Consent Form What’s changed?

1. Consent Form What’s changed? The NCI template and the Common Rule Revisions ‘Compliance’ 2019 Alison van Nie Research Ethics Officer OCREB

2. NCI ICF template • Internal revision process in 2016 • Revised key sections identified through prior evaluations, including costs, extra tests, and general integration of biomarker research • Met internally to review and finalize Revision #1 • Stakeholder review in 2016 • Distributed Revision #1 to prior working group members, Groups, and other NCI entities • Received 29 responses; reviewed and reconciled comments and edits • Final Revisions to the Common Rule, January 2017 • Released by OHRP on January 19, 2017 and effective January 19, 2019 • NCI implemented changes to the consent template to comply with the Final Rule requirements1 • Conducted iterative review with plain language specialist and finalized Revision #2 • Stakeholder review in 2017 • Circulated Revision #2 & received 18 responses; reviewed and reconciled comments and edits • Final revised template published, October 2017 • Two minor updates published December 12, 2017 • One minor update November 2018

3. WHO participated??? • NCTN Group members and staff • Patient advocates • 5 Working Groups for the NCI Concise Informed Consent Template Project (stakeholders with expertise including: CRAs investigators, IRB Chairs, CIRB Chairs and members, nurses, Cooperative Group regulatory and development staff) • NCI and Government colleagues (including FDA, OHRP, CCTG)

4. NCI Informed Consent Template Revision: Key Changes • Compliance with new OHRP Common Rule requirements • New “Overview and Key Information” section at the beginning of the ICD • More information about storage and potential use of identifiable information or identifiable bio-specimens • Additional information and examples for trials with genomic testing • Clarification of “Costs” and “Exams, Tests, and Procedures” sections to address potential billing and insurance coverage issues • Better delineation between routine, clinically indicated tests and procedures that may be done more frequently than usual but are still billable, and tests and procedures done for research purposes that are not billable • Improvements to readability and language to facilitate patient understanding • Formatting changes to improve usability for ICD authors

5. The Common Rule is the popular term for the Federal (U.S.) Policy for the Protection of Human Subjects, 45 CFR part 46, which outlines the criteria and mechanisms for IRB review of human subject’s research. The U.S. Department of Health and Human Services and fifteen other Federal Departments and Agencies have issued final revisions to the Federal Policy for the Protection of Human Subjects (the Common Rule). The effective date: January 21, 2019. The Final Rule strengthens protections for people who volunteer to participate in research, while ensuring that the oversight system does not add inappropriate administrative burdens, particularly to low-risk research. It also allows more flexibility in keeping with today’s dynamic research environment. The Final Rule will now generally expect consent forms to include a concise explanation – at the beginning of the document – of the key information that would be most important to individuals contemplating participation in a particular study, including the purpose of the research, the risks and benefits, and appropriate alternative treatments that might be beneficial to the prospective subject.

6. Consent Must Begin With… “Informed consent must begin with a concise and focused presentation of the key information that is most likely to assist a prospective participant or legally authorized representative in understanding the reasons why one might or might not want to participate in the research.” “This part of the informed consent must be organized and presented in a way that facilitates comprehension.” 45 CFR 46.116

7. What Is Key Information? • The preamble provides the following list of topics that the Common Rule departments and agencies indicated generally would encompass the key information required to satisfy 116(a)(5)(i): • Provide information any ‘reasonable person’ would want to know • Begin with a ‘concise and focused presentation’ of ‘key information…organized and presented in a way that facilitates comprehension • 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 participant’s participation, and the procedures to be followed in the research • The reasonably foreseeable risks or discomforts to the prospective participant • The benefits to the prospective participant or to others that may reasonably be expected from the research • Appropriate alternative procedures or courses of treatments, if any, that might be advantageous to the prospective participant • The preamble language is not legally binding on the Common Rule agencies’ future interpretation

8. Present information in ‘sufficient detail’ but not ‘merely provide lists of isolated facts’ • State what will happen to any identifiable private information or identifiable biospecimens collected and whether they will be stripped of identifiers and used for future research without consent • State that biospecimens may be used for commercial profit, and whether or not the subject will share in that profit • State whether clinically relevant research results will be returned to subjects and under what conditions • State whether research involving biospecimens will or might include whole genome sequencing

9. Key Information: • What are the main reasons a participant will want to join this study? • What are the main reasons a participant will not want to join this study? • What is the research question the study is trying to answer? Why is it relevant to the participant? • What aspects of research participation or this particular study are likely to be unfamiliar to a prospective participant, diverge from a participant’s expectations, or require special attention? • What information about the participant is being collected as part of this research? • What are the types of activities that participants will do in the research? • What impact will participating in this research have on the participant outside of the research? For example, will it reduce options for standard treatments? • How will the participants’ experience in this study differ from treatment outside of the study? • In what ways is this research novel? • •Note: Content derived from a working document out of the July SACHRP public meeting

10. Who Is the Reasonable Person and What Do You Need to Tell Them? “…information that a reasonable person would want to have in order to make an informed decision about whether to participate and an opportunity to discuss that information.” Later qualified by the words: “...in understanding the reasons why one might or might not want to participate in the research.” 45 CFR 46.116

11. Consent as a Whole “Informed consent as a whole must present information in sufficient detail relating to the research, and must be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective participant’s or legally authorized representative’s understanding of the reasons why one might or might not want to participate.” 45 CFR 46.116

12. Basic Elements of Informed Consent • Summary of new basic element: • Notice about whether information and bio-specimens collected as part of the current research might be stripped of identifiers and used for future research • Consent form needs to state: • •That the de-identified information or bio-specimens could be used for future research without additional consent (notice of traditional secondary research uses); or • •That the participants’ information or bio-specimens will not be used for future research (use with caution)

13. 3 New Additional Elements When appropriate: A statement that the participant’s bio-specimens (even if identifiers are removed) may be used for commercial profit and whether the participant will or will not share in this commercial profit; A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to participants, and if so, under what conditions; and For research involving bio-specimens, 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

14. Studies Using Genetic Testing of Tumour Tissue Alone to Identify Potentially Inheritable Mutations – sample language The genetic test used in this study will test your tumor for (*a genetic change or genetic changes*), (*specify which changes, e.g., BRCA1*). This change also may be in your normal tissue and passed down through your family. For example, these genetic changes may be passed down to your children in the same way that eye and hair color are passed down. Since this study is only testing tumor tissue, we will not know if a genetic change in your tumor is also in your normal tissue. If you want to find out if the change is in your normal tissue, then you will need to get other tests done outside of this study. Genetic tests of normal tissue can reveal information about you and also about your relatives. Your study doctor will talk with you about what testing your normal tissue may mean for you and your family. He or she also may suggest that you talk with a genetics counselor to learn more. You or your insurance plan would have to pay for any genetic tests and visits to a genetic counselor done outside of this study.

15. Genomic Testing – sample language • Studies Using Investigational Genetic Test Results to Determine Study Eligibility and Assign Patients to Study Groups • As part of this study, we are also studying a genetic test. The test is designed to find out if your tumor has the genetic changes that are needed for this study. If it does, we will assign you to a study group based on the genetic changes in your tumor. • Because this genetic test is still being studied, there is a risk that the test results may be wrong. If the test results are wrong, you may be included in this study even though it may not offer the best treatment option for you. Or, you may not be included in this study even though it may offer a good treatment option for you.

16. National Consent Working Group Member Organizations and Community participants: • National-CCTG • NL Health Research Ethics Authority • ON OCREB - Chair • U Saskatchewan REB • Alberta Innovates • ON UHN • BCC REB • NL Cancer Care Program, Eastern Health

17. Mandate • The mandate of the National Consent Working Group (NCWG) is to develop common oncology informed consent form (ICF) templates that can be adopted nation-wide by Research Ethics Boards (REBs) and health sciences researchers. • The NCWG decided in early 2018 to adopt the NCI US template with minimal adjustments for Canadian requirements. •  The main objectives NCWG are: • To develop and maintain ICF templates that are compliant with best practices, national standards and applicable regulations and guidelines; • To strive for a reading level of Grade 6-8; • To evaluate, and to align when appropriate, with established templates (e.g., NCI US); • To evaluate, and incorporate when appropriate, relevant updates and (user) feedback; • To facilitate broad adoption of the national ICF templates in order to promote harmonization and standardization; • To collaborate with stakeholders – e.g., Industry/pharmaceutical trial sponsors, academic and cooperative group sponsors, Canadian Institutes of Health Research (CIHR), Canadian Cancer Clinical trials Network (3CTN), Network of Clinical Trial Networks (N2). • Responsibilities…….. • use best efforts to integrate the ICF template(s) into local practice and update WG on local practice that may affect integration; • use best efforts to promote and facilitate the adoption of the ICF templates nationally.

18. Adaption of NCI US template: • HIGHLIGHTS of NCWG consent template and instructions documents • Follows NCI US consent template wording VERY closely; the goal was to adopt the NCI US template with edits to include TCPS2 requirements and occasionally for brevity or clarity with regards to Canadian participation • Adopts Canadian template formatting, as described in Instructions for Consent Authors • Separates lengthy instructions to consent authors throughout NCI US template into a separate document • Only exams, tests and procedures that are related to clinical trial are to be listed (#12) • Reproductive risk information is concise and split between Risk (#13) and Responsibilities (#14) sections • Optional studies information and consent check boxes are included within main ICF (#20) • Includes TCPS2 requirements: • Correlative study specimens: where sent, retention period and withdrawal • Conflict of Interest • Informed Consent Form (ICF) is 29 pages and Instruction Guide for ICF Authors is 9 pages

19. A new approach to the ICF • Focus on research and not clinical care; • Limit the information; • Include all optional research in the same ICF; • Exceptions: e.g., pre-screening if for a key eligibility criteria • Consider including incidental/actionable findings • Advocate for a principle based document in which revisions should be minimal. Contact: Chair of the working group Alison van Nie alison.vannie@oicr.on.ca