1. Legally Effective Informed Consent VA Requirements Kevin L. Nellis, M.S., M.T. (A.S.C.P.) Program Analyst Program for Research Integrity Development and Education (PRIDE)

2. Topics General requirements Required elements Additional elements FDA element for Clinical Trial Documentation Waiver of documentation Waiver of informed consent 2

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4. General Requirements No investigator may involve a human being as a subject in research covered by VHA Handbook 1200.05 unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative (LAR) 4

5. Circumstances Under Which Informed Consent May Be Sought Investigator seek informed consent only under circumstances that: Provide the prospective subject /LAR sufficient opportunity to read the informed consent document when applicable Provide the prospective subject,/LAR, sufficient opportunity to consider whether or not to participate Minimize the possibility of coercion or undue influence 5

6. Circumstances Under Which Informed Consent May Be Sought Information given to the subject/LAR must be in language understandable to the subject or the subject’s LAR No informed consent, whether oral or written, may include any exculpatory language Made to waive, or appear to waive, subject's legal rights; or Releases, or appears to release investigator, sponsor, institution, or its agents from liability for negligence 6

7. Person Obtaining Informed Consent If someone other than the investigator conducts the informed consent process, the investigator must formally and prospectively designate in writing in the protocol or the IRB application Person so designated must have received appropriate training to perform this activity Must be knowledgeable about the research to be conducted and the consenting process Must be able to answer questions about the study 7

8. Observing the Process The IRB has the authority to observe or have a third party observe the informed consent process 8

9. Informed Consent Form VA Form 10-1086 Use the most current IRB-approved version of VA Form 10-1086 Include all required elements, unless waived by IRB Include any additional elements required by the IRB Must contain a designated block for each required signature and date “Block” may be a labeled line, window of a table, or other format 9

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11. Required Elements Statement that the study involves research Explanation of the purposes of research Expected duration of the subject's participation (e.g., length of the subject’s commitment) A description of the procedures to be followed Identification of any procedures that are experimental 11

12. Required Elements Reasonably foreseeable risks or discomforts (e.g., Physical, social, legal, economic, psychological risks, or other) from the research Risks solely from treatments or services to be the responsibility of the health care provider, should not be described in the consent form Include language advising subjects to review the risks of such clinical treatments or services with their health care provider(s) 12

13. Required Elements Describe any benefits to the subject or to others that may reasonably be expected from the research Disclose appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject 13

14. Required Elements Describe extent to which confidentiality of records identifying the subject will be maintained, and if appropriate, state: Federal agencies including, but not limited to, the FDA, OHRP, ORO, and the VA Office of the Inspector General (OIG) may have access to the records FDA may choose to inspect research records that include the subject’s individual medical records 14

15. Required Elements For research involving more than minimal risk: An explanation as to whether any compensation is available if injury occurs, and An explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained NOTE: VA provides care for all research-related injuries (38 CFR 17.85) 15

16. Required Elements Explain whom to contact For answers to pertinent questions about The research The subjects' rights Research-related injury to the subject At least one contact must be someone other than the investigator or study personnel 16

17. Required Elements Provide a statement(s) that Participation is voluntary Refusal to participate involves no penalty or loss of benefits to which the subject is otherwise entitled Subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled 17

18. Required Elements VA requires the following elements of informed consent: Name of the study Name of the PI or Local Site Investigator (LSI) in multi-site studies Sponsor of the study 18

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20. Additional Elements Required by Common Rule, When Appropriate Unforeseeable risks to subject, fetus, or embryo Anticipated circumstances when subjects can be terminated from the research Consequences of withdrawal from the study Additional Costs Subjects in VA research cannot be charged, nor their insurance be billed, for research Veterans may pay co-payments for medical care and services; but not for research 20

21. Additional Elements Required by Common Rule, When Appropriate Statement that any significant new findings which may relate to the subject’s willingness to continue participation, developed during the course of the research, will be provided to the subject Approximate number of subjects involved in the study 21

22. Additional Elements Required by VA, When Appropriate That the investigator believes that the human biologic specimens obtained could be part of, or lead to the development of, a commercially valuable product If the specimens are to be retained after the end of the study for future research Where the specimens will be retained Who will have access to them How long they will be retained 22

23. Additional Elements Required by VA, When Appropriate If any of the data will be retained after the study for future research Where the data will be stored Who will have access to the data If the subject will be re-contacted for future research whether within VA or outside VA 23

24. Additional Elements Required by VA, When Appropriate Statement regarding any payment the subject is to receive for participating in the study and how the payment is to be made If the subject will receive a report of the aggregate results or any results specific to the subject 24

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26. FDA Amended Informed Consent Requirements on January 4, 2011 Effective date is March 7, 2011 Must be compliant for clinical trials that are initiated on or after March 7, 2012 Statement is required on all informed consent documents (e.g., including short form and written summary) Required by FDA Amendments Act of 2007 (FDAAA) Designed to promote transparency 26

27. Applicable Clinical Trials Required only for applicable clinical trials Defined in FDAAA, 42 U.S.C. 282(j)(1)(A), section 402(j) (1)(A) of PHS Act NIH/NLM has elaborated on the meaning of ‘‘applicable clinical trial’’ http://prsinfo.clinicaltrials.gov/fdaaa.html http://prsinfo.clinicaltrials.gov/ElaborationsOnDefini tions.pdf http://prsinfo.clinicaltrials.gov/ElaborationsOnDefini tions.pdf 27

28. The Statement is… ‘‘A description of this clinical trial will be available on http://www.ClinicalTrials.gov as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.’’ http://www.ClinicalTrials.gov 21 CFR part 50.25(c) 28

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30. Documentation of Informed Consent Informed consent must be documented prospectively by the use of a written consent form approved by the IRB, unless documentation of informed consent has been explicitly waived by the IRB Email communications do not constitute documentation of informed consent 30

31. Consent Form VA Form 10-1086, Research Consent Form, must be used One exception: a DoD informed consent form may be employed for active duty military personnel participating in VA research at DoD sites when VA- specific language is not necessary (e.g., when language for treatment of research related-injury is not needed because active duty military personnel are covered by DoD) 31

32. Consent Form for VA Research Must use the most recent IRB-approved informed consent form (VA Form 10-1086) Requirement to utilize VA Form 10-1086 to document informed consent applies to all VA-approved research including, but not limited to, studies in which VA investigators working on VA Research enroll subjects at the affiliate hospital or other sites outside VA (e.g., community centers or shopping malls) 32

33. Consent Form for VA Research Must contain version date (e.g., in a header or footer) on each page IRB approval date must be documented by the use of a stamp or preprinted box on each page of the informed consent form Must be signed and dated by Subject or LAR Person obtaining informed consent Witness, if required by IRB 33

34. Consent Form for VA Research Original filed in the investigator’s research file Copy must be provided to the subject or LAR Where applicable, a copy must be placed in the medical record (see VHA Handbook 1907.01) NOTE: If using facsimile, the person who obtains informed consent must sign and date the facsimile and measures must be employed to ensure the confidentiality and privacy 34

35. Consent Form for VA Research Informed consent form may be either Written informed consent (long form) Short form written consent document stating that the elements of informed consent required by 38 CFR 16.116 have been presented orally to the subject or the subject’s LAR See VHA Handbook 1200.05 for additional requirements 35

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37. Waiver of Documentation of Informed Consent IRB may waive documentation of informed consent, if The only record linking subject and 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 37

38. Waiver of Documentation of Informed Consent IRB may waive documentation of informed consent, if 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 38

39. Waiver of Documentation of Informed Consent Unless IRB has granted a waiver of informed consent the investigator, or designee, must still perform an adequate informed consent process IRB must document its determinations regarding a waiver of documentation of informed consent in the IRB minutes or in the protocol file IRB may require the investigator to provide subjects with a written statement regarding the research (e.g., information sheet, FAQs, letter, etc) 39

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41. IRB May Alter Element(s) Or Waive Informed Consent, If It Finds And Documents: The research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and The research could not practicably be carried out without the waiver or alteration 41

42. IRB May Alter Element(s) Or Waive Informed Consent, If It Finds And Documents: Research involves no more than minimal risk to the subjects Waiver or alteration will not adversely affect the rights and welfare of the subjects Research could not practicably be carried out without the waiver or alteration; and Whenever appropriate, the subjects are provided with additional pertinent information after participation 42

43. Waiver of Informed Consent Other applicable Federal, State, or Local Laws. The informed consent requirements in this VHA Handbook 1200.05 are not intended to preempt any applicable Federal, state, or local laws which require additional information to be disclosed in order for informed consent to be legally effective The IRB must document its determinations regarding a waiver of informed consent in the IRB minutes or in the protocol file 43

44. Key Points Legally effective informed consent encompasses both the “process” and the “form” Incorporate all VA and Common Rule requirements into the process IRB may waive documentation of informed consent; or may alter elements or waive informed consent IRB must document findings 44

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