Balancing Protection and Progress in Pediatric Palliative Care Research: Stakeholder Perspectives Free

A multidisciplinary PPC research team proposes a cross-sectional, qualitative descriptive study of the perspectives of adolescents and young adults (AYA) with life-limiting illnesses and their parents after a discussion about an end-of-life (EOL) decision. Patient and parent or guardian (hereafter, parent) participants would participate in separate, semistructured interviews with a researcher about their perception of the conversation, anything about the conversation that was helpful or not helpful, and information that was important to them when making the decision. The interview questions were reviewed by an institutional family advisory council and IRB. Each participant would be offered a $20 gift card in gratitude for their participation.

The study sample would include 20 to 30 patient/parent dyads (40–60 participants) who receive care at a large children’s hospital (∼300 beds) and participate in a treatment decision-making conversation at EOL. To be eligible, patients must (1) be aged 12 to 24 years; (2) have been diagnosed with a life-limiting illness; (3) have participated in a goals-of-care conversation where EOL was discussed and/or a decision about care (eg, continuation of disease-directed intervention or not, concurrent care or hospice enrollment, resuscitation status, etc) was made within the past 2 weeks; (4) understand the seriousness of their illness state according to the parent; (5) be able to read and converse in English; and (6) be willing to assent/consent to study participation.

Parents must be (1) the primary caregiver of the AYA, (2) 18 years of age or older, (3) able to read and converse in English, and (4) willing to consent to study participation and provide permission for their AYA to participate if they are <18 years of age. Exclusion criteria include AYAs and parents who are unable to read, write, or understand English, or who are otherwise unable to complete study procedures (interview).

Participants would be recruited over a 6 month period. Clinicians will review or refer potentially eligible patients to the research team. Research personnel review and document eligibility using the medical record, and the principal or coinvestigator confirms all eligible patients before consent and assent procedures are initiated. Data would be collected at a time convenient for the AYA/parent and include completion of a brief sociodemographic questionnaire and an audio-recorded interview of 5 open-ended questions (∼30–45 minutes). A system to monitor recruitment, data collection, and general conduct of the study includes detailed team training, weekly research team meetings, and secured data collection and storage. Should the IRB approve this study?

Parents have directed researchers to explore the impact of serious pediatric illness on their children and families.¹  Although it is natural to be protective of patients and families at EOL, generating evidence through research is required for scientific advancement. Balancing tensions of progress and protection involves maximizing opportunity and access to participate, while acknowledging risks of harm and providing appropriate protections and resources.

The research design is informed by our previous experiences interfacing with children, family members, clinicians, and IRB representatives on PPC research, including formal and informal feedback. We attempt to minimize harm and maximize benefit by having trained and experienced PPC researchers conduct the interviews,²  including qualitative interviews that allow participants to share their story,³  and allowing for flexibility in interview location and mode (phone or virtual).^4,5 

Clear, broad inclusion criteria allow children and their families the opportunity to accept or decline research participation. They can assess whether participation is possible and good for them. Preventing this opportunity through overprotection could diminish autonomous choice. Researchers enhance protection of participants by using consent and assent processes to open conversations about potential risks and protections put in place to address such risks.

Support for equitable inclusion in research can be a foundation for services that minimize disparities and enhance access to high-quality care. Excluding non-English speakers and those unable to read or write could limit utility of the research because there is a gap in multicultural palliative care research.^6–10  Simultaneously, including these populations without appropriate supportive language resources is unjust and disrespects participants’ individual rights, needs, interests, and feelings.^11–13  Limited funding and institutional support (eg, research assistants, interpretation services) can make conducting a study inclusive of non-English speakers difficult. For researchers to do inclusive and ethically sound research that amplifies missing voices, adequate institutional support is required.

It is important to avoid preemptive exclusion on the basis of unrealized harms. Researchers should acknowledge generalized risks of emotional harms to each person and family, noting each potential participant has unique susceptibilities to these risks.³  However, these unique susceptibilities should not prevent participation in research but should be acknowledged when presenting the opportunity to participate in research. The rigor of research findings will improve by: (1) avoiding preemptive exclusion in research design, and (2) recruiting marginalized people.¹⁴ 

Participants can have a range of emotional responses to taking part in PPC research, particularly within the context of an EOL decision, from distress to gratitude. It is important to differentiate, and not conflate, an emotional response during an interview with harm or distress. Existing data indicate parents deny distress from participating in EOL research¹⁵  and may find therapeutic benefit,^16,17  with more benefits than burdens.³  Although parents report, “It can be hard, but not bad,”¹⁸  they appreciate telling their story, contributing to science that can help other children and families,^16,19–21  and see participation as a way to make meaning of their situation and contribute to the child’s legacy.^3,16  They describe few burdens, such as feeling sad because of reflecting on the impact of illness or logistical challenges associated with actual participation.³ 

Researchers can align protections offered with anticipated risks and develop protocols to address anticipated risk, as described by Draucker and colleagues.²  For example, if researchers anticipate sadness during an interview, they can include only trained interviewers experienced in working with children and parents, and providing psychosocial support; provide monitoring of emotional reactions; and offer frequent breaks, as other researchers of sensitive topics suggest.^2,22,23  Researchers could elicit help from the participant’s clinical interdisciplinary team before, during, and after interacting with participants to minimize risks.

Family advisory councils can be helpful in addressing risks of harm and gathering insights on phrasing and contextual considerations. Some investigators work with advisory boards to develop protocols that guide responses to research-induced distress. Creating active partnerships in the context of family-focused research is an important step to strengthen PPC research and minimize limitations. Partnership with family stakeholders can: (1) clarify actual risks, (2) identify times when harm may manifest, and (3) provide feasible and acceptable ways to assess for harm and intervene.¹⁵ 

Strategies to advance PPC research in the future are:

1. Methodological flexibility informed by key stakeholders can provide study rigor, along with sensitively and practically meeting potential participants where they are in their journeys. Inviting stakeholders to participate in question generation, and in study and procedure development will make results more relevant, generalizable, and transferrable to clinical practice.

2. Inclusion of medical interpreters on the research team will enhance equity and access to studies for non-English speakers.

3. Evaluation of range of emotional reactions to pediatric EOL research, defining those that warrant consideration as adverse events and which protective measures are most helpful, could enhance our understanding of benefits and burdens and provide evidence to base future research protections.

We believe this discussion and strategies rooted in lived experience will help advance PPC research, research ethics, and clinical practice.

The IRB likely would designate this hypothetical study as nonexempt because it involves interviews with adolescents. Assuming a nonexempt designation, they would evaluate whether it falls within 1 of the categories of approvable research with minors and would evaluate the risk/benefit ratio, make sure risks are minimized, and ensure vulnerable populations are protected. Accessing an IRB member or consultant with a background in serious pediatric illness and who has experience working with AYA near EOL would be important to provide an informed review.

Considering the proposed methods, researchers will likely glean better understanding of child and parent individual experiences after making an EOL decision. IRB analysts may request additional information such as:

1. who specifically will complete the interviews and what is their experience in relation to this group/population;

2. if it is possible to conduct interviews by phone, which may help the child and parent express themselves a little more freely; and

3. a copy of the interview guide, to fully understand what topics will be discussed and how emotionally stressful the study may be.

Some families might not meet inclusion criteria or be in a position to participate in the study. Excluding non-English speakers and those who are unable to read or write may limit utility of the results and may not provide the team with a full evaluation of the conversation. Those excluded on the basis of language or education level may already feel isolated and need help addressing their specific needs, so including them would be beneficial to the palliative care program and expand services for all those in need. Ideally, the protocol will also include a plan to enroll a wide variety of patients who reflect characteristics such as stage of disease/proximity to death, whether child receives pain medication, and types of caregivers because these factors may affect perceptions of the conversation.

The IRB is responsible for evaluating the potential risks and their probability, the degree of potential harm, the potential benefits, and whether such benefits outweigh risks. A potential benefit of participating in this study may be the opportunity to provide direct feedback on the EOL decision-making experience and to reflect further on the decision process. There may be a psychological benefit to knowing one is contributing to the improvement of care for future patients. The importance of including family units in the EOL decision-making process is imperative to create and implement effective palliative care programs. Allowing participants to specifically discuss how they felt about the conversation with the health care team and information that was important to them when making a decision is essential to support families, help guide treatment decision-making, provide resources, and educate clinicians and support staff about EOL best practices for all ages.

The primary risk may be psychological and emotional distress. Asking families to express how they felt about the EOL decision conversation and information provided could add to the intense emotions or stress associated with serious illness and the pain of accepting EOL. Input from the family advisory council is crucial for this reason.

Valuable research often carries some risk, and the IRB’s job is to ensure risks are minimized by using sound research practices and avoiding any unnecessary exposure to risk. Aspects that require scrutiny are the separation of minors from their parents during the interviews; the adequacy of the consent and assent process to fully prepare participants for the emotional risk; and whether the scientific design is likely to achieve the study aims.

Considering these concerns, the family advisors already vetted the plans to conduct interviews separately. The IRB must also look at research team qualifications for conducting interviews with adolescents and may recommend social workers, psychologists, child life specialists, or chaplains be part of the study team, if not already present. To further minimize risk, investigators can include a follow-up check-in with the participants after the interview, along with offers of additional support if needed. The consent/assent must be explicit about potential for emotional distress, as well as explaining that responses will be shared only in aggregate with the hospital staff to assuage concerns about impact on future care.

This study could be determined to be minimal risk, if the concerns are addressed, because “the probability and magnitude of harm or discomfort anticipated in the research are not greater, in and of themselves, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”²⁴  It does not need to show direct benefit to participants, though this study does offer that prospect to both the AYAs and their parents.

I am Omar’s mother. He was diagnosed with acute lymphoblastic leukemia at the age of 2. He went through chemotherapy twice and then through a bone marrow transplant. As a mother whose son lost his battle to leukemia on April 7, 2012, I believe this study would benefit many grieving families. Although many hospitals already provide some kind of EOL care, this study would help researchers understand what parents actually need, what actually benefits grieving parents, what needs to be added, and what can be improved so hospitals can help many more children and families in a way that suits their needs. I appreciate how this study would help us tell part of our story to help other families, share what we think was helpful during important discussions, and provide insights about what could be improved. I think this kind of study would be an opportunity to improve small things parents remember about these important discussions or stressful times, such as how a doctor or nurse talks to you slowly and calmly or helps you feel supported.

We should recognize what would be hard for families participating in this study. Researchers should be mindful of certain challenges, such as timing, focus of the study, relationships, and understanding the need to meet families where they are. Researchers would need to think about timing and be flexible in their approach to conducting palliative care research. There are times such as when their child might have relapsed or is not doing well when it might be too stressful to invite parents to participate in a study. Parents could be worried about work, finances, or their other children, or just having a hard day. Also, they may not be eating or sleeping well (child or parent) or do not want to leave their child. An individualized approach would be important. Families might not be willing to talk about their experience because it could be difficult to express feelings about their loss. Doing so might bring about grief or depression or other difficult feelings. A better time might be when the child is more stable or maybe just another day, so conducting interviews when it works best for the family would be important. These would be difficult conversations but could end in a positive result.

Each family has a story to tell. Understand that each parent’s responses to their child’s situation will be different. Researchers can use a thoughtful, caring approach. Parents may want to help others but may not participate because the topic is personal, sensitive, or may be upsetting to other family members. Researchers should respect relationships created with families who participate in research.

There are some protections or supports researchers can institute for families through partnership. For example, hearing about the study from parents who have already participated or having a parent to ask about the study would be helpful. This would show the study is done with care and concern for the family’s well-being. As a mother, I would relate to and understand another parent and they would understand me. Having support from other families who have gone through similar experiences would be helpful. Having someone parents can contact with questions or a shoulder to lean on would be a great resource.

I would recommend these concrete actions:

• Engage in “patient- and family-centered research:” approach parents as individuals, be flexible, and “meet people where they are.”

• Respect relationships.

• Seek guidance from family advisory boards or invite parents to join research teams to provide feedback on study design or recruitment procedures.

After receiving supplemental information, the IRB requested the study protocol be modified to include a follow-up check-in with the participants after the interview. The investigators agreed and the study was approved. The investigators met their recruitment goals and there were no adverse events during the study. Most participants declined the additional support offered during the follow-up check-in.

Over time, there have been efforts to balance protecting children and adolescents from the risks of research with extending the benefits of research to them.²⁶  The concern to protect individuals who have life-limiting conditions, are nearing the end of their lives, or are grieving from potential harm is understandable. Some putative protections, such as asking providers for permission to approach potential participants as opposed to guidance regarding when to contact them, may not prevent harm and may impede research. The commentators make several helpful recommendations regarding how to advance PPC research and respect participants, including the importance of forming partnerships between researchers, children and families, and clinicians.

AYA

adolescents and young adults

EOL

end of life

IRB

institutional review board

PPC

pediatric palliative care