Research Coordination Research Coordination GuidanceGuidance
The Committees on Human Research The Committees on Human Research
ServingServingUniversity of Vermont & Fletcher Allen Health CareUniversity of Vermont & Fletcher Allen Health Care
The following material is intended as The following material is intended as guidance on how to achieve good guidance on how to achieve good standards and/or best practices in the standards and/or best practices in the conduct of research with human subjects. conduct of research with human subjects.
It is meant to be an adjunct to the basic It is meant to be an adjunct to the basic human subjects protection training human subjects protection training information provided in the required on-information provided in the required on-line tutorial. line tutorial.
The goal is to provide practical advice and The goal is to provide practical advice and tips on how to implement good practices to tips on how to implement good practices to achieve high quality research results while achieve high quality research results while ensuring the protection of research ensuring the protection of research participants.participants.
Good Clinical Practice (GCP)Good Clinical Practice (GCP)
Developed for clinical research, GCP is an Developed for clinical research, GCP is an international ethical and scientific quality international ethical and scientific quality standard applied to human subject standard applied to human subject research that impacts:research that impacts:
Study designStudy designConductConductRecord managementRecord managementData collection and reportingData collection and reporting
Good Clinical PracticeGood Clinical Practice
Compliance with GCP standards Compliance with GCP standards provides public assurance that the provides public assurance that the
rights, safety and well-being of rights, safety and well-being of human subjects are protected and human subjects are protected and that the study data are credible. that the study data are credible.
Applying GCP Standards to ALL Applying GCP Standards to ALL Types of ResearchTypes of Research
The principles established by GCP The principles established by GCP are typically applied to biomedical are typically applied to biomedical research, but it is recommended that research, but it is recommended that they also be applied to other studies they also be applied to other studies which have an impact on the safety which have an impact on the safety and well-being of human subjects. and well-being of human subjects. This includes research in the This includes research in the behavioral sciences.behavioral sciences.
GCPGCP ObjectivesObjectives
Basic Principles of GCPBasic Principles of GCP Compliance with ProtocolCompliance with Protocol IRB Reporting RequirementsIRB Reporting Requirements The Process of Informed ConsentThe Process of Informed Consent Record & Data ManagementRecord & Data Management PI & Research Member PI & Research Member
ResponsibilitiesResponsibilities
Principles of GCPPrinciples of GCP
The rights, safety, and well-being of The rights, safety, and well-being of the research subjects are the most the research subjects are the most important considerations and should important considerations and should prevail over interests of science and prevail over interests of science and society (E6: 2.3)society (E6: 2.3)
Principles of GCPPrinciples of GCP Each individual involved in study conduct should Each individual involved in study conduct should
be qualified by education, training, and be qualified by education, training, and experience to perform his or her respective tasks experience to perform his or her respective tasks (E6: 2.8)(E6: 2.8)
The principal investigator should be qualified by The principal investigator should be qualified by education, training, and experience to assume education, training, and experience to assume responsibility for the proper conduct of the study, responsibility for the proper conduct of the study, should meet all the qualifications specified by the should meet all the qualifications specified by the applicable regulatory requirements, and should applicable regulatory requirements, and should provide evidence of such qualifications through provide evidence of such qualifications through up-to-date CV and/or other relevant up-to-date CV and/or other relevant documentation requested by the sponsor, IRB, documentation requested by the sponsor, IRB, and/or the regulatory authorities (E6: 4.1.1)and/or the regulatory authorities (E6: 4.1.1)
Principles of GCPPrinciples of GCP
Informed consent should be obtained Informed consent should be obtained from every subject prior to study from every subject prior to study participation (E6: 2.9)participation (E6: 2.9)
All study information should be All study information should be recorded, handled, and stored in a recorded, handled, and stored in a way that allows its accurate way that allows its accurate reporting, interpretation and reporting, interpretation and verification (E6: 2.10)verification (E6: 2.10)
Principles of GCPPrinciples of GCP
The confidentiality of records that could The confidentiality of records that could identify subjects should be protected, identify subjects should be protected, respecting the privacy and confidentiality respecting the privacy and confidentiality rules in accordance with the applicable rules in accordance with the applicable regulatory requirements (E6: 2.11)regulatory requirements (E6: 2.11)
Systems with procedures that assure the Systems with procedures that assure the quality of every aspect of the study should quality of every aspect of the study should be implemented (E6: 2.13)be implemented (E6: 2.13)
Compliance with the IRB-approved Compliance with the IRB-approved ProtocolProtocol
A study should be conducted in compliance with A study should be conducted in compliance with the protocol that has received prior IRB approval the protocol that has received prior IRB approval (E6: 2.6 & 4.5.1)(E6: 2.6 & 4.5.1)
If you conduct research that deviates from the If you conduct research that deviates from the IRB approved protocol then you are in IRB approved protocol then you are in noncompliancenoncompliance
Serious and continuing noncompliance is Serious and continuing noncompliance is reportable to federal regulatory authorities, reportable to federal regulatory authorities, sponsors and institutional officialssponsors and institutional officials
IRB Reporting RequirementsIRB Reporting Requirements
Protocol AmendmentsProtocol Amendments
Protocol DeviationsProtocol Deviations
Unanticipated Problems Involving Unanticipated Problems Involving Risks to Subjects or OthersRisks to Subjects or Others
Protocol AmendmentsProtocol Amendments
Changes to the study must be submitted Changes to the study must be submitted for IRB review (E6: 4.4.3 & 4.10.2)for IRB review (E6: 4.4.3 & 4.10.2)
Examples of study changes:Examples of study changes:– Study proceduresStudy procedures– Adding, revising or eliminating measuresAdding, revising or eliminating measures
Surveys, questionnaires, data collection forms, etc.Surveys, questionnaires, data collection forms, etc.
– Recruitment materialsRecruitment materials– Study termination, suspensions, and final Study termination, suspensions, and final
closure (E.6: 4.12 & 4.13)closure (E.6: 4.12 & 4.13) Only implement protocol changes Only implement protocol changes afterafter
you receive notice of IRB approvalyou receive notice of IRB approval
Protocol DeviationsProtocol Deviations
Report promptly to the Committee Report promptly to the Committee deviations from the IRB-approved protocol deviations from the IRB-approved protocol that increasethat increase or may increaseor may increase risk to risk to subjects or others (E6: 4.5.2 & 4.5.3)subjects or others (E6: 4.5.2 & 4.5.3)
Report all other protocol deviations at time Report all other protocol deviations at time of continuing reviewof continuing review
Provide an action plan to avoid recurrenceProvide an action plan to avoid recurrence– Amend protocol Amend protocol – Create departmental or study specific SOPsCreate departmental or study specific SOPs
Unanticipated Problems Involving Unanticipated Problems Involving Risks to Subjects or Others (UAPs)Risks to Subjects or Others (UAPs)
Report local events that meet all 3 of the Report local events that meet all 3 of the criteria below:criteria below:
1)1) UnexpectedUnexpected
2)2) Related to the study Related to the study ANDAND
3)3) Pose harm or a Pose harm or a potentialpotential for harm to subjects for harm to subjects or others or others
(E6: (E6: 4.11)4.11)
Different Types of Potential UAPsDifferent Types of Potential UAPs
Physical (e.g. adverse events)Physical (e.g. adverse events) Emotional or psychological harm (e.g., Emotional or psychological harm (e.g.,
stress and anxiety)stress and anxiety) Social harm (e.g., stigma)Social harm (e.g., stigma) Financial harm (e.g., loss of employment Financial harm (e.g., loss of employment
or insurability)or insurability) Legal harm (e.g., criminal or civil liability)Legal harm (e.g., criminal or civil liability) Invasion of privacy or embarrassment due Invasion of privacy or embarrassment due
to breaches of confidentiality to breaches of confidentiality
The Process of Informed ConsentThe Process of Informed Consent
Create an Informed Consent ProcessCreate an Informed Consent Process– Informed consent is not a single event Informed consent is not a single event
or just a form to be signedor just a form to be signed– Need a detailed plan that describes the Need a detailed plan that describes the
informed consent processinformed consent processOngoing ConsentOngoing Consent
– Ongoing discussions regarding the study Ongoing discussions regarding the study is imperative in assessing a subject’s is imperative in assessing a subject’s willingness to continue study willingness to continue study participationparticipation
Obtaining Legally Effective Obtaining Legally Effective Informed ConsentInformed Consent
Before informed consent may be obtained, Before informed consent may be obtained, the investigator, or a person designated the investigator, or a person designated by the investigator, should provide the by the investigator, should provide the subject ample time and opportunity to subject ample time and opportunity to inquire about details of the study and to inquire about details of the study and to decide whether or not to participate (E6: decide whether or not to participate (E6: 4.8.7)4.8.7)
All questions about the study should be All questions about the study should be answered to the satisfaction of the subject answered to the satisfaction of the subject (E6: 4.8.7)(E6: 4.8.7)
Obtaining Legally Effective Obtaining Legally Effective Informed ConsentInformed Consent
Prior to a subject's participation in the Prior to a subject's participation in the study, the informed consent form should study, the informed consent form should be be signed and datedsigned and dated by the subject and by by the subject and by the person who conducted the informed the person who conducted the informed consent discussion (E6: 4.8.8)consent discussion (E6: 4.8.8)
Prior to participation in the study, the Prior to participation in the study, the subject should receive a copy of the subject should receive a copy of the signed and dated informed consent form signed and dated informed consent form (E:6 4.8.11)(E:6 4.8.11)
Sharing New InformationSharing New Information The informed consent form should be revised The informed consent form should be revised
whenever important new information becomes whenever important new information becomes available that may be relevant to the subject's available that may be relevant to the subject's consent. consent.
The subject should be informed in a timely The subject should be informed in a timely manner if new information becomes available that manner if new information becomes available that may be relevant to the subject's willingness to may be relevant to the subject's willingness to continue participation in the trial. continue participation in the trial.
Revised informed consent form(s) or consent Revised informed consent form(s) or consent addendums must receive IRB approval in advance addendums must receive IRB approval in advance of use.of use.
The communication of this information should be The communication of this information should be documented. documented.
(E.6: 4.8.2)(E.6: 4.8.2)
Record & Data ManagementRecord & Data Management
PI must ensure that research records PI must ensure that research records are:are:
– AccurateAccurate– CompleteComplete– LegibleLegible– Available for auditsAvailable for audits
(E6: 4.9.1 & (E6: 4.9.1 & 4.9.7)4.9.7)
Data Collection Instruments (DCI)Data Collection Instruments (DCI)
Review protocol thoroughly to create Review protocol thoroughly to create useful DCIs to collect imperative data useful DCIs to collect imperative data pointspoints
Forms/instruments must include:Forms/instruments must include:– Data collection Data collection datesdates– Subject Subject identifiersidentifiers
Source DocumentsSource Documents
Source documents are original documents, Source documents are original documents, data, and records (i.e. medical records, data, and records (i.e. medical records, chart notes, lab reports, memos, subject chart notes, lab reports, memos, subject diaries and checklists, x-rays, pharmacy diaries and checklists, x-rays, pharmacy dispensation logs, etc.)dispensation logs, etc.)
Data reported on DCIs should be Data reported on DCIs should be consistent with source documents consistent with source documents otherwise discrepancies should be otherwise discrepancies should be explained and documented (E6: 4.9.2)explained and documented (E6: 4.9.2)
Correcting DataCorrecting Data Any changes or correction to data should be Any changes or correction to data should be
– DatedDated– InitialedInitialed– Explained (if necessary)Explained (if necessary)– Do not obscure original dataDo not obscure original data
Example:Example: #010 #010 MMH 6/21/07MMH 6/21/07
“ “Subject #001 was seen today, 06/01/2007, for a follow-up Subject #001 was seen today, 06/01/2007, for a follow-up study visit. She reported no significant changes since her study visit. She reported no significant changes since her last visit. She had questions about when she would receive last visit. She had questions about when she would receive study payments. PI to follow-up with subject regarding her study payments. PI to follow-up with subject regarding her questions.”questions.”
(E6: 4.9.3)(E6: 4.9.3)
Maintaining Essential DocumentsMaintaining Essential Documents
Essential Documents are those documents Essential Documents are those documents which individually and collectively permit which individually and collectively permit evaluation of the conduct of a study and evaluation of the conduct of a study and the quality of the data produced.the quality of the data produced.
These documents serve to demonstrate These documents serve to demonstrate the compliance of the investigator with the the compliance of the investigator with the standards of GCP and with all applicable standards of GCP and with all applicable regulatory requirements.regulatory requirements.
(E6: (E6: 8.1)8.1)
Maintaining Essential DocumentsMaintaining Essential Documents
Filing essential documents in a timely Filing essential documents in a timely manner can greatly assist in the successful manner can greatly assist in the successful management of a study.management of a study.
These documents are also the ones which These documents are also the ones which are usually audited by the sponsor and are usually audited by the sponsor and inspected by the regulatory authorities as inspected by the regulatory authorities as part of the process to confirm the validity part of the process to confirm the validity of the study conduct and the integrity of of the study conduct and the integrity of data collected.data collected.
Maintaining Essential DocumentsMaintaining Essential Documents
Most Essential Documents are Most Essential Documents are maintained in either the:maintained in either the:
Regulatory BinderRegulatory Binder
Subject FilesSubject Files
Regulatory BinderRegulatory Binder Copy of IRB application and all corresponding Copy of IRB application and all corresponding
documents submitted and approved by the IRBdocuments submitted and approved by the IRB Copies of correspondence to and from the IRB Copies of correspondence to and from the IRB
including initial IRB approval letter, copies of including initial IRB approval letter, copies of consent form(s), assent form(s), parental consent form(s), assent form(s), parental permission form(s) with IRB approval stamppermission form(s) with IRB approval stamp
Continuing review forms and approvalsContinuing review forms and approvals Amendment forms and approvalsAmendment forms and approvals Copies of any advertisement(s) and IRB Copies of any advertisement(s) and IRB
approvalapproval Copy of related grant applicationCopy of related grant application
Regulatory BinderRegulatory Binder
Screening LogsScreening Logs Enrollment LogsEnrollment Logs Randomization LogsRandomization Logs
Refer to the “Regulatory Binder: Set-Refer to the “Regulatory Binder: Set-up and Maintenance” available on up and Maintenance” available on IRB’s Education Website for more IRB’s Education Website for more detailed guidance on the contents of detailed guidance on the contents of a typical regulatory binder.a typical regulatory binder.
Subject FilesSubject Files Signed consent forms, assent forms, or parental Signed consent forms, assent forms, or parental
permission forms permission forms Consent forms may be kept in a secure and Consent forms may be kept in a secure and
separate location from the data, however there separate location from the data, however there must be a key to link consent documents to real must be a key to link consent documents to real datadata
Source documents (e.g. blood test results or x-Source documents (e.g. blood test results or x-rays)rays)
Data Collection Instruments (i.e. forms, surveys)Data Collection Instruments (i.e. forms, surveys)– Proof that all inclusion/exclusion criteria were assessedProof that all inclusion/exclusion criteria were assessed– Follow-up AssessmentsFollow-up Assessments– Exit ProceduresExit Procedures
Principal Investigator Must EnsurePrincipal Investigator Must Ensure
All persons assisting with the study are All persons assisting with the study are adequately informed about the protocol, the adequately informed about the protocol, the investigational products, and their study-related investigational products, and their study-related duties and functions (E6: 4.2.4).duties and functions (E6: 4.2.4).
Prompt reporting to the IRB of any changes in Prompt reporting to the IRB of any changes in research activity including any changes to the research activity including any changes to the protocol, and/or consent form(s) and protocol, and/or consent form(s) and unanticipated problemsunanticipated problems
No change in approved research may be initiated No change in approved research may be initiated without the IRB’s approval except under without the IRB’s approval except under conditions where it is necessary to eliminate conditions where it is necessary to eliminate apparent immediate hazards to human apparent immediate hazards to human participantsparticipants
Members of the Research Team Members of the Research Team Must:Must:
Adhere rigorously to the IRB Adhere rigorously to the IRB approved protocolapproved protocol
Inform PIInform PI of all unanticipated of all unanticipated problemsproblems
Ensure the adequacy of the informed Ensure the adequacy of the informed consent processconsent process
Take measures necessary to ensure Take measures necessary to ensure adequate protection for subjectsadequate protection for subjects
Useful ToolsUseful Tools
The following tools are available on The following tools are available on the IRB’s Education Website:the IRB’s Education Website:
– Regulatory Binder: Set-up and Regulatory Binder: Set-up and MaintenanceMaintenance
– Human Subjects Protection Program: Human Subjects Protection Program: Investigator Self-AssessmentInvestigator Self-Assessment
ReferencesReferences
Good Clinical Practice: Consolidated Good Clinical Practice: Consolidated Guideline ICH Topic E6Guideline ICH Topic E6
Where to go for more Information?We are here to help!
The Research Protections Office is located off campus at
245 South Park, Suite 900, Colchester and our phone number is 656-5040.
Website: http://www.uvm.edu/rpo/
