To establish assent guidelines for investigator's enrolling children and adolescents in research studies requiring informed consent and parental permission.
When children or minors are involved in research, the regulations require the assent of the child or minor and the permission of the parent(s), in place of the consent of the subjects. Federal regulations entrust each research institution's Institutional Review Board (IRB) with determining what the assent process should involve and how the child's assent (or dissent) should be documented. The IRB shall determine that adequate provisions are made for soliciting the assent of the children, when in the judgment of the IRB the children are capable of providing assent.
Assent – a child's affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.
Children – are persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted. (In California, the legal age is 18 years old [Calif. Family Code, Sections 6500-6502]).
Emancipated Minor – a legal status conferred upon persons who have not yet attained the age of legal competency as defined by state law, but who are entitled to treatment as if they had, by virtue of assuming adult responsibilities, such as self-support, marriage or procreation. (also Mature Minor).
Guardian – an individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care.
Parent – a child’s biological or adoptive parent.
Permission – the agreement of parent(s) or guardian to the participation oftheir child or ward in research.
It is the ethical mandate of IRBs to protect the rights and welfare of human research subjects. IRBs are obligated to ensure that research studies do not endanger the safety or well-being of human subjects or undermine public confidence in the conduct of research. The special vulnerability of children makes consideration of involving them as research subjects particularly important. To safeguard their interests and to protect them from harm, special ethical and regulatory considerations are in place for reviewing research involving children. The Office of Human Research Protection's Title 45 CFR Part 46, Subpart D provides for "Additional Protections for Children Involved as Subjects of Research" (see Appendix A). Assent is also required under the FDA regulations under Title 21 CFR Part 50, Subpart D.
While children may be legally incapable of giving informed consent, they nevertheless may possess the ability to assent to or dissent from participation. Out of respect for children as developing persons, children should be asked whether or not they wish to participate in the research, particularly if the research: (1) does not involve interventions likely to be of benefit to the subjects; and (2) the children can comprehend and appreciate what it means to be a volunteer for the benefit of others.
Federal regulations require that IRBs classify research involving children into one of four categories and document their discussion of the risks and benefits of the research study. The four categories of research involving children are as follows:
- Research not involving greater than minimal risk to the research participant
- Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subject.
- Research involving greater than minimal risk with no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition.
- Research not otherwise approvable, but which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.
The CHS IRB must determine for each protocol - depending on such factors as the nature of the research and the age, status, and condition of the proposed subjects - whether all or some of the children are capable of assenting to participation. Where appropriate, the IRB may choose to review on a case-by-case basis whether assent should be sought from given individual subjects. However, assent shall be required if the child is capable and the research does not provide a prospect of direct benefit that would otherwise not be available.
The IRB has the authority to override parental preferences about whether or not a child assents or otherwise participates in research decisions (45CFR46.408). Parents may not stipulate that their child be refrained from involvement in research-related decisions, if the IRB has determined that the child is capable of making such decisions.
For some research activities, the IRB may require that:
If needed, the IRB shall consult legal counsel about the applicability of any state laws affecting consent for a proposed research project.
- Either an IRB member or an advocate for the child be present during the assent and permission procedures to verify the child's understanding and to support the child's preferences.
- The parent(s) or a close family member be present during the research, especially if a young child will be exposed to significant discomfort or inconvenience, or if the child will be required to spend time in an unfamiliar place.
The child should be given an explanation of the proposed research procedures in a language that is appropriate to the child's age, experience, maturity, and condition. This explanation should include a discussion of any discomforts and inconveniences the child may experience if he or she agrees to participate.
Assent must be obtained from children who are capable of understanding. Thus, in addition to explaining the study to the parents, the investigator must explain the purpose, risks and benefits to the child in language that he/she can understand, and the child must affirmatively agree to participate. A child's mere failure to object is not assent.
The investigator should never ask for a child's assent if he or she is planning to overrule it if the child answers the "wrong way." If the IRB has not approved a waiver of consent for the study, and if the child is otherwise eligible to provide assent (the child is competent to make a decision related to the complexity of the research), the investigator may not override the child's decision, nor let the parents override it. Per the regulations, this is "disrespectful to persons" and thus unethical.
Some types of research may not be as critical to a young person's well-being. For example, some clinical trials may study the effects of support groups on children's or teens' recovery from cancer. While participating in such a study might help young people, it is not critical to their survival; therefore, they have the right to make the final decision about whether or not to take part.
In general, the lower the risk to the child (to the patient's well-being), the more say the child has in the decision making process/final decision. Additional information regarding pediatric research is available in Appendix B, Points to Consider in Pediatric Research.
Age-Specific Assent Recommendations
The federal regulations do not require that assent be sought from children starting at a specific age, but that their assent should be sought when, in the judgment of the IRB, the children are capable of providing their assent. Having taken into account the ages, maturity, and psychological state of the children involved in a study at the time of review, the CHS IRB expects an honest and experienced evaluation of the child's assenting capacity from the investigator. As such, the IRB has provided the investigator with the authority to recommend assenting capacity and to make an informed decision regarding seeking assent from a patient on a case-by-case basis. Bearing this in mind, the following age-specific assent recommendations have been approved by the CHS IRB. These recommendations are also outlined in the Assent Decision Table in Appendix C.
Ages Less Than 7 – Assent is automatically waived for children younger than 7 years old. For subjects below the age of 7, a statement must be included in the consent signed by the investigator stating that the subject has been verbally informed of the procedures involved in the protocol in language that the child can understand. In addition, the consent must contain a statement signed by either a parent or legal guardian stating that they will permit the child to participate in the study.
Ages 7 – 14 – AA children's assent may be requested for all participants ages 7-14, if, in the opinion of the investigator, the child is emotionally and intellectually capable of providing assent. For children between the ages of 7 and 14, the request for assent should include: (1) a general description of the purpose of the child's participation; (2) a brief description of the experimental tasks; (3) an assurance that the child's participation is voluntary and that he or she may withdraw from the study at any point; and (4) an offer to answer questions. The assent form shall be an age-appropriate attachment to the last page of the consent form. (see the Sample Assent Form for Children Ages 7 – 14, in Appendix D).
Ages Over 14 – Assent is required for children over 14. Therefore, an IRB waiver must be requested if the investigator determines that a child is incapable of assenting. For this age group, the IRB recommends using the same informed consent form presented to adults and adding a signature line for the patient above that of the parents. Regulations state that informed consent forms be written at the 6th to 8th grade level. The CHS IRB feels that this would be at a language appropriate to the average 14 year old child's level of comprehension. If, for any particular patient, the investigator feels differently, the investigator can ask the IRB for permission to use the standard assent form used for 7 - 14 year olds. Such requests should be made in writing.
Ages Over 18 – Once a child has reached the age of 18 in the State of California, the child may provide consent. The investigator should be especially sensitive to the child's wishes if they do not coincide with that of the parents. If the child is already enrolled in the research, upon turning 18, the investigator must provide the subject with the Addendum for Reconsenting Subjects who Subsequently Turn 18 Years of Age (Appendix E). This form is to be provided to the subject with the originally signed and dated consent form. The subject must be allowed to re-review the consent form with the investigator and shall be instructed to sign the Reconsenting Addendum, if he/she would like to continue participation in the research. A copy of the signed and dated Reconsenting Addendum shall be provided to the subject, along with a copy of the consent document.
Waiver of Assent. Assent can be waived if the child is either not capable of assent or if being in the research is in the child's best interest (compared to the non-research alternatives). When the research offers the child the possibility of a direct benefit that is important to the health or well-being of the child and is available only in the context of the research, the IRB may determine that the assent of the child is not necessary [45 CFR 46.408(a)]. Additionally, in such circumstances a child's dissent (which should normally be respected) may be overruled by the child's parents, at the IRB's discretion.
If a child says "no", and there are non-research alternatives that offer an equivalent benefit, the IRB shall not waive assent. (Thus the IRB could conceivably waive assent for a two year old based on capacity, but not waive assent for a 12 year old based on the availability of non-research alternatives for the same research project).
The regulations allow the IRB to find that the permission of one parent is sufficient for research to be conducted under 45 CFR 46.404 (minimal risk research) or 45 CFR 46.405 (research involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects).
Both parents must sign if the study is greater than minimal risk and there is no prospect of direct benefit above and beyond what can be expected from standard care/therapy. Under these circumstances (where research is covered by 45 CFR 46.406 and 45 CFR 46.407), both parents must give permission unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child [45 CFR 46.408(b)].
The IRB recommends using the following procedure for obtaining the consent of patients when only one parent is present at the time of enrollment, but the study requires the permission of both:
- Have the parent present sign the consent form and give him/her a copy of the form to take home, with instructions for the absent parent to review and sign the consent form copy. Have the parents return this signed copy to the investigator.
- If the study requires subsequent follow-up visits with the investigator, and the other parent (who was absent at the time of enrollment) comes in with the child for the treatment or office visit, have him/her sign the original consent form.
- If the other parent never comes in while the patient is on active study, write a note on the signature page of the original consent form, such as "father never appeared for signature throughout patient's treatment history, but has signed and returned a copy of the consent form."
Waiver of Parental Permission
The requirement for parental permission may be inappropriate in some cases. Examples include research involving older adolescents who, under applicable law, may consent on their own behalf for selected treatments (e.g., treatment for venereal disease, drug abuse, or emotional disorders). The IRB waives the requirement for parental permission in these situations. However, the investigator must make the request to waive parental permission in writing and submit it as part of the IRB application.
In other research (e.g., research on child abuse or neglect), there may be serious doubt as to whether the parents' interests adequately reflect the child's interests. In these cases, the IRB shall devise alternative procedures for protecting the rights and interests of the children asked to participate, including, perhaps, the court appointment of special guardians.
In treatment studies that provide a direct benefit that is unavailable outside of the research context (e.g. some childhood cancer protocols using experimental medications), the IRB may waive the assent requirement, recognizing that this may avoid setting up a conflict between the parent and child's wishes.
When research involves the provision of experimental therapies for life-threatening diseases such as cancer, however, the investigator should be sensitive to the fact that parents may wish to try anything, even when the likelihood of success is marginal and the probability of extreme discomfort is high. Should the child not wish to undertake such experimental therapy, difficult decisions may have to be made. In general, if the child is a mature adolescent and death is imminent, the child's wishes should be respected.
Phase III clinical trials generally compare a standard treatment (with known risks and benefits) to an "experimental" new treatment. The experimental treatment is under study because it has not been proven and it is not known whether the new treatment is better or worse than the standard treatment. While the experimental treatment is always hoped to be better, researchers cannot make any firm conclusions about the benefits and risks of the new treatment until the clinical trial is completed and the results are carefully analyzed. Usually patients are randomized to either the standard or experimental arm of the clinical trial. In this situation, even though a child usually cannot receive the experimental treatment without participating in the clinical trial, the patient can always receive standard treatment without enrolling in a clinical trial. Because of this, the child's assent and the permission of both parents are required to initiate enrollment.
There are occasionally medical diagnoses or circumstances, such as relapse of the cancer, for which the available treatment methods have an acknowledged poor outcome and enrollment in a clinical trial is the only means to receive a promising new treatment intervention. In such a situation, a child's assent is not required for a clinical trial, and permission from only one parent or guardian is required. Although a legal requirement for assent is waived in these circumstances, the research team is still expected and encouraged to obtain a child's assent.
Disagreement Among Parties
The investigator may solicit the help of the IRB in making a determination regarding assenting, parental permission, or waivers, but it is not the intention of the IRB to arbitrate regarding enrollment decisions. Difficult cases of disagreement shall be resolved by open discussion among all the parties. Representatives of the IRB and Bioethics Committees, the CHS Pediatric Clinical Social Worker, and the investigator shall convene as a subcommittee in order to help resolve any issues and assist with the goal of reaching a non-coercive agreement among parties. The pediatric clinical social worker acts as a non-partial mediator and the child's advocate. The following recommendations are designed to help provide guidelines in the event of a disagreement among members of the family and/or physician:
If a patient’s parents want the child to enroll, but the child does not,the parents have no recourse to enroll the child, unless the investigator feels that enrollment is of direct benefit to the child in a way that no other therapy could be. If this is the case, the investigator is asked to contact the IRB in writing explaining:
- Age of child
- Child’s diagnosis and prognosis with and without study enrollment
- Parent’s wishes
- A description of the treatment study (with complete information regarding the advantages of enrollment versus the risks)
- Reason investigator thinks study therapy would be directly beneficial to the patient.
Based on the information provided, the IRB will review the case and determine whether or not assent can be waived, and the parents' decision can be honored. If necessary, as per above, representatives of the IRB and Bioethics Committees, the pediatric clinical social worker, and the investigator shall convene as a subcommittee in order to help resolve any issues and assist with the goal of reaching a non-coercive agreement among parties.
If the patient lives with both parents and the parents disagree: Due to the negative effect such disagreement would have on family dynamics and parental boundaries, a child will not be enrolled in a study if no consensus can be reached following discussions between the investigator, clinical social worker, nurse, and family - unless the investigator feels that enrollment is of direct benefit to the child in a way that no other therapy could be. In such situations, the same procedures will be followed as per the guidelines in the preceding section.
If one parent has sole, legal custody of the child, and the parents disagree regarding patient enrollment, the decision of the custodial parent shall be binding (assuming the child has either given assent or assent has been waived by the IRB).
Exemption From Review.
The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or observation of public behavior, does not apply to research with children covered by Subpart D, except for research involving observations of public behavior when the investigator(s) do not participate in the activities being observed. The remaining exemptions in 45 CFR 46.101(b)(2) apply to research involving children.
See also Children’s Assent Guidelines policy for the following appendices:
COTTAGE HEALTH SYSTEM POLICY
|ORIGINAL POLICY EFFECTIVE DATE:
||9/06, 3/07, 1/11, 5/11