Approval Criteria – Informed Consent Angela Bain, IRB Administrator abain@uga.edu 706-542-3821

Criteria for Approval 45 CFR 46.111 25 CFR 56.111 Minimized Risks Reasonable Risk/Benefit Ratio Equitable Subject Selection Informed Consent Process Informed Consent Documentation Data Monitored for Safety Confidentiality/Privacy Maintained Vulnerable Populations Protected

Approval Criteria Informed Consent Process (4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by §46.116. Ethical principle from the Belmont Report – Respect for Persons. Respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection.

What is §46.116? This section of the regulations give us the general requirements for informed consent. Except as provided elsewhere in the policy (which we will talk about in a minute), 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.

General Requirements for Informed Consent Investigator must give the subject sufficient time and opportunity to consider whether they want to participate or not Investigator must make all efforts to minimize the possibility of coercion or undue influence. Information must be presented in language that the subject can understand There must be no exculpatory language through which the subject is made to waive any legal rights or releases the investigator, sponsor, or institution from liability for negligence.

8 Basic Elements of Informed Consent

Study involves research; study description Research acknowledgement Purpose of the study Expected duration of the subject’s participation Procedures (description) Specify which procedure are experimental We want to ensure that there is a statement informing the participants that this is research We cant to ensure that the participant understands the purpose of the research The participant must be informed on how long their research participation will take out of their time The participant must be informed of all research procedures they will be asked to complete It must be clear to the participant if any procedures are experimental

A description of any reasonably foreseeable risks or discomforts A description of any benefits to subject and/or society A disclosure of any alternative procedures, if any A statement describing the extent, if any, to which confidentiality will be maintained. 2. What are the risks? They can be physical, psychological, social, even legal. Is the nature and magnitude of the risk distinguished with as much clarity as possible? 3. Are the estimates of the harms or benefits reasonable? 4. If there are experimental procedures, especially medical procedures, the participant must be informed of any alternatives they may have to that treatment. 5. Who knows/needs to know? Who has access to the info? For example, the FDA may inspect records when the research falls under their purview.

Compensation and treatment for research related injuries Contact Information Voluntary Participation Refusal to participate will involve no penalty or loss of benefit to which the subject is otherwise entitled Informed consent is an ongoing process – the subject can withdraw at any time. 6. For research involving more than minimal risk. There should be an explanation of compensation or medical treatment provided, if any. If there is a risk that some of the treatment may not be covered by insurance. Payment responsibilities. Where further information may be obtained. 7. Whom to contact for questions related to the research – the PI. Questions related to subject’s rights – IRB. Research related injury, complaints, or other issues. 8. To me, this is the most important statement in the entire consent form. The subject must be aware that participation is voluntary. They must also be aware that if they do not participate, they will not be punished – either by not receiving services from their physician or any other services they may be currently receiving. Students must also be aware that refusal to participate will not affect their grades or class standing. They must also be aware that even though they have consented to research participation, they are not obligated to continue if they decide to stop participation.

Risks that are currently unforeseeable When appropriate, one or more of the following elements may also be provided. Risks that are currently unforeseeable Investigators may terminate participation Additional costs to the participant Consequences of subject’s withdrawal New findings that may alter subject’s willingness to participate Number of subjects involved in the study. These can be added at the discretion of the IRB

Additional guidance: no first person language Additional guidance: no first person language. HHS and FDA consider the use of first person wording to be suggestive and frown on it’s use. Using terms such as “I understand…” seems to misplace emphasis on legal statements rather than on explanatory wording that would enhance the subjects comprehension. Subjects are not in a position to judge whether the information provided is complete. They may certify that they understand the statements in the consent document and are satisfied with the explanation provided by the consent process but they should not be required to certify completeness of disclosure such as “This study has been fully explained to me” or “I fully understand this study” The IRB should ensure that technical and scientific terms are adequately explained or that common terms are used.

The IRB has special powers The IRB can approve a consent process that leaves out or alters some or all of the elements that we just talked about. The IRB can even waive the requirement to obtain informed consent all together.

How/When can the IRB Alter or Waive Consent????? Research activities present no more than minimal risk Waiver or alteration will not adversely affect rights and welfare of subjects. Research could not practicably be carried out without the waiver or alteration. When appropriate, subjects will be given pertinent information after participation The IRB determines level of risk – we have discussed this at previous meetings of the social and behavioral committee. The presentation can be found on the IRB Member Training Resources page. I may also provide the same training to this committee some time in the future. In explaining why the research will not adversely affect the rights or welfare, it is important to recognize the right of individuals to determine whether or not to participate in research. It is important to address why a waiver would not adversely impact the subjects. In situations where the investigator is seeking to waive consent all together, the IRB must ensure that there are protections in place and ensure that by granting the waiver, rights of the subjects are not affected. In situations where the investigator is seeking to alter some of the consent process (this is usually in studies that involve deception), the IRB will typically ask that information is given to the subject after participation is completed and that the subject is given an opportunity to withdraw their data if they so choose. This does not mean that it is not practicable to get consent; it literally means that it would not be practicable to conduct the research. This typically is applicable in chart review studies where there is no possible way to find the patients and obtain consent. There are also some situations where the investigator has access to the prospective subject but getting full consent would make it impossible to actually conduct the study or would threaten the scientific validity of the research results. This it typical when deception is used. This pretty much goes back to what I mentioned in #2 about how the IRB will ask the investigator to fully inform the subject after the participation is completed. Also, for some types of research it may be appropriate to make the study results available to the individual subjects or to the broader community from which the subjects were drawn. This could be in the form of newsletters or fliers in a doctors office to inform those who were subjects.

Approval Criteria Documentation of Consent (5) Informed consent will be appropriately documented, in accordance with, and to the extent required by §46.117.

What is §46.117? This section of the regulations give us general requirements for documentation of informed consent. What are these requirements?

Consent Documentation It must be signed and dated by the subject/Legally Authorized Representative (LAR) A copy must be given to the person signing the form Subject must be given adequate time to read it before signing it Short form consent process – used when dealing with subjects whose primary language is not English A short form written consent document, stating that the elements of informed consent have been presented verbally to the subject or the subject's legally authorized representative. When this method is used, there must be a witness to the oral presentation. Also, the IRB must approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness will sign both the short form and a copy of the summary, and the person actually obtaining consent will sign a copy of the summary. A copy of the summary shall be given to the subject or the representative, in addition to a copy of the short form.

More special powers of the IRB The IRB may waive the requirement for documentation, in certain circumstances (§46.117(c)) (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. Criteria 1: When the data to be collected is very sensitive, this criteria can be used to justify not obtaining documentation of consent. The regulations indicate that the subject should be asked if he/she wants to sign or not. Criteria 2: This usually applies to screening consents, internet surveys. Can only be used when there is not more than minimal risk in the questions being asked of the subject. 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.

What about the FDA? 21 CFR § 50.20 

Language for Clinical Trials "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." When seeking informed consent for applicable clinical trials, the following statement shall be provided to each clinical trial subject in informed consent documents and processes. This will notify the clinical trial subject that clinical trial information has been or will be submitted for inclusion in the clinical trial registry databank. Also, very important: Consent documents should not contain unproven claims of effectiveness or certainty of benefit that may unduly influence potential subjects. Overly optimistic representations are misleading and violate FDA regulations concerning the promotion of investigational drugs or investigational devices as well as the requirement to minimize the possibility of coercion or undue influence.

The FDA can inspect records There must be a statement in the confidentiality section of the consent form to note “the possibility that the FDA may inspect the records” The subject cannot be given the option of having their data removed from the study database upon withdrawal. When studies fall under the oversight of the FDA….

Waivers and Documentation The FDA does not allow waivers of consent or documentation of consent except: 21 CFR 50.23  Subject is in a life threatening situation Military operations Public health emergencies 21 CFR 50.24  Emergency research 21 CFR 56.109 (c)(1) Documentation may be waived if the IRB determines there is no more than minimal risk and no procedures which written consent would normally be required. In the event that an IRB waives the requirement for written documentation of informed consent, FDA recommends that the elements of informed consent be reviewed verbally with the subject or the subject's legally authorized representative. Additionally, the IRB may require the investigator to provide subjects with a written statement regarding the clinical investigation. The FDA recommends that when an IRB waives the documentation requirement for informed consent in circumstances where there is minimal risk of harm, the consent process and discussion be described and noted in the records relating to the clinical investigation. 30 (d)(1) Under 10 U.S.C. 1107(f) the President may waive the prior consent requirement for the administration of an investigational new drug to a member of the armed forces in connection with the member's participation in a particular military operation. The statute specifies that only the President may waive informed consent in this connection and the President may grant such a waiver only if the President determines in writing that obtaining consent: Is not feasible; is contrary to the best interests of the military member; or is not in the interests of national security. The statute further provides that in making a determination to waive prior informed consent on the ground that it is not feasible or the ground that it is contrary to the best interests of the military members involved, the President shall apply the standards and criteria that are set forth in the relevant FDA regulations for a waiver of the prior informed consent requirements of section 505(i)(4) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)(4)). Before such a determination may be made that obtaining informed consent from military personnel prior to the use of an investigational drug (including an antibiotic or biological product) in a specific protocol under an investigational new drug application (IND) sponsored by the Department of Defense (DOD) and limited to specific military personnel involved in a particular military operation is not feasible or is contrary to the best interests of the military members involved the Secretary of Defense must first request such a determination from the President, and certify and document to the President that the following standards and criteria contained in paragraphs (d)(1) through (d)(4) of this section have been met.

Well, that’s it. I’ll stop now before Gerry falls asleep.