Wendy Lloyd
BA, LPN, CIP,CCRP
Regulatory Affairs and Compliance Specialist
 Identify
consent process requirements
 Distinguish between IRB, PI/Designee consent
process responsibilities
 Identify with what went wrong? Audit results,
FDA Warning Letters and OHRP Determination
Letters
 Summarize tips to avoid deficiencies
 "A
word is not a crystal, transparent and
unchanged; it is the skin of a living thought
and may vary greatly in color and content
according to the circumstances and the time
in which it is used"
— Oliver Wendell Holmes Jr.
 DHHS
– 45 CFR Part 46
 FDA 21 CFR
 Part 50 (Informed Consent)
 Part 56 (IRB)

No investigator may involve a human
being as a subject in research covered
by these regulations unless the
investigator has obtained the legally
effective informed consent of the
subject or the subject's legally
authorized representative

The information that is given to the
subject or the representative shall be
in language understandable to the
subject or the representative and
include the elements of consent
 An
IRB shall require that information given to
subjects as part of informed consent is in
accordance with 50.25.
 The
IRB may require that information, in
addition to that specifically mentioned in
50.25, be given to the subjects when in the
IRB's judgment the information would
meaningfully add to the protection of the
rights and welfare of subjects.






Detailed description of the method for obtaining informed
consent
All informed consent documents submitted for IRB approval
Changes in ICD’s are submitted as amendments
Consent must contain all required elements
Consent is documented in writing through the use of a
current IRB-approved ICD, unless waived
PI assures the informed consent process in research is an
ongoing exchange of information throughout the course of
the research and it is documented
Fetuses, Pregnant Women, and
Human In Vitro Fertilization
 Prisoners
 Children
 Elderly
 Cognitively Impaired
 Minorities
 Etc.

FDA Mandates
ICH/GCP 4.8 suggests
FDA
has no regulations
concerning delegation of
consenting although it is
discussed in the FDA
Information Sheets
FDA
only requires that a copy
of consent be provided to
subject
consent is obtained the
same day that the subject's
involvement in the study
begins, the subject's medical
records/case report form
should document that consent
was obtained prior to
participation in the

ICH allows the
delegation of the
informed consent
process to a designee

ICH recommends the
person conducting
the informed consent
process sign and date
the consent form

ICH recommends that
the subject receive a
signed and dated
copy of the consent
form
If
research“FDA Consent information sheet”
FDA and ICH BOTH require the IRB to review
The informed consent,
process,
 protocol,
 advertisements, and
 the Investigator's Brochure


ICH/GCP 3.1 also recommends IRB submission of:
 Subject recruitment procedures
 Written information provided to subjects
 Information about subject compensation
 Investigator's current CV and/or other
documents evidencing qualifications
DHHS
OHRP
FDA
Other Federal
Agencies (NIH,
CDC and CMS
State Law
Institution
IRB Policy
Policy
IRB Policy
Department
Policy
Research
Team SOP’s
Study
Protocol/
Contract
Depending on funding
ICH/GCP

A document that provides a summary of the
research and explains the subjects rights as a
participant

It is designed to outline and be a reference
regarding what is expected of the participant
 Disclosure
of relevant information to
prospective subjects about the research;
 their
comprehension of the information, and
 their
voluntary agreement, free of coercion
and undue influence, to research
participation.
http://ohsr.od.nih.gov/info/sheet6.html

Simplicity

Summary

QOL

How many adverse events?

How many visits?

Know how many subjects are on study?

This dose

Different dose
Cognition/capacity
 Level of education
 Social/cultural values
 Language
 Age
 Environment
 Anxiety/fear
 Pain
 Influence of medications
 Quality of disclosed information
 Readability of informed consent

“the belief that the purpose of a clinical trial is to benefit the
individual patient rather than to gather data for the purpose of
contributing to scientific knowledge”
 The
subject believes that his medical needs
will determine his assignment to a treatment
group or the PI will modify the protocol to
serve his own medical need.
 The
subject has unreasonable expectations
about the likelihood of benefit from study
participation. In this example the subject
believes the PI will not administer treatment
that might harm them, but rather, will
provide interventions that only help them.

Harris Interactive Online Studies of 2031 and 2261 adults
 Only a minority of the public is confident that clinical
trials subjects
are not treated like guinea pigs
do not suffer more pain or side effects
than with standard of care treatment
receive high quality care
receive honest accurate information
2002
24%
2005
54%
13%
32%
25%
53%
48%
However
 83 % believe it is essential and very important all new
pharmaceutical products be tested on humans before
they are approved for general use
www.harrisinteractive.com/news/allnewbydate.asp?NewsID=213
www.harrisinteractive.com/news/allnewbydate.asp?NewsID=941
2,261 US adults over 18 surveyed online April 2005
I understood that participation was voluntary.
I understood that I was agreeing to participate in a clinical
research study.
I fully understood what was required of me (number of
visits, how long the study lasted, etc.).
I knew I could stop participating in the study at any time.
I felt comfortable asking additional questions regarding the
study.
I was assured confidentiality of all personal information
that I provided, with the exception of those allowed by
federal law.
I felt secure that my confidentiality was protected
throughout the study.
I was made aware of the benefits involved in participating
in the clinical research study.
I was made aware of the risks involved in participating in
the clinical research study.
I understood that I could choose other treatment options,
including no treatment at all.
The informed consent document was easy to read and
understand.
2004
%
90
2005
%
84
89
83
81
78
79
75
79
75
73
73
71
69
74
68
74
65
66
63
60
61
www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=941
2,261 US adults over 18 surveyed online April 2005
%
Said purpose of the study was "clear" after reading the
informed consent
85
Agreed their questions were answered by the study
team regarding the informed consent process
80
Said the study coordinator conducted the informed
consent process.
54
Read the informed consent by themselves
48
www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=941
Non compliance
Complaints to the IRB,
the institution, the
OHRP or the FDA
ME
NIH
Research Team
Compliance Officer
Institutional Official
Government
Public
Members
COG
Family
Advocates
FDA
YOU
Sponsor
Investigator
Educators
Auditors
IRB Chair and
Translator
Press / Media
Pharmacist
DOD
OHRP
The person must be trained regarding informed consent
process and be knowledgeable about study

FDA Requirements:
 IRB must know who will conduct consent process
 FDA does not require the that the PI personally
conduct the consent process.

ECOG Requirements:
 “Legally, it is the physician’s responsibility to discuss
the study with the patient and obtain the written
consent.”
 “After an initial discussion it may be the physician,
nurse, or CRA who provides further details to the
patient.”
7.2.6 “Presenting the Consent Form to the Patient,” ECOG Protocol Management
Ongoing
 Interactive process
 Different for every subject
 Different for every study
 Essential for study success
 IRB approved
 Providing clear definition between where
standard of care leaves off and research
begins
 Allows re-education
 Requires re assessment of subject
understanding with each visit

 Emergency,
life threatening situation that
requires intervention
 Minimal
risk study with IRB approval

Although the regulations
place the burden of
responsibility on the PI, the
protection of human
research subjects is a
shared responsibility among
all research professionals
involved in the conduct of
the study

Members of a research team
have a moral obligation to
uphold the ethical and
regulatory standards by
which human subjects
research is conducted
Ultimate protector of the subject’s rights
and safety
 Be personally certain that each subject is
adequately informed and freely consents
to participate in the investigator’s research
 Assure that every reasonable precaution is
taken to reduce risk to a minimum for the
subject
 The investigator is responsible for whom
he delegates authority to
 Follow the protocol

 Obtain
consent before initiating ANY studyspecific procedures
 Provide a quiet, comfortable, and private
setting
 Explain the consent procedures and process
to the subject
 Ensure sufficient time to consider all options
 Access the subject's reading abilities,
cognitive status now and throughout study
 Requires accessing subjects understanding
 Ensure
the subject is the one who wants to
participate, free from coercion or other
undue influence
 Consistent with IRB approved process
 Provide additional safeguards as required
 Provide new information promptly
 Provide a copy of the consent document and
each revised consent document to the
subject
 Document process and response from patient
 Establish a relationship with the subject
 Provide privacy
 Assess views on research vs. standard of care
 Keep the subject in the center of the process
 Be an active listener
 Ask open-ended questions
 Be aware of non-verbal messages
 Empathize with the subject’s concerns
 Be a teacher by educating the subject and
verifying his understanding of the research study
 Assure withdrawal is possible at ANY time
 Inform other options are available
 Be available anytime for any question
 Do not rush the process or the subject
Know the protocol
Introduce yourself and
state who referred you
 Do not depend on subject
enrolling
 You are not a salesman
 Provided consent
document for review
 Methods of conveying
information differs
 Check list
 Read consent to subject
 Read highlights /review
calendar
 Video
 Electronic
 Web-based resources


Informed Consent Worksheet


Date of Consent:__________________ Name of Study:_____________________________

IRB Study Number:__________________________

Patient Name:_____________________ Patient MRN:_________________ _Study ID#:__________

The following has been explained to the potential study subject, and the subject has been offered the opportunity to
ask questions regarding the study:
TOPIC


COMMENTS

Purpose of the study
_________________________________

Qualifications to participate
_________________________________

Location and participants
_________________________________

What will happen during the study
_________________________________

Risk and benefits
_________________________________

Study related injury or illness
_________________________________

Alternative treatments
_________________________________

Confidentiality
_________________________________

Study costs
_________________________________

Compensation
_________________________________

Who to contact with questions
_________________________________

Voluntary participation
_________________________________

Termination of participation
_________________________________

Questions or comments: __________________________________________________________________

__________________________________________________________________

Does the patient state an understanding of the study and procedures and agree to participate? ___yes ___no

_____________________________________


Person administering consent
Signed copy given to patient? ___yes ___no
__________________________
Date / Time
Copy in patients chart? ___yes ___no
INFORMED CONSENT & RECONSENT
Clinical Research Trial: ________________________________
PRESENTATION CHECKLIST
Version Date:________________
Physician discussed diagnosis and treatment options (standard of care, no treatment)
Physician discussed clinical research trial including the following:
•
Description of the clinical research trial, its goals, and medications involved
•
Voluntary participation
•
Anticipated duration of participation
•
All known risks: reported side effects and management of known side effects and…
•
Possibility of unknown side effects
•
Potential and reasonable expected benefits
•
Treatment groups and randomization (if applicable)
•
Required study procedures
•
Follow-up after completion of study treatment
•
Rights and responsibilities of research participants (including contraception if applicable)
•
Confidentiality
•
Compensation / Additional Costs
Consent presented to patient / legal representative / legal guardian
Time allowed for patient / legal representative / legal guardian to read consent and ask questions prior to
signing consent
Patient / legal representative / legal guardian acknowledged understanding of the clinical trial and
indicated questions were answered to their satisfaction
Patient / legal representative / legal guardian signed informed consent
Patient / legal representative / legal guardian received a copy of each signed research consent form
Study specific procedures were not done prior to consent being signed
Contact information provided to patient / legal representative / legal guardian for study related concerns
Performance Status today (per protocol): Karnofsky / __________ Lansky ECOG / Zubrod / WHO ___________
Consent document(s) signed on: / / Amount of time explaining the consent:________________
Time consent signed:_______ AM/PM
**Translation Services: Translated document(s) and / or interpreter provided as needed:
q NO (translation services not needed) _____ YES List language provided:______________________
Any additional comments regarding translation:____________________________________________
Physician’s Signature (print name):____________________________________Physician (sign): Date:________________________
 Ask
if problems arose since
last visit (A/E’s)
 Provide new information if
applicable
 Encourage questions each
visit
 Talk about what comes next
 Re-assess subjects desire
to continue each visit
 Assess compliance (diary,
meds etc)
 If
subject regains cognitive ability
 New information becomes available
 Significant protocol changes
 New surrogate is identified
 IRB instructs you to re-consent
 Investigator has the option to re-consent for
longitudinal data collection time points

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


Method of presentation
Voluntary participation
Environment
Complete explanations
Length of time devoted to the process
Simple explanations
Adequate time offered to ask questions
How subject demonstrates understand
of the study and desire to participate
Promptness of reporting new
information
You know you want to:
 Volunteer
to have your consenting process
observed
 Contact
Wendy Lloyd by phone (936-7106) or
by email (wendy.lloyd@vanderbilt.edu)
in advance or just prior to consenting
 If
SOP’s exist are they followed?
 Confirm consent process documentation
 Implementation of changes only after IRB
approval
 Correct version non expired consent used
 All options completed by subject
 Consent signed and dated by all parties
 Consent signed prior to ANY procedures
 Consented by trained individuals

Signatures of subject and consenting person on different dates

Consent and study procedures on same date

Consent was performed by an untrained or unqualified care provider

Person consenting is not listed as KSP

Check boxes within the consent incomplete

Crossed out sections or white out used in the IRB approved consent

Unable to locate consent for subject on study

Subjects not re-consented with revised consent as instructed

Ineligible subjects enrolled

Multiple consent documents for same patient with no explanation why

Person consenting did not state the purpose or procedures of the
study

Consent document left on clip board for subjects to complete and
return to nurse if interested

Person consenting the subject did not sign the form






Confirm all personnel consenting subjects are KSP
Document training and qualifications of all KSP
Establish one place to retrieve ONLY the latest IRB
approved consent
Conduct random audits of the consent
documentation
Review the FDA Warning Letters and FDA IRB
Information Sheets –“A Guide to Informed
Consent”
Become familiar with the Regulations, state law,
institutional and IRB Policies
 Know
the protocol
 Only do what you are trained to do
 Volunteer for consent observation
 Ask
subjects if they felt fully informed
 Seek
education
 Stay organized
 If you find something don’t hide it
 Network
 Become certified
 If you don’t know ask






January 19 – PI failed to obtain ICD for subjects (? Number),
During response PI gave ICD to FDA not IRB approved
January 28 – PI failed to obtain consent with complete study
info, conducted lab tests for two subjects without consent
February 18- PI failed to consent 1 subject (hand writing not
subjects), enrolled 4 ineligible subjects
February 24 – PI failed to obtain legally authorized ICD: child
was enrolled with 1 parent signature, child was in DHS custody
February 25 – PI failed to obtain legally authorized consent;
implemented changes in the investigational plan without
approval
March 2 – 7 of 25 subjects met EXCLUSION criteria, failed to
properly consent 3 subjects, 1 was told would receive
investigational device but received control device






March 18 – PI failed proper monitoring of the
investigational study
March 10 – PI failed to notify subjects following study
participation regarding safety events
March 21- PI failed to consent 2 subjects, 4 ineligible
subjects enrolled
March 24- IRB approved protocol allowing consent
following study procedures instead of before
April 1- PI failed to consent 1 subject, response letter
found consent but it was visibly altered and the PI did
not alter it.
June 28 – PI failed to consent with updated consent for
7 subjects, enrolled 7 subjects who were ineligible.






January 28 – IRB did not document specific criteria when approving
waiver or alteration of consent
January 29 – IRB did not waive consent for subjects, PHI was
obtained from family members and the approved consent did not
contain the appropriate risk language
April 8 – PI retain PHI on subject for a study without approval or
consent. PI also implemented study changes (a 3rd intervention)
without IRB approval
June 3 – PI decided not to inform subjects of new drug information
since they had completed the study and PI did not conduct all
follow-up visits (although subject was in the office) per protocol
requirements
Nov 24 – IRB approved research involving pregnant woman/fetus
that held the prospect of direct benefit to the fetus. Only one
signature line was on the consent instead of the required two. IRB
also approved telephone and electronic consents for studies
however did not properly waive documentation or alteration of
consent.
May 10- subject complained he was encouraged to continue a study
he did not wish to continue in
 Each
interaction is different because every
subjects, circumstance, question,
communication style is different.
 It
is up to each one of us to take the consent
process serious and fully inform each subject

By possibly increasing
subject recruitment and
retention on a wide scale

Playing a substantial role
in shaping public
perceptions of the value
of clinical research
For federal guidance on obtaining informed consent of human research
subjects, see the following websites:
General requirements for informed consent
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.20
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.23
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.24
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.25
Documentation of informed consent
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.27
Research involving pregnant women, fetuses or neonates
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.204
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.205
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.206
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.207
Research involving children (also found in 21 CFR 50.50-56)
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.404
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.405
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.406
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.407
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.408
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.409
Pediatric research “assent”decision matrix
http://www.hhs.gov/ohrp/panels/407-01pnl/riskcat.htm
Office for Human Research Protections (OHRP) informed consent tips
http://www.hhs.gov/ohrp/policy/index.html
OHRP informed consent FAQ
http://answers.hhs.gov/ohrp/categories/1566
Vanderbilt IRB Policy
http://mcapps01.mc.vanderbilt.edu/IRB/policy&procedures.nsf/(WebTa
bleOfContents)/8AF759048966C29D86257731005ECD1F?OpenDocument
If you have additional comments or questions
feel free to contact me
Wendy Lloyd
Wendy.lloyd@vanderbilt.edu
615-936-7106