18 August 2015 Role & Responsibilities of Principal Dr. R. Sathianathan Professor of Psychiatry, SRMC, Porur & Former Director, Institute of Mental Health, Chennai
Principal Investigators & GOOD CLINICAL PRACTICE (GCP) Purposes of GCPs Protect the rights, safety and welfare of research subjects Assure the integrity of clinical data Compliance with ICH GCP standard provides public assurance that the rights, well-being and confidentiality of trial subjects are protected and that trial data are credible
DEFINITION OF GCP ICH definition of Good Clinical Practice International ethical and scientific quality standard for designing, conducting, recoding, and reporting trials that involve the participation of human subjects Standard for design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials that provides assurance that data and reported results are credible and accurate and that rights, integrity and confidentiality of trial subjects are protected
PRINCIPLES OF GCP Clinical trials should be conducted in accordance with the ethical principles that have their origin in the declaration of Helsinki and that are consistent with applicable regulatory requirements. Foreseeable risks should be weighed against anticipated benefits for the individual and for society as a whole; a trial should only be imitated if anticipated benefits justify the risks. The rights, safety, and well being of the trial subjects are the most important considerations, prevailing over interests of science and society The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.
PRINCIPLES OF GCP Clinical trials should be scientifically sound, and described in a clear, detailed protocol. A trial should be conducted in compliance with the protocol and amendments(s) that have received prior Institutional Review Board approval. The medical care given to, and medical decisions made for subjects should always be the responsibility of a qualified physician. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).
PRINCIPLES OF GCP Freely given informed consent should be obtained from every subject prior to clinical trial participation. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality of the individual. Investigational products should be manufactured, handles, and stored in accordance with applicable Good Manufacturing Practice (GMP).
Roles & Responsibilities of PI Objectives Identify the members of the clinical research team; Describe their primary roles and responsibilities; Recognize the types of sponsor/cro Investigator site visits; Apply the roles and responsibilities of the Clinical Research Associate and the Clinical Research Coordinator
Clinical Research Team Sponsor Contract Research Organization (CRO) Investigational Sites/Institution/Investigator Ethics Committee/Institutional Review Boards (IRBs) Regulatory Agencies [Food & Drug Administration (FDA)] Research Subjects/Patients/Participants Others For example: Central Labs, Randomization services, safety Boards
Who is a Principal Investigator? A Principal Investigator is the primary individual responsible for the preparation, conduct, administration of a research grant, Agreement & Contract training, compliance with applicable laws and regulations and institutional policy governing the conduct of sponsored research.
GENERAL QUALIFICATIONS An Investigator must be: An appropriately qualified person; Trained and experienced in clinical research; Familiar with the background of the study drug and requirements of the study; Known to have high ethical standards and professional integrity.
GENERAL Obtain IRB approval of a study protocol and informed consent; Enroll the required number of qualified subjects and obtain informed consent from all subjects; Administer (or supervise the administration of) the study drug/device and maintain accurate accountability for all clinical supplies received b the site; Observe, measure, and record the effect of the drug/device; Record all other data pertinent to the study;
Cont. General Evaluate, manage, and report adverse experiences; Submit protocol changes to the IRB for approval; Notify the IRB if any problems which pose a threat to the welfare of the subjects; Retain and make study documentation available to sponsor representatives and FDA inspectors for data verification purposes, and Comply with all other procedures as specified in the protocol, sponsor SOPs, and Good Clinical Practice (GCP).
Control of the Investigational drug/device [21 CFR 312.61 & 21 CFR 812.110] Investigator must administer the product only to subjects under the Investigator s personal supervision, Or under the supervision of a sub-investigator responsible to the investigator; Investigator must not supply investigational product to any person unauthorized/unqualified.
Record keeping and record retention [21 CFR 312.62 & 21 CFR 812.140] Investigator must maintain the accurate, complete, and current records relating to investigator s participation in an investigation; Study Correspondence: Investigator is required to keep all correspondence with another investigator, IRB, sponsor, monitor, or FDA regarding work on a clinical trial.
Cont. Record keeping and record retention [21 CFR 312.62 & 21 CFR 812.140] Disposition of Investigational Product: Investigator required to maintain adequate records of receipt, use and disposition of investigational product e.g. dates dispensed, quantity used by subject, etc. Case Histories: Examples, Source Documents and Case Report Forms; Investigator required to prepare and maintain adequate and accurate records of all observations and other data pertinent to investigation on each subject participating.
Cont. Record keeping and record retention [21 CFR 312.62 & 21 CFR 812.140] Records retention: Investigator must retain study related records for two years following date marketing application approved, or for two years after withdrawal off application, e.g. investigator completing trial in 1980 must retain all study records until 1997, if application for approval such as NDA, not approved until 1996.
INVESTIGATOR REPORTS [21 CFR 312.64 7 21 CFR 812.150] Progress reports Investigator much furnish study progress reports to IRB and sponsor; Investigator progress reports are required annually by IRB, although some IRBs require more frequent reporting; Both sponsor and/or FDA may request more frequent reporting for special circumstances.
Cont. INVESTIGATOR REPORTS [21 CFR 312.64 7 21 CFR 812.150] Safety Reports: Investigator must promptly report to sponsor any adverse effect that may reasonably be regarded as caused by or, probably caused by investigational product Timing of these reports usually spelled out in study protocol If investigator deems safety event to meet regulatory criteria for serious, Investigator must report adverse event immediately to sponsor
Cont. INVESTIGATOR REPORTS [21 CFR 312.64 7 21 CFR 812.150] Safety Reports: For device trials, unexpected effects must also be reported immediately to sponsor; Investigator must report safety events to the reviewing IRB as required by that IRB; Typically, events reported immediately to sponsor are also reported promptly to IRB.
Cont. INVESTIGATOR REPORTS [21 CFR 312.64 7 21 CFR 812.150] Final Report: Investigator provides sponsor and IRB/TEC with final report shortly after completing participation in trial; Usually includes number of subjects enrolled, completed, withdrawn, number of deaths, SAEs and protocol violations. Templates
ASSURANCE OF IRB REVIEW [21 CFR 312.66 & 21 CFR 812.110] Investigator assures that IRB in compliance with Part 56 of CFR, and responsible for IRB initial and continuing review and approval of the study; Investigator must promptly report to IRB all changes in research activity and all unanticipated problems involving risks to humans;
Cont. ASSURANCE OF IRB REVIEW [21 CFR 312.66 & 21 CFR 812.110] Investigator will not make changes in reassert without prior IRB approval, except where necessary to eliminate apparent immediate hazards to subjects; Investigator must be familiar and compliant with the reviewing IRB s requirements for submission of information and reports; Examples of information required by the IRB may include: Safety information and events, protocol deviations, and study progress reports.
INSPECTION OF RECORDS & REPORTS [21 CFR 312.68 & 21 CFR 812.145] Investigator must allow properly authorized FDA representatives to inspect facilities and study records.
Clinical Trial Chain of Command Good Clinical Practice Investigator Sponsor Patient Institutional Review Board (IRB) FDA
Delegation of Study Tasks Common for PI to delegate many study tasks to study site staff members FDA requires documentation of delegation and supervision by the PI Commonly a delegation listing is used in the form of a delegation log The log template can be supplied by sponsor or site may use their own PI must assure that delegation is to qualified individuals: with adequate training, education and/or experience Including: direct staff, outside department, 3 rd party Refer to FDA Guidance, PI responsibility, OCT 2009
Delegation of Tasks Delegation should be supported through documentation PI should assess the adequacy of the delegation and supervise the staff Refer to 2009 FDA Guidance for Investigator Responsibilities CRA should monitor for adequate and accurate documentation of delegation This includes review of credentials of delegates and of performance by the delegates, as well as supervision by the PI
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