Balancing Disclosure of Diagnosis and Assent for Research in Children With HIV

Children comprise a large subgroup of patients with human immunodeficiency virus (HIV) infection, and their treatment must be defined by pediatric clinical trials. Children's participation in research trials requires the fully informed consent of the parent or legal guardian,¹ to whom most of the information is commonly directed.² However, for nontherapeutic trials, the Code of Federal Regulations also requires that assent (the “affirmative agreement to participate in research”) be obtained from children at appropriate developmental ages.³ It also assigns to institutional review boards (IRBs) the duty to “determine that adequate provisions are made for soliciting the assent of the children . . . capable of providing assent.”³

Truly meaningful assent requires that children's conditions be appropriately disclosed to them.⁴ However, disclosure of diagnosis to children with HIV is a complex issue⁵ that, when poorly managed, can cause harm to the child and family.⁶ For various reasons, parents may be reluctant to allow disclosure of HIV infection to their child.⁷ They often worry that children will not exercise discretion and that the child or family will be stigmatized. Cases of maternally transmitted HIV infection may be complicated by parental guilt and a desire to avoid further harm to the child through premature disclosure.

Therefore, 3 important questions arise. Can a child who has reached the age of assent participate in pediatric HIV research without knowing his or her diagnosis of HIV or AIDS? What does “disclosure of diagnosis” mean in the context of pediatric HIV? What should be the response of a clinician or researcher when a parent of a child who has reached the age of assent will not agree to a developmentally appropriate process of disclosure? In this Commentary, we consider these questions and offer a practical stepwise disclosure method.

Can children at the age of assent participate in HIV research without knowing their diagnosis? The assent process allows children who understand the research in question and are capable of making their own decisions to participate in their care. It is morally optimal to seek assent from any child, regardless of age, who can understand his or her medical condition, communicate his or her preferences, reach a reasonable decision, and understand its consequences.⁸ However, the Code of Federal Regulations allows the IRB to waive assent if “the research holds out a prospect of direct benefit that is important to the health or well-being of the children, and is available only in the context of the research.”³ Thus, assent may be waived for therapeutic but not nontherapeutic research. Given the effective medications now routinely used in “good clinical practice” for treatment of HIV, a waiver of assent would be ethically appropriate only if the therapeutic benefit from participation in a clinical trial is potentially greater than the benefit received from conventional treatment. Therefore, valid assent requiring appropriate disclosure of the child's condition is a legal requirement for participation in nontherapeutic trials and, we suggest, should be an ethical requirement for participation in many therapeutic trials.

What does “disclosure of diagnosis” mean in the context of pediatric HIV? Benefit of disclosure of the diagnosis in general is supported by several sources. Children with various chronic illnesses cope better and experience fewer psychological problems when appropriately informed about the nature and consequences of their illness.⁹ But how is disclosure defined? The Code of Federal Regulations states that when assent is required, the IRB “shall also determine whether and how assent must be documented.”³ This requirement suggests the desirability of a specific, consistent process for disclosure of the diagnosis to support meaningful assent.

The American Academy of Pediatrics (AAP) Committee on Pediatric AIDS recommends that physicians fully disclose the diagnosis of HIV to older adolescents, both to allow them to assist in their care and to reduce the likelihood of unprotected sex.¹⁰ For younger children, the AAP strongly encourages disclosure of HIV status via a process that is prospectively discussed and planned with the parents. However, these recommendations do not address enrollment in research studies. The IRB guidebook published by the Office for Human Research Protections¹¹ suggests that children invited to participate in research “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.”

Many clinicians who care for children with HIV use a stepwise approach to disclosure of HIV status for meaningful assent to nontherapeutic research, basing the stages of the process on the child's developmental status and on parental wishes.^{12 - 13} This process is also useful when assent is required by the IRB for therapeutic trials. The method has been formalized by the HIV Clinical Program at St Jude Children's Research Hospital as a 10-step checklist (Box). For example, preschoolers often ask questions such as “Why do I take medicine and other people don’t?” At this age, the response usually centers on the goal of “staying well.” In older children (5 years or older), the discussion moves toward explaining that the medication is needed because of a viral infection (not yet named). When the clinicians and parents agree that the child is mature enough for full disclosure, the HIV virus is named. Weight given to assent from a child in the context of a clinical trial is a variable changing with both chronological age and perceived maturity and sophistication of the child's understanding.¹⁴ Parents must be involved in deciding when the time is right to fully disclose the diagnosis to their child; must explain the threat of stigma in the classroom, the workplace, or among daily contacts; and must allow the child to participate fully in managing disclosure to others. Parents are often relieved to find that the disclosure process takes into account the needs of the entire family.

What should be done when a child has reached the age of assent but the parents will not agree to disclosure of the HIV diagnosis, even as a developmentally appropriate process, in situations in which the assent process cannot be waived? Such a patient might be offered standard medications rather than enrollment in a research trial. Standard “off-trial” therapy for a time may allow the growth of trust between the family and health care team and permit further discussion and education before disclosure is renegotiated. However, if a parent refuses even a staged disclosure process, the child is not eligible to participate in nontherapeutic pediatric HIV research. In difficult cases, institutional ethics committees can help to resolve conflicts about treatment decisions, facilitate clear communication, and provide a forum for discussion of hospital policy.¹⁵

This Commentary is intended to raise awareness of and perhaps help to resolve the tension inherent in 3 ethical imperatives: the need for patient assent in pediatric trials, the urgency of advancing HIV research (both therapeutic and nontherapeutic), and the avoidance of harm in disclosing an HIV diagnosis to children. As a rule, a developmentally appropriate assent process should not be bypassed in research studies of any sort. For children younger than 14 years (at which time the AAP recommends full disclosure for all patients, with a preference for earlier disclosure as appropriate), full disclosure of the diagnosis may not be necessary for meaningful assent. Rather, it may be necessary only that the child and family be engaged in an established disclosure process. Such a process requires that the clinician or researcher obtaining assent be familiar with the child's development and progress through the disclosure algorithm. In addition, the language to be used in the assent process should be discussed and agreed on in advance with the family. At age 14 years, most children ordinarily are able to understand the implications of an HIV diagnosis and are ready for full disclosure. Wider debate and consensus building about assent and disclosure are needed among agencies that sponsor pediatric HIV research in the United States and internationally.