Dominic Chiarelli, JD

by Dominic Chiarelli

Suggesting an Approach to Assent that Keeps the Child in Mind

Institution Bulletin vol 5, issue 2

Research involving children is essential to improving childhood health.  Without it, un-validated practices persist and new breakthrough treatments lag.[1]  Advancements in pediatric care, however, have been slow due to a hesitancy to include children in research.  This hesitancy stems in part from the belief that children are a vulnerable population deserving of special protections.  Although this is true, and certain types of research should not be done in children, children do deserve the opportunity to take part in research.  This choice, if presented, is called assent.

Institutional Review Boards (“IRBs”), like Quorum, are responsible for determining that a research plan makes adequate provisions for obtaining the assent of child participants.[2]  This determination is highly context specific and depends on the circumstances of the research and the children involved.  Appropriately, the federal regulations afford quite a bit of flexibility for whether [ad id=”13996″ align=”right”]assent should be required, what it should entail, and how it should be documented.  The key to taking advantage of this flexibility and constructing a respectful and effective assent plan is to understand both the ethical underpinnings and the regulatory framework of assent.  This article aims to get you started.

Why seek assent?

Respect for the individual autonomy of all persons is a central tenant of human subjects research.[3]  In the context of children, this desire is complicated as often children lack the necessary capability, legally or morally, to make health care decisions for themselves.  In fact, in the rare circumstance where children do have the necessary capability, they often still cannot understand the important, yet subtle, distinctions between clinical practice and research.  The solution from an ethical standpoint has been to only require a child’s agreement to the extent they are capable providing it, either as a group or as an individual, and to seek the permission of the child’s parents or guardian according to the standards of informed consent.[4]  Taken together, this process is considered the equal of informed consent and it ties a child’s sense of autonomy to the choices they are capable of making.

Who is a child?

The regulations define a child as any person, under the applicable law, 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.[5]  The applicable law is always the law of state in which the research occurs.  The laws between states vary, sometimes significantly.  For example, in California, the legal age of majority is eighteen, but children aged seven and older must provide assent for research involving an experimental drug.[6]  In Alabama, the legal age of majority is nineteen and there is no requirement that children assent to research involving experimental products.[7]  A child may attain the ability to consent based on reaching the age of majority, emancipation, self-sufficiency, marriage, or for specific types of medical care (i.e., sexual transmitted diseases, pregnancy, or drug addiction).  The question of who is a minor according to state law can be complex and may require legal counsel.

What is assent?

Assent is a child’s affirmative agreement to participate in research.[8]  It requires action, a willingness to partake, and is not the mere failure to object.  This willingness is demonstrated by a child’s action or words and it must be present throughout the research.  If a child who has provided assent resists a certain procedure, this dissent should be respected except when the procedure is necessary to assure the safety of the participant.[9]

Assent does not mean a complete understanding of the research and the rights of research participants.[10]  A child only needs to understand what they are being asked to do and that they have a choice in determining whether this happens.[11]  This means assent can be less than what is required for informed consent.  The most important aspect of the assent process is that the information provided be meaningful to the participant and help them to make their decision.  Depending on the circumstances, this means the assent process may need to go beyond a formal discussion with investigators and include special measures like videotapes/photographs of research procedures, pre-visits to the site to see the equipment and staff, or putting families in touch with other families who have participated in research.[12]

When is assent necessary?

Assent must be obtained whenever required by an IRB.  Generally, an IRB will only require assent from children who have the capability to make an informed decision based on their age, maturity, and psychological state.[13]  The most common standard is that children cognitively aged seven and above have the capability to make some form of decisions about themselves and are thereby able to provide assent.[14]  This assessment usually happens for the research population as a whole, but it may also occur on a case-by-case basis or by procedure.

On the other hand, an IRB may determine that assent is not necessary for research participation, regardless of capability, if the intervention or procedure holds out a prospect of direct benefit that is important to the health or well-being of the child and this benefit is only available in the context of the research.[15]  This exception to assent generally applies to any clinical investigation involving a drug, device, or other therapy that is not otherwise available to the potential participants.  The concept of respect for individual autonomy nonetheless suggests that, in these cases, researchers should still consider whether to seek assent from participants with the requisite age, maturity, and psychological state to make such decisions.  Data has suggested that for most children this capability is present by the time they reach the cognitive age of fourteen, and the practice of always seeking assent from these children has been adopted by many pediatric institutions.[16],[17]  It is important to remember, however, that if an IRB requires assent it must be obtained before proceeding with the intervention.

An IRB may also waive the assent requirement under the same circumstances as a waiver of informed consent.[18]  A waiver may be appropriate if the research is minimal risk, it offers no prospect of direct benefit, and having to obtain assent could make the research impracticable.  Some examples include a study regarding a method to improve classroom dynamics or a post-marketing surveillance study of an approved device for a rare indication.  In both cases, maximum participation is required in order for the research to meet its objectives; and assent, which may place the research’s success at the whims of children, may not be practicable.  It is also interesting to note that the FDA regulations recognize waivers in the context of assent, but not consent.[19]

How is assent obtained?

When an IRB determines that assent is required, it must also determine whether and how it is documented.[20]  The regulations make no attempt to define when written assent should be required.  In practice, this determination usually depends on the capability of the children and the context of the research.  For example, children under age seven may lack sufficient reading comprehension skills for an assent form to be meaningful; or, an assent form may not improve the assent process for an observational minimal risk study in which parental permission has been waived.

[ad id=”14000″ align=”right”]If an IRB determines verbal assent is appropriate, the assent process should be fully described in the protocol and assent noted in the research record once obtained.[21]  Researchers may also find it helpful in this circumstance to use an assent script when presenting the research.

If an IRB determines written assent is appropriate, a standalone assent form should be developed that is child-centric and cognitively appropriate.  A child-centric form may include pictures or other graphics that help to explain difficult concepts.  A cognitively appropriate form uses a reading level appropriate to the youngest child who is expected to use the form.  The reading level can and should be lowered as much as possible by simplifying the terms and the sentence structure.  This is often easier said than done.  Please see our download for examples of simplified descriptions for common medical terms.  Depending on the age range of participants and the complexity of the research, it may even be necessary to create more than one assent form that spans two distinct age groups.  Alternatively, the assent form could also be modified to include a prompt to request the parental permission form if the reader desires more detailed information.

An assent form does not need to include all the elements of informed consent or even a signature.  It should instead focus on the purpose of the research, the procedures and their risks, and the ability to stop participating at any time.  A child’s decision is most influenced by feeling they understand the information presented and that their participation may be helpful, or even necessary, to completing the research.[22]  Somewhat surprisingly, many children appear comfortable making decisions regarding their participation independent of their parents.[23]  All this emphasizes that every effort should be made to ensure the information presented is meaningful to the child and makes them feel a part of the decision making process.  For example, a child’s decision to participate is more likely influenced by the particulars of a tanner stages puberty assessment than the steps taken to ensure the privacy of their data.[24]

Does assent need repeating?

Assent is an ongoing process and may need to be repeated or supplemented.  A child who reaches the legal age of majority while actively participating in research must be re-approached and their informed consent obtained prior to any further research interventions.[25]  A child who reaches a cognitive age while in the research in which a more complete assent form is available should also be re-approached and given the opportunity to more completely consider their continued participation.  This is usually not specifically addressed in the research plan or the IRB approval, but it is considered most respectful to participants.

How to design your own assent plan

By understanding the purpose of assent and the flexibility available, researchers can provide the most appropriate and respectful plan for IRB review and approval.  All assent plans should carefully consider whether assent should be required, what assent should entail, and how it should be documented.  Assent is a unique space in human subjects protections in that it allows researchers real creativity in how they fulfill the intentions of the regulations.  Researchers should take advantage of this flexibility and design assent processes that move beyond the confines of informed consent and that provide children the most appropriate information in the most meaningful fashion.

Quorum fully supports these efforts and looks forward to continuing our work with researchers on developing meaningful and impactful assent plans for including children in research.

Special thanks to Jennifer Kogut, CIP and Emily Schauer of Quorum’s Consent Form Development team for key contributions to this article and their development of the Simplified Assent-Form Language Toolkit.

References

[1] Protections for Children in Research, A Report to Congress in Accord with Section 1003 of P.L. 106-310, Children’s Health Act of 2000, available at: http://archive.hhs.gov/ohrp/reports/ohrp502.pdf

[2] 21 CFR 50.55(a); 45 CFR 46.408(a)

[3] The Belmont Report, Part A (April 18, 1979), available at: http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html

[4] 21 CFR 50.55(a) & 21 CFR 50.55(f); 45 CFR 46.408(a) &  45 CFR 46.408(b)

[5] 21 CFR 50.3(o); 45 CFR 46.402(a)

[6] California Health and Saf. Code §111530 & §24170-241795

[7] Alabama Code 1975 §26-1-1

[8] 21 CFR 50.3(n); 45 CFR 46.402(b)

[9] Informed Consent, Parental Permission, and Assent in Pediatric Practice, Committee on Bioethics, Pediatrics 1995;95;314 http://pediatrics.aappublications.org/content/95/2/314.full.pdf

[10] Informed Consent Information Sheet, Guidance for IRBs, Clinical Investigators, and Sponsors (DRAFT), Section F, July 2014, available at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM405006.pdf

[11] Id.

[12] Children’s Hospital Boston, Informed Consent/Permission/Assent Process, CIPP 071.001.01 (2012), available at: http://www.childrenshospital.org/~/media/research-and-innovation/office-of-clinical-investigation/cipp_071_001_01_informed_consent_process_policy.ashx?la=en

[13] 21 CFR 50.55(a); 45 CFR 46.408(a)

[14] Reports and Recommendations, Research Involving Children, The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Recommendation #7, September 6, 1977, available at: http://videocast.nih.gov/pdf/ohrp_research_involving_children.pdf

[15] 21 CFR 50.55(a); 45 CFR 46.408(a)

[16] Assent in pediatric research: theoretical and practical considerations, DS Weller, J Med Ethics 2006; 32:229–234.

[17] Seattle Children’s Research Institute, Parental Permission and Child Assent, IRB-020 (2013), available at: http://www.seattlechildrens.org/pdf/IRB-020/

[18] 21 CFR 50.55(d); 45 CFR 46.408(a)

[19] 21 CFR 50.55(d)

[20] 21 CFR 50.55(g); 45 CFR 46.408(e)

[21] Informed Consent Information Sheet, Guidance for IRBs, Clinical Investigators, and Sponsors (DRAFT), Section F, July 2014

[22] A questionnaire on factors influencing children’s assent and dissent to non-therapeutic research, J Med Ethics. 2006 May; 32(5): 292-297, available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649075/

[23] Id.

[24] Id.

[25] Informed Consent Information Sheet, Guidance for IRBs, Clinical Investigators, and Sponsors (DRAFT), Section F, July 2014; OHPR FAQ What Happens if a child reaches the legal age of consent while enrolled in a study?, available at: http://www.hhs.gov/ohrp/policy/faq/children-research/child-reaches-consent-during-study.html

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