Approaching Assent with the Child in Mind

Approaching Assent with the Child in Mind

Presenter Areas of Expertise FDA, OHRP, and HIPAA laws, regulations, and guidance, as well as the comparable legal frameworks in Canada Life science research and IRB review, including pediatric research, clinical trial compliance and monitoring, institutional policy improvements, and intellectual property rights Educations & Certifications Juris Doctor from the University of Washington in 2009 Admitted to the Washington State Bar Association (WSBA) in 2010 Registered Patent Attorney and member of the Washington Patent Law Association Previous Experience Before joining Quorum Review's regulatory department, Mr. Chiarelli worked as a regulatory analyst and IRB Member with Seattle Children's Research Institute where he was also a member of their Children's Intellectual Property Group Prior to obtaining his Juris Doctor, Mr. Chiarelli, who holds a B.S. in Biology, Magna Cum Laude, worked as clinical research assistant at several major cancer research centers in Australia, Spain, and the U.S. 2

Overview Topic Page Children are a Vulnerable Population 4 Assent Requires Action 11 Capability Determines Whether Assent is Beneficial 14 The Process of Assent Maximizes the Benefits 23 Role of the Family in Assent 30 Conclusions 33 3

Children are a Vulnerable Population 4

Unique Children are Not Just Small Adults! Children are unique from adults and unique from each other: Biologically Social/Behaviorally 5

Research Research is Essential to Improving Childhood Health Research validates current medical practices and promotes new treatments Research with children has lagged due in part to serious ethical concerns Little Albert 6

Autonomy Children Lack Autonomy to Make Own Health Care Decisions Respect for persons is central to human subjects protections: Individuals should be treated as autonomous agents Persons with diminished autonomy are entitled to protection Who is an autonomous person? An autonomous person is capable of deliberation and able to act according to those deliberations. 7

Protections Regulations Afford Children Additional Protections Research with children requires at least three additional protections: Prospect of direct benefit for any intervention or procedure that is more than a minor increase over minimal risk, Permission by parents or guardians for participation, and Adequate provisions are made for soliciting assent 8

Assent Assent as an Additional Protection Assent promotes the principles of respect for persons and beneficence: Children should be treated with dignity and respect Sharing in decisions benefits development as individuals 9

Dynamic Requirements are Intentionally Dynamic IRBs are able to tailor assent requirements relative to the circumstances The considerations include: Capability of the targeted research population Information necessary to facilitate a decision Method of providing this information and capturing the decision 10

Assent Requires Action

Affirmative Assent is an Affirmative Agreement to Participate in the Research Assent must be: Demonstrated by words or actions and is not the mere failure to object Present throughout and can be withdrawn in full or in part at any time 12

Assent not Consent Distinguished from Informed Consent Assent is not: A complete understanding of the research or the rights of a research participant Beholden to a set of formal requirements in terms of what is provided and how 13

Capability Determines Whether Consent is Beneficial

Capability Assent is Necessary According to Capability An IRB will require assent whenever children are capable as defined by: Ability to consider the information provided Ability to make a decision based on that information 15

Based on Age The Rule of Sevens Children 6 Unable to consider participation or make a decision Describe procedures, but do not explain or ask permission Children 7-13 Able to consider participation, possibly unable to make decision Describe research and seek permission for non-therapeutic interventions Children 14 Able to consider participation and able to make all decisions Describe research and seek permission for participation 16

Based on Age Age May Be a Poor Indicator in Certain Circumstances A child s developmental age may exceed or lag their chronological age: 12 year old with refractory ALL? 16 year old with autism? 17

Based on Law Capability by Definition A child is any person who has not attained the legal age of majority or otherwise does not have the legal ability to consent to the treatments or procedures involved in the research. State law can grant children the ability to consent for themselves, for example: Emancipation Self-sufficiency Mature Minor Marriage Specific types of medical care - sexually transmitted diseases, pregnancy, or drug addiction 18

Based on Benefit Prospect of Direct Benefit Assent may not be necessary regardless of capability if the research holds out the prospect of direct benefit that is available only in the context of research 19

Example - Plat-01 What are the assent requirements for the following: Study: A Pediatric Trial of Genetically Modified Autologous T Cells Directed Against CD19 for Relapsed CD19+ Acute Lymphoblastic Leukemia (NCT01683279) Age range: 1 to 26 years Procedures: Medical record review Blood draw HIV Testing Infusion of CAR+T cells Future research with blood and marrow Optional extra blood Optional extra marrow 20

Example - Plat-01 Procedure Age Law Benefit Assent Deliberate Decide Medical record review 7+ 7+ 18 Y 14 and up due to benefit Blood/marrow draws 7+ 7+ 18 Y 14 and up due to benefit HIV Testing 7+ 14+ 14 Y 14 and up due to law Infusion of CAR+T cells 7+ 14+ 18 Y 14 and up due to decision or benefit Future research 14+ 14+ 18 N 14 and up due to deliberate + decision Genetic research 14+ 14+ 18 N 14 and up due to deliberate + decision Optional extra blood 7+ 7+ 18 N 7 and up due to deliberate + decision Optional extra marrow 7+ 7+ 18 N 7 and up due to deliberate + decision 21

Waiver Waiver of Assent is Available Regardless of Capability An IRB may waive the assent using the criteria for waiver of informed consent. This may be appropriate for research involving: Classroom dynamics Post-market surveillance Research using existing materials 22

Formulating a Process that Maximizes the Benefits

Process Assent Does Not Require a Written Document Assent may be sought or supplemented using: Videotapes and photographs of research procedures, Pre-visits to the site of the research to see and experience equipment, or Arranging for potential families to speak with other families who have participated in the research or research 24

Assent Form(s) An Assent Form, If Used, Must Be Understandable Assent forms should be developed to be age appropriate and child-centric Common to create a simplified form for children aged 7-13 Usually limited only to research activities in which assent will be sought and written at a lower readability level Additional steps may be necessary to improve comprehension Form may include more use of graphics, colloquialisms (e.g., Dr. Nancy), and emphasize more what as opposed to why 25

Simplified A Simplified Standalone Assent Can Be More Understandable 7-13 14-17 26

Child-Centric Forgoing Signatures Written assent does not require a signature, so why include it? Most children no longer learn cursive In 2006, 85% of teenagers taking the SAT did not use cursive writing and instead printed their essays in block letters! Signatures are no longer considered the gold standard for identification Signatures are not routinely required to open accounts for web-based services like Facebook, Instagram, Twitter, Snapchat, or even Mobile Phone Accounts. 27

Ongoing Assent Must Be Present Throughout Assent may require repeating or supplementation: Assent should track capability and process may change depending on the development of the individual participants Consent must be sought once a participant reaches the legal age of majority and prior to any additional research activities What about the continued use of identifiable private information or samples? 28

Dissent Failure to Obtain or Maintain Assent Assent, if required, must be obtained prior to proceeding with the research Assent, if required, must be present throughout the research and can be withdrawn for a procedure or for the intervention as a whole 29

Role of Family in Assent

Parents Parent(s) Should Play a Role in Assent Process Investigators should typically seek parental permission before assent Parent can help establish child s capability for assent 31

Permission Parental Permission Must Be Sought in Addition to Assent Assumption is that parents are acting in the best interest of their children More than one parent s permission may be required by the IRB or by regulation based on the nature of the research 32

Conclusions

Key Take Aways 1) Research with children is ethical even in the absence of benefit if it s considered part of the maturation process 2) Researchers, sponsors, and IRBs are all responsible for developing appropriate and respectful assent plans that move beyond the limitations of informed consent 3) Any assent plan should always carefully consider: Whether and to what extent assent should be required (capability) How should it best be obtained (maximize benefit) 34

Resources Available for download at: bit.ly/irb-resources 35

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Thank You for Your Attention!