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  • Reviewed: 05/26/2005

Children's Assent to Clinical Trial Participation

If you are considering enrolling your child in a clinical trial, this guide should help you better understand the concept of "assent" (a child's agreement to participate) as well as some of the larger issues surrounding young people's participation in trials.

If you are interested in learning more about the issue of children's participation in clinical trials, the National Library of Medicine has compiled a bibliography of resources on clinical research that also includes a section devoted to children's issues. The NCI's Cancer Information Service also provides a fact sheet on the topic of children's cancer centers.

Portions of this guide are based on the article "Consent (Assent) for Research with Pediatric Patients" by Marion E. Broome, Ph.D., RN, FAAN.

Introduction

What happens if the prospective participant in a clinical trial is not an adult, but a child or teenager? What, if anything, should be done to educate the young person about the trial and ensure that he or she is given a say in whether or not to participate?

At one time, it was assumed that young people lacked the ability to consent to participation in clinical research. Instead, parents or guardians went through the informed consent process on their behalf and gave what was known as "proxy consent."

Over the past couple of decades, medical and legal experts have given much thought to the special issues surrounding children's participation in clinical trials. In the eyes of the law, children under 18 are not adults; therefore, legal permission for their participation must be given by parents or guardians after going through the informed consent process on their behalf.

However, many people involved in treating young people believe that the child or adolescent should play a role in the decision to enter a research study. The American Academy of Pediatrics calls this "empower[ing] children to the extent of their capacity" and talks about this shift in thinking in "Informed Consent, Parental Permission, and Assent in Pediatric Practice." The National Commission for Protection of Human Subjects of Biomedical and Behavioral Research established age 7 as a reasonable minimum age for involving children in some kind of assent process. It is felt that most children this age can understand information tailored for their knowledge and developmental level.

Health care providers want young people to know that they have a say in what happens to them and that their questions and input are valued. Encouraging their involvement in decision-making is done out of respect for their rights as individuals and the desire to give them a sense of ownership in what happens during the trial. Even though children cannot "consent," because true consent implies full understanding, they are now routinely asked whether they agree (assent) or do not agree (dissent) to participate. Their parents or guardians are no longer asked to give "proxy consent" but instead give "informed permission."

Parents reviewing written information about a clinical trial for their child can interact with the research team and learn how the study will work, its objectives, the possible benefits and risks of participating, and the child's rights and responsibilities. In this way, they can make a fully informed decision about whether or not to give "informed permission" for their child's participation in the clinical trial.

Tip for Parents and Guardians -- Informed Consent:

Be sure to check out Informed Consent, which provides essential background for understanding the concept of assent and describes the process you will go through before giving permission for your child to take part in a clinical trial.

Federal regulations state that parents and guardians must participate in an informed consent process --- just as they would do if they themselves were considering enrolling in a clinical trial --- and give legal permission for their child to enroll. This process must follow the guidelines established for the general requirements of informed consent.

The Assent Process

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. IRBs are panels of medical specialists, nurses, social workers, medical ethicists, and patient advocates who review clinical trial protocols at institutions that conduct medical research.

The Institutional Review Board Guidebook published by the Department of Health and Human Services (DHHS) Office for Human Research Protections suggests that "[t]he 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.

Tip for Parents and Guardians -- Children's Expectations:

Many parents feel the desire to protect their child from learning about the possible discomforts and inconveniences of the trial, and only tell them about the good that may come of it. However, it's essential they be given a complete picture of what the trial involves and have access to as much information as they want. This is likely to help them understand what is expected of them, and how they may feel, as they participate in research.

Like the informed consent process, the assent process is intended to be an ongoing, interactive conversation between the research team and the child or young adult. The research team may include doctors (who are often principal investigators and leading the study), nurses, social workers and other health care professionals. The process is not about getting the young person "to sign on the dotted line"; rather, it is about making sure they understand the trial and what it means to participate. By engaging young people in understanding the research project, health care providers and young patients may become "partners" in the project. Children are likely to feel more in control and more involved in the trial as a result.

Although the assent process varies from institution to institution, certain elements remain constant. Before the process can begin, parents or guardians must give permission for their children to participate. Then, the child or teenager may be provided with a form that explains, in concrete and age-appropriate terms, the purpose of the research, what they will be asked to do, and what procedures they will undergo. For older adolescents (ages 16 or older), this might look very much like the adult informed consent document. For younger children, the terms and explanations will be greatly simplified into words they can understand.

Usually, the principal investigator in charge of the study, or a nurse or other health professional working with the investigator, explains the information and gives the child a chance to ask questions. The process typically takes place apart from parents or the key researchers on the study, so that the young person does not feel undue pressure. In some cases, though, especially when teenagers are involved, the assent process may turn into a discussion that includes parents, the potential participant, and researchers.

Whatever form it takes, the process should always make clear that the young person has the right to leave the trial, at any time and for any reason, without penalty or consequences, and that any information gathered will be kept confidential.

The research team may use other approaches in addition to written forms, conversations, and question-and-answer sessions. These might include videotapes, diagrams, pictures, or drawings. Researchers also may provide a chance for the young person to speak with other children or teens who have been in similar trials and are willing to talk about their experiences.

Tip for Parents and Guardians -- Learning Styles:

If your child seems to be struggling with the information the research team presents, ask about other strategies that might be tried. For instance, if your child learns better through seeing or hearing information, rather than just reading it, ask about videotapes or other visual aids.

It may take several sessions before the research team feels that the young person has developed a clear understanding of the what the trial involves. At that point, he or she is asked to indicate assent or dissent either by signing the form or checking off a box that says "yes" or "no" (again, it will depend on age and capabilities). A "no" answer, or dissent to participation, should be considered binding. Occasionally, as discussed elsewhere in this guide, situations exist where a young person's assent is not required.

Tip for Parents and Guardians -- Watch for Gaps:

Although a child or adolescent may say that he or she understands that a choice exists, they may not be able to identify all the possible options and consequences. If there seem to be gaps in your child's understanding, it may help to go back over the information.

When Assent Is Not Required

An assent process for children or young adults is not required if one or the other of the following situations exists (but parent or guardian consent is still required):

1. The child is found incapable of participating, or

2. The clinical trial offers a treatment or procedure that "holds out a prospect of direct benefit that is important to the health or well-being of the child and is available only in the context of the research." In other words, researchers are not required to ask for children's assent to participation if the study offers a treatment that is thought to be a better option than those currently available, or if it offers the only alternative.

In life-threatening situations, such as that of a child with cancer, the second situation listed above may be especially relevant. In the case of Phase III clinical trials, the trial will 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 is not known whether the new treatment is better or worse than the standard treatment. (For information about the phases of clinical trials, see Clinical Trials Take Place in Phases.)

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.

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, although permission from a parent or guardian is still required.

Tip for Parents and Guardians -- You Have Final Say:

Some of the newest approaches to treating children's cancers are available only through clinical trials, and your doctor may recommend one as essential to your child's treatment plan. In such critical cases, you have the final say over whether or not your child will participate. Nevertheless, the child should still be actively involved in the decision-making process.

Although a legal requirement for assent is waived in these circumstances, the research team is still expected and encouraged to obtain a young person's assent, even if parents or guardians must give the final say. In all other cases, though, the young person's decision should be considered binding.

Other types of clinical trials 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.

Tip for Parents and Guardians -- Participation Not Required:

Keep in mind that your child always has the right to receive treatment off a clinical trial (that is, to not participate in any clinical trial).

What's Required by Law

As already mentioned in our discussion of informed consent, the Department of Health and Human Services' (DHHS) Regulations for the Protection of Human Subjects (Title 45, Part 46 of the Code of Federal Regulations, Protection of Human Subjects; also referred to as 45 CFR 46) set standards for the informed consent process, the formation and function of Institutional Review Boards, and many other protective measures. Subpart D of 45 CFR 46 specifies "[A]dditional DHHS Protections for Children Involved as Subjects in Research." Established in 1983 and reviewed in 1991, these additional protections apply to all research involving children and is conducted or supported by DHHS, which includes National Cancer Institute-sponsored clinical trials.

The Subpart D regulations assign Institutional Review Boards with the responsibility for ensuring that any clinical trials involving children meet the following criteria (Go directly to Subpart D if you'd prefer to read them in their entirety.):

  • The research does not involve "greater than minimal risk."
  • If it does present more than minimal risk, it must offer an "intervention or procedure that holds out the prospect of direct benefit" for the individual child, or "a monitoring procedure that is likely to contribute to [their] well-being." However, the IRB must ensure that the risk is justified by anticipated benefits, and that the risk-benefit ratio is "at least as favorable" as that of alternative approaches.
  • If the research involves "greater than minimal risk and no prospect of direct benefit" to the child, it must be "likely to yield generalizable knowledge" about their disease or condition. The IRB is charged with ensuring that the level of risk is reasonable, and that the research will most likely provide important general information that leads to better understanding of the condition.
  • Any other research that does not appear to meet these criteria but "presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children" must be considered by the IRB on a case-by-case basis, and must be approved by the Secretary of the Department of Health and Human Services.

These Federal regulations go on to state that "adequate provisions" must be made for soliciting the assent of children, when the IRB determines that they are capable of participating in such a process based on their age, maturity, and state of mind.

Tip for Parents and Guardians -- Level of Risk:

Institutional Review Boards (IRBs) are required to make sure that any clinical trial is likely to provide important information about how to better help young people, without posing an unacceptable level of risk. Whatever trial you are considering has already undergone intensive review by an IRB with this goal in mind.

Assent Is Essential

Over the past few years, the National Institutes of Health, the U.S. Food and Drug Administration, and the American Academy of Pediatrics have emphasized the need to include more children and adolescents in clinical trials. You may be wondering why this is even necessary --wouldn't it just be simpler to require that all trial participants be over age 18? While it might be simpler, it would not be good medical practice. Many diseases only affect children, and advances in treating these diseases depends on research studies. For those diseases that do affect both adults and children, a treatment that helps adults may not help children in the same way.

Fortunately, there are many cancer clinical trials designed specifically for children because childhood forms of cancer are often very different from adult forms. Researchers studying new treatments for adults with cancer generally do not include children in their clinical trials, but instead are encouraged to work with pediatric cancer specialists to assure timely and appropriate evaluations of their new treatment approaches in children.

For many years, the NCI has supported a nationwide clinical research system focusing exclusively on children. The research system is devoted to developing and carrying out clinical trials to identify more effective treatments for children with cancer. This network involves hundreds of researchers from the U.S. and around the world who have joined forces to form the Childrens Oncology Group (COG) . The NCI also supports the Pediatric Brain Tumor Consortium, a network of medical centers that work together to evaluate promising treatments for children with brain tumors, and the New Approaches to Neuroblastoma Therapy (NANT), a consortium of research institutions investigating early phase therapies for high-risk and relapsed neuroblastoma. Furthermore, the NCI's own Pediatric Oncology Branch conducts phase I and phase II trials for children whose cancer has recurred or has not responded to treatment.

You can find most of these pediatric cancer trials through the NCI's database of clinical trials. If you go to the database and look at the scroll-down menu under "types of cancer," you will see that you can search for trials specific to childhood forms of cancer such as brain tumor and leukemia. Furthermore, if you choose a type of cancer that is more common in children, such as Wilms' tumor or retinoblastoma, you will find trials designed specifically for them.

You can also call the NCI's Cancer Information Service at 1-800-4-CANCER for assistance locating a clinical trial.

Including More Children

In June 1996, the National Institutes of Health (NIH) and the American Academy of Pediatrics held a joint workshop evaluating the participation of children in clinical research. Both groups were concerned that treatments developed and tested through clinical trials involving adults were being used to treat children without having adequate data on this special population. One of the outcomes of the workshop was a recommendation that the NIH develop a policy for including children in clinical research. This led to the following two events:

  • An NIH announcement (January 1997) stating that the NIH was engaged in developing a policy and plan for requiring researchers to include children in proposed clinical trials whenever appropriate. The announcement also recommended that "when there is a sound scientific rationale for including children in research, investigators should be expected to do so unless there is a strong overriding reason that justifies their exclusion from the studies." Applicants for NIH funding would now be expected to address this issue in their proposals.
  • NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects (March 1998): This policy states that children "must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. Therefore, proposals for research involving human subjects must include a description of plans for including children. If children will be excluded from the research, the application or proposal must present an acceptable justification for the exclusion." In other words, any clinical trial for a disease that affects both adults and children must include children, unless there is a compelling reason not to do so. For instance, a new treatment might present more risk than is allowed for children, or it might make more sense to conduct a separate clinical trial for them.

The NIH's Office of Extramural Research provides information on its Web site about the plan for the inclusion of children policy.

The U.S. Food and Drug Administration (FDA) has taken steps to encourage the evaluation of new drugs for children with serious medical conditions. Towards this goal, the FDA has proposed regulations calling for changes in the testing of prescription drugs. These changes would ensure that manufacturers specifically examine the drugs effects on children if the medications are to have clinically significant use in children. For more information about the FDA's efforts to involve more children in drug trials, go to the pediatric medicine section of the FDA Web site.