Informed Consent: Regulatory Basics

1. Informed Consent: Regulatory Basics Laura Odwazny Office of the General Counsel Department of Health and Human Services May 21, 2010 This presentation does not constitute legal advice. The views expressed are the presenters� own, and do not bind the U.S. Department of Health and Human Services or its components.

2. Regulatory requirements HHS protection of human subjects regulations, 45 CFR part 46 Subpart A is the Common Rule FDA protection of human subjects regulations, 21 CFR part 50 (informed consent) and part 56 (IRB)

3. Ethical principles Respect for Persons � Autonomy Informed consent Voluntary participation Freedom to withdraw without penalty Protect privacy/confidentiality Beneficence Risks minimized, benefits maximized Risks justified by potential benefits Conflicts of interest are appropriately managed

4. Ethical principles (2) Justice � equitable distribution of risks and benefits Appropriate protection of vulnerable populations No exclusion of those who may benefit

5. 3 key features of informed consent Disclosing to potential research subjects information needed to make an informed decision Facilitating the understanding of what has been disclosed Promoting the voluntariness of the decision about whether or not to participate in the research

6. Informed consent is an active process of sharing information between an investigator and the subject, not just the signing of a form

7. Regulatory requirements

8. Informed consent 45 CFR 46.116 � General requirement for informed consent �Except as provided elsewhere by this policy, no investigator may involve a human being as a subject in research covered by this policy unless the investigator has obtained the legally effective informed consent of the subject or the subject�s legally authorized representative.�

9. General requirements - informed consent Circumstances of consent must give subject opportunity to consider participation, and minimize possibility of coercion or undue influence Consider payment, free drug or device Information given must be in language understandable to the subject

10. General requirements � informed consent Prohibition on exculpatory language Can�t waive or appear to waive subject�s legal rights Can�t release or appear to release investigator, sponsor, institution or its agents from liability for negligence

11. 8 required elements[45 CFR 46.116(a) and 21 CFR 50.25(a)] Statement that study is research; information about purposes, duration, procedures, experimental procedures Reasonably foreseeable risks or discomforts Reasonably expected benefits to subject or others Alternative procedures

12. 8 required elements[45 CFR 46.116(a) and 21 CFR 50.25(a)] Extent, if any, to which confidentiality of records identifying subject will be maintained Information on compensation for injuries/medical treatment (unless minimal risk) Contact person for information on research, injury, subject�s rights Voluntary participation, no penalty or loss of benefits for refusal or withdrawal

13. 6 additional elements[45 CFR 46.116(b) and 21 CFR 50.25(b)] Statement that there may be risks which are unforeseeable Under what circumstances investigator could terminate subject�s participation Additional costs to subjects Consequences of subject�s withdrawal from research; procedures for termination

14. 6 additional elements[45 CFR 46.116(b) and 21 CFR 50.25(b)] Statement that subjects will be told of new findings which might affect willingness to continue to participate Approximate # of subjects in study

15. More points on informed consent Regulations do not recognize �passive consent� Consent required unless waived by IRB If consent not waived, documentation required unless waived by IRB Regulations do not recognize �secondary subject� Deception research Requires waiver of consent

16. More points on informed consent (2) Discovery of new information � how to provide to subjects? No need for prior IRB review before providing already-enrolled subjects with info which may affect their willingness to participate Informed consent form should be amended

17. When reviewing informed consent language, consider� Who will consent subjects? When and where are subjects approached about participation? Need for re-consent? Longitudinal study Minors who reach age of majority Temporary decisional impairment

18. Waiver of informed consent

19. Waiver of informed consent � 45 CFR 46.116(c)[not for FDA-regulated research] Waiver may be of some or all of the required elements, or of requirement for consent in toto IRB must find and document: Research conducted by or subject to approval of state/local governmental officials and designed to study public benefit or service programs procedures for obtaining benefits/services from such programs changes in or alternatives to such programs or procedures, or changes in methods or levels of payment for benefits or services under such programs; and Research could not practicably be carried out without waiver

20. Waiver of informed consent � 45 CFR 46.116(d)[not for FDA-regulated research] Waiver may be of some or all of the required elements, or of requirement for consent in toto IRB must find and document: Minimal risk research; Waiver will not adversely affect subjects� rights and welfare; Research could not practicably be carried out without waiver; and When appropriate, subjects provided with additional pertinent information after participation

21. Emergency research waiver of consent For limited class of research in emergency settings, both FDA and OHRP have waived general requirement for informed consent if certain conditions are met. OHRP guidance on emergency waiver: http://www.hhs.gov/ohrp/humansubjects/guidance/hsdc97-01.htm

22. Documentation of informed consent and waiver of documentation

23. Documentation of informed consent � 45 CFR 46.117(b)(1) (long form) Written consent document including required elements of informed consent Language understandable to the subject or LAR Opportunity for subject or LAR to read Signed by subject or LAR Copy given to subject or LAR

24. Documentation of informed consent � 45 CFR 46.117(b)(2) (short form) Written consent document stating required elements of informed consent were presented orally Witness to oral presentation IRB approved written summary of presentation Signed by witness Signed by person obtaining consent Copy given to subject/LAR Form documenting presentation Signed by subject/LAR Signed by witness Copy given to subject/LAR

25. Waiver of documentation [not permitted in FDA-regulated studies] IRB must find: Signed consent document provides the only link to the subject�s identity and principal risk is breach of confidentiality; or Minimal risk research; no procedures requiring consent in a non-research context IRB may require investigator to give subjects written statement regarding the research

26. Specific regulatory provisions applicable to vulnerable populations

27. Decisionally impaired subjects Adult with temporary or permanent decisional incapacity can only be enrolled if consent by a �legally authorized representative� (LAR) LAR=individual or judicial or other body authorized under applicable law to consent to subject�s participation in the procedures involved in the research

28. What Is Applicable Law? ��authorized under applicable law�� No national standard State and local law E.g., state statutes, regulations, case law on point, formal opinion of State Attorney General, or a combination thereof. Must address the issue of surrogate consent Because there is no national standard for a legally authorized surrogate decisionmaker, you must look to state and local law.Because there is no national standard for a legally authorized surrogate decisionmaker, you must look to state and local law.

29. What Is Applicable Law? (2) ��to consent�to the subject�s participation in the procedure(s) involved in the research.� Laws specifically addressing surrogate consent to participation in research CA, NY Laws addressing surrogate consent to medical procedures

30. What If a State Has No Applicable Law? LAR can consent to participation of a decisionally incapacitated person only if: Court-appointed guardian Authorized by advance directive executed in accordance with State law There are some states with no applicable law. In these states, for research subject to the Common Rule, a legally authorized representative can consent to participation of a decisionally incapacitated person only if they have been appointed through guardianship proceedings or authorized by an advance directive that State law allows to be used to appoint a surrogate decisionmaker. My view is that the absence of applicable state statues is one that the states� legislatures must address, and determine appropriate standards for the state. As a federal agency, OHRP should not be making decisions that are in the province of the state to make.There are some states with no applicable law. In these states, for research subject to the Common Rule, a legally authorized representative can consent to participation of a decisionally incapacitated person only if they have been appointed through guardianship proceedings or authorized by an advance directive that State law allows to be used to appoint a surrogate decisionmaker. My view is that the absence of applicable state statues is one that the states� legislatures must address, and determine appropriate standards for the state. As a federal agency, OHRP should not be making decisions that are in the province of the state to make.

31. 45 CFR part 46, subpart B � Pregnant Women (not applicable to FDA-regulated research) 45 CFR 46.204(f) � Research involving pregnant women or fetuses 45 CFR 46.205(a)(2) � Research involving neonates Consenting individuals (pregnant women, father) must be fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate

32. 45 CFR part 46, subpart D � Research Involving Children �Children� by definition do not have legal ability to consent to the research procedures Emancipated minor/mature minor may or may not be considered a �child,� depending on nature of research Parent/guardian provides permission for child to participate in research [45 CFR 46.408] Either 1 or both parents, depending on circumstances Child assent Required if IRB determines children are capable

33. Research involving children � waiver of permission or assent [not for FDA-regulated research] Parental/guardian permission may be waived if: Subpart A waiver of consent requirements met (45 CFR 46.116); or Research designed to study conditions in children/population for which parental permission would not protect the subjects (e.g. neglected or abused children), and both: appropriate substitute mechanism in place to protect children, and waiver not inconsistent with Federal, state, or local law (45 CFR 46.408(c).

34. Research involving children � waiver of permission or assent (2) IRB may waive requirement for parental or guardian permission under 45 CFR 46.408(c) even if the research involves more than minimal risk Emergency research waiver also applicable to research involving children Assent may be waived if Subpart A waiver of consent requirements met (45 CFR 46.116)

35. Resources OHRP FAQs on Informed Consent: http://www.hhs.gov/ohrp/informedconsfaq.pdf

36. Questions?