Recruiting participants to clinical trials is always challenging. But when the trial involves pediatric participants in a decentralized study environment, the process becomes a lot more complicated.

Children cannot consent to be part of a trial and should not be relied on to complete assessments, follow rigorous treatment regimens or show up to appointments, whether face-to-face or virtual. They also function in a world of evolving caregivers, which can include teachers, babysitters, extended family and/or parents living in different homes with multiple siblings. Each of these adults holds sway over that child’s day-to-day activities and must play a role in making sure they adhere to the trial protocols and have transportation to appointments that cannot be completed virtually.

It is imperative that clinical research continues to involve children in order to accurately assess the safety and effectiveness of treatments and preventatives. Last month, the FDA issued Draft Guidance document on the Ethical Considerations for Clinical Investigations of Medical Products Involving Children, further reinforcing the need for additional safeguards in pediatric studies as the participants are unable to consent for themselves. Though the document serves as guidance for Institutional Review Boards (IRBs) to assess risk to children in approving a study protocol, it can also aid those involved in designing protocols for decentralized studies involving a pediatric population.

If sites want to retain participants in pediatric studies, they must treat parents and/or caregivers as key stakeholders in the clinical journey. This engagement begins in recruiting.

eConsent and the remote parent

In an ideal situation, both parents are present in the initial recruiting process and are jointly aligned on whether the child should participate in a trial; however, that’s not always the case.

One study of parental consent found that when 3001 families were contacted to participate in newborn screening for Fragile X syndrome, fathers were not present in 589 cases, including 158 fathers who were ultimately determined to be “not reasonably available.” Their reasons to be deemed “not reasonably available” included military deployment, incarceration, living out of state, or they were not involved in the mother’s life.

Parents who are “not reasonably available” as mentioned above are less of a concern in regard to the success of the participant’s trial experience, as they likely would not be involved or have obligations to fulfil as a caretaker would. In other circumstances, one parent may simply not be available to engage in the recruitment process, leaving the trial coordinator to assume their commitment based on the other parent’s feedback. That lack of accessibility can hinder recruiting and delay the consent process, which is a common challenge in pediatric trials.

The study highlights the complexity of requiring joint parental involvement in pediatric trials when consent is required from both parents. It also underscores how important it is for site staff to communicate the need for both parents to participate in live or virtual initial outreach conversations. This early connectivity provides site staff with ample opportunity to educate and engage both parents, to identify potential barriers to participation, and to note red flags where one parent is strongly averse to consenting to the trial. These aversions may not be communicated by the other parent in solo conversations, causing recruiters to assume the pediatric participant is on track to participate, only to face push back later or result in early withdrawal from the trial.

The IRB will have the final say in whether the parent, or guardian in some cases, must give consent, as well as to whether assent must be obtained from participants under 18 and how it is documented. In general, permission should be obtained from both parents before a child is enrolled in research. Under 45 CFR part 46 which is the FDA regulation under which research is being conducted, the IRB may find that the permission of one parent is sufficient. Under some provisions, the IRB may require permission must be obtained from “both parents, 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." For additional reading on the intricacies of clinical research involving pediatric participants, visit hhs.gov.

Decentralized clinical trials (DCTs) can help to ease this challenge by making engagement with both parents easier to accomplish, even if they are divorced, living in different states, dealing with complex work schedules, or deployed. Using virtual meetings and electronic consent (eConsent) systems that include online educational materials gives study coordinators and parents the flexibility to connect with less disruption and to ensure both parents’ concerns are addressed in a neutral setting. It also sends the message to parents that the DCT process is adaptable to everyone’s needs.

One portal for everyone

Once a pediatric participant is enrolled in a trial, site staff need to determine the who, when and where of the minor participant’s schedule, and how it will be affected by the trial.

Typically, in a DCT study, a study participant will be provided a portal with single log-in where both parents can access trial information, reminders, appointment schedules, and to communicate with site staff as needed. Oftentimes, a joint email account is also setup to ease communication barriers. This platform should be easy to use by multiple parties and include options to forward emails, alerts, etc. so both parents can stay abreast of their child’s experience throughout the study. That ease of use and shared virtual environment ensures assessments, appointments, treatments, and other activities can be completed regardless of their location or which caregiver’s device is available. No matter who the child is spending time with, they can stay fully up to date on all of their trial tasks.

A foundation of trust

Many DCTs include home health visits from a consistent nurse or clinical care provider. These home health workers often become a constant in the child and caregiver’s life, providing a consistent adult to help them navigate the trial experience.

If parents are living in separate locations, the cadence of these visits has to be aligned to the child’s time with each parent. To avoid confusion, site staff should involve the nurse in the onboarding process so all adults can work together to build a home visit plan and align the visits with the preferred home location when possible.

Early interactions with the visiting nurse will set expectations for all family members and help parents think through the logistics of these interactions. It also builds a foundation of trust and continuity among the nurse(s), child and caregivers that are valuable throughout the trial.

For studies that are not fully decentralized and require the pediatric participant to attend visits at the site, providing added childcare, or other support systems for siblings and caregivers can greatly improve the trial experience for the entire family.

Into adulthood

As pediatric participants grow older, they will take responsibility for more aspects of their trial experience. This requires an agile trial model that is designed to adapt to their changing needs from the outset.

For example, parents may begin the trial completing electronic clinical outcomes assessments (eCOA) for the participant via a caregiver role, but once the participant reaches a certain age or level of maturity, they may be capable of completing the task. Setting up the eCOA system to support both user types and providing the necessary training will ease this transition process.

Older pediatric participants may also begin attending site or virtual visits on their own, uploading data from their wearable devices, and/or having private conversations with visiting nurses or physicians. Participants who reach their 18th birthday while enrolled in a trial may need to consent at that time, as informed consent is viewed as an ongoing process throughout the trial. Through a decentralized approach, this reconsent process is made much easier by allowing the participant to complete this step without having to travel to the site. The participant will also be given the choice as to whether they want their parents to retain access to their study data.

In long term studies, this evolution from child-to-teen-to-adult must be built into the trial design so that participants, parents, and site staff can seamlessly adapt to the child’s growing maturity and ability to take responsibility for their own experiences. This evolution will vary for every trial and participant, so flexibility will be key.

Make parents part of the team

In pediatric trials, parents (or guardians) determine the success and continuity of the treatment experience. If sites want these trials to run smoothly, they need to engage the caregivers from the outset and set clear expectations for their involvement in the trial. Getting both parents on board early on will foster a positive trial experience for everyone involved.