What an IRB Member Should Know about Informed Consent in Regulated Research

1. What an IRB Member Should Know about Informed Consent in Regulated Research CIP Course Lesson 4

2. Informed Consent What are the general regulatory requirements for consent? What information must be provided? How must consent be documented? What is a short form? May an IRB waive the requirement for a signature on a form? May an IRB waive the requirement for consent? Are there other exemptions to the requirement for consent? What are the requirements when the research changes?

3. What are the general regulatory requirements for consent?

4. Research that is Federally Funded or Supported Each institution engaged in research which is covered by this policy and which is conducted or supported by a federal department or agency shall provide written assurance satisfactory to the department or agency head that it will comply with the requirements set forth in this policy. 45 CFR 46.103(a) Issue for analysis: When is institution “engaged” in “research” “covered by this policy”

5. Seeking consent is fundamental in research involving humans. The requirement for consent comes from the principle of “Respect for Persons” found in the Belmont Report. Informed consent for research includes both a document and a process. The IRB should review both the document and the process to ensure that informed consent is obtained in compliance with: IRB requirements The protocol The ethical principles of the Belmont Report ICH (when applicable) Regulations

6. Since individuals are giving the study the right to use them or information about them to collect data – we owe them the upmost respect and protection.

7. Belmont Report Respect for Persons Information Comprehension Voluntariness

8. Common Rule FDA Regulations

9. Except as provided elsewhere in this policy [in Sec. 50.23 if under FDA jurisdiction) no investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. 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 rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence. Federal regulation s 45 CFR 46 and 21 CFR 50.20

10. Legally effective Sufficient time Avoiding undue influence Avoiding coercion Understandable No waivers of liability

11. “….no investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative

12. Legally Effective Informed Consent Person providing consent - has authority - has all required information …and the person obtaining consent documents this information.

13. Legally Effective Informed Consent Procedure for obtaining legally effect informed consent should include: Requiring evaluation of consent document to ensure that the document includes all required information Requirement for assessing whether individual giving consent has authority to consent

14. Time to Consider Take consent form home? Obtain consent before the day of surgery, if research involves elective surgery Consider timing of consent for research conducted in an urgent or emergent situation

15. An investigator shall seek such consent only under circumstances that ... minimize the possibility of coercion or undue influence.

16. Coercion – threat of harm if individual doesn’t agree.

17. Minimizing Coercion Consider using someone who is not a “authority figure” to conduct consent discussion. Assure individual that he or she will not be penalized or harmed if he or she decides not to enroll or decides to withdraw from study. Conduct the consent process in a safe, comfortable location. .

18. Undue influence – belief that individual will benefit if he or she agrees.

19. Minimizing Undue Influence Language should not be overly reassuring. Do no underemphasize risks or overemphasize the potential benefits Amount of compensation should not unduly influence participants to participate without carefully considering risks and responsibilities associated with participation Compensation should not be contingent upon completing the study

20. An investigator shall seek such consent only under circumstances that ... minimize the possibility of coercion or undue influence.

21. The information that is given to the subject or the representative shall be in a language understandable to the subject or the representative.

22. Assessing understanding – Ask questions Are we offering you your usual medical care or are we asking you to be in a research study? Do you have to take part in this study or is it okay to say “no?” What is the purpose of the study? Tell me what will happen to you in this study. Tell me about the risks you will face if you join this study. Tell me about any benefits you could receive if you join this study. Suppose you want to drop out of the study – when can you drop out? .

23. 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.

24. ICH E-6 If the individual cannot read the consent document – Investigators must ensure the consent discussion is witnessed by an impartial witness. The impartial witness must sign the consent form attesting that the information in the document was accurately presented to the individual and apparently understood by the individual and the individual consented freely

25. Dr. Rogers want us to approve the enrollment of a participant who does not speak or read English without first obtaining a written translation of the consent form. This is her study of the investigational drug for ovarian cancer.

26. This is a very difficult study with many procedures. The drug includes significant risk. How will Dr. Rogers ensure that the participant understands the procedures and the risks?

27. She plans to use a commercial translation service by phone.

28. How will she know whether the information is being appropriately translated? In today’s society, the probability is not remote that Dr. Rogers will need to demonstrate in court that the individual understood the risks and benefits when consent was obtained. I am not satisfied that this process will result in true informed consent.

29. So, you are suggesting that we disapprove the request. Wouldn’t a disapproval result in the participant being denied access to a potentially effective treatment?

30. You are correct. But, the drug is unproven. If the consent were for “treatment,” I would not hesitate to approve the consent process. However, this is research. Perhaps, the standard should be higher….

31. Different IRBs will come to different conclusions on issues such as this. FDA Guidance states that ad hoc translation of the consent document should not be substituted for a written translation. Now, let’s look at another issue. .

32. This study will involve participants who are between 15 and 25 years of age. I recommend that the Board require assent from the participants who are minors.

33. But the study involves an investigational treatment for a sexually transmitted disease (STD). All participants will be able to consent to diagnosis and treatment of their STD. If we require assent from minors instead of consent, we will not be obtaining legally effective consent as required by the regulation.

34. So… if the children can consent to the treatment involved in the study, then they can also consent to participate in a clinical trial of the treatment they receive?

35. Yes. The regulation defines a child as an individual who cannot consent to the procedures involved in the study. In this case, the participants are not children.

36. It is important for investigators to obtain consent that is legally effective. IRB members and investigators should be aware of the requirements. Let’s look at another issue .

37. This next study will be done in the ER and will recruit patients who are admitted with chest pain. I identified two issues with informed consent for this study. The first issue is that consent must be obtained within one hour of presentation in the ER . The second issue is that the patients will be in pain and under stress. They might also be sedated.

38. This investigational drug looks very promising. We need to figure out how to overcome the issues.

39. Nevertheless, it is our responsibility to ensure that informed consent is obtained under circumstances that minimize coercion and undue influence and that allow the participant sufficient time to consider the risks.

40. I recommend that we require a person who is not providing treatment to the patient conduct the consent process. We should also require participants – or their LAR, when appropriate – to correctly answer a list of questions about the research before consent is obtained and that the entire process be witnessed.. At the same time, we need assurances from Dr. Rogers that the consent process will not result in treatment delays.

41. Do you think the other members will agree with the recommendations? .

42. 2. What information must be provided?

43. A statement that the study involves research, an explanation of the purposes of the research and expected duration, a description of the procedures to be followed, and identification of any procedures which are experimental. .

44. A statement that the study involves research, an explanation of the purposes of the research and expected duration, a description of the procedures to be followed, and identification of any procedures which are experimental. .

45. Issues to consider: Does the consent form include a statement that the project involves research? Are the purposes of the research explained and do they match the objectives outlined in the protocol? Are the experimental procedures identified? Is the duration of the subject’s participation clearly described? .

46. A description of any reasonably foreseeable risks or discomforts to the subject .

47. Examples of Risk Is there any chance participants will suffer pain or injury if they enroll? Could participants face a financial impact if they enroll? Could participation result in psychological or emotional harm? Is there any risk to the participant’s privacy? . Could participation result in damage to the individual’s reputation? Are there any legal risks?

48. Are the risks of each procedure required by the protocol included? Does the description of the risks include overly reassuring language that could unduly influence the individual to not fully consider a risk? Are the confidentiality risks adequately explained? Were any risks omitted? For research of an investigational drug or device, does the consent form include any claims that the? .

49. A description of any benefits to the subject or others which may be reasonably expected from the research .

50. If there is no direct benefit to the subject, is this information clearly explained? If there is a potential for direct benefit, is the information explained in a balanced manner? Are the potential benefits to society accurately summarized? Payment to research subjects should not be included in the discussion of benefits. Payment is considered a recruitment incentive, not a benefit of the research.