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CLINICAL STUDY AND BASIC CONCEPT GOOD CLINICAL PRACTICE

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GOOD CLINICAL PRACTICE Investigator s Brochure For investigational (not FDA-approved) drug trials Summary of significant physical, chemical, pharmaceutical, ... – PowerPoint PPT presentation

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Title: CLINICAL STUDY AND BASIC CONCEPT GOOD CLINICAL PRACTICE


1
CLINICAL STUDY AND BASIC CONCEPTGOOD CLINICAL
PRACTICE
  • Presented by
  • Aarohi Shah
  • M.Pharm

Dept of Pharmaceutics and Pharmaceutical
Technology
2
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.

3
CLINICAL STUDY AND BASIC CONCEPT
  • Types of clinical trials
  • Treatment trials
  • Prevention trials
  • Diagnostic trials
  • Screening trials
  • Quality of Life trials

4
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.

5
CLINICAL STUDY AND BASIC CONCEPT
Clinical Trials Clinical Trials Clinical Trials Clinical Trials Clinical Trials Clinical Trials Clinical Trials Clinical Trials Clinical Trials Clinical Trials
Preclinical testing F I L E IND at FDA Phase I Phase II Phase III F I L E NDA at FDA FDA Phase IV
Years 3.5 F I L E IND at FDA 1 2 3 F I L E NDA at FDA 2.5 12 Total Additional post marketing testing
Test population Lab and Animal Studies F I L E IND at FDA 20 to 80 healthy volunteers 100 to 300 patient volunteers 1000 to 3000 patient volunteers F I L E NDA at FDA Review process/ Approval Additional post marketing testing
Success rate 5000 compounds evaluated F I L E IND at FDA 5 enter trials 5 enter trials 5 enter trials F I L E NDA at FDA 1 approved Additional post marketing testing
6
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

7
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

8
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

9
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

10
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

11
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

12
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

13
GOOD CLINICAL PRACTICE
  • Some important terms (Glossary)
  • Investigator
  • Sponsor
  • Subject /Trial Subject
  • Investigators Brochure
  • Non Clinical Study
  • Protocol
  • Blinding (Masking)
  • Institutional Review Board (IRB)
  • Adverse Event (AE)
  • Serious Adverse Event (SAE)

14
GOOD CLINICAL PRACTICE
  • Elements of GCP
  • IRB
  • Investigator
  • Sponsor
  • Clinical trial protocol and protocol amendments
  • Investigator Brochure
  • Essential documents

15
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.

16
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 subjects primary physician
  • Ensure adequate medical care for SAEs.
  • Maintained records should be accurate, complete,
    legible and timely.

17
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

18
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

19
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
    subjects primary physician about subjects
    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 subjects rights.

20
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

21
GOOD CLINICAL PRACTICE
  • Investigator Investigational Products
  • It is the investigators responsibility for
    investigational product(s) accountability at the
    trial site
  • The investigator or person who is designated by
    the investigator should maintain records of
  • 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

22
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.

23
GOOD CLINICAL PRACTICE
  • Investigators 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.

24
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

25
GOOD CLINICAL PRACTICE
  • Progress Reports
  • The investigator should submit written summaries
    (where required by applicable regulatory
    requirements) of the trials 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.

26
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)

27
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

28
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 trials outcome
  • Reports to regulatory authorities if applicable

29
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.

30
References
  • www.fda.gov
  • www.google.com
  • EMEA, Inspections
  • Stanford school of medicine FACILITATING
    TRANSLATIONAL RESEARCH AND MEDICINE
  • CLINICAL RESEARCH

31
Thank You
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