Regulatory Authority
Governing Clinical Trials
Anthony J. Minisi, MD
Director, Cardiology Fellowship
Program
Regulatory Authority
Governing Clinical Trials
Current trials governed by:
Good Clinical Practices
 Good Laboratory Practices
 Good Manufacturing Practices
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Good Clinical Practices
“A standard for the design, conduct,
performance, monitoring, auditing,
recording, analysis, and reporting of
clinical trials that provides assurance
that the data and reported results are
credible and accurate, and that the
rights, integrity, and confidentiality of
trial subjects are protected.”
ICH-GCP [1.24]
Good Laboratory Practices
An array of standards and
regulations to guide the planning,
performance, monitoring, recording,
reporting, and archiving of laboratory
studies
 Designed to assure that data are
reliable and can be used
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Good Manufacturing Practices
A collection of standards regulating
the manufacturing, processing,
packaging, and storage of drugs or
devices
 Designed to assure that these
processes are consistent and
reproducible

US Food, Drug, and Cosmetic
Act--1938

Developed in response to elixir of
sulfanilamide tragedy
 First
statutory regulation of cosmetics
and therapeutic devices
 Required drug manufacturers to provide
scientific proof that new products were
safe
 Provided specific authority for factory
inspections
Nuremburg Code--1947
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Developed in response to unethical
medical experimentation on human
subjects by German scientists during WW
II
First set of standards for the review and
conduct of human research requiring:
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Voluntary consent of subjects
Justifiable reason for experimentation
Protection of participants
US Kefauver-Harris Drug
Amendment--1962

Developed in response to
thalidomide tragedy requiring:
 Manufacturers
prove efficacy as well as
safety before marketing a new product
 Informed consent be obtained from all
participants

Outlined a process for clinical testing
that still applies today
Declaration of Helsinki--1964

Defined ethical standards for the
conduct of human research
 Research
in humans should be based
on results of laboratory and animal
experimentation
 Research protocols should be reviewed
by an independent committee prior to
initiation
 Risks should not exceed benefits
Declaration of Helsinki--1964

Defined ethical standards for the
conduct of human research
 Informed
consent should be obtained in
all research subjects
 Only medically and/or scientifically
qualified individuals should conduct
human research
US National Research Act--1974
National Commission for the Protection of
Human Subjects of Biomedical and
Behavioral Research
 Defined basic ethical principles for the
conduct of human research
 Formulated guidelines to ensure that
human research is conducted in
accordance with these ethical principles
 Required establishment of an IRB at all
institutions conducting human research
The Belmont Report--1979

Outlines basic ethical principles
developed by the National
Commission
 Respect
for persons
 Beneficence
 Justice

Addresses distinction between
medical practice and research
The Belmont Report--1979

Respect for Persons
 Individuals
should be treated as
“autonomous agents” whose freedom to
act on opinions, choices, and
considered judgments should be given
priority
 Individuals with diminished autonomy
are entitled to additional protections
The Belmont Report--1979

Beneficence
 Obligation
to conduct research in a
manner that maximizes potential
benefits and minimizes possible risks

Justice
 Selection
of subjects should be
equitable and the burdens of research
should be borne by those most likely to
benefit from the research results
International Conference on
Harmonisation (ICH)--1990
Convened to devise a unified
standard governing clinical research
in the US, European Union, and
Japan
 Designed to facilitate the mutual
acceptance of data generated from
clinical trials by regulatory
authorities in each jurisdiction

ICH Principles
Studies should be conducted in
accordance with the Declaration of
Helsinki
 Risks and benefits should be
carefully scrutinized
 Rights, safety, and well-being of
study subjects of paramount
importance

ICH Principles
Information from preliminary studies
of the investigational product should
support the study
 Studies should be scientifically
rigorous and outlined in a formal
protocol
 All studies should be reviewed and
approved by a convened IRB

ICH Principles
A qualified physician should be
responsible for all medical care and
decisions
 All study staff should have appropriate
education, training, and experience
 All study subjects should freely give
informed consent prior to participation
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ICH Principles
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Study data should be recorded and stored
in a manner that allows its accurate
reporting, interpretation, and verification
Confidentiality of records should be
protected
Investigational products should be
manufactured, handled, and stored in
accordance with GMP
QA procedures should be in place
Investigator Responsibilities
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Hire study staff with
appropriate
qualifications
Delegate study tasks
appropriately
Use investigational
product per protocol
Comply with GCP and
other regulatory
requirements
Participate in data
monitoring, auditing,
and site inspection
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Provide sufficient
resources
Provide medical care
Conduct study
procedures per protocol
Obtain IRB approval
Obtain informed
consent
Maintain records and
submit reports
Safety reporting
Investigator Responsibilities
FDA Form 1572—Section 9 “Commitments”
 I agree to conduct the study in accordance with the
protocol and will only make changes to the protocol
after notifying the sponsor, except when necessary to
protect the safety, rights, or welfare of subjects
 I agree to personally conduct or supervise the
described investigation
 I agree to inform any study subjects that the drugs are
being used for investigational purposes and I will
ensure that the requirements related to obtaining
informed consent and IRB review and approval are
met
FDA Form 1572--Commitments
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I agree to report to the sponsor adverse experiences
that occur in the course of the study
I have read and understand the information in the
Investigator’s Brochure, including the potential risks
and side effects of the drug
I agree to ensure that all study staff are informed in
meeting the above commitments
I agree to maintain adequate and accurate records
and to make those records available for inspection
FDA Form 1572--Commitments
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I agree that an IRB will be responsible for the initial
and continuing review and approval of the clinical
investigation
I agree to promptly report to the IRB all changes in the
research activity and all unanticipated problems
involving risks to human subjects or others
I will not make any changes in the research without
IRB approval, except where necessary to eliminate
hazards to human subjects
WARNING: A willfully false statement is a criminal
offense USC Title 18, Sec 1001
Sponsor Responsibilities
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QA and QC
Medical expertise
Trial management
Selection of
investigators
Financial support
Compliance with
regulatory issues
Protocol generation and
amendment
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Confirmation of IRB
review and approval
Supply investigational
product with appropriate
information
Case report forms
Safety monitoring
Data monitoring
Site audit/inspection
Report submission