Transcript Good Clinical Practice

Jennifer McCormick MA, CRC
Karla Lichter RN CCRC
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Good clinical practice is an international
ethical and scientific quality standard for
designing, conducting, recording and
reporting clinical trials.
FDA issued guidance in 1994 & 1995.
In 1996 the guidelines were endorsed by the
ICH (International Conference on
Harmonization)
GCPs are divided up into the following eight
sections:
 Glossary of terms
 Principles of ICH GCP
 IRB responsibility/guidelines
 Investigator responsibility/guidelines
 Sponsor responsibility/guidelines
 Clinical protocol & amendments
 Investigator Brochure
 Essential Documents
Objectives:
Review the 13 Principles of GCP
Identify relevant GCP’s for investigators and
sites
Demonstrate competency of GCP (section 4)
Principles of GCP
 Clinical trials should be conducted in
accordance with the ethical principles that
have their origin in the Declaration of Helsinki
and consistent with GCP and applicable
regulatory requirements.
 Before a trial is initiated, foreseeable risks
should be weighed against the anticipated
benefit.
Principles of GCP
 Rights, safety & well being of trial subjects
must prevail over interests of science &
society
 Non clinical & Clinical information on an
investigational product should be adequate to
support the clinical trial
 Clinical trials must be scientifically sound &
described in a detailed protocol
Principals of GCP
 A trial should be conducted in compliance
with the protocol & received IRB approval
 Medical decisions & care of subjects should
be responsibility of qualified physician
 Each individual involved in conducting a trial
should be qualified by education, training &
experience to perform respective tasks
Principals of GCP
 Freely given informed consent should be
obtained prior to trial participation
 All trial information should be recorded,
handled & stored in a way that allows
accurate reporting, interpretation &
verification
 Confidentiality of records (de-identify)
Principals of GCP
 Investigational Product should be
manufactured, handled & stored in
accordance with Good Manufacturing Practice
& the protocol
 Systems with procedures that assure the
quality of every aspect of the trial should be
implemented
Investigator Qualifications
 Investigator(s) should be qualified by
education, training & experience, should
meet all the qualifications specified by
applicable regulatory requirements & should
provide evidence of qualifications through an
up dated CV
 Investigator should be familiar with the
investigational product as described in the
protocol/Investigator Brochure
Investigator Qualifications
 Investigator should be aware of and comply
with GCP & regulatory requirements
 Investigator/site should permit
auditing/monitoring by sponsor & applicable
regulatory authorities
 Investigator should maintain a list of
appropriately qualified persons whom tasks
have been delegated.
Adequate Resources
 Investigator should demonstrate potential for
recruiting the required number of subjects within
the recruitment period
 Investigator should have sufficient time to
conduct & complete the trial
 Investigator should have adequate number of
qualified staff & adequate facilities
 Investigator should ensure all persons assisting
with the trail are informed of the protocol,
investigational product & their trial related duties
Medical Care of Trial Subjects
 A qualified physician who is an investigator or
sub-investigator should be responsible for all
trial related medical decisions
 Ensuring & following a subject’s participation
in a trial the investigator should ensure
adequate medical care is provided for AE’s,
significant lab values related tot the trial. The
investigator should inform a subject when
medical care is needed for intercurrent illness
Medical Care of Trial Subjects
 It is recommended the investigator inform the
subject’s PCP about the subject’s
participation & if the subject agrees to the
primary physician being informed
 Although a subject is not required to give a
reason for withdrawing from a trial, the
investigator should make a reasonable effort
to obtain the reason for withdrawal
Communication with IRB
 Before initiating a trial, the investigator
should have written & dated approval from
the IRB for the protocol, ICF, ICF updates,
subject recruitment material or other written
information provided to the subject
 Investigator should provide the IRB with the IB
and any IB updates
 During the trial the investigator should
provide the IRB all documents subject to its
review.
Compliance with the Protocol
 Investigator should conduct the trial in
compliance with the protocol, sponsor,
regulatory authorities and IRB. The investigator
& sponsor should sign the protocol or other
contract to confirm agreement
 Investigator should not deviate from the protocol
without agreement by the sponsor & IRB except
when necessary to eliminate immediate hazards
to a subject or if the changes are
logistic/administrative ( i.e. change in phone
number or monitor)
Compliance with the Protocol
 Investigator or a person designated by the
investigator should documents & explain any
deviation
 Investigator may deviate from the protocol to
eliminate an immediate hazard to subject
without prior IRB approvable. As soon as
possible the deviation & reason for the
deviation should be reported to the IRB,
sponsor & if applicable regulatory authorities
Investigational Product (IP)
 Responsibility for the IP accountability at the
site rests with the investigator/institution
 Where allowed this duty can be assigned to a
designated pharmacist or appropriate
individual who is under the supervision of the
investigator/institution
 Records should be maintained on product
delivery to the site, inventory at the site, use
by the subject and return of unused IP from
the subject and return to the sponsor
Investigational Product (IP)
 Records should include dates, quantities,
batch/serial numbers, expiration date &
unique code numbers assigned to the IP &
subjects. Documentation should specify
subjects were provided the doses specified by
the protocol & reconcile all IP received from
the sponsor
 IP should be stored as specified by the
sponsor & in accordance with applicable
regulatory requirements
Investigational Product (IP)
 Investigator should ensure the IP is used on
accordance with the approved protocol
 Investigator or designated person should
explain the correct use of the IP to each
subject & check at intervals each subject is
following the instructions
Randomization and Un-blinding
 Investigator should follow the randomization
& un-blinding procedures in accordance to
the protocol.
 If un-blinding occurs the investigator should
promptly document the reason for unblinding & notify the sponsor
Informed Consent
 In documenting and obtaining consent the
Investigator must comply with applicable
regulatory requirements, GCP, Declaration of
Helsinki & IRB
 ICF should be revised when important new
information is available and approved by the
IRB prior to use. The subject or subject’s
legal representative should be informed in a
timely manner & the communication of this
information should be documented
Informed Consent
 Investigator/staff should not unduly influence
or coerce the subject to participate or
continue to participate
 Language should not appear to release the
investigator, institution, sponsor or agents
from liability for negligence
 Investigator or designated person should fully
inform the subject or legal representative all
aspects of the trial
Informed consent
 Language written or oral should be
nontechnical as practical & be understandable
 Ample time for review, decision to participate
& inquire about details of the trial should be
provided to the subject or legal
representative
 Prior to subject participation the ICF should
be signed & dated by the subject/legal
representative and person obtaining consent
Informed Consent
 If a subject/legal representative is unable to
read an impartial witness should be present
during the entire consent discussion. After
the discussion and the subject/legal
representative has orally consented & if
capable signed & dated the ICF the witness
should personally sign & date the ICF. The
witness signature attests the information was
accurately explained & understood by the
subject/legal representative
Informed Consent
 The informed consent should contain all
required elements
 Prior to participation the subject/legal
representative should receive a copy of the
current signed/dated ICF and any updated ICF
 Assent should be obtained from minors or
subjects with impaired cognitive function. If
capable the subject should sign/date the ICF
Informed Consent
 Nontherapeutic trials may be conducted in subject
with consent of a legal representative provided the
following is fulfilled:
◦ Objectives of the trial cannot be met by means of a trial in
subjects who can give informed consent
◦ Foreseeable risks are low
◦ Negative impact on the subject’s well-being is minimized &
low
◦ Trial is not prohibited by law
◦ IRB is sought on inclusion of such subject & written
approval covers this aspect
Such trials should be conducted in subjects having the
disease or condition for which the IP is intended. Subjects
should be closely monitored & withdrawn if unduly distressed
Informed consent
 A nontherapeutic trial (no clinical benefit to the
subject) should be conducted in subjects who
personally give consent & sign/date the ICF
 In an emergency situation when prior consent is
not possible the consent of the legal
representative if present should be obtained. If
the legal representative is not available
enrollment of the subject should require
measures described in the protocol with
documented approval by the IRB. The subject’s
legal representative should be notified as soon as
possible
Records and Reports
 Investigator should ensure the accuracy,
completeness, legibility & timeliness of data
reported
 Data on the CRF which are derived from
source documents should be consistent with
the source or discrepancies explained
 Any change or correction should be initialed,
dated & explained (if necessary) & should not
obscure the original entry.
Records and Reports
 Investigator should maintain the trial
documents as specified in Essential
Documents for the Conduct of a Clinical Trial
& applicable regulations
 Essential documents should be retained 2 yrs
after the last approval of a marketing
application in an ICH region or longer if
required by the sponsor or regulatory
requirements
Records and Reporting
 Financial aspects of the trial should be
documented in an agreement between the
sponsor and investigator
 Upon requests of the monitor, auditor, IRB or
Regulatory authority the investigator should
make available for direct access to all
requested trial related records.
 Investigator should submit written summaries
of the trial status to the IRB annually or more
often if requested
Records and Reports
 Investigator should promptly provide written
reports to the sponsor, IRB, if applicable
regulatory authority/institution any changes that
significantly affects the conduct of the trial
and/or increases risk to the subject
 All SAE’s should be reported within the time
periods defined by the sponsor and other
applicable regulatory authorities
 AE’s and/or lab abnormalities identified as
critical in the protocol to safety evaluations
should be reported to the sponsor within time
periods defined
Records and Reporting
 For reported deaths, the investigator should
supply the sponsor, IRB with any additional
requested information(autopsy reports)
 If a trial is prematurely suspended for any reason
the investigator should ensure appropriate
therapy & FU for the subjects & inform the
regulatory authorities
 If investigator terminates a trial without prior
agreement of the sponsor, the investigator
should inform and provide detailed written
explanation to the sponsor, IRB and regulatory
authorities
Records and Reporting
 If the sponsor terminates a trial the
investigator should promptly inform (if
required) the institution and IRB. The
investigator should provide a written
explanation of the termination
 If the IRB terminates the trial the investigator
should inform the institution (if required) and
the sponsor & provide the sponsor an
explanation
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Upon completion of the trial, the investigator
should (if applicable) notify the institution,
notify the sponsor & IRB and provide a
summary of the trial’s outcome.
Questions