 Identify
consent process requirements
 Distinguish between IRB, PI/Designee consent
process responsibilities
 Identify with what went wrong?
 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 46.116
Common Rule
 FDA 21 CFR 50.25
 Part 50 (Informed Consent)
 Part 56 (IRB)
 ICH GCP E-6 Section 4.8.10
“No investigator may involve a human being as a
subject in research… unless the investigator has
obtained the legally effective informed consent
of the subject or the subject’s legally authorized
representative
 An investigator shall seek such consent only under
circumstances that provide the prospective
subject or the representative sufficient
opportunity to consider whether or not to
participate and that
 minimize the possibility of coercion or undue
influence.
 The information that is given to the subject or the
representative shall be in language
understandable to the subject or the
representative”
 45 CFR 46.11


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

information exchange including
 subject recruitment
materials,
 verbal instructions,
 written materials,
 questions and answer sessions
and
 signature documenting
consent with date.
Protecting study volunteers in research Cynthia McGuire
Dunn, MD & Gary Chadwick, PHARM.D, mph 1999.
 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
Detailed description of the method for
obtaining informed consent
 Who
 Where
 The process submitted for IRB approval
 Changes in the process are submitted as
amendments
 PI assures the informed consent process in
research is an ongoing exchange of information
throughout the course of the research and it is
documented

Oral
Telephonic
E consent
Video
Facsimile
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





41% Study nurse
21% PI
19% No one
12% Family member
8% Other
Source: 2002 Center Watch Survey of 1,561 Study Volunteers
Fetuses, Pregnant Women, and
Human In Vitro Fertilization
 Prisoners
 Children
 Elderly
 Cognitively Impaired
 Minorities
 Etc.

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.
When the study is closed and final reports are
issued
 At each interaction, the investigator must
reassure
 Voluntary participation continues
 New information is given to the subject

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

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 review 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 and/or Dept policy
ICH/GCP
 Emergency,
life threatening situation that
requires intervention
 Minimal
risk study with IRB approval
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
 Follow the protocol and IRB approved
study documents

 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
 Access 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
During the interview be aware of the things you
might be saying that would affect voluntariness or be
coercive
 “free drug” “free treatment” “I think this is best
for you” “do this for me”
Document process and response from patient
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


 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 (test back)
 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
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
 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
Non compliance
Complaints to the IRB,
the institution, the
OHRP or the FDA
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









Method of presentation appropriate for
type of study and population
Voluntary participation
Environment
Length of time devoted to the process
Adequate time offered to ask questions
How subject demonstrates understand
of the study and desire to participate
Promptness of reporting new
information
Auditing/Compliance Reviews
 If
SOP’s exist are they followed
 Confirm consent process IRB approved
 Change implemented only after IRB approval
 Consent signed prior to ANY procedures
 Consenting person has appropriate training
 Consenting person listed as KSP
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










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
Unable to locate consent for subject on study
Subjects not re-consented with revised consent as instructed
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








Only use approved consent process
Confirm all personnel consenting subjects are KSP
Document training and qualifications of all KSP
Confirm person consenting knows the protocol
Conduct random audits of the consent process
documentation ( if form created, confirm use)
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
Call the VHRPP
 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

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


Measure the immediate level of patient comprehension at the time
surgical consent is obtained and the effect of time on this level of
understanding.
100 subjects
consented
When test
administered
Percent of Correct
answers
98
Preoperatively
70.70
75
1st Post op (no more
than 2 weeks)
59.50
39
1st Post op (no more
than 2 weeks)
60.8
In addition, the effect of sex (no difference), education level
(college scored better), and age (<50 scored higher) on
comprehension.
http://www.ncbi.nlm.nih.gov/pubmed/22005875 2011 study Crepeau AE, McKinney
 18
year old with
partial ornithine
transcarbamylase
deficiency
 Usually fatal in
infancy
 The first person to
die from gene
therapy
 FDA
suspended all gene therapy
trials and other experiments
 Hearings on quality of oversight and
safety
 President Clinton demanded
improvements in consent and access
to information about gene therapy
research
 Gelsinger
v. Univ. of Penn. (C.P. Phila.
Co., 2000)
 18 year old boy died during a gene transfer
experiment for ornithine transcarba – mylase
deficiency.
 PI founded company that sponsored trial –
owned 30% of stock
 University of Pennsylvania owned 5% of stock
 University’s Conflicts of Interest Committee
was aware of the potential conflict of
interest between the parties – allowed study
to proceed
Gelsinger v. Univ. of Penn.
One of the many counts Intentional Assault and
Battery
Informed consent process did not disclose
 Monkey deaths
 Previous adverse events
 Relationship between PI and sponsor
 True efficacy results



Confidential settlement
Sued University trustees, PI, sponsor and hospital
 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