Transcript CLINICAL STUDY AND BASIC CONCEPT GOOD CLINICAL PRACTICE

CLINICAL STUDY AND BASIC
CONCEPT
GOOD CLINICAL PRACTICE
Presented by:
Aarohi Shah
M.Pharm
Dept of Pharmaceutics and Pharmaceutical Technology
CLINICAL STUDY AND
BASIC CONCEPT
What is a Clinical Trial?
A clinical trial (clinical research) is a
research study in human volunteers
(preclinical trail – in animals) to
answer specific health questions.
Carefully conducted clinical trials are
the fastest and safest way to find
treatments that work in people and
ways to improve health.
CLINICAL STUDY AND
BASIC CONCEPT
Types of clinical trials
Treatment trials
Prevention trials
Diagnostic trials
Screening trials
Quality of Life trials
CLINICAL STUDY AND
BASIC CONCEPT
Clinical trials, FDA approval
Before a company initiates clinical trials
(i.e. testing in humans), it must conduct
extensive experiments in animal and
human cells and in live animals (Preclinical
Trial)
If this stage of testing is successful, the
company files an Investigational New Drug
(IND) application with the Food and Drug
Administration (FDA) to request permission
to conduct clinical trials.
CLINICAL STUDY AND
BASIC CONCEPT
Clinical Trials
Preclinical
testing
Years
F
I
L
E
3.5
Phase I
Phase II
Phase III
1
2
3
I
N
D
Test
population
Lab and
Animal
Studies
at
5000
compounds
evaluated
FDA
2.5
N
D
A
20 to 80
healthy
volunteers
100 to 300
patient
volunteers
F
D
A
Success
rate
F
I
L
E
5 enter trials
1000 to
3000
patient
volunteers
at
Review
process/
Approval
F
D
A
1
approved
Phase IV
12
Tot
al
Additional
post
marketing
testing
CLINICAL STUDY AND
BASIC CONCEPT
Preclinical trials
Trial carried out on to the animal species
Objective: To evaluate safety, toxicity and tolerance
data (by applying the factor for conversion of
animal data to human data)
Study
Drug metabolism pathway
PK of the drug
PK-PD relation
Protein binding
Tissue distribution
Development of methodology for quantification of
drug and metabolite in biological fluid
Long term toxicity
Placental transfer kinetic
CLINICAL STUDY AND
BASIC CONCEPT
Phase 1
Trial carried out on healthy volunteers except AIDS
or Cancer.
Study
Dose-concentration (in plasma)-response-toxicity
study
IV, single dose study (for checking bioavailability)
Radioactive tracer study (for evaluation of first
pass metabolism)
Evaluation of suitability of preclinical animal model
(to predict pharmacological effect in human)
Effect of food
CLINICAL STUDY AND
BASIC CONCEPT
Phase 2
First time trial on patient and conducted
in OPEN manner
Study
Evaluation of difference in PK and PD
between the healthy volunteer and
patient
To search new therapeutic effect of
the drug
CLINICAL STUDY AND
BASIC CONCEPT
Phase 3
Study
Search less common side effect of drug
(which is conc. independent)
Comparison with the marketed drug
Drug-drug interaction
Study in special population like age, sex
race etc.
Develop the dosage form
CLINICAL STUDY AND
BASIC CONCEPT
Phase 4
Post marketing surveillance
Not well planned study but random
study
Some rare side effect or toxicity may
come out
GOOD CLINICAL PRACTICE
Good Clinical Practice (GCP) is an international
ethical and scientific quality standard for
designing, recording and reporting trials that
involve the participation of human subjects.
Compliance with this standard provides public
assurance that the rights, safety and well being of
trial subjects are protected, consistent with the
principles that have their origin in the Declaration
of Helsinki, and that the clinical trial data are
credible.
Regulations tell you what you are required to do by
law. Guidelines tell you the best way to do it
GOOD CLINICAL PRACTICE
FDA GCP Regulations
Regulations contained in 21 CFR Part 50, 56, and 312
Part 50 (applies to consenting of subjects),
Part 56 (applies to IRB responsibilities) and
Part 312 (applies to IND submissions, sponsor responsibility,
and investigator responsibility)
GCP Guidelines- International Conference on
Harmonization
The objective of ICH GCP Guidelines is to provide a unified
standard for European Union, Japan and United States to
facilitate the mutual acceptance of clinical data by the
regulatory authorities in the jurisdiction.
Published by the FDA in Federal Register in May, 1997
Adopted by all parties as GCP standard (considered law in
European Union; considered “final guidance” in the US)
Based on the Declaration of Helsinki
GOOD CLINICAL PRACTICE
Some important terms (Glossary)
Investigator
Sponsor
Subject /Trial Subject
Investigator’s Brochure
Non Clinical Study
Protocol
Blinding (Masking)
Institutional Review Board (IRB)
Adverse Event (AE)
Serious Adverse Event (SAE)
GOOD CLINICAL PRACTICE
Elements of GCP
IRB
Investigator
Sponsor
Clinical trial protocol and protocol
amendments
Investigator Brochure
Essential documents
GOOD CLINICAL PRACTICE
Institutional review board (IRB) or Independent
Ethics Committee (IEC)
It consists of reasonable number of members, who
collectively have qualifications and experience to
review and evaluate the science and medical
aspects as well as ethics of proposed trials.
It should perform the functions in accordance with
written procedures, maintain written records of its
activities and minutes of its meetings and should
comply with GCP.
Acts as a safe guard to the rights of the trial
subject
Should consider the qualification of the
investigator for the proposed trial
Should conduct continuing review of each ongoing
trial at intervals appropriate to the degree of risk.
GOOD CLINICAL PRACTICE
Investigator
Qualified to perform study should have
Appropriate education, training and experience to assume
responsibility and should provide evidence of such
qualifications.
Sufficient time to devote to study timelines.
Personally conduct or supervise study.
Adequate and qualified staff and facilities.
Awareness of and compliance with GCP.
Familiar with the investigational product and inventory.
Adherence to protocol requirements.
Inform subject’s primary physician
Ensure adequate medical care for SAEs.
Maintained records should be accurate, complete, legible
and timely.
GOOD CLINICAL PRACTICE
Investigator-Communication with IRB
Obtaining written and dated IRB approved consent
form
Submission of Investigational Brochure
Ongoing communication
Report of SAEs
IND Safety Reports
Significant protocol deviations
The investigator should submit written summaries
of the status of the trial to the IRB annually or
more frequently, if requested by the IRB
GOOD CLINICAL PRACTICE
Investigator- Communication with the
Sponsor/CRO
Reporting of any AEs or SAEs
Notification of changes in staff and address
Retention of all pertinent study information and
records until notified in writing that records are no
longer required
Coordination of publication plans
If trial is blinded, the investigator should promptly
document and explain to the sponsor any:
Premature unblinding
Accidental unbliniding
Unblinding due to serious adverse events
GOOD CLINICAL PRACTICE
Investigator-Communication with Study Subjects
Obtaining valid written informed consent
The information language should be non-technical and
understandable to the subject/LAR/impartial
Provide subject a copy of a fully executed consent
Provide subject with any new information
Answer questions at any time
The investigator must inform the subject when medical care
is needed for inter-current illness(es) of which investigator
becomes aware.
It is recommended that the investigator inform subject’s
primary physician about subject’s participation in study.
If subject wishes to withdraw from the study, the investigator
should make reasonable effort to ascertain the reasons –
while fully respecting the subject’s rights.
GOOD CLINICAL PRACTICE
Investigator- Investigator – Compliance with Protocol
The investigator should conduct the trial in compliance with:
The protocol agreed to by the sponsor
If required, protocol agreed to by the regulatory authority(ies)
Ultimately given approval by the IRB
The investigator should not implement any deviation from, or
changes of the protocol without:
Agreement by the sponsor
Prior review and documented approval from the IRB of an
amendment
Exception: where necessary to eliminate an immediate hazard
(s) to trial subjects or when the changes involve only logistical
or administrative aspects of the trial. However, as soon as
possible, the implemented deviation or change, the reason for
it, and, if appropriate, the proposed protocol amendment(s)
should be submitted to:
– The IRB for review and approval
– To the sponsor for agreement
– If required, to the regulatory authorities
GOOD CLINICAL PRACTICE
Investigator – Investigational Products
It is the investigator’s responsibility for investigational product(s)
accountability at the trial site
The investigator or person who is designated by the investigator
should maintain records of:
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The product(s) delivery to the site
The inventory at the site
The use by each subject
The return to the sponsor or disposition of unused
products
The records should include:
Date, quantities, batch/serial numbers, expiration dates and
the unique code numbers assigned to the product(s) and subjects
Products should be stored as specified by the sponsor and in
accordance with applicable regulatory requirements
Should explain to the subject:
Correct use of the product
Should check at appropriate intervals that the subject is following the
instructions properly to use the product
GOOD CLINICAL PRACTICE
Investigator – Records and Reports
Records should be accurate, complete,
legible and timely pertinent to the data
reported to the sponsor in the CRFs (Case
Report Forms) and other required reports
All corrections to a CRF should be dated,
explained and should not obscure the
original entry whether the entry is written or
electronic changes or corrections.
The investigator should retain records of
the changes and corrections.
GOOD CLINICAL PRACTICE
Investigator’s Brochure
For investigational (not FDA-approved)
drug trials
Summary of significant physical, chemical,
pharmaceutical, pharmacological,
toxicological, pharmacokinetic, metabolic,
and clinical information that is relevant to
the investigational product
Relevant animal and clinical studies,
adverse events, etc.
GOOD CLINICAL PRACTICE
FDA Form 1572 – to initiate clinical trials
Investigator agrees to comply with conditions required by
FDA for use of investigational articles
“Contract” that the investigator signs/dates
“Warning: A willing false statement is a criminal offense”
Content of Form 1572
Principal Investigator name/address
Name/address of site(s) of study conduct
Name/address clinical labs (local/central)
Name/address IRB
Names of key personnel with study participant contact
Submit CVs of key personnel (signed/dated) listed in form
GOOD CLINICAL PRACTICE
Progress Reports
The investigator should submit written summaries
(where required by applicable regulatory
requirements) of the trial’s status to the institution.
The investigator should submit written summaries
of the status of the trial to the IRB annually or
more frequently, if requested by the IRB
The investigator should promptly provide written
reports to the sponsor and the IRB and where
required by the regulatory authorities, the
institution on any changes significantly affecting
the trial and/or increasing the risk to subjects.
GOOD CLINICAL PRACTICE
Safety Reporting
All serious adverse events (SAE) should be reported immediately to
the sponsor except for those SAEs that the protocol or other
document identifies as not needing immediate reporting
The immediate and follow up reports should identify Subjects by
unique code numbers assigned to trial, but not with identifiers
(name, address, identification numbers)
The immediate reports should be followed promptly by detailed,
written reports
Adverse events and/or laboratory abnormalities identified in the
protocol as critical to safety evaluations should be reported to the
sponsor within the time periods specified by the sponsor in the
protocol
For reported deaths, the investigator should supply the sponsor and
the IRB with any additional requested information (e.g., autopsy
reports and terminal medical reports)
GOOD CLINICAL PRACTICE
Premature Termination or Suspension of a Trial
If the trial is suspended or prematurely terminated for any reason
the investigator should promptly Inform the trial subjects, should
assure appropriate therapy and follow-up and where required,
should inform the regulatory authorities and the IRB
If the investigator terminates or suspends a trial without prior
agreement of the sponsor, the investigator should inform the
institution, regulatory authorities(if required), the sponsor and the
IRB with detailed written explanation of the termination or
suspension
If the sponsor terminates/suspends a trial, the investigator should
promptly inform the institution (per applicable regulatory
requirements) and the IRB and provide written explanation of the
termination/suspension
If the IRB terminates/suspends its approval, the investigator should
inform the institution and the investigator should promptly notify the
sponsor and provide the sponsor with a detailed written
explanation of the termination or suspension
GOOD CLINICAL PRACTICE
Final Report
Upon the completion of the trial, the
investigator should inform and provide
the IRB and the sponsor:
All required reports
Summary of the trial’s outcome
Reports to regulatory authorities if
applicable
GOOD CLINICAL PRACTICE
Records Retention Requirements
Essential documents should be retained until at least two (2)
years after the last approval of a marketing application in an
ICH region.
These documents should be retained, however, if required
by the applicable regulatory requirements (state or federal)
or by an agreement with the sponsor.
It is the responsibility of the sponsor to inform the
investigator as to when these documents no longer need to
be retained.
Upon request of the monitor, auditor, IRB or regulatory
authority, the investigator/institution should make available
for direct access all requested trial-related records.
References
www.fda.gov
www.google.com
EMEA, Inspections
Stanford school of medicine;
FACILITATING TRANSLATIONAL
RESEARCH AND MEDICINE
CLINICAL RESEARCH