ORIENTATION FOR NEW CLINICAL
RESEARCH PERSONNEL
MODULE 1
Presented by
NC TraCS Institute
UNC Office of Clinical Trials
UNC Network of Clinical Research Professionals
OVERVIEW OF ORIENTATION
PROGRAM & INTRODUCTION TO
CLINICAL RESEARCH
Marie Rape, TraCS Regulatory Core
Overall Agenda for Orientation
• Module 1:
Introduction to Clinical Research, Education, and IRB
• Module 2:
Study Implementation, Documentation, and GCPs
• Module 3:
Contracting, COI, and Hospital Administrative Elements
• Module 4:
Clinical Trial Management, Budgeting, Hospital and
Research Accounting
Module 1: Introduction and IRB
• Overview of orientation program – Marie Rape
• Introduction to clinical research – Marie Rape
• UNC Network of Clinical Research Professionals,
available educational programs – Michelle Duclos
• OHRE and IRB overview – Tim Kuhn
Module 2: Study Implementation and
Good Clinical Practices
• Roles of research personnel, study implementation –
Michelle Duclos
• Good Clinical Practices (GCP) and study
documentation – Marie Rape
• Informed consent process, HIPAA – Claudia Christy
Module 3: Contracting and Hospital
Administrative Elements
• Conflicts of interest – Joy Bryde
• Contracts and clinical trial agreements – Aylin Regulski
• ClinicalTrial.gov and ICMJE requirements – Monica Coudurier
• Investigational Drug Service – Sue Pope
• Investigational Device Policy – Aylin Regulski
Module 4: Clinical Trial Management,
Budgeting, and Accounting
• Overview of the Clinical Research Management System
(CRMS) – Ed Finerty/Laura Cowan
• Hospital 98 accounts and research billing – Nancy Rose
and Amelia Rountree
• Budgeting and accounting of research funds – Jill Cunnup
• Medicare coverage analysis – Jill Cunnup
Overall Objectives
• Define human subject / clinical research
• Discuss various options available for training of research personnel
• Review human subject research protection and the IRB
• Define appropriate responsibilities for study team members
• Describe steps for successful implementation of a study
• Describe appropriate management of study documentation
• Define Good Clinical Practices (GCP)
• Review the informed consent process
• Discuss research compliance and required approvals at UNC
• Review basic elements of contract negotiation and grant management
• Review use of the Clinical Research Management System (CRMS)
• Describe process for managing hospital research accounts and bills
• Describe steps for managing budgets and accounting of funds
Speaker
Office / Dept.
Represented
Phone
number
Email
Marie Rape
NC TraCS
919-966-6844
Marie_rape@med.unc.edu
Michelle Duclos
NCRP
919-484-0931
Michelle_duclos@med.unc.edu
Tim Kuhn
OHRE / IRB
919-843-3854
timkuhn@unc.edu
Claudia Christy
NC TraCS
919-843-9445
cgc@med.unc.edu
Joy Bryde
COI office
919-843-5328
jbryde@email.unc.edu
Aylin Regulski
OCT
919-843-7894
aylin@unc.edu
Monica Coudurier
OCT / CT.gov
919-843-2333
m_coudurier@unc.edu
Sue Pope
IDS
919-966-2371
Spope@unch.unc.edu
Ed Finerty
CRMS
919-843-2861
Edmund_finerty@med.unc.edu
Laura Cowan
CRMS
919-843-0726
Laura_cowan@med.unc.edu
Nancy Rose
Hosp. Accounting 919-966-4887
nrose@unch.unc.edu
Amelia Rountree
Hosp. Billing, 98# 919-966-7603
arountre@unch.unc.edu
Jill Cunnup
Budgeting
Jillyan_cunnup@med.unc.edu
919-966-0134
Who should attend Orientation?
• Personnel involved in clinical (human) research
• Study coordinator
• Social/Clinical research assistant
• Research nurse
• Research associate
• Regulatory personnel
• Investigators
• Involved in any type of clinical research
• Social Behavioral research
• Clinical trials
• Investigator initiated research
• Federal grants
• Biomedical research
Definition of Clinical Research
Clinical Research defined by NIH as
• Patient-oriented research: research involves a particular
person or group of people or uses materials from humans.
• Studies of mechanisms of human disease
• Studies of therapies or interventions for disease
• Clinical trials
• Studies to develop new technology related to disease
• Epidemiological and behavioral studies: studies
examine distribution of disease, factors that affect health,
how people make health-related decisions.
• Outcomes and health services research: studies seek to
identify the most effective and most efficient interventions,
treatments, and services.
Conducting Quality Research
• The overarching objective of clinical research is to develop
generalizable knowledge to improve health and/or increase
understanding of human biology
• However, research asking socially valuable questions can
be designed or conducted poorly leading to scientifically
unreliable or invalid results.
Study personnel are key to conducting quality research!
• Knowledge of research best practices, good clinical practices,
keeping abreast of regulatory requirements, and training needs
are key to conducting quality research.
Knowing the Resources Available
Topic
Unit/Office
Website
Telephone
Training for Research Staff
Network for Clinical Research
Professionals (NCRP)
http://tracs.unc.edu/clinical-research/networkfor-clinical-research-professionals-ncrp.html
na
Resources, NCRP, CRMS, upcoming events
Research Central
http://tracs.unc.edu/clinical-research/clinicalresearch-management-system-crms.html
na
Human subjects
Office of Human Research Ethics
http://research.unc.edu/offices/humanresearch-ethics/index.htm
919-966-3113
Online IRB application
OHRE
https://apps.research.unc.edu/irb/
na
Human subjects research, GCP, and RCR
training
CITI on-line training
http://research.unc.edu/offices/humanresearchethics/researchers/training/index.htm
HIPAA Policies, Training
HIPAA online Training
http://www.med.unc.edu/security/hipaa
Research facts and figures about UNC
UNC Research
http://research.unc.edu/index.htm
na
Sponsored projects
Office of Sponsored Research (OSR)
http://research.unc.edu/offices/sponsoredresearch/index.htm
919-966-3411
Proposal & Award Development
RAMSeS
https://apps.research.unc.edu/ramses/
919-966-3411
Clinical Trials, Contracts, CT.gov
Office of Clinical Trials
919-843-2698
Investigational Drugs
Investigational Drug Service (IDS)
http://research.unc.edu/offices/clinicaltrials/index.htm
http://pharmacy.intranet.unchealthcare.org/se
rvices/investdrugs
843-9919, (manager)
Clinical research support/Guidance
NC TraCS
tracs.unc.edu
966-6022
Submission Tool, 98 account, budgeting
Clinical Research Management System
843-0726 (Laura)
Research Studies Recruitment
Find Clinical Research at UNC
Clinical Research Unit
CTRC
Data and Safety Monitoring Boards
TraCS DSMB
IND/IDE Guidance
TraCS IND/IDE Program
http://tracs.unc.edu/clinical-research/usecrms.html
http://tracs.unc.edu/index.php?option=com_tr
acs_forms&view=rro&layout=searchable&Ite
mid=1267
http://tracs.unc.edu/ctrc/clinical-andtranslational-research-center.html
http://tracs.unc.edu/regulatory-services/nctracs-institute-dsmb.html
http://tracs.unc.edu/regulatoryservices/ind/ide-support.html
Cancer Research
Lineberger Comprehensive Cancer Center
(LCCC)
http://unclineberger.org/
919-966-3036
Oncology Protocol Review
Oncology Protocol Review Comm.
http://unclineberger.org/homemain/protocolreview
919-966-3036
na
na
843-1070
919-966-6844
919-843-9514
Training, Training, Training
Training is key to keeping abreast of best practices and
regulatory requirements. You need to take responsibility
for staying informed and educated!
Pre-Requisites for Orientation
• Completion of CITI Good Clinical Practice (GCP) Online
Training, available at www.citiprogram.org
• Completion of CITI Ethics Online Course, available at
www.citiprogram.org
STUDY COORDINATOR
EDUCATION
Michelle Duclos, President NCRP
Why Coordinator Education?
The investigator should ensure that any individual to
whom a task is delegated is qualified by education,
training and experience (and state licensure where
relevant) to perform the delegated task.
Documentation of training is essential for meeting the
guidelines put forth by regulatory agencies for the
conduct of Human Subject Research.
Study Coordinator Education
Documentation of Coordinator Education may be part
of the investigator/ department/division/center
processes. This may include (dependent on type of
research being conducted)
•
•
•
•
•
•
Completion of Human Research Ethics Training
Completion of Good Clinical Practices Training
CV and/or state licensure
Job Skill Training (such as conducting an EKG)
Training plan per your specific job title
Documentation of Training for each protocol
Example Training/Education Checklist
Example Matrix of Training
Study Coordinator Education
OHRP – Office of Human Research Protection
Responsibilities of UNC
• Before any human subjects research can be conducted, the
institution must provide the department or agency a written
Assurance that it will comply with the requirements of the Policy
www.hhs.gov/orhp
• The HHS regulations are intended to implement the basic ethical
principals governing the conduct of human subject research
General Responsibilities
All parties involved, institution, investigator, and IRB must actively
engage in ensuring human subject protection and this is only
achieved through proper training/education of all research
professionals
The purpose of the UNC-NCRP is to promote
excellence in the conduct of clinical, social, behavioral,
and translational research through a forum of
education, professional development
and mentoring programs
NCRP Educational Programs
• Lunch and Learns/Educational Seminars
• Mentoring
• Certification
• Committees
• Best practices
• Education
• Mentoring
• Listserv –
Current Projects
• Developing a career ladder with Office of Vice Chancellor for
Research
• Developing a coordinator handbook – release date Oct 2012
• Organizing ACRP/SoCra Certification study groups - ongoing
• Working towards developing a social/behavioral research coordinator
handbook
• Developing a Recruitment Toolkit to be available on website
• Developing SOPS and best practices, available on website – release
date Oct 2012
• Education through DID YOU KNOW series sent out via list serv
• Increasing awareness of NCRP
• NCPR wants to help you! Please let us know what you need to do
your job better!
Who to Contact
• To join the list serv, contact Michelle Duclos at
mduclos@med.unc.edu
• To serve on a committee, contact the committee chair
• Information regarding committees and upcoming events
can be found on our web site –
www.uncncrp.org
IRB OVERVIEW
Tim Kuhn
IRB Training Coordinator
Office of Human Research Ethics
Objectives
• List three types of IRB review
• Describe two IRB-related responsibilities for investigators
after receiving IRB approval for a study
• Describe which Events ARE reportable to the UNC IRB
• State what the UNC-CH IRB requires for ethics training
• Update on On-line IRB submissions
• Questions
ohre.unc.edu
• Regulatory Documents: OHRE Standard Operating
Procedures (SOPs); IRB Rosters
• For Researchers: Submission Instructions; Frequently
Asked Questions (FAQs); Student Guidance
• Deadlines and Meeting Dates
• Access to Ethics Training (CITI: Human Subjects Protection
“IRB” Modules)
• On-Line Submissions: Web portal for reporting UPs/AEs;
On-line Application; On-line Submission FAQs; Training
Videos and Printable Aids
• Resources: Links to useful information
US REGULATORY REQUIREMENTS
• All human subjects research must have prior approval by an
Institutional Review Board
• Independent review to protect rights and welfare of subjects
• Informed consent must be obtained (unless waived by the IRB)
• An “Assurance” to the federal government binds UNC-
Chapel Hill to uphold ethical and regulatory requirements
• License to receive extramural grants
• Can be suspended for violations
What is Research?
• Federal Regulations define Research as a systematic
investigation designed to develop or contribute to
generalizable knowledge
• Innovative clinical care is not necessarily research
• QA/QI is not necessarily research
WHAT IS A HUMAN SUBJECT?
• Federal Regulations define a human subject as a living
individual about whom an investigator obtains...
• data through interaction or intervention
•
•
•
•
randomized clinical trial
exposure to controlled conditions
systematic gathering of physiologic or psychological data
identifiable private information
• medical records review
• study of existing biologic specimens
Compulsive Buying Patterns in College
Students
• Who: Undergraduate students
• What: surveys of self esteem and buying habits
• When: class time (tacked on at the end)
• Where: recruited through university classes
• Why: assess prevalence of compulsive buying,
measure habits against low self esteem measures
Additional details:
• Questionnaire includes questions about drug and
alcohol use (current and past)
• Consent form requests signature
• PI requests an “exemption”
What is an IRB?
(Institutional Review Board)
• A committee mandated by federal regulations.
• Protects the rights and welfare of human subjects in
research activities through independent review of
proposed research.
What does an IRB do?
• Educates researchers about the IRB review process and
requirements
• Approve, disapprove or modify research involving human
subjects
• Conduct continuing review of research
• Observe, monitor, audit research
• Suspend or terminate approval of research
IRB Membership
• At least 5 members, not all men, not all women (UNC
•
•
•
•
•
IRBs have 10-15 members)
Not all members of one profession
Diversity
Expertise appropriate to the research
At least one scientist, one non-scientist
At least one member not otherwise affiliated with the
institution
UNC-CH IRBs
• Biomedical (A,B,C,D): Expertise is focused on medical,
dental, surgical, physiological, or pharmacological
research
• Non-Biomedical (E): Expertise is focused on research in
behavioral and social sciences; the humanities; and
research in a public health or nursing context
Growth in Volume and Complexity of
Research Requiring IRB Review
1999-2011
12000
10000
Nursing
8000
Dental
6000
Public Health
Behavioral
4000
Biomedical
2000
0
1999
2001
2003
2005
2007
2009
2011
Level of Risk Generally
Determines Level of IRB Review
Full Board Review
Minimal Risk?
Is it on the list?
9 Categories defined by Regs
Expedited
Is it on the list?
6 Categories defined by Regs
“Exempt”
2. Are there Human Subjects?
Not Human Subjects
Research
1. Is it Research?
RISK
Types of Risk
• Physical (e.g. pain, drug side effects, or injury)
• Psychological (e.g. emotional distress)
• Social (e.g. stigmatization)
• Economic (e.g. loss of job—breach of confidentiality that
relates to stigma, or workplace competency issues)
• Legal (requirements to report some illegal activities, whether
the focus of the study, or which emerge without prompting)
“Exempt” Research
45 CFR 46.101(b)
• Six categories, defined by regulations
• PI may request an exemption
• IRB will make the determination
• Exempt from continuing review, once approved by the IRB
• Investigator obligated to conduct research as described in
protocol
“Exempt” Research*
45 CFR 46.101(b)
1. Normal educational practices in
established educational settings
2. Educational tests, surveys,
interviews, or observation of public
behavior -unless identified &
sensitive**
3. Research on elected or appointed
public officials or candidates for
public office
4. Research using existing data, if
publicly available or recorded
without identifiers
5. Evaluation of public benefit
service programs
6. Taste and food quality evaluation
and consumer acceptance studies
* Exception for prisoners
** Exception for children
42
Expedited Review
45 CFR 46.110
• Nine categories, defined by regulations
• Chair or designated member
• IRB Members informed
• Reviewer may not disapprove
Criteria for IRB Approval:
Expedited or Full Board review
1.
Risks minimized
2.
Favorable risk: benefit ratio
3.
Equitable selection of subjects
4.
Informed consent sought
5.
Informed consent documented
6.
Monitoring plan for safety
7.
Privacy and confidentiality protected
8.
Additional safeguards for vulnerable populations
45 CFR 46.111 and 21 CFR 56.111
The IRB Meeting
Voting on possible actions
Approved
Minor
contingencies
required for
approval
Deferred
(major
changes
required)
Disapproved
When You Get a Contingency Memo:
• Don’t despair and don’t take it personally
• It is rare for study not to raise at least one question from
the IRB
• The PI should respond point by point in writing to the
memo and make the corresponding changes to the
application and consent forms
When You Get a Contingency Memo:
Approved!
• Research may proceed upon receipt of written
documentation of IRB approval
• Investigator has a responsibility to report to the IRB
• Changes BEFORE they are implemented
• Unanticipated problems or serious adverse events that
may occur during the research
What if you want to change the
protocol?
• Once your study is approved, you may submit
modifications
• All protocol changes must be approved by the IRB
before implementation.
• All changes to documents used with subjects (consent
forms, questionnaires, recruitment materials, etc.) must
be approved by the IRB before using.
Modifications to Approved Studies
• The IRB assesses if the modification changes the level
of risk:
• Do subjects need to be made aware of the new
information?
• If a revised consent form is included, is it accurate?
Continuing Review or “Renewal”
• No approval is valid for longer than one year from the initial
review
• Expired (lapsed) approval = no approval
• Must meet same criteria for approval as at initial review
• IRB continues to review risk: benefit
• Adverse event reporting
• Unanticipated problems
Continuing Review or “Renewal”
• The IRB assesses whether the study is proceeding as
expected:
• Is the number of subjects enrolled < the number approved?
• Have there been unanticipated problems or new information
that suggests a change in risk:benefit?
• Are there trends in protocol deviations that may need to be
addressed?
• Do monitoring reports or Data Safety Monitoring Committee
reports suggest issues that may need to be addressed?
• Are there changes requested for the upcoming approval
period?
From OHRP Guidance
Under 45 CFR part 46: Do not report A;
Report B and C.
Vast majority of
AEs are NOT
REPORTABLE
Small proportion
of AEs are UPs-REPORTABLE
REPORTABLE UPs
include “events” that
are NOT AEs
What is a UP?
Federal guidance defines as: Any incident, experience, or outcome
that meets all of the following criteria:
1. Unexpected (in terms of nature, severity, or frequency) given (a)
the research procedures that are described in the protocol-related
documents, such as the IRB-approved research protocol and
informed consent document; and (b) the characteristics of the
subject population being studied;
2. Related or possibly related to a subject’s participation in the
research; and
3. Suggests that the research places subjects or others at a
greater risk of harm (including physical, psychological, economic,
or social harm) related to the research than was previously known
or recognized.
Reporting UPs to the UNC IRB
An event that satisfies the first two criteria:
1.is unexpected
2.is related or possibly related to participation in research
is reportable to the IRB using the on-line system
The researcher is asked to provide a risk assessment
however, risk will be determined by the IRB.
Likely Outcomes of Reportable UPs
According to federal guidance, “unanticipated problems
involving risks to subjects or others” warrant consideration
of:
1. Substantive changes to the protocol or informed consent
process/document; or
2. Corrective actions in order to protect the safety, welfare,
or rights of subjects
UPs vs. AEs
Most adverse events (AEs) are not unanticipated problems
(UPs)
• AEs that are expected in terms of specificity, severity, and
frequency (e.g., described in the protocol, Investigator
Brochure, the literature, or the consent form) are not Ups
• AEs that are unrelated to the research or there is simply
insufficient information to address causality are not Ups
• AEs that do not place subjects at greater risk of harm than
was considered by the IRB when it approved the research
are not UPs
“Serious Adverse Event” (SAE)
Any adverse event temporally associated with the subject’s
participation in research that meets any of the following criteria:
1.results in death;
2.is life-threatening (places the subject at immediate risk of death from
the event as it occurred);
3.requires inpatient hospitalization or prolongation of existing
hospitalization;
4.results in a persistent or significant disability/incapacity;
5.results in a congenital anomaly/birth defect; or
6.any other adverse event that, based upon appropriate medical
judgment, may jeopardize the subject’s health and may require
medical or surgical intervention to prevent one of the other outcomes
listed in this definition
Reportable Events
Include ALL Protocol
Violations
IND Safety Reports
• Individual IND safety reports from external sites should not be
reported to the IRB unless accompanied by an aggregate
analysis (e.g., DSMB report) that establishes their significance
and a corrective action plan that addresses the problem.
• IND Safety Reports shall be maintained by the Investigator and
should be reported in summary (e.g., not individual reports) to
the IRB at the time of continuing review.
• IND safety reports from external sites that ARE accompanied by
an aggregate analysis that establishes their significance (e.g.,
DSMB report), includes a corrective action plan, and that meet
the criteria for a UP should be reported using the on-line system
and changes to protocol or consent form should be submitted, if
applicable
Data Safety Monitoring Boards
(DSMB) Reports
• Some reports from a DSMB or other independent
safety monitoring group provide the aggregate
analysis of individual IND Safety Reports, and if this
report establishes their significance, includes a
corrective action plan, and meets the criteria for a UP,
it should be reported using the on-line system and
changes to the protocol and consent form should be
submitted, if applicable
• Other reports from a DSMB or other independent
safety monitoring group should be provided to the IRB
as they become available, or at least as often as the
study undergoes continuing review
Time Frame for Reporting
• Serious Adverse Events (SAE) that meet the criteria for a
UP should be reported to the IRB using the on-line system
ASAP, but no later than one week
• All other UPs should be reported to the IRB using the on-
line system ASAP, but no later than two weeks.
Example
Nausea during chemotherapy treatment
Q1: Did the event occur at a site for which UNC IRB has
direct oversight? YES
Q2: Was the event unexpected? NO
The event IS NOT Reportable
Example
Sudden death during chemotherapy treatment Q1: Did
the event occur at a site for which UNC IRB has direct
oversight? YES
Q2: Was the event unexpected? YES
Q3: Was the event related or possibly related to the
research? YES
The event IS Reportable using the on-line system
Example
Lost laptop used for research study
Q1: Did the event occur at a site for which UNC IRB has
direct oversight? YES
Q2: Was the event unexpected? YES
Q3: Was the event related or possibly related to the
research? YES
The event IS Reportable using the on-line system
Example
Severe psychological stress from completing a survey
on risk-prone behaviors
Q1: Did the event occur at a site for which UNC IRB has
direct oversight? YES
Q2: Was the event unexpected? YES
Q3: Was the event related or possibly related to the
research? YES
This event IS Reportable using the on-line system
Example
Fainting during blood draw
Q1: Did the event occur at a site for which UNC IRB has
direct oversight? YES
Q2: Was the event unexpected? NO
This event IS NOT Reportable
Example
IND safety report received by investigator from an
external site. The report states that the investigator
(at which the event occurred) has determined that
the event is reportable. No documentation of
aggregate analysis or corrective action plan
provided.
• Q1: Did the event occur at a site for which UNC
IRB has direct oversight? NO
• Q2: Has a determination been made by the
Sponsor, DSMB/DMC, etc., that the event meets
criteria for UP? NO
The event has not been determined to be an UP and is
therefore NOT Reportable to the UNC IRB
Example
Sponsor letter that provides the findings of interim
review identifying previously unrecognized risks.
• Q1: Did the event occur at a site for which UNC IRB has
direct oversight? NO
• Q2: Has a determination been made by the Sponsor,
DSMB/DMC, etc., that the event meets criteria for UP?
YES
The event IS a UP and therefore IS Reportable to the UNC
IRB using the on-line system (and submit changes to
protocol or consent form, if applicable)
Protocol Violations and Deviations
Protocol Violations are a variance from the study protocol that:
• Has harmed or increased the risk of harm to one or more research subjects.
• Has damaged the scientific integrity of the data collected for the study.
• Results from willful or knowing misconduct on the part of the investigator(s).
• Demonstrates serious or continuing noncompliance with federal regulations,
State laws, or University policies.
Protocol Deviations are a variance from the study protocol that:
• Is generally noted or recognized after it occurs.
• Has no substantive effect on the risks to research participants.
• Has no substantive effect on the scientific integrity of the research plan or
the value of the data collected.
• Did not result from willful or knowing misconduct on the part of the
investigator(s).
Examples of Protocol Violations
• Proceeding with the research without IRB approval
• Failing to follow IRB-approved procedures
• Implementing any changes without IRB approval
• Enrollment of subjects who do not meet eligibility
criteria
• Proceeding with research interventions prior to
obtaining written informed consent
• Missed or significantly delayed safety visits or tests.
• Medication errors
Examples of Protocol Deviations
• Performing a planned procedure on a different
timetable than previously specified in the research
protocol because of an unforeseen disruption such as
a subject’s vacation or illness
• Study visits out of window (not affecting subject risk)
• A mechanical failure such as a recording device
malfunction
• Late PK specimens
Reporting Protocol Violations and
Protocol Deviations
Protocol Violations should be reported to the IRB within
one (1) week of the investigator becoming aware of the
event using the same online reporting mechanism used to
report UPs.
Protocol Deviations should be summarized and reported to
the IRB at the time of continuing review. Deviations should
not be reported individually as they occur.
ohre.unc.edu
• Regulatory Documents: OHRE SOPs (eg, 19.0
Reporting of UPs and AEs to the IRB and 23.0 Protocol
violations, deviations and exceptions)
• Online Submissions / UPs and AEs
• Relevant Links:
• Computer Based Training module
• Decision tree for determining reportability
• OHRP Guidance
• FDA Guidance
• Web portal for online reporting
When can I close my study?
• Renew the study as long as data analysis of identifiable
data is on-going
• When you are completely done with all interventions,
follow-up and data analysis, the study should be closed
• If IRB approval of a study expires, no new subjects may
be enrolled and all ongoing research activities must stop
OBTAINING CONSENT
• Obtaining consent is a PROCESS in which...
• investigator discloses all relevant information
• potential subject has opportunity to ask questions
• investigator answers questions
• subject signs a consent form
• The consent form is a permanent record of...
• information conveyed
• subject’s willingness to participate
Written Consent Forms
• Required elements are covered in templates generated by
the on-line application
• Language must be understandable to subject or
representative
• Some elements, including signatures, may be waived
under certain circumstances
45 CFR 46.116, 21 CFR 50.25
REQUIRED ELEMENTS
• Study involves research
• Purpose
• Duration of the subject’s participation
• Description of the procedures
• Foreseeable risks and discomforts
• Reasonably expected benefits to subject or others
45 CFR 46.116, 21 CFR 50.25
REQUIRED ELEMENTS
• Alternatives, if any
• Confidentiality
• Compensation for injury (> minimal risk)?
• Contacts for questions about the research, research-
related injury, subjects’ rights
• Voluntary participation, refusal without loss of benefits,
withdraw at any time
45 CFR 46.116, 21 CFR 50.25
Human Subjects Protection Training
• To access CITI, go to ohre.unc.edu / For Researchers /
•
•
•
•
Ethics Training / CITI on-line course
If you have CITI training at another institution, add an
affiliation at UNC-CH, your training records will be
transferred electronically
When registering, enter your UNC-CH PID
(9 digits, no hyphen, no space).
Choose Human Subjects Protection (“IRB”) modules
rather than GCP or RCR training
Complete the Basic Course most appropriate to your
area of research
Tips for Successfully Navigating
the IRB Review Process
IRB on-line Contact Information
• E-mail:
irb_questions@unc.edu
• Phone:
919-966-3113
• On-line Help Desk: David Tegnell 919-966-3685
On-line Submissions
• Smart form approach
• Single form builds on itself:
•
•
•
•
•
NHSR – Exemption – Full application
System builds consent forms
Electronic Routing and Approvals
On-line communication to and from the IRB
Include a cover memo that explains special circumstances
On-line Submission Training – web-based videos and
printable aids
Plan ahead!
• Your application may be one of 100’s submitted that week
• Full Board only meets once per month
• Pay attention to dates and deadlines
• Complete the application as directed
• Provide consents; recruitment materials; and supporting
documents
• If you have questions while completing the application or
consents, call 966-3113 or email irb_questions@unc.edu
Transition from Paper to Online
Type of Submission Route of Submission
New Studies
Online
Modifications
To new study started online
 online
To existing study started on paper
 Can stay on paper until next renewal
 Can submit online, requiring conversion of
full application (OPTIONAL)
Renewals
 Ongoing study
 Data analysis only
Online
Online – but greatly abbreviated
Closure
Created online
Existing on paper
Online
Online or paper
Reference #: Provide to IRB
(Before submission)
Routing of IRB Submissions
PI and/or
Study Staff
Drafts
Application
Certification by
PI
(and Faculty
Advisor if
Student PI)*
PI’s Home
Department
(Chair or
Dept Review
Committee)
Administering
Department
(if any)
Oncology
PRC or
CTRC
(if relevant)
Non-IRB Issues (if any)
*Note that student research will follow same routing process as any project
IRB
Department Approvers
By approving, the Home or Administering department affirms that:
• The research is appropriate for the investigator and Department
• The investigator(s) are qualified to conduct the research
• There are adequate resources (financial, support, and facilities)
available
• For units that have a local review committee for pre-IRB review, this
requirement has been satisfied
• The department supports the application and its review by the IRB
• The department agrees to accept responsibility for managing data
security risks in consultation with departmental or campus security
personnel
Where’s my application?
Where’s my application?
Check to
see who
has
certified
Check to
see who
has been
notified to
certify
Where IRB
Marked
Documents
Will be
located
CONFIRM
Training
and COI
Research Data Security
Grading System
Subject
IDs
Sensitive
Questions
Security
Level
Requirements*
---
---
I
Password protection
YES
---
II
Level I plus secure network
---
YES
II
Level I plus secure network
YES
YES
III
Level II plus encryption, vulnerability
scans, security audits
* Note that schools and departments will be expected to play a more central
role in ensuring security requirements are met. Investigators should consult
with IT managers for their units.
IT Expert within the Approving Department
(Department Responsible for the Study)
Requesting an Exemption
Requesting an Exemption
Requesting an Exemption
Consent Process for Exemptions
A.4. Study design, methods and procedures
A.4.A. Biomedical methods and procedures
99
A.4.A. Biomedical methods and procedures
What is a clinical trial?
• Although there are many definitions of clinical trials, they are generally
considered to be biomedical or health-related research studies in human
beings that follow a pre-defined protocol.
• Clinicaltrials.gov includes both interventional and observational types of
studies.
• Interventional studies are those in which the research subjects are assigned
by the investigator to a treatment or other intervention, and their outcomes
are measured.
• Observational studies are those in which individuals are observed and their
outcomes are measured by the investigators.
Consent Form Template
What if you have questions about this study?
• You have the right to ask, and have answered, any questions you may have
about this research. If you have questions, complaints, concerns, or if a
research-related injury occurs, you should contact the researchers listed on
the first page of this form.
• A description of this clinical trial will be available on www.clinicaltrials.gov, as
is required by US law. This web site will not include information that can
identify you. At most, the web site will include a summary of the results. You
can search this web site at any time.
102
Investigational Drug Service Approval
Investigational Drug Service
OHRE SOP 30.8.4
An agent (drug) will be considered investigational if both
the following two criteria are met:
1. administration of the agent is part of a protocol that
requires IRB approval
2. a subject is required to sign an Informed Consent
Form before receiving the agent
Researchers using investigational drugs in studies must
register all studies with the IDS Pharmacy.
Approval letter from IDS should be uploaded in your IRB
submission
Investigational Drug Service
IDS Website:
http://pharmacy.intranet.unchealthcare.org/services/investdrugs/
Contact information, FAQs, IDS forms
Radiation Safety Committee Approval
Radiation Safety Committee
OHRE SOP 30.9
• Projects in which subjects are exposed to ionizing radiation must
receive approval from UNC Radiation Safety Committee before final
IRB approval can be granted.
• Studies involving the use of radiation, such as those requiring patients
to be X-rayed, are not eligible for expedited review by IRB, even if all
of the other procedures in the study have been deemed to pose no
more than minimal risk.
• Approval letter from Radiation Safety Committee should be uploaded
in your IRB submission
Radiation Safety Committee
Forms available at http://ehs.unc.edu/ehs/forms.shtml#rad
(UNC EHS website, click on forms, Human Use of Radiation in Research)
Optional Cover Memo to the IRB
IRB Contact Information
• Website: ohre.unc.edu
• E-mail:
irb_questions@unc.edu
• Phone:
919-966-3113
• Fax:
919-966-7879
• On-line Help Desk:
David Tegnell 919-966-3685
• Address: 105 Mason Farm Road
Medical School Building 52 (CB # 7097)
• E-mail (training): irb_training@unc.edu
Tim Kuhn 919-843-3854
timkuhn@unc.edu
PLEASE VISIT
TRACS.UNC.EDU / RESEARCH CENTRAL
FOR A COPY OF THIS PRESENTATION
& ADDITIONAL HELPFUL INFORMATION