1. MANISHA VERMA
16CRM 2488
GE-511
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2. INTRODUCTION
 Clinical research
 Sponsor
 CRO
 Investigator
 Co-investigator
 CRA
 IRB
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3. Investigator / Principal Investigator
 ICH GCP - investigator is any person responsible for the
conduct of the clinical trial at a trial site.
 Sponsor decision
 Primary responsibility- ensuring the ethical conduct of the
research study.
 Ensuring informed consent is appropriately obtained.
 Oversees all aspects of a clinical trial from protocol design,
recruitment, data collection, analysis and interpretation of
results.
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4. Qualifications
 21 CFR 812.13(a) -A sponsor shall select investigators
qualified by training and experience to investigate the
investigational product. FDA does not regulate whether the PI
has to be a MD.
 ICH GCP 4.1.1: The investigator should be qualified by
education, training and experience to assume responsibility for
the proper conduct of the trial.
 IRB –reviewing investigator’s qualifications.
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5. Roles and Responsibilities
 Responsible for the conduct of the trial according to the
protocol and the GCP guidelines
 Documentation of SOPs
 Delegation of Responsibilities
 Knowledge of Human Research Protection Standards
 Evaluation of Adequacy of Resources
 Training Requirements
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6. Understanding the Regulations and
GCPs
 Certain regulations and guidelines that an investigator must be
familiar with
1. FDA regulations for clinical trials-
 Investigational products under FDA jurisdiction - several
parts of Title 21 CFR
 Part 50 (Protection of Human Subjects).
 Part 312 (Investigational New Drug Application (INDA)
 Part 314 (Applications for FDA approval to market a new
drug
2. ICH guidelines for Good Clinical Practices.
3. The Declaration of Helsinki.
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7. Investigator interaction with
Institutional Review Board (IRB)
 IRB- any board, committee or group formally designated
by an institution to review, approve the initiation of and to
conduct periodic review of biomedical research involving
human subjects.
 Materials submitted to the IRB by an investigator:
1. Current signed CV
2. Proposed study protocol
3. Investigator brochure
4. Proposed informed consent form
5. All subject advertisements and recruitment procedures
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8. 6. Form FDA 1572 (statement of investigator form)
7. Any other specific forms or materials required by the
IRB, such as an application form.
• Investigator is required to submit periodic reports to the
IRB, detailing the progress of the study.
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9. Investigator responsibilities
towards informed consent
 INFORMED CONSENT: A process by which a subject
voluntarily confirms his or her willingness to
participate in a particular trial, after having been
informed of all aspects of the trial that are relevant to
the subject's decision to participate.
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10. Supervision of the conduct of
clinical trials
 The investigator should develop a plan for the supervision and
oversight of the clinical trial at the site.
1. Routine meetings with staff & sponsor’s monitors.
2. Routine meetings with IRB.
3. Procedure for the timely correction and documentation of
problems identified.
4. Procedure for ensuring that the consent process is being
conducted in accordance with regulations.
5. Ensuring that source data, source document are accurate &
original.
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11. 6. Ensuring that information in source documents is
accurately captured on the case report forms (CRFs).
7. Dealing with data queries and discrepancies identified.
8. Ensuring study staff comply with the protocol.
9. Addressing medical and ethical issues that arise during
the course of the study in a timely manner.
 Investigative site study files.
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12. Working with study subjects
 Most difficult as well as most rewarding aspects.
 Ensure that the ethical principles are followed while working
with study subjects.
 Recruitment of study subjects.
 Information to potential study subjects.
 Retention of study subjects.
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13. Study closure
 Procedure for study closure & conditions under which it must
be closed.
 Duties are usually shared by the CRC and the CRA.
 Reasons for study closure.
 Investigator‘s final report to the sponsor and the IRB.
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14. Adverse events and safety
monitoring
 Reporting on safety - is one of the most important tasks the
investigator and CRC perform.
 By signing form1572, the investigator also commits to
reporting AE to the sponsor.
 ADR, AE & SAE.
 Assess the relationship between an adverse event &
investigational product.
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15. Investigator role in audits
 Role of the investigator in the audit is to be present.
 Provide quiet and comfortable place
 Assemble all necessary documents
 Provide the documents that are requested by the inspector
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16. CONCLUSION
 Investigator is any person responsible for the conduct of the
clinical trial at a trial site. When it comes to the conduct of
clinical research, an investigator has numerous responsibilities
from the designing of the protocol , study design, recruitment
subjects, understand the regulations, interact with the IRB.
During a clinical trial, it is important that clinical investigators
successfully meet all research expectations, including
regulatory requirements and the Guidelines for Good Clinical
Practice. Therefore, an investigator must take each and every
step to conduct the clinical research in a manner which does
not harm the integrity and rights of participants of the research.
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17. REFERENCES
1. WHO. Proposed WHO Guidelines for Good Clinical Practice
(GCP) for Trials on Pharmaceutical Products. 1992; 6: 170.
2. Miller FG, Rosenstein DL. The Therapeutic Orientation to
Clinical Trials. N Eng J Med. 3 Apr 2003; 348(14): 1383-
1385.
3. Protecting Research Subjects- What must be done. N Eng J
Med. 2000; 343(11): 808-810.
4. Chadwick D.G. Protecting Study Volunteers in Research.
2004; 1: 38-41.
5. Beecher H. K. Consent in Clinical Experimentation: Myth
and Reality. J.A.M.A. 1966; 195(34): 23.
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18. 6. Emanuel E.J., Wendler D, Grady C. What makes Clinical
Research Ethical?. JAMA .2000;283: 2701-2711.
7. Levine RJ. Ethics and regulation of clinical research. Yale
University Press; 1988.
8. Nicole A. Medical Practice Management; 2011.
http://www.bmk secure solutions .com/files/investigator
responsibilities.pdf (accessed 28 October 2016).
9. Appelbaum P.S. Examining the Ethics of Human Subjects
Research. Kennedy Inst Ethics J. 1996; 6: 283-287.
10. Angell M. Industry-sponsored clinical research: a broken
system. JAMA. 3 Sep 2008; 300(9):1069-1071.
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