Children in Research

• According to Tennessee State law, the legal age for consent is 18 years of age. In research, “children” are defined as any 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.

45 CFR 46.404:  The proposed research poses no greater than minimal risk to children.

• Where parental permission is to be obtained, the IRB may find that the permission of one parent is sufficient

45 CFR 46.405: The proposed research poses greater than minimal risk to children and includes an intervention or procedure that DOES hold out the prospect of a direct benefit for the individual child or a monitoring procedure that is likely to contribute to the child's well-being.

• Where parental permission is to be obtained, the IRB may find that the permission of one parent is sufficient 

45 CFR 46.406: The proposed research poses greater than minimal risk to children and is presented by an intervention or procedure that DOES NOT hold out the prospect of direct benefit for the individual subject, or by a monitoring procedure which is not likely to contribute to the well-being of the subject, BUT is likely to yield generalizable knowledge about the subject's disorder or condition.

• Where permission is to be obtained from parents, both parents must give their 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 46.407: Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children. 

• The IRB will submit the study to the Office of Human Research Protections (OHRP) for review and certification.
  • Where permission is to be obtained from parents, both parents must give their 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.

• “Not reasonably available” does not apply to situations when a parent is at work, traveling, not immediately available by electronic means, or living in another state or country, without more to justify the investigator’s inability to reach the parent and seek permission. A parent who is “not reasonably available” is one who cannot be contacted by phone, email, mail or other mediums:  for example, a parent on active military duty. 
• For more guidance, refer to Parental Permission in Research Involving Children, Focusing on “Not Reasonably Available” at the following link:
  • https://www.hhs.gov/ohrp/sachrp-committee/recommendations/attachment-d-november-13-2018/indes.html
• The IRB recommends that when a researcher submits a study that will require two-parent consent (e.g. approvable under 45 CFR 46.406), the researcher should highly consider including a remote/eConsent plan in their initial IRB application. As noted above, not having an IRB-approved eConsent document and IRB-approved remote consenting process is not adequate justification for waiving the consent of the second parent. 

• No, assent is not consent. At a minimum, the child should understand the purpose of the research (in age-appropriate terms), be provided with an explanation of the procedures, and be informed that their participation is voluntary and that they have the right to withdraw (change their mind) at any time. For children whose age and maturity level limits their ability to fully comprehend the nature of the research activity but who are still capable of being consulted about participation in research, it may be appropriate to focus on conveying an accurate picture of what the actual experience of participation in research is likely to be (for example, what the experience will be, how long it will take, whether it might involve any pain or discomfort). 
• The assent procedure should reflect a reasonable effort to enable the child to understand, to the degree they are capable, what their participation in research would involve.
• The VUMC IRB has developed assent form templates that are recommended for use by investigators conducting pediatric research. These templates are available for use on the HRPP website. 
• Assent Forms can include pictures if such use will help facilitate understanding by the child (example: cartoon image of a child getting an x-ray; image of a ruler to show measurement of height as a research activity; smiley face next to assent signature line)

• Per the federal regulations, it is up to the IRB to decide whether or not assent must be documented and if it must be documented, the way in which it will be documented. 
• The VUMC IRB recommends that investigators document assent on a separate written assent form for the child.
• An Investigator must take into account the ages, maturity, and psychological state of the children involved when planning methods to obtain and document assent. The VUMC IRB recommends that assent forms be written according to the following:
• For children ages 13-17: Given that it is generally recommended that adult consent forms be written at a 6^th-8^th grade reading level, the assent form for children ages 13-17 may be written in a similar language as the adult consent. The VUMC IRB website includes two suggested assent templates for this age group. 
• For children ages 7-12: A simple assent form written at a comprehension level appropriate for a 7-year-old should be utilized. The VUMC IRB website includes a suggested assent template for this age group. 
• For children under 7: An oral script in very simple language should be utilized. Verbal, rather than written assent by the child, is recommended for this population.
• Although age is used as the primary criteria in determining an appropriate means of obtaining assent, factors such as literacy and mental development must also be considered. The need for flexibility in the methods for obtaining assent from children is recognized by the VUMC IRB. Because a single method for obtaining assent may not be appropriate for all potential participants, investigators may need to be prepared to use different approaches with different participants. 
  • Examples:

1. The investigator may determine that it is more appropriate for a specific 13-year-old participant with lower literacy and mental development to be assented with the IRB approved 7-12 year old assent form. As with any consent/assent process, the primary concern is that the participant is able to understand the explanation that is presented to them. The investigator is responsible for maintaining clear documentation of the assent process, so variations in the assent form utilized to obtain assent should be explained in the documentation of consent/assess process maintained in the research records. 
2. A 7-year-old child is unable to write their name. The study team will document the child’s verbal assent in the research records (including the date and time verbal assent was obtained, any questions or concerns the child expressed during the process, the resolution of those questions and concerns and who obtained the verbal assent).

• The VUMC IRB recommends that the assent form for children ages 13-17 closely mimic the adult consent form. 
  • For studies that are enrolling children who will likely turn 18 while on study, it is recommended that all of the same information from the adult consent form be provided to the child in their assent form. Some of the more “adult” concepts, like Cost and Payment in Case of Injury should be provided to these child participants as soon as they are mature enough to understand them. 
  • For studies that are enrolling children who will likely not turn 18 while on study, the researcher can consider utilizing the simplified 13–17-year-old assent template found on the HRPP website. This template closely mimics the adult consent form, with the exception of a few concepts that may not be applicable to these children, such as Cost and Payment in Case of Injury. 

• The regulations at 45 CFR 46.408(a) identify three types of circumstances where the IRB may determine that waiver of children’s assent is appropriate:
  1. if the capability of some or all of the children is so limited that they cannot reasonably be consulted;
  2. if the intervention or procedure involved in the research holds out the prospect of direct benefit to the health or well-being of the children and is available only in the context of the research.
  3. if the research meets the same conditions as those for waiver or alteration of informed consent in research involving adults, as specified in the regulations at either 45 CFR 46.116(c) or 45 CFR 46.116(d).
• If a child is capable of assent and the Institutional Review Board (IRB) requires that assent be sought (e.g. the waiver of assent criteria have not been met), it must be obtained before the child can participate in the research activity. Thus, if the child dissents from participating in research, even if his or her parents or guardian have granted permission, the child’s decision prevails.

• Dissent is a child’s negative expressions, verbal and/or non-verbal, that they object to participation in the research activities. Younger children or older children with developmental delay may not have the same ability to express their desire to withdraw from the research. Because these children may not have the same ability to express their desire to withdraw, investigators are urged to rely on dissenting behaviors. The investigator should describe in the IRB application what dissenting behaviors, when observed, may result in the child being withdrawn from the research. Examples of dissenting behaviors may include: crying, refusing to cooperate, refusing to look at the researcher and moving away from them. 

• The federal regulations do not directly address the topic of obtaining child assent remotely.
• The IRB will take into account the nature of the proposed research and the age, maturity, and psychological state of the child when determining whether assent can be obtained remotely.
• As with in-person assent, when remote assenting procedures are to be used, the investigator must be able to directly assess the child’s ability to engage in decision-making and assess their willingness to participate in the research.
• Methods for conducting a child assent process remotely could include via videoconferencing (e.g. Zoom or Teams) or on the phone.
• Investigators will have to take the Children’s Online Privacy and Protection Act (COPPA) into account when conducting online research with children. 
  • COPPA requires that operators of commercial websites or online services obtain verifiable parental consent before collecting personal information online from children under the age of 13.
  • Additional Information: Complying with COPPA: Frequently Asked Questions

• HRPP Procedure IV.B.1 indicated that the person obtaining consent should document the consent process in the participant’s medical record or the participant’s research record. While there is no regulatory or institutional requirement for the child assent process to be documented outside of the signed assent form, the VUMC IRB recommends that the child assent process be documented in a similar manner to the adult/parent consent process. This is especially critical for special circumstances in which the assent documentation is not as would be expected. Some examples of special circumstances include:
  • If a study was approved by the IRB with a requirement for two-parent consent but only one parent was deemed to be “reasonably available”, the documentation of the assent process should provide the rationale/justification for only obtaining one parent’s consent. 
  • If the person obtaining assent chooses to assent a 13 year old child on the IRB-approved assent form intended for children 7-12 years old, the person obtaining assent should document their rationale for using the 7-12 assent form (e.g. the child’s maturity and reading level were far below that of a typical 13 year old and the shorter assent form was deemed to be more appropriate to facilitate the child’s understanding of the research).
• The VUMC IRB offers a “Documentation of Informed Consent Process Tool” on the HRPP website that was developed to assist study teams with meeting the requirements for HRPP Procedure IV.B.1. This tool is available for use with any study and can be printed for a study regulatory binder or kept electronically. The VUMC IRB recommends that this tool, or something similar, be used to document the assent process for children and any special circumstances surrounding this process. 

• The Office for Human Research Protections (OHRP) notes that informed consent should be viewed as an ongoing process throughout the duration of a research study. When a child who was enrolled in research with parental or guardian permission subsequently turns 18, the subject’s participation in the research is no longer regulated by the requirements of 45 CFR part 46.408 regarding parental or guardian permission and subject assent.
• If there is continued interaction with subjects who were first enrolled as children, “re-consenting” when a subject’s legal status changes will usually be required.
• If the study does not involve any ongoing interactions or interventions with the participants, but continues to meet the regulatory definition of “human subjects research” (for example, it involves the continued analysis of identifiable specimens or data), a plan to “re-consent” the now-adult subject should be in place. The IRB may consider, if appropriate, a waiver under 45 CFR 46.116(d) of the requirements for obtaining informed consent in order for the subjects to continue their participation in the research.
• Ensure the IRB application describes the plan, if relevant to the research, to “re-consent” children who turn 18 while enrolled in the study.

• When recruiting children into a research study, the child should not be directly targeted for recruitment, as the parent/guardian should be approached first. Initial outreach/advertisements should be targeted towards parents/guardians.