COMMON PROBLEMS IN
INFORMED CONSENT
Jeri R. Barney, JD, MS
Michele Antisdel, MBA/CCRP
HRPP Compliance Manager
IRB Regulatory Analyst
Human Research Protection Program (HRPP)
May 16, 2013
Discussion
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Consent Process
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Consent Requirements
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Common Problems in Informed Consent
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Suggestions for Improvement
Consent Process
What is Informed Consent?

Example of Ethical Principle of Respect for
Persons

Not a document, but a process

Starts at initial contact (e.g., recruitment)
Informed Consent Process

Continues through study participation
 an
informed participant is better able to adhere
to the protocol and therefore provide evaluable
data
 research
staff members are obligated to share
any new information related to subject’s
participation (e.g., newly identified side effects,
etc)
Informed Consent Process

Handing a participant the consent document and
asking them to read and ask questions is NOT
Informed Consent
Consent Requirements
8 Basic Elements in an ICF
The following eight basic elements of informed consent are required to
be provided in the course of the consent process. The investigator must
ensure that these elements and any others required by the IRB are
presented in such a manner as to facilitate the prospective
participant’s ability to understand involvement in the research study.
1. Invitation to Participate
2. Risks
3. Benefits
4. Alternatives to Participation
5. Confidentiality Statement
6. Compensation for Medical Treatment
7. Who to contact (and when) with problems/how to withdraw
8. Voluntary Participation
Consent Requirements

In addition to the 8 required elements, one or more of the following
elements are to be provided to the subject when appropriate to the
study:

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


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Procedures- in lay terms! Tell which are experimental
Research not medical treatment & purpose of the research
Possibility of unforeseeable risks
The consequences of a subject's decision to withdraw from the research
and procedures for orderly termination of participation by the subject.
A statement that significant new findings developed during the course of
the research which may relate to the subject's willingness to continue
participation will be provided to the subject.
How long/duration of participation
Subject responsibilities
The approximate number of subjects involved in the study.
For FDA regulated studies: clinicaltrials.gov
Regulatory Requirements
45 CFR 46.116 (HHS) and 21 CFR 50.20 (FDA) provide the general requirements for
informed consent.
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 (e.g., for a minor child this would be the
parent or guardian).
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.
No informed consent, whether oral or written, may include any exculpatory language
through which the subject or the representative is made to waive or appear to waive
any of the subject's legal rights, or releases or appears to release the investigator, the
sponsor, the institution or its agents from liability for negligence.
Consent Requirements Continued
Documentation of informed consent.
 Informed consent will be documented by the use of a written
consent form approved by the IRB and signed by the subject or
the subject's legally authorized representative. A copy is given to
the person signing the form.

A consent form may be either of the following:
A
written consent document (consent form or compound consent
and authorization form) that embodies the elements of informed.
 A short form written consent document stating that the elements of
informed consent have been presented orally to the subject or the
subject's legally authorized representative.
Consent Requirements Continued
Documentation of informed consent.

An IRB may waive the requirement for the investigator to obtain a signed consent form for
some or all subjects if it finds either:

(1) That the only record linking the subject and the research would be the consent
document and the principal risk would be potential harm resulting from a breach of
confidentiality. Each subject will be asked whether the subject wants documentation
linking the subject with the research, and the subject's wishes will govern; or

(2) That the research presents no more than minimal risk of harm to subjects and
involves no procedures for which written consent is normally required outside of the
research context.
If the study is FDA regulated, FDA regulations allow a waiver of informed consent only
under very specific limited circumstances (21 CFR 50.23 and 21 CFR 50.24).

In cases in which the documentation requirement is waived, the IRB may require the
investigator to provide subjects with a written statement regarding the research. The
document is called an “Information Sheet”.
Common Problems in Informed Consent
Office for Human Research Protections
(HRPP) Compliance Oversight Letters
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
OHRP reviewed 235 compliance oversight
determination letters issued to 146 institutions
51% of the institutions reviewed were cited for
noncompliance and deficiencies related to IRB
approved informed consent documents/processes
(2nd highest after deficiencies related to the initial
IRB review process (56%))
19 determinations of noncompliance for research
conducted w/o legally effective informed consent
Current FDA Statistics
Office of Scientific Investigations
Center for Drug Evaluation & Research (CDER)
(Updated: January 2013)
Source
http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/
UCM256376.pdf
Frequency of Clinical Investigator-Related Deficiencies Based on
Post-Inspection Correspondence Issued* (CDER, FY 2012)
183 Domestic Inspections,
116 Foreign Inspections
*Based on letter issue date; Inspections may have multiple deficiencies, [OSI database as of January 24, 2013]
Note that this does not denote number of inspections completed in FY 2012, but rather number of inspection reports
evaluated and closed in FY2012
Frequency of Clinical Investigator Related Deficiencies Based on PostInspectional Correspondence Issued:
Official Action Indicated (OAI) Final classification* (CDER, FY 2012)
9 OAI Inspections
*Based on letter issue date; Inspections may have multiple deficiencies, includes OAI untitled letters, [OSI database as
of January 24, 2013] Note that this does not denote number of inspections completed in FY 2012, but rather number
of inspection reports evaluated and closed in FY2012.
Examples of Common Consent Issues
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Failure to re-consent when new information becomes
available
Use of expired forms or non-validated/unapproved forms
PI or consent personnel did not sign/date the form
Failure to provide copies of the forms to subjects
Providing all but the last page of the consent document to
subjects
Keeping only the last page of the consent document in
study files
More Examples

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Failure to obtain written informed consent
(neglecting to have subjects sign a consent form)
Missing consent documents
No documentation that consent process took place
and no signed consent document on file
Use of wrong form (e.g., child signing parental
permission form, patient signing “healthy control”
form, or subject signing the wrong version)
Even More Examples
Parental permission obtained after child assent
(may suggest that study interventions took place
prior to securing legally effective consent)
 Enrolling non-English speaking subjects without
using a proper interpreter (e.g., using a family
member or boyfriend/girlfriend to translate)
 Failure to get HIPAA research (RAF) signed
 Changes made to the consent documents by
hand AND without IRB approval (e.g., crossed
out information about procedures, increased
amount of payment)

Suggestions for Improvement
Suggestions for Improvement
ICF Version Control Tips


Use of expired forms or unapproved forms
Use of wrong form (child signing parental permission form or subject
signing the wrong version)
Check the Validation Box on the last page of the consent form
BEFORE you consent the subject (for paper forms). For electronic forms
check the header/footer for the IRB approval. In addition; check the
version date to make sure you’re using the most current copy.
Throw Out Expired or Outdated Versions of the consent documents
IMMEDIATELY. Maintain the original in the regulatory binder for the
study records but any copies of expired or outdated documents should
be destroyed, and electronic copies should be moved to archive folder
on computer.
Suggestions for Improvement
ICF Version Control Tips
Use Consent Form Log listing the different versions, version
dates, expiration dates and a brief description
For example: Version 1: 5/2/12 Initial approval, Healthy
Control, Healthy Control with Study Drug;
Version 2: 10/13/12 Amendment, Healthy Control subject
payment added, Healthy Control with Study Drug subject
payment added, study drug dosage reduced.
Discuss New ICF Versions at regular staff meetings to inform
all personnel of changes and to ensure all staff will use the
correct version. If you do not have regularly scheduled
meetings, be sure to inform study personnel in other ways (e.g.,
via email notices).
Keep different versions in different folders. Color code and
CLEARLY label on the folder AND in the footer of the form
itself.
Suggestions for Improvement
Providing Copies & Keeping Forms

Failure to provide copies of the forms to subjects
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Providing all but the last page of the consent document to subjects
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Keeping only the last page of the consent document in PI files

PI or consent personnel did not sign/date the form
Make a checklist and an enrollment note template
Immediately after signing make a copy and give the copy to subject or have subject
sign duplicate copy.
Create & stick to a process for where the signed ICF is kept (subject chart/folder,
separate consent form binder)
Educate staff so they know to provide FULL copy to subjects and keep FULL original for
records
Review the signed form for completeness BEFORE subject leaves and again BEFORE
filing in your files
DO NOT have PI pre-sign the forms
Suggestions for Improvement
Amendments & Consent Addendums


Changes made to the consent documents by hand AND without
IRB approval (e.g., crossed out information about procedures,
increased amount of payment)
Failure to re-consent when new information was available
Educate staff: if changes are necessary they MUST be submitted to
the IRB as an amendment and approved before implementing
Announce addendum in staff meeting or via email
Reconsent log
Check when subject’s next visit is and put a note in his/her chart
and in your calendar, mark visit in red, etc.
Put copy of the addendum in the subject chart or binder prior to
next visit
Suggestions for Improvement
Failure to Obtain Consent
Failure to obtain written informed consent (forgot to have subjects
sign a consent form) or failure to have HIPAA RAF signed
 Missing consent documents
 No documentation that consent process took place & no signed
consent document on file
• Consent should be the VERY FIRST research activity (even if subjects
had a form previously mailed to them) and the VERY LAST thing you
do before subject leaves
• Switch to a compound form (or staple it to the consent). REMEMBER
to add the RAF to reapproved consents (RAFs don’t get approved
every year)
• Use an enrollment note
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Suggestions for Improvement
Failure to Obtain Consent
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

Failure to obtain written informed consent (forgot to have
subjects sign a consent form) or failure to have HIPAA RAF
signed
Missing consent documents
No documentation that consent process took place & no signed
consent document on file
• Double check each other; Implement a monitoring process to
check for consent forms (and other issues) on a routine basis
• Have process and place for signed forms to be kept
• Ensure all study staff know where to find current forms
• Remember what hat you’re wearing
What You Can Do


Institute Processes/Form Good Habits
 Consent form log
 Always check the expiration dates on forms
 Double check each other
 Monitor your own studies on a regular basis
 Talk to the staff about problem trends
Assign Responsibility
 PI is ultimately responsible
 One staff member responsible for consent forms
 Each staff member responsible for their own activities
What You Can Do



Education
 HRPP education sessions
 Website policies, templates, instructions:
http://www.yale.edu/hrpp/index.html
 Communicate with staff (meetings or emails)
Communicate with IRB Regularly
Ask for help
 If you don’t know the answer, it’s better to ask first
 Study start-up consultations
 QA/QI Reviews
 Call with specific questions (203) 785-4688
Questions?
Call 203-785-4688
michele.antisdel@yale.edu
jeri.barney@yale.edu
References
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HRPP website: http://www.yale.edu/hrpp/
http://www.yale.edu/hrpp/policies/index.html
http://www.yale.edu/hrpp/responsibility/compliance
.html
OHRP website: http://www.hhs.gov/ohrp/
FDA website: http//www.fda.gov/