by Tori Lallemont

Six Tips for Parental Permission in Pediatric Research

Institution Bulletin vol 5, issue 2

Getting consent from the parent or guardian is the first and often most critical step in enrolling a child into a research study. Health & Human Services’ (HHS) Common Rule at 45 CFR Part 46 and the Food and Drug Administration (FDA) at 21 CFR Part 50 require “permission” (also referred to as informed consent) from the one or both parents or guardians (referred to as “parents” throughout this article) in order to enroll children in research with limited exceptions. Permission from one parent is adequate for most types of research, although some types of research require permission from both parents. This article intends to address common issues and questions about parental permission from researchers and IRB professionals.

One Parent Permission

Obtaining permission from one parent is sufficient under the regulations for the following types of research:

  • Research “presenting no more than minimal risk to children”[1]
  • Research presenting more than minimal risk to children that offers the “prospect of direct benefit” [2]

TIP 1: Be aware that the regulations permit the IRB to determine both parents must provide permission for research fitting into the categories listed above.

Reasons an IRB may require permission from both parents may include:

  • The research requires participation from both parents (for example, providing support as a caregiver)
  • The research involves a participant population with a serious disease (such as an investigation of a new oncology drug with serious side effects – full support of both parents may be an additional safeguard for the child)

TIP 2: If you are a researcher, you may want to consider whether obtaining permission from both parents will be helpful for your study, even if the IRB does not require it.

Obtaining “buy in” from both parents may help ensure you are enrolling participants that will have a support system to get them to study visits on time, take the investigational product as directed, and communicate more effectively if there is an adverse event.

Two Parent Permission

Obtaining consent from both parents is required from the below referenced categories:

  • Research involving “a minor increase over minimal risk,” yet does not offer any “prospect of direct benefit,” but is “likely to yield generalizable knowledge about the subjects’ disorder or condition…” [3]
  • Research involving children that is not approvable in one of the other three categories provided that “the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of serious problems affecting the health and welfare of children” [4]

Consent from one parent for these categories is only acceptable if one parent is deceased, unknown, incompetent, not reasonably available, or when only one parent has legal responsibility for the care and custody of the child. Many question what “not reasonably available” means.

TIP 3: Mere inconvenience to reach the second parent to obtain permission is not an acceptable justification to say the parent is “not reasonably available.”

The “not reasonably available” exception is intended for situations such as absence due to oversees military service in which a parent is not in regular contact with their family, incarcerated parents, or a parents whose whereabouts are not generally known.

Role of Placebo

Placebo controlled trials, while often offering superior scientific design, may provide some challenges as it pertains to obtaining parental permission. Any consent discussion with parents should clearly convey if placebo will be used in a study.

TIP 4: Placebos should never be characterized as offering the prospect of direct benefit in a consent discussion.

Although some individuals may have a positive “placebo effect,” the FDA has affirmed the administration of a placebo cannot be considered to offer the prospect of direct benefit to participants.

The FDA requires IRBs to evaluate the risks of the placebo arm from the active treatment arm separately. If the placebo arm poses more than minimal risk to participants, it will fall under a category requiring both parents to provide consent. For example, placebo arms with a skin biopsy, a significant number of blood draws, or a delay in treatment, may fall under the 45 CFR 46.407/21 CFR 50.53 category (“a minor increase over minimal risk,” yet does not offer any “prospect of direct benefit,” but is “likely to yield generalizable knowledge about the subjects’ disorder or condition…”). Placebo arms featuring sham surgery, PICC line placement, or a significant delay in treatment for a serious condition may fall under the 45 CFR 46.408/21 CFR 50.54 category (research involving children that is not approvable in one of the other three categories provided that “the [ad id=”14000″ align=”right”]research presents a reasonable opportunity to further the understanding, prevention, or alleviation of serious problems affecting the health and welfare of children”).

TIP 5: If the IRB determines the placebo arm falls under a category requiring both parents to provide permission, both parents must provide consent if the study is blinded regardless if permission from one parent would be adequate for the active arm.

Permission from both parents for blinded placebo controlled studies is necessary as the study design will not permit the parent to know which study arm (placebo or active) that their child will be on, and therefore, even if permission from one parent would be adequate for the active arm, the more conservative consenting approach must be taken.

Therapeutic Misconception

TIP 6: Parents often perceive research as a way to receive cutting-edge therapy, which leads to therapeutic misconception (i.e., the belief that the primary intent of the research is to treat the condition rather than generate scientific knowledge).

It is important the study team member conducting the consent discussion be aware of this bias and discuss therapeutic misconception with parents. It is also important for any consent discussion to convey clear information regarding how risky the research is relative to the care a child could receive outside of the study.

Conclusion

For additional information regarding pediatric trials, please download Quorum Review’s “Special Considerations for Pediatric Trials” or contact us.

References

[1]45 CFR 46.404/21 CFR 50.51
[2]45 CFR 46.405/21 CFR 50.52
[3]45 CFR 46.407/21 CFR 50.53
[4]45 CFR 46.408/21 CFR 50.54

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