Regulatory Authority Governing Clinical Trials - VCU Cardiology by pptfiles

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									 Regulatory Authority
Governing Clinical Trials

     Anthony J. Minisi, MD
Director, Cardiology Fellowship
            Program
       Regulatory Authority
      Governing Clinical Trials

Current trials governed by:
l   Good Clinical Practices
l   Good Laboratory Practices
l   Good Manufacturing Practices
   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

l   An array of standards and
    regulations to guide the planning,
    performance, monitoring, recording,
    reporting, and archiving of laboratory
    studies
l   Designed to assure that data are
    reliable and can be used
Good Manufacturing Practices

l   A collection of standards regulating
    the manufacturing, processing,
    packaging, and storage of drugs or
    devices
l   Designed to assure that these
    processes are consistent and
    reproducible
    US Food, Drug, and Cosmetic
             Act--1938

l   Developed in response to elixir of
    sulfanilamide tragedy
    n   First statutory regulation of cosmetics
        and therapeutic devices
    n   Required drug manufacturers to provide
        scientific proof that new products were
        safe
    n   Provided specific authority for factory
        inspections
        Nuremburg Code--1947

l   Developed in response to unethical
    medical experimentation on human
    subjects by German scientists during WW
    II
l   First set of standards for the review and
    conduct of human research requiring:
    n   Voluntary consent of subjects
    n   Justifiable reason for experimentation
    n   Protection of participants
        US Kefauver-Harris Drug
           Amendment--1962

l   Developed in response to
    thalidomide tragedy requiring:
    n   Manufacturers prove efficacy as well as
        safety before marketing a new product
    n   Informed consent be obtained from all
        participants
l   Outlined a process for clinical testing
    that still applies today
Declaration of Helsinki--1964

l   Defined ethical standards for the
    conduct of human research
    n   Research in humans should be based on
        results of laboratory and animal
        experimentation
    n   Research protocols should be reviewed
        by an independent committee prior to
        initiation
    n   Risks should not exceed benefits
Declaration of Helsinki--1964

l   Defined ethical standards for the
    conduct of human research
    n   Informed consent should be obtained in
        all research subjects
    n   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
   n Defined basic ethical principles for the
     conduct of human research
   n Formulated guidelines to ensure that
     human research is conducted in
     accordance with these ethical principles
   n Required establishment of an IRB at all
     institutions conducting human research
    The Belmont Report--1979

l   Outlines basic ethical principles
    developed by the National
    Commission
    n   Respect for persons
    n   Beneficence
    n   Justice
l   Addresses distinction between
    medical practice and research
    The Belmont Report--1979

l   Respect for Persons
    n   Individuals should be treated as
        “autonomous agents” whose freedom to
        act on opinions, choices, and
        considered judgments should be given
        priority
    n   Individuals with diminished autonomy
        are entitled to additional protections
    The Belmont Report--1979

l   Beneficence
    n   Obligation to conduct research in a
        manner that maximizes potential
        benefits and minimizes possible risks
l   Justice
    n   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

l   Convened to devise a unified
    standard governing clinical research
    in the US, European Union, and
    Japan
l   Designed to facilitate the mutual
    acceptance of data generated from
    clinical trials by regulatory
    authorities in each jurisdiction
            ICH Principles

l   Studies should be conducted in
    accordance with the Declaration of
    Helsinki
l   Risks and benefits should be
    carefully scrutinized
l   Rights, safety, and well-being of
    study subjects of paramount
    importance
            ICH Principles

l   Information from preliminary studies
    of the investigational product should
    support the study
l   Studies should be scientifically
    rigorous and outlined in a formal
    protocol
l   All studies should be reviewed and
    approved by a convened IRB
            ICH Principles

l   A qualified physician should be
    responsible for all medical care and
    decisions
l   All study staff should have appropriate
    education, training, and experience
l   All study subjects should freely give
    informed consent prior to participation
             ICH Principles

l   Study data should be recorded and stored
    in a manner that allows its accurate
    reporting, interpretation, and verification
l   Confidentiality of records should be
    protected
l   Investigational products should be
    manufactured, handled, and stored in
    accordance with GMP
l   QA procedures should be in place
Investigator Responsibilities
l   Hire study staff with   l   Provide sufficient
    appropriate                 resources
    qualifications          l   Provide medical care
l   Delegate study tasks    l   Conduct study
    appropriately               procedures per protocol
l   Use investigational     l   Obtain IRB approval
    product per protocol    l   Obtain informed consent
l   Comply with GCP and     l   Maintain records and
    other regulatory            submit reports
    requirements
l   Participate in data     l   Safety reporting
    monitoring, auditing,
    and site inspection
Investigator Responsibilities
FDA Form 1572—Section 9 “Commitments”
l 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
l I agree to personally conduct or supervise the
  described investigation
l 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

l   I agree to report to the sponsor adverse experiences
    that occur in the course of the study
l   I have read and understand the information in the
    Investigator’s Brochure, including the potential risks
    and side effects of the drug
l   I agree to ensure that all study staff are informed in
    meeting the above commitments
l   I agree to maintain adequate and accurate records
    and to make those records available for inspection
FDA Form 1572--Commitments
l   I agree that an IRB will be responsible for the initial
    and continuing review and approval of the clinical
    investigation
l   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
l   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
l   QA and QC                 l   Confirmation of IRB
l   Medical expertise             review and approval
l   Trial management          l   Supply investigational
l   Selection of                  product with appropriate
    investigators                 information
l   Financial support         l   Case report forms
l   Compliance with           l   Safety monitoring
    regulatory issues         l   Data monitoring
l   Protocol generation and   l   Site audit/inspection
    amendment                 l   Report submission

								
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