Good Clinical Practice-2

8/3/2019 Good Clinical Practice-2

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Good Clinical PracticeInvestigator Role and

ResponsibilitiesQualification: Appropriate education, training and

experience to assumeresponsibility and should provideevidence of such

qualifications.Familiarity with the Test Article: Should bethoroughly familiar with the testarticle described in theinvestigators brochure.

Compliance: Should comply with GCPprocedures and applicableregulationsMonitoring: Should permit monitoring and

auditing by the sponsorand appropriate regulatoryagencies


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Good Clinical PracticeInvestigator -

ResourcesDemonstrate potential for recruiting requirednumber of subjects

Have sufficient time to properly conduct andcomplete the trial within the agreed periodMust have adequate number of qualifiedpersonnel and facilities to conduct the trialproperly and safely

Investigator must make sure personnelassisting in the study are adequately informedabout the protocol, investigational products(s)and trial-related duties and functions


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Good Clinical PracticeInvestigator Medical Care of Trial

SubjectsA qualified physician, who is an investigator or sub-investigator for the trial must be responsible for all trial-related medical decisions.

During and following subjects participation in a trial, theinvestigator should ensure that adequate medical careis provided to a subject for any adverse events(including lab values).

The investigator must inform the subject when medicalcare is needed for inter-current illness(es) of whichinvestigator becomes aware.It is recommended that the investigator inform subjectsprimary physician about subjects participation (subjects agreement to this requirement is required)If subject wishes to withdraw from the study, theinvestigator should make reasonable effort to ascertainthe reasons while fully respecting the subjects rights.


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Good Clinical PracticeInvestigator Communication

with IRBBefore Initiating a trial the investigatormust have in his/her position:

Written date approval letter for the trial period

Written and approved informed consent formConsent form updates (if any)Subject recruitment procedures (e.g.,advertisements)Any other information to be provided to the subjectsProvide a current copy of the Investigators brochureIf the Investigators Brochure is updated, theinvestigator must supply a copy of the updatedbrochure to the IRBAny other documents that are subject to review by

the IRB


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Good Clinical PracticeInvestigator Compliance with

Protocol

The investigator should conduct the trial in compliancewith:

The protocol agreed to by the sponsorIf required, protocol agreed to by the regulatory authority(ies)

Ultimately given approval by the IRB The investigator/institution should sign the protocol, or analternative contract, to confirm the agreement

The investigator should not implement any deviationfrom, or changes of the protocol without:

Agreement by the sponsor

Prior review and documented approval from the IRB of anamendment except where necessary to eliminate an immediatehazard (s) to trial subjects or when the changes involve onlylogistical or administrative aspects of the trial (e.g, change in themonitor(s), change of telephone number without IRB approval.However, as soon as possible, the implemented deviation orchange, the reason for it, and, if appropriate, the proposed protocolamendment(s) should be submitted to:

The IRB for review and approval


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Good Clinical PracticeInvestigator Investigational

ProductsIt is the investigators responsibility forinvestigational product(s) accountability at thetrial site

The investigator or person who is designated bythe 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 productsThe records should include:

Date, quantities, batch/serial numbers, expiration dates andthe unique code numbers assigned to the product(s) andsubjects

Maintain records that document adequately:Doses rovided to sub ects as s ecified in the rotocol


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Good Clinical PracticeInvestigator Investigational

Products (Cont.d)

Products should be stored as specified bythe sponsor and in accordance with

applicable regulatory requirementsProducts should be used only inaccordance with the approved protocolShould explain to the subject:

Correct use of the productShould check at appropriate intervals thatthe subject is following the instructionsproperly to use the product


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Good Clinical PracticeInvestigator Randomization

Procedures and Unblinding

The investigator should follow trialsrandomization procedure

Ensure that the code is broken only inaccordance with protocolIf trial is blinded, the investigator shouldpromptly document and explain to the

sponsor any:Premature unblindingAccidental unbliniding

Unblinding due to serious adverse events


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Good Clinical PracticeInvestigator Informed Consent of

Trial Subjects

Obtaining Informed Consent: Investigator should comply with regulatory requirementsShould adhere to GCP and ethical principles (Declaration of

Helsinki)Should have approved consent form

Informed Consent DocumentShould follow the guidelines of informed consent documentprovided by the universityShould be revised whenever important new informationbecomes available that may be relevant to the subjectsconsentAll revised consent forms must be approved by the IRB inadvance of use

The subject or subjects legally authorized representativeshould be informed in a timely manner should newinformation become available and communication of thisinformation should be documented

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Good Clinical PracticeInvestigator Informed Consent of

Trial SubjectsSubject Consent and ParticipationAvoid coercion or unduly influence a subject to participate orcontinue to participate in a trialConsent Language and Information to the subject or subjects LAR

Oral and written information pertaining to the trial, including the writtenconsent form should contain any language that waive or appear to waivethe subject or subjects LAR any legal rights or liability for negligence

The investigator or his/her designate should fully inform the subject or if the subject is unable to provide informed consent, the subjects LAR of allpertinent aspects of trial including the written information that has been

approved by the IRB.If subject/LAR is unable to read, an impartial witness must be presentduring the entire informed consent discussion

The information language should be non-technical and understandable tothe subject/LAR/impartial witnessProvide ample time and opportunity to inquire about details of the trial

and all questions about the trial should be answeredOnce the subject/LAAR has signed the consent, the witness should sign


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Good Clinical PracticeInvestigator Records and

ReportsRecords should be accurate, complete, legible and timelypertinent to the data reported to the sponsor in the CRFs (CaseReport Forms) and other required reportsData reported on the CRFs should be derived from the source

document. It should be consistent with the source documentsand all discrepancies from the source documents must beclearly explainedAll corrections to a CRF should be dated, initialed, explainedand should not obscure the original entry whether the entry iswritten or electronic changes or corrections.

Sponsors are required to provide guidance to the investigatorson procedures to assure that changes and corrections in CRFsmade by sponsors designated representatives aredocumented, are necessary and are endorsed by theinvestigator. The investigator should retain records of thechanges and corrections.

The investigator should maintain the trail documentation asspecified under Essential Documents to be kept before, during


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Investigator Records andReports

Records Retention

RequirementsEssential documents should be retained until at leasttwo (2) years after the last approval of a marketingapplication in an ICH region and until there are nopending or contemplated marketing application in anICH region or at least two (2) years have elapsed sincethe formal documentation of clinical development of theinvestigational product.

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 theinvestigator as to when these documents no longerneed to be retained

The financial aspects of the trial should be documentedin an agreement between the sponsor and theinvestigator/institution


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Good Clinical PracticeInvestigator Progress

Reports

The investigator should submit writtensummaries (where required by applicable

regulatory requirements) of the trials status tothe institution. The investigator should submit writtensummaries of the status of the trial to the IRBannually or more frequently, if requested by the

IRB The investigator should promptly providewritten reports to the sponsor and the IRB andwhere required by the regulatory authorities,the institution on any changes significantlyaffecting the trial and/or increasing the risk to


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Good Clinical PracticeInvestigator Safety

ReportingAll serious adverse events (SAE) should be reportedimmediately to the sponsor except for those SAEs that theprotocol or other document identifies as not needing immediatereporting

The immediate reports should be followed promptly by detailed,written reports

The immediate and follow up reports should identify Subjects byunique code numbers assigned to trial, but not with identifiers(name, address, identification numbers)

The investigator should also comply with the applicableregulatory requirement(s) related to the reporting of unexpected SAEs to the regulatory authority(ies) and the IRBAdverse events and/or laboratory abnormalities identified in theprotocol as critical to safety evaluations should be reported tothe sponsor within the time periods specified by the sponsor inthe protocol

For reported deaths, the investigator should supply the sponsorand the IRB with any additional requested information (e.g.,

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Good Clinical PracticeInvestigator Premature

Termination or Suspension of a

TrialIf the trial is suspended or prematurely terminated forany reason the investigator should promptly Inform thetrial subjects, should assure appropriate therapy and

follow-up and where required, should inform theregulatory authorities and the IRBIf the investigator terminates or suspends a trial withoutprior agreement of the sponsor, the investigator shouldinform the institution, regulatory authorities(if required), thesponsor and the IRBProvide the sponsor and the IRB a detailed written explanationof the termination or suspensionIf the sponsor terminates/suspends a trial , the investigatorshould promptly inform the the institution (per applicableregulatory requirements) and the IRB and provide writtenexplanation of the termination/suspensionIf the IRB terminates/suspends its approval, theinvestigator should inform the institution and the investigator


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Good Clinical PracticeInvestigator Final Reports

Upon the completion of the trial, the

investigator should inform and provide theIRB and the sponsor:

All required reportsSummary of the trials outcomeReports to regulatory authorities if applicable


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Good Clinical PracticeInvestigator Records and Reports

Essential Documents to be Kept beforeTrial Commences

Investigators BrochureSigned protocols, amendments (if any) and sample CRFInformation given to the trial subjects

Informed ConsentApplicable translations of informed consent (if any)Any other written informationAdvertisements for subject recruitmentSubject compensation

Financial aspects of the trialCompensation document for trial-related injurySigned agreements of all involved parties

Investigator and sponsorInvestigator and CRO (if any)Investigator/institution and regulatory authorities (if any)

Approval letter from the IRBIRB CompositionAuthorization or notification from the regulatoryagencies (where required)

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Essential Documents to be Kept before Trial Commences

CV of investigator and sub-investigators evidencingqualificationsNormal values of labs /technical procedures included inthe protocolMedical/laboratory and technical procedures of tests

CertificationAccreditationEstablished Quality control (QC assessments)Other validations

Sample labels attached to investigational productcontainers

Instructions for handling investigational products and trial-related materials (sometimes this information is includedin the investigators brochure)Shipping records of investigational products and trial-related materialsCertificates of analysis of investigational products shipped

Decoding procedures for blinded trialsMaster randomization list

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Essential Documents to be Kept Duringthe Trial

Investigators brochure updatesAny revisions to:

Protocol, amendments and CRF

Informed consent formWritten information provided to subjects/LARAdvertisement

Dated, IRB approved documents of:Protocol amendmentsRevisions of informed consent, information to subjects/LAR

Advertisements and any other documents givenContinuing review of trial

Dated Regulatory approved documents of:Authorizations and notificationsProtocol amendments and other documents


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Investigator Records andReports


Curriculum Vitae of new investigators and sub-investigatorsUpdates to normal value(s) range(s) for medical lab technicalprocedure(s), test(s) included in the protocolUpdates on medical/laboratory/technical procedure tests

CertificatesAccreditationEstablished quality control/external quality assessmentOther validations

Documentation of investigational products and trial-relatedmaterials shipmentCertificate(s) of analysis for new batches of investigationalproductsMonitoring visit reportsRelevant communications other than site visits (Letters, meetingnotes and notes of telephone calls)Signed informed consent formsSource documents

Signed, dated and completed CRFDocumentation of CRF Corrections


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Notification by the originating investigator to sponsorof serious adverse evens and related reportsNotification by investigator (if applicable) toregulatory authorities and IRB of unexpected seriousadverse reactions and of other safety informationNotification by sponsor to investigators of safetyinformationSubject screening log

Subject identification code listSubject enrolling logInvestigational product(s) accountability at the sireSignature sheetRecord of retained body fluids/tissue samples (if any)

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oo n ca rac ceInvestigator Records and Reports

Essential Documents to be Kept After Completion or Termination of the

Trial Investigational product(s) accountability atsireDocumentation of investigational product(s)destructionCompleted subject identification code list ( topermit identification of all subjects enrolled in thetrial in case of follow up is required this informationshould be kept in a confidential manner and foragreed period of time )

Audit certificate (if required)Final trial close-out monitoring reportTreatment allocation and decodingdocumentation returned to sponsor todocument any decoding that may haveoccurredFinal report by investigator to IRB where