturous human experiments in
the concentration camps especially on twins:

– Infected one twin with a “germ”. When s/he died, the other twin
was killed and their organs compared at autopsy.
– Sewed twins together to create a siamese twin.

– Injected chemicals into the eyes of children in an attempt to

change their eye color.  

– Studied subjects with genetic traits so as to better “purify the

Aryan super race”.

– Performed cross transfusions to “make boys into girls and girls

into boys”.
 2. Post war response(1)
*Nuremberg Doctors’ Trial – 1946 –47
• 23 defendants; all except 3 were
physicians
• 15 found guilty
– 7 were hanged (4 physicians)
– 5 sentenced to life in prison
– 4 sentenced to 10-20 years in prison
– 7 were acquitted and freed.
*Separate Trial:
31 “underlings” were also found guilty; 22 of
them were hanged.
 3. Post war response(2)
Nuremberg Code of Medical Ethics (1948)
• Nuremberg Code is the most important document in the
history of the ethics of medical research.

• The Code was formulated in August 1947, in Nuremberg,

Germany by the American judges involved in the Nuremberg
Doctor’s trial.

• It served as a blueprint for today’s principles that ensure the

rights of subjects in medical research.

• Adopted by the World Medical Association

• True informed consent; freely given; prior to experimental

procedures

• Truly necessary, well thought out experiments in which the expected

benefits justify the risks and there is no unnecessary psychological
or mental suffering or injury.
 4. Declaration of Helsinki (1964)
• In 1964, the World Medical Association (WMA)
assembly adopted the Nuremberg code.

• Since then the general assemblies of the WMA

have made recommendations to guide physicians
in clinical research involving human subjects.

• Although not legally binding, the Declaration

forms the foundation of all other significant
international documents on the ethical conduct
of biomedical research.
 Declaration of Helsinki
• The Declaration of Helsinki was responsive to the
revelations of the Nuremberg trials conducted after
World War II,
– It sought to ensure that human subjects involved in clinical
research would, in future, have their rights, safety and well-
being placed above all other considerations in clinical
research.

• The document has been revised 5 times since it was first

published in 1964 (latest Edinburg, 2000).
 Components of Declaration of Helsinki
• The Declaration of Helsinki covers all the important
ethical considerations, such as:
– the involvement of a qualified physician in any clinical trial,

– putting the well-being of the trial subject before science

and society,

– the use of scientific principles in the design of the trial

– the need for informed consent

– a review by an ethics committee.

 5. Tuskegee syphilis study (1932-1972)
• This was an infamous clinical study conducted between
1932 and 1972 by the U.S. Public Health Service to study
the natural progression of untreated syphilis in rural
African-American men in Alabama.

• The study was known as “Tuskegee Study of Untreated

Syphilis in the Negro Male.”

• Eunice Rivers (a nurse) and Dr. Dibble  (both blacks)

tracked participants/patients.

• Press later labeled it “racial medicine”.

 Tuskegee syphilis study (1932-1972)
•  Investigators enrolled in the study a total of 600
impoverished sharecroppers from Macon
County, Alabama.

– Of these men, 399 had previously contracted syphilis before

the study began, and 201 did not have the disease.

• The men were given free medical care, meals, and free
burial insurance for participating in the study.

• None of the men infected were ever told they had the
disease, nor were any treated for it with penicillin after
this antibiotic became proven for treatment.
 Tuskegee syphilis study (1932-1972)
• By 1947, penicillin had become the standard treatment for
syphilis.
– Choices available to the doctors involved in the study might
have included treating all syphilitic subjects and closing the
study, or splitting off a control group for testing with
penicillin.

– Instead, the Tuskegee scientists continued the study without treating any
participants; they withheld penicillin and information about it from the
patients.

• In addition, scientists prevented participants from accessing

syphilis treatment programs available to other residents in the
area.
 Tuskegee syphilis study (1932-1972)
• The study continued, under numerous US
Public Health Service supervisors, until 1972,
when a leak to the press resulted in its
termination on November 16 of that year.

• The victims of the study included numerous

men who died of syphilis, 40 wives who
contracted the disease, and 19 children born
with congenital syphilis.
 6. Belmont report
• The Tuskegee Syphilis Study led to the
1979 Belmont Report and the establishment of
the Office for Human Research
Protections (OHRP).

•  It also led to federal laws and regulations

requiring Institutional Review Boards for the
protection of human subjects in studies involving
human subjects.
 Belmont report: 1979
• The Belmont report explains the three fundamental ethical principles for
using any human subjects for research as:

– Respect for persons: protecting the autonomy of all people and treating
them with courtesy and respect and allowing for informed consent.
Researchers must be truthful and conduct no deception;

– Beneficence: The philosophy of "Do no harm" while maximizing benefits

for the research project and minimizing risks to the research subjects;

– Justice: ensuring reasonable, non-exploitative, and well-considered

procedures are administered fairly — the fair distribution of costs and
benefits to potential research participants — and equally.
 ICH-GCP
• The ICH-GCP is a harmonised standard that:
• protects the rights, safety and welfare of human subjects,
• minimises human exposure to investigational products,
• improves quality of data,
• speeds up marketing of new drugs
• decreases the cost to sponsors and to the public.
• Compliance with this standard provides public
assurance that the rights, safety and well-being of
trial subjects are protected and consistent with the
principles of the Declaration of Helsinki, and that the
clinical trial data is credible 
 ICH GCP Principles
• ICH GCP is based on 13 principles.

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