Common Problems in Informed Consent

1. 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

2. Discussion • Consent Process • Consent Requirements • Common Problems in Informed Consent • Suggestions for Improvement

3. Consent Process

4. 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)

5. 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)

6. Informed Consent Process • Handing a participant the consent document and asking them to read and ask questions is NOT Informed Consent

7. Consent Requirements

8. 8 Basic Elements in an ICF The following eight basic elements of informed consent are requiredto 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

9. 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

10. 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.

11. 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.

12. 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”.

13. Common Problems in Informed Consent

14. 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

15. Current FDA StatisticsOffice of Scientific InvestigationsCenter for Drug Evaluation & Research (CDER)(Updated: January 2013) Source http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM256376.pdf

16. 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

17. Frequency of Clinical Investigator Related Deficiencies Based on Post-Inspectional 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.

18. 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

19. 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)

20. 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)

21. Suggestions for Improvement

22. 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.

23. 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.

24. 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

25. 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 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

26. 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

28. 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

29. 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

30. 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

31. Questions? Call 203-785-4688 michele.antisdel@yale.edu jeri.barney@yale.edu

32. References • 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/