COMMON PROBLEMS IN INFORMED

CONSENT

Jeri R. Barney, JD, MS Michele Antisdel, MBA/CCRPHRPP Compliance Manager IRB Regulatory Analyst

Human Research Protection Program (HRPP)May 16, 2013

Discussion

Consent Process

Consent Requirements

Common Problems in Informed Consent

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 Participate2. Risks3. Benefits4. Alternatives to Participation5. Confidentiality Statement

6. Compensation for Medical Treatment7. Who to contact (and when) with problems/how to

withdraw8. 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: 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 Requirements45 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 ContinuedDocumentation 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 ContinuedDocumentation 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

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 StatisticsOffice 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)

*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

183 Domestic Inspections,116 Foreign Inspections

Frequency of Clinical Investigator Related Deficiencies Based on Post-Inspectional Correspondence Issued: Official Action Indicated (OAI) Final classification* (CDER, FY 2012)

*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.

9 OAI Inspections

Examples of Common Consent Issues

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

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 ImprovementICF 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 ImprovementICF 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 ImprovementProviding Copies & Keeping Forms

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 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 ImprovementAmendments & 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 implementingAnnounce addendum in staff meeting or via emailReconsent logCheck 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 ImprovementFailure 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

Suggestions for ImprovementFailure 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

• 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 203-785-4688michele.antisdel@yale.edu

jeri.barney@yale.edu

References

HRPP website: http://www.yale.edu/hrpp/ http://www.yale.edu/hrpp/policies/index.ht

ml http://www.yale.edu/hrpp/responsibility/co

mpliance.html OHRP website: http://www.hhs.gov/ohrp/ FDA website: http//www.fda.gov/