Research Coordination
Guidance
The Committees on Human Research
Serving
University of Vermont & Fletcher Allen Health Care
09-23-11
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The following material is intended as
guidance on how to achieve good
standards and/or best practices in the
conduct of research with human subjects.
 It is meant to be an adjunct to the basic
human subjects protection training
information provided in the required online tutorial.
 The goal is to provide practical advice and
tips on how to implement good practices to
achieve high quality research results while
ensuring the protection of research
participants.
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
Good Clinical Practice (GCP)
Developed for clinical research, GCP is an
international ethical and scientific quality
standard applied to human subject
research that impacts:
Study
design
Conduct
Record management
Data collection and reporting
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Good Clinical Practice
Compliance with GCP standards
provides public assurance that the
rights, safety and well-being of
human subjects are protected and
that the study data are credible.
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Applying GCP Standards to ALL
Types of Research
The principles established by GCP are
typically applied to biomedical
research, but it is recommended that
they also be applied to other studies
which have an impact on the safety
and well-being of human subjects.
This includes research in the
behavioral sciences.
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GCP Objectives
 Basic
Principles of GCP
 Compliance with Protocol
 IRB Reporting Requirements
 The Process of Informed Consent
 Record & Data Management
 PI & Research Member
Responsibilities
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Principles of GCP
 The
rights, safety, and well-being of
the research subjects are the most
important considerations and should
prevail over interests of science and
society (E6: 2.3)
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Principles of GCP


Each individual involved in study conduct should
be qualified by education, training, and
experience to perform his or her respective tasks
(E6: 2.8)
The principal investigator should be qualified by
education, training, and experience to assume
responsibility for the proper conduct of the study,
should meet all the qualifications specified by the
applicable regulatory requirements, and should
provide evidence of such qualifications through
up-to-date CV and/or other relevant
documentation requested by the sponsor, IRB,
and/or the regulatory authorities (E6: 4.1.1)
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Principles of GCP
 Informed
consent should be obtained
from every subject prior to study
participation (E6: 2.9)
 All
study information should be
recorded, handled, and stored in a
way that allows its accurate
reporting, interpretation and
verification (E6: 2.10)
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Principles of GCP


The confidentiality of records that could
identify subjects should be protected,
respecting the privacy and confidentiality
rules in accordance with the applicable
regulatory requirements (E6: 2.11)
Systems with procedures that assure the
quality of every aspect of the study should
be implemented (E6: 2.13)
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Compliance with the IRB-approved
Protocol



A study should be conducted in compliance with
the protocol that has received prior IRB approval
(E6: 2.6 & 4.5.1)
If you conduct research that deviates from the
IRB approved protocol then you are in
noncompliance
Serious and continuing noncompliance is
reportable to federal regulatory authorities,
sponsors and institutional officials
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IRB Reporting Requirements
 Protocol
Amendments
 Protocol
Deviations
 Unanticipated
Problems Involving
Risks to Subjects or Others
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Protocol Amendments
Changes to the study must be submitted
for IRB review (E6: 4.4.3 & 4.10.2)
 Examples of study changes:

– Study procedures
– Adding, revising or eliminating measures
 Surveys,
questionnaires, data collection forms, etc.
– Recruitment materials
– Study termination, suspensions, and final
closure (E.6: 4.12 & 4.13)

Only implement protocol changes after
you receive notice of IRB approval
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Protocol Deviations
Report promptly to the Committee
deviations from the IRB-approved protocol
that increase or may increase risk to
subjects or others (E6: 4.5.2 & 4.5.3)
 Report all other protocol deviations at
time of continuing review
 Provide an action plan to avoid recurrence

– Amend protocol
– Create departmental or study specific SOPs
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Unanticipated Problems Involving
Risks to Subjects or Others (UAPs)
Report local events that meet all 3 of the
criteria below:
1) Unexpected
2) Related to the study AND
3) Pose harm or a potential for harm to
subjects or others
(E6: 4.11)
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Different Types of Potential UAPs
Physical (e.g. adverse events)
 Emotional or psychological harm (e.g.,
stress and anxiety)
 Social harm (e.g., stigma)
 Financial harm (e.g., loss of employment
or insurability)
 Legal harm (e.g., criminal or civil liability)
 Invasion of privacy or embarrassment due
to breaches of confidentiality

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The Process of Informed Consent
 Create
an Informed Consent Process
– Informed consent is not a single event
or just a form to be signed
– Need a detailed plan that describes the
informed consent process
 Ongoing
Consent
– Ongoing discussions regarding the study
is imperative in assessing a subject’s
willingness to continue study
participation
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Obtaining Legally Effective
Informed Consent


Before informed consent may be obtained,
the investigator, or a person designated
by the investigator, should provide the
subject ample time and opportunity to
inquire about details of the study and to
decide whether or not to participate (E6:
4.8.7)
All questions about the study should be
answered to the satisfaction of the subject
(E6: 4.8.7)
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Obtaining Legally Effective
Informed Consent


Prior to a subject's participation in the
study, the informed consent form should
be signed and dated by the subject and by
the person who conducted the informed
consent discussion (E6: 4.8.8)
Prior to participation in the study, the
subject should receive a copy of the
signed and dated informed consent form
(E:6 4.8.11)
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Sharing New Information




The informed consent form should be revised
whenever important new information becomes
available that may be relevant to the subject's
consent.
The subject should be informed in a timely
manner if new information becomes available
that may be relevant to the subject's willingness
to continue participation in the trial.
Revised informed consent form(s) or consent
addendums must receive IRB approval in
advance of use.
The communication of this information should be
documented.
(E.6: 4.8.2)
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Record & Data Management
 PI
must ensure that research records
are:
– Accurate
– Complete
– Legible
– Available for audits
(E6: 4.9.1 & 4.9.7)
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Data Collection Instruments (DCI)
 Review
protocol thoroughly to create
useful DCIs to collect imperative data
points
 Forms/instruments
must include:
– Data collection dates
– Subject identifiers
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Source Documents


Source documents are original documents,
data, and records (i.e. medical records,
chart notes, lab reports, memos, subject
diaries and checklists, x-rays, pharmacy
dispensation logs, etc.)
Data reported on DCIs should be
consistent with source documents
otherwise discrepancies should be
explained and documented (E6: 4.9.2)
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Correcting Data

Any changes or correction to data should be
–
–
–
–

Dated
Initialed
Explained (if necessary)
Do not obscure original data
Example:
#010 MMH 6/21/07
“Subject #001 was seen today, 06/01/2007, for a follow-up
study visit. She reported no significant changes since her
last visit. She had questions about when she would receive
study payments. PI to follow-up with subject regarding her
questions.”
(E6: 4.9.3)
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Maintaining Essential Documents


Essential Documents are those documents
which individually and collectively permit
evaluation of the conduct of a study and
the quality of the data produced.
These documents serve to demonstrate
the compliance of the investigator with the
standards of GCP and with all applicable
regulatory requirements.
(E6: 8.1)
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Maintaining Essential Documents


Filing essential documents in a timely
manner can greatly assist in the
successful management of a study.
These documents are also the ones which
are usually audited by the sponsor and
inspected by the regulatory authorities as
part of the process to confirm the validity
of the study conduct and the integrity of
data collected.
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Maintaining Essential Documents
 Most
Essential Documents are
maintained in either the:
Regulatory
Subject
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Binder
Files
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Regulatory Binder






Copy of IRB application and all corresponding
documents submitted and approved by the IRB
Copies of correspondence to and from the IRB
including initial IRB approval letter, copies of
consent form(s), assent form(s), parental
permission form(s) with IRB approval stamp
Continuing review forms and approvals
Amendment forms and approvals
Copies of any advertisement(s) and IRB
approval
Copy of related grant application
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Regulatory Binder
 Screening
Logs
 Enrollment Logs
 Randomization Logs
 Refer
to the “Regulatory Binder: Setup and Maintenance” available on
IRB’s Education Website for more
detailed guidance on the contents of
a typical regulatory binder.
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Subject Files




Signed consent forms, assent forms, or parental
permission forms
Consent forms may be kept in a secure and
separate location from the data, however there
must be a key to link consent documents to real
data
Source documents (e.g. blood test results or xrays)
Data Collection Instruments (i.e. forms, surveys)
– Proof that all inclusion/exclusion criteria were assessed
– Follow-up Assessments
– Exit Procedures
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Principal Investigator Must Ensure



All persons assisting with the study are
adequately informed about the protocol, the
investigational products, and their study-related
duties and functions (E6: 4.2.4).
Prompt reporting to the IRB of any changes in
research activity including any changes to the
protocol, and/or consent form(s) and
unanticipated problems
No change in approved research may be initiated
without the IRB’s approval except under
conditions where it is necessary to eliminate
apparent immediate hazards to human
participants
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Members of the Research Team
Must:
 Adhere
rigorously to the IRB
approved protocol
 Inform PI of all unanticipated
problems
 Ensure the adequacy of the informed
consent process
 Take measures necessary to ensure
adequate protection for subjects
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Useful Tools
The following tools are available on
the IRB’s Education Website:
– Regulatory Binder: Set-up and
Maintenance
– Human Subjects Protection Program:
Investigator Self-Assessment
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References
 Good
Clinical Practice: Consolidated
Guideline ICH Topic E6
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Where to go for more Information?
We are here to help!
University of Vermont
Research Protections Office
213 Waterman Building
85 South Prospect Street
Burlington, Vermont 05405
(802) 656-5040
http://www.uvm.edu/rpo/
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