ORPP&E Workshop: Informed Consent Tools

1. ORPP&E Workshop: Informed Consent Tools Soundia A. Duche, MA, MS Chief, Education and Training ORPP&E (formerly PRIDE) Dial in: (562) 247-8321 Access Code: 294-015-941 Slides in “Handout” Tab January 11, 2019

2. Training Outline Dial in: (562) 247-8321 Access Code: 294-015-941 Slides in “Handout” Tab • Brief Review of Study-specific Informed Consent Requirements • Brief Review of Broad Consent Requirements • Brief Review of Waiver of Informed Consent and Waiver of Documentation of Informed Consent Requirements • Examples of templates, forms, and reviewer checklists

3. Informed Consent

4. Full Disclosure: Informed Consent & HIPAA • Unless informed consent is waived by the IRB, the Common Rule requires that investigators obtain the legally effective informed consent of the subject or the subject’s legally authorized representative prior to involving a human being as a subject in research • With very few exceptions, FDA regulations require that investigators obtain the legally effective informed consent of the subject or the subject’s legally authorized representative prior to involving a human being as a subject in research • The Privacy Rule (Health Insurance Portability and Accountability Act of 1996 - HIPAA) describes when written authorization is required before the use or disclosure of health care information that is not for a “permissible purpose” (i.e., treatment, payment, or healthcare operations) and specifies exceptions allowed by the regulations.

5. Belmont Principles • Common Rule Approval Criteria Respect for Persons Treat Individuals as Autonomous Agents Protect those with Diminished Autonomy Justice Equal Distribution of Burdens and Benefits • Informed consent will be sought from each prospective subject or the subject’s legally authorized representative; • Informed consent will be appropriately documented; • When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects. • Selections of subjects is equitable. The IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations. Beneficence Do No Harm Maximize Benefits Minimize Risks • Risks to subjects are minimized: (i) By using procedures consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes; • Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonable be expected to result; • When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects; • When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

6. 2018 Requirements and New Standards for Informed Consent • Reasonable person standard • The consent process should provide information that a reasonable person would want to help them decide if they wish to participate in the research study or not • Informed consent process should facilitate subject understanding • Not sufficient to simply provide a list of isolated facts • Information must be presented in sufficient detail and in an organized way to facilitate subject’s understanding of the reasons why one might or might not want to participate in the study • Two types of consent: Study-specific consent and Broad Consent • Broad consent is specific to the storage, maintenance, or secondary use of identifiable data and/or identifiable biospecimens

7. Required Elements for Study-Specific Informed Consent • With the exception of Broad Consent, inclusion of a concise summary at the beginning of the ICF presenting key information that subject should know about the research study • 8 basic elements of informed consent unchanged • New element: For all studies that involve the collection of identifiable private information or identifiable specimens, include a statement on whether specimens if subsequently de-identified will be used for future research or not • 6 additional elements of informed consent unchanged • 2 new additional elements required when research involves biospecimens: • Additional element #7: Statement whether specimens may be used for commercial profit and if subject will share in the profit • Additional element #9: Statement whether research might include whole genome sequencing • New additional element #8: Statement whether clinically relevant research results will be disclosed to subjects and if so under what conditions

8. Key Information Final rule does not specify the types of information that should or should not be included, however preamble gives some insight. • Suggests that the key information would include the following: • The fact that consent is being sought for research and that participation is voluntary; • The purposes of the research, the expected duration of the prospective subject’s participation, and the procedures to be followed in the research; • The reasonably foreseeable risks or discomforts to the prospective subject; • The benefits to the prospective subject or to others that may reasonably be expected from the research; and • Appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the prospective subject. • University of Kentucky Informed Consent Template • University of Kentucky Sample Key Information Page –clinical trial • University of Kentucky Sample Key Information Page – minimal risk study

9. Required Elements for Study-Specific Informed Consent (continued) • Additional FDA Requirements: For clinical trials, the following statement must be provided to each human subject as part of the informed consent process, “A description of this clinical trial will be available on http://www.clinicaltrials.gov as required by US Law. This website will not include information that can identify you. At most, the website will include a summary of the results. You can search this website at any time.” • Additional VA-specific elements (VHA Directive 1200.05, Paragraph 17(d) and 17(e) • A statement that VA will provide treatment for research related injury in accordance with applicable federal regulations; • When appropriate, a statement that informs VA research subjects that they or their insurance will not be charged for any costs related to the research (see para 15d(7)). • For Studies with Certificates of Confidentiality (CoC) • Subjects must be informed that a CoC has been issued

10. Requirements for Broad Consent • Specific to storage, maintenance, and secondary use of identifiable data/specimens • Can be used as an alternative to general informed consent requirements • Broad consent can only be used when data or biospecimens are collected solely for research purposes for VA-approved research • Broad consent form can be a separate form or combined with a traditional ICF • If combined, information provided to subjects for broad consent must be clearly discernable from the research-specific consent. • Broad consent must be documented for VA-approved research • The IRB cannot waive documentation of informed consent for Broad consent

11. Broad Consent: Required Elements First 4 elements are from the basic elements of Informed Consent Required Elements: • A description of any reasonably foreseeable risks or discomforts to the subject; • A description of any benefits to the subject or to others that may reasonably be expected from the research; • A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained; • A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled;

12. Next 2 elements (5 & 6) are from the additional elements of Informed Consent (2018 Requirements) Broad Consent: Required Elements (continued) • When appropriate, a statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit; • When appropriate, for research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen). • A general description of the types of research that may be conducted with the identifiable private information or identifiable biospecimens. This description must include sufficient information such that a reasonable person would expect that the broad consent would permit the types of research conducted; • A description of the identifiable private information or identifiable biospecimens that might be used in research, whether sharing of identifiable private information or identifiable biospecimens might occur, and the types of institutions or researchers that might conduct research with the identifiable private information or identifiable biospecimens; Last 6 elements (7-12) are new and specific to Broad Consent

13. Broad Consent: Required Elements(continued) Last 6 elements (7-12) are new and specific to Broad Consent • A description of the period of time that the identifiable private information or identifiable biospecimens may be stored and maintained (which period of time could be indefinite), and a description of the period of time that the identifiable private information or identifiable biospecimens may be used for research purposes (which period of time could be indefinite); • Unless the subject or legally authorized representative will be provided details about specific research studies, a statement that they will not be informed of the details of any specific research studies that might be conducted using the subject’s identifiable private information or identifiable biospecimens, including the purposes of the research, and that they might have chosen not to consent to some of those specific research studies; • Unless it is known that clinically relevant research results, including individual research results, will be disclosed to the subject in all circumstances, a statement that such results may not be disclosed to the subject; and • An explanation of whom to contact for answers to questions about the subject’s rights and about storage and use of the subject’s identifiable private information or identifiable biospecimens, and whom to contact in the event of a research-related harm.

14. Documentation of Informed Consent in VA Research • Unless a waiver or alteration is approved by the IRB, the written informed consent form must contain the elements of informed consent described in VHA Directive 1200.05 as approved by the Institutional Review Board (IRB). • IRB cannot waive or alter any of the elements required for Broad Consent (38 CFR 16.116(f)(2)). • The informed consent form may be combined with the HIPAA Authorization form. • Unless the IRB waives documentation of informed consent, the Informed consent form, must be signed and dated by the Subject or the subject’s legally authorized representative (LAR) • The requirement that the individual obtaining consent sign the form has been removed.

15. Revised Common Rule: Waiver/Alteration of Informed Consent • Requirements for waiving/altering informed consent for research involving public benefit and service programs conducted or subject to the approval of state or local government remains substantially unchanged • Requirements for waiving/altering informed consent for minimal risk research - One additional requirement has been added: (i) The research involves no more than minimal risk to the subjects; (ii) The research could not practicably be carried out without the requested waiver or alteration; (iii) If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format; (iv) The waiver or alteration will not adversely affect the rights and welfare of the subjects; and (v) Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation (38 CFR 16.116(f)(3)) Waiver or Alteration of Informed Consent Form

16. Revised Common Rule: Waiver of Informed Consent (Caveat) • IRB cannot waive or alter any of the elements required for Broad Consent (38 CFR 16.116(f)(2)). • IRB cannot waive consent for the storage, maintenance, or secondary use of identifiable information or specimens if a subject has refused to agree to Broad Consent (38 CFR 16.116(f)). • With the exception of Broad Consent, the IRB can approve a complete waiver of informed consent if the required criteria have been met.

17. Revised Common Rule: Alteration of Informed Consent (Caveat ) • Alterations: IRBs can not approve a consent procedure that omits/alters the general requirements of informed consent found in 38 CFR 16.116(a). The consent process must ensure the following: • Legally effective informed consent is obtained under circumstances that • provide the subject/LAR sufficient opportunity to decide whether to participate; • minimize coercion/undue influence and • does not include any exculpatory language through which the subject/LAR is made to waive/appear to waive and of their rights or releases/appears to release the investigator, sponsor, institution or its agents from liability for negligence • Information is provided to subjects/LARs in a language they can understand • Sufficient information is provided to allow them to make an informed decision • With the exception of Broad Consent, a short summary of key information related to participation in the study is provided upfront as part of the consent process

18. Revised Common Rule: Screening and Recruiting Activities Use of identifiable information or identifiable specimens without the subject’s consent for the purpose of screening, recruiting, or determining eligibility of prospective subjects can be approved by the IRB if the following requirements are met: • Investigator obtains information through oral or written communication with the prospective subject, or • Investigator obtains identifiable private information or identifiable biospecimens by accessing records or stored identifiable biospecimens. (38 CFR 16.116(g))

19. Revised Common Rule: Waiver of Documentation of Consent Addition of a third option for waiving documentation of informed consent: An IRB may waive the requirement for the investigator to obtain a signed informed consent form for some or all subjects if it finds any of the following: • That the only record linking the subject and the research would be the informed consent form and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject (or legally authorized representative) will be asked whether the subject wants documentation linking the subject with the research, and the subject’s wishes will govern; • 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; or • If the subjects or legally authorized representatives are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to subjects and provided there is an appropriate alternative mechanism for documenting that informed consent was obtained. (38 CFR 16.117(c)(1)) Waiver of Documentation of Informed Consent Form

20. Posting Clinical Trial Consent Forms • One IRB-approved informed consent form used to enroll subjects must be posted by the awardee or the Federal department conducting the clinical trial on a publicly available Federal website after the last study visit by any subject and no later than 60 days after the last study visit by any subject. • Consent forms must be posted on either https://clinicaltrials.gov or a docket folder on http://Regulations.gov (Docket ID: HHS-OPHS-2018-0021). • VHA Directive 1200.05 provides additional details on who is responsible for posting the consent form.

21. Templates

22. Templates • University of Kentucky Informed Consent Template • University of Kentucky Sample Key Information Page –clinical trial • University of Kentucky Sample Key Information Page – minimal risk study • VA Combined ICF/HIPAA Sample Form • Informed Consent Reviewer Form • Waiver or Alteration of Informed Consent Form • Waiver of Documentation of Informed Consent Form Additional Sample Consent Key Information Pages can be found on University of Kentucky’s Office of Research Integrity Website: https://www.research.uky.edu/office-research-integrity/sample-applications-and-protocol-development-resources

23. Resources

24. Important Links • Final Rule for the Delay (published June 19, 2018) • Revised Common Rule (published January 19, 2017) • Pages 7259 to 7274 contain the Text of the Final Rule • Current Common Rule • VHA Handbook 1200.05 • ORD Policies and Guidance Documents • Cyberseminar Recordings: https://www.research.va.gov/pride/cyberseminars/default.cfm

25. Templates • University of Kentucky Informed Consent Template: https://www.research.uky.edu/office-research-integrity/sample-applications-and-protocol-development-resources • University of Kentucky Sample Key Information Page –clinical trial: https://www.research.uky.edu/uploads/ori-placebo-controlled-clinical-trial-key-information-sample-pdf • University of Kentucky Sample Key Information Page – minimal risk study: https://www.research.uky.edu/uploads/ori-nonmedical-testing-and-survey-key-information-sample-pdf • Additional Sample Consent Key Information Pages can be found on University of Kentucky’s Office of Research Integrity Website: https://www.research.uky.edu/office-research-integrity/sample-applications-and-protocol-development-resources

26. Questions?