Introduction
Hematopoietic stem cell transplantation (HCT) is a transformative therapy for children experiencing malignant or nonmalignant disorders. While transplant offers hope for cure and/or improved quality of life, the success of HCT is tied to adherence (Pai et al. Reference Pai, Rausch and Drake2018) which, as defined by the World Health Organization, is “the extent to which a person’s behavior – taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider” (Sabaté Reference Sabaté2003; Amonoo et al. Reference Amonoo, Deary and Wang2023). Therefore, in the context of pediatric HCT, adherence extends beyond compliance with medication schedules. It encapsulates a commitment to infection control measures, dietary restrictions, and stringent follow-up regimens (Sabaté Reference Sabaté2003). However, within pediatric HCT, current literature emphasizes medication adherence. For instance, adults report rates of medication nonadherence post-HCT from 0 to 75% (Khera et al. Reference Khera, Chow and Leisenring2011; Morrison et al. Reference Morrison, Martsolf and Wehrkamp2017; Belaiche et al. Reference Belaiche, Décaudin and Caron2021). In adolescents with cancer and post-HCT, rates range from 21 to 60% (Smith et al. Reference Smith, Rosen and Trueworthy1979; Festa et al. Reference Festa, Tamaroff and Chasalow1992; Butow et al. Reference Butow, Palmer and Pai2010; McGrady et al. Reference McGrady, Davies and Pai2014; McGrady and Pai Reference McGrady and Pai2019). In pediatric HCT, rates range from 42 to 75% (Phipps and DeCuir-Whalley Reference Phipps and DeCuir-Whalley1990; McGrady et al. Reference McGrady, Davies and Pai2014; Pai et al. Reference Pai, Rausch and Drake2018), increasing over time (McGrady et al. Reference McGrady, Davies and Pai2014; Morrison et al. Reference Morrison, Martsolf and Wehrkamp2017; Posluszny et al. Reference Posluszny, Bovbjerg and Syrjala2022), and children miss at least 1 dose of medication 3 days a week (McGrady et al. Reference McGrady, Davies and Pai2014). Medication nonadherence has been associated with a higher incidence of infections in children post-HCT (Pai et al. Reference Pai, Rausch and Drake2018). While medication nonadherence poses clear risks, there is a gap in the literature regarding understanding the interplay of aspects of adherence beyond medication; therefore, this study aims to fill that gap.
Previous literature commonly examines barriers and facilitators in the context medication adherence; however, these barriers likely also affect other aspects of care. The most reported barrier is difficulty managing numerous medications (Hoegy et al. Reference Hoegy, Bleyzac and Rochet2019; Chardon et al. Reference Chardon, Klages and Joffe2022). Other barriers include long-term therapy, medication changes, transition of care (Hoegy et al. Reference Hoegy, Bleyzac and Rochet2019), refusal, bad taste, administration method, and refills (Chardon et al. Reference Chardon, Klages and Joffe2022). Medication barriers typically emerge after discharge and decrease over time (Chardon et al. Reference Chardon, Klages and Joffe2022). Additionally, family caregivers are frequently unaware of potential post-HCT barriers before discharge (Chardon et al. Reference Chardon, Klages and Joffe2022), making combatting barriers difficult. However, families may develop strategies to enhance their child’s adherence (facilitators), such as recognizing medication benefits, maintaining organization, social support, and establishing routines (Morrison et al. Reference Morrison, Martsolf and Wehrkamp2017; Hoegy et al. Reference Hoegy, Bleyzac and Rochet2019). Age-related adherence facilitators include nasogastric (NG) tube for younger children and increased autonomy for adolescents (Chardon et al. Reference Chardon, Klages and Joffe2022). Therefore, it is imperative to examine adherence barriers and facilitators, beyond medication, from both caregivers’ and children’s perspectives to help families post-HCT.
To broaden the understanding adherence post-HCT, examining both children and caregivers is essential because according to the Biobehavioral Family Model, biological, psychological, and social family factors impact individual and family health (Woods and Denton Reference Woods and Denton2014). Furthermore, effective familial support and communication are integral for proper post-HCT care (Hoegy et al. Reference Hoegy, Bleyzac and Rochet2019). For instance, a qualitative study in adults post-HCT found familial responsibilities as a barrier and caregiver support as a facilitator to adherence (Amonoo et al. Reference Amonoo, Deary and Wang2023). Caregiver emotional well-being, treatment plan understanding, transition of care, and financial concerns affect pediatric adherence (Chardon et al. Reference Chardon, Klages and Joffe2022). Family caregivers providing support, effective communication, trust, and high-quality bonds more effectively guide children post-HCT (Butow et al. Reference Butow, Palmer and Pai2010). Additionally, more social support for children decreases comorbidities and complications post-HCT (Nørskov et al. Reference Nørskov, Yi and Crouch2021). Simultaneously, the child’s age, cognitive development, and psychological resilience impact adherence (Butow et al. Reference Butow, Palmer and Pai2010). Therefore, various factors influencing the family caregiver–child relationship contribute to the child’s adherence, underscoring the need for a holistic understanding of adherence in pediatric HCT to inform tailored interventions addressing families’ needs.
This qualitative study explored the unique experiences of children and their caregivers, focusing on the multifaceted aspects of adherence post-HCT. While Amonoo et al. (Reference Amonoo, Deary and Wang2023) conducted a similar study in adults, it is important to recognize children face distinct challenges. Additionally, most adherence literature focuses on medication adherence. Therefore, a dyadic, qualitative approach was used to examine the psychosocial, familial, and healthcare factors influencing children’s adherence. The study aimed to (1) explore adherence barriers and facilitators for medications and restrictions/guidelines and (2) examine the experience of children and their caregivers with the complex post-HCT regimen. This study contributes to the existing HCT literature regarding barriers and facilitators and adds novelty by including the individual perspectives of children and qualitatively examining the multi-faceted aspects of HCT adherence.
Methods
Procedures
Eligible caregivers and children were recruited through the HCT outpatient clinic at a large Midwestern, free-standing children’s hospital (February–September 2020). During a routine clinic visit or via phone, a study team member obtained informed consent/assent and interviewed caregivers and children. This study was reviewed and approved by the local Institutional Review Board (#STUDY00000680).
Participants
Twenty-nine participants were enrolled (14 caregivers and 15 children), representing 15 families. Most participants (n = 28) were matched caregiver–child dyads; however, the child sample includes 1 child who was 18 years old and their own caregiver. Children and caregivers meeting inclusion criteria, confirmed through a medical chart review, were approached during clinic visits. The inclusion criteria for children (8–18 years old) specified having an underlying malignant or nonmalignant disease, receiving an allogeneic HCT, and being at least 1–12 months off immunosuppression (patients typically wean off during the first 100 days post-transplant). Caregivers or children who were non-English speaking and/or had developmental delays were excluded. Convenience sampling was used to obtain a demographically diverse sample across age, sex, race/ethnicity, and diagnoses.
Data collection
One trained nursing research assistant, 2 clinic nurses, and 1 doctorate-level nurse scientist conducted interviews using a semi-structured interview guide (Table 1). The interview guide was developed by 2 PhD-prepared investigators, the PI and psychologist (MS, CG), with a team of clinical experts. Through an iterative process, initial drafts were refined with expert feedback from HCT clinicians to ensure comprehensive content and clarity. Sample size was guided by the principle of data saturation and achieved when no new themes emerged, ensuring the depth necessary for comprehensive analysis (Hennink and Kaiser Reference Hennink and Kaiser2022).
Table 1. Pediatric HCT adherence interview guides
Data analysis
Demographic data were analyzed using descriptive statistics. Interview data were managed using NVivo 13 (2020, R1), a qualitative data analysis software, and analyzed using thematic analysis (Sundler et al. Reference Sundler, Lindberg and Nilsson2019). The analysis technique included (1) becoming familiar with the interviews, (2) generating initial codes, and (3) searching for themes. Child interviews were coded first, followed by caregiver interviews. The first 3 interviews from the child group and first 3 interviews from the caregiver group were analyzed using open coding. Two research team members (MS, KV) independently analyzed the remaining 23 interviews. Analysis was done by separating the dyads’ interviews by child and caregiver responses and analyzing them individually. Themes were derived across all child and caregiver interviews to provide the full picture of the family experience. However, few ideas were specific to the caregivers or children. After the themes were established, responses within dyads were associated and compared (Table 2) (Eisikovits and Koren Reference Eisikovits and Koren2010). Data analysis continued until thematic saturation was achieved. Saturation was monitored through discussions among the research team. To enhance credibility, member checking was conducted with a subset of caregivers (n = 5).
Table 2. Themes and exemplar quotes from caregivers and children dyads post-HCT
Results
Fourteen caregivers and 15 children (n = 29) participated. Demographic characteristics are described in Table 3 (caregivers) and Table 4 (children). The average length of caregiver interviews was 10 minutes (range: 5–18 minutes) and the average length of child interviews was 10 minutes (range: 3–18 minutes). One dyad completed the interview simultaneously (28 minutes). Additionally, half of the caregivers (n = 7, 50%) mentioned the child was responsible for managing their own medications and 43% (n = 6) indicated the child was responsible for knowing when to take them. Consistent across children and caregivers, the primary themes were (1) family navigation and self-management of post-HCT medications and restrictions and (2) advice from families on navigating post-HCT care. The first theme has 3 subthemes: (1a) maintaining organization and a structured routine for medication management, (1b) emotional, social, and practical adaptations to managing medications, and (1c) managing aspects of care and daily restrictions that hinder post-HCT life. The second theme has 2 subthemes: (2a) communication as a cornerstone of care and (2b) practical strategies to maneuver post-HCT treatment.
Table 3. Caregiver characteristics (N = 14)
Table 4. Child characteristics (N = 15)
Family navigation and self-management of post-HCT medications and restrictions
Maintaining organization and a structured routine for medication management
Caregivers and children highlighted the importance of a structured routine and staying organized to manage medications via (1) having a routine/chart, (2) following a schedule, (3) discovering a good method of administration, (4) using alarms/notifications, and (5) managing the quantity of medications. Eight caregivers and 2 children endorsed maintaining a routine and/or using a chart to stay organized, such as initially using a chart to create a routine, keeping the medications close to where they slept, putting out the week’s medications, or having a mental routine, “I had a routine in my head … her nurse gave us a chart, and she highlighted … she put morning, afternoon, evening … so that helped me early on because we went from being in the hospital where the nurses are around the clock and now mama got to do it” (mother of a 9-year-old girl). Caregivers (n = 4) expressed challenges following the medication schedule because of taking care of other children. Caregivers (n = 4) and children (n = 3) had difficulties remembering which medication to take when, “It’s just real hard. There is a lot of pills and at different times of the day” (13-year-old boy). Caregivers (n = 3) reported waking up their child as a barrier, “The actual pill taking wasn’t the issue. Waking him up was more an issue” (mother of a 15-year-old boy).
Another way to manage medications reported by caregivers (n = 4) and children (n = 4) was sticking with a successful method of administration. Caregivers reported using flavorful drinks, taking pills over liquid, or crushing up the pills into food or the NG tube made administration easier. Children reported taking medications at the Ronald McDonald house or in the hospital made it easier. Other children also reported using applesauce or a baby bottle to help, “I always make Mommy pretend like I was a baby and put it in like a baby bottle and I would take it like that. I don’t know why, but yeah, that’s just what was in my head” (9-year-old girl). Three caregivers and 1 child reported using phone notifications/alarms, “It became habit … but I always set an alarm just so I wouldn’t forget” (mother of a 15-year-old boy). Caregivers (n = 2) and children (n = 2) expressed difficulties keeping track of all the medications and how a successful management strategy helped.
Emotional, social, and practical adaptations to managing medications
While maintaining a routine and organization was a primary facilitator, caregivers and children described additional facilitators and barriers to medication adherence. They emphasized necessary adjustments for a successful transition to life post-HCT such as (1) combatting the bad taste of the medications, (2) managing side effects/symptoms, (3) acquiring knowledge of the process, (4) having parental help, (5) changing doses, (6) taking the medications at home, (7) setting goals, and (6) handling prescription refills. Caregivers (n = 5) and children (n = 1) reported the bad taste of medication as a barrier. Whether the child needed a flavorful drink, or the medication crushed into food, there was a shared sentiment that administering bad tasting medication was hard, “It was horrific, was horrible, it was always screaming, chaotic. So, we had to come up with different ways to introduce the meds” (grandparent of a 9-year-old girl). Another barrier reported by caregivers (n = 3) and children (n = 5) was medication symptoms/side-effects, such as lower extremity pain, vomiting, nausea, no appetite, thicker gums, hair growth, fevers, fatigue, and/or stomach pain, “Sometimes my body wouldn’t handle it well … sometimes I would throw it up. Sometimes I would be okay. Sometimes I just wouldn’t be able to take it, or it would take me a while to take it. So, it was kinda hard” (18-year-old male).
Three caregivers (no children) reported prior medical knowledge enabled them to handle the medications better, seek out necessary information, and “prepare [the child] ahead of time about medications and make some suggestions as far as how to take certain medications” (mother of a 16-year-old boy). Two children (no caregivers) discussed having their caregiver’s help made taking medications easier, “Having my mom there with me to help me measure it out” (14-year-old boy). One child (no caregivers) mentioned the difficulties of the doses changing and how “the doses were always awkward. Like they’d go sky high and then they had to go super low” (15-year-old boy). One child (no caregivers) also expressed how taking the medications at home and setting goals to take all the pills made it easier. One caregiver (no children) reported challenges keeping up with the prescription refills, “Trying to think, like, to get them refilled. I felt like I was always going to the pharmacy … that was the most challenging thing” (mother of a 9-year-old girl). Lastly, some caregivers and children reported easy adherence or no problems. Four children expressed that taking the medication wasn’t too bad, there was not a bad taste, and it was easy, “It wasn’t hard. I didn’t feel any different, and it didn’t taste too bad” (14-year-old boy); 6 caregivers reported facing no problems with their child taking their medications, “He didn’t really have any issues taking the medication” (mother of a 14-year-old boy).
Managing aspects of care and daily restrictions that hinder post-HCT life
While adherence to medication regimens poses challenges, the post-HCT guidelines and restrictions often introduce a variety of additional challenges. Most commonly, caregivers (n = 9) and children (n = 8) reported difficulties with the restricted social time at school and with friends. Across caregivers, there was a consensus that it “was a big challenge for [the child], not going back to school, not being able to get around [their] friends” (mother of a 15-year-old girl). Of the 8 children that reported limited social interactions, 1 expressed, “It wasn’t that big of a problem” (16-year-old boy), while 7 expressed it was hard, “I didn’t like that I wasn’t able to go to school, because I love seeing my friends and playing with them” (15-year-old boy). Additionally, 2 children (no caregivers) expressed their enjoyment of homeschool specifically, and how it benefitted them, “Being homeschooled was kind of an easy way to get my grades back into this year” (16-year-old boy). Two children and 2 caregivers also reported their child had difficulties feeling isolated from their inability to leave their house, “He felt very isolated and lonely and it was horrible, and he couldn’t wait to go back to school” (mother of a 14-year-old boy); “I felt lonely. I felt secluded, isolated” (14-year-old boy). In terms of wearing a mask, 1 caregiver and 5 children expressed difficulties and frustrations with wearing a mask and how having a routine helped, “You would have your mask with your baseball hat … if we’re going to go out, you grab your hat, and you’re in your mask” (mother of a 13-year-old boy); “I hate wearing a mask, but it’s something you just gotta do” (18-year-old male). One child (no caregivers) expressed that wearing a mask “is what it is, because you just have to wear the mask, and now everybody has to … I was just setting the trend” (11-year-old girl).
Advice from families on navigating post-HCT care
Communication as a cornerstone of care
When asked about advice for future families and providers, caregivers and children reported various strategies centered around good communication: (1) involve your child, (2) communicate with the medical team, (3) maintain open communication, and (4) listen to doctors. Three caregivers (no children) expressed that it was helpful to involve their child in the treatment process; it “empowered [them] to take control of their own health” (mother of a 15-year-old girl), allowed children to understand their diagnosis and treatment. Three caregivers and 2 children described the importance of communicating with the medical team. Whether noting symptoms, sharing opinions, or leaning on them for support, caregivers shared the sentiment it was important “to keep good contact with the providers” (grandparent of a 9-year-old girl). The children suggested talking to the doctors so they know what is going on because, as 1 child shared, “if you don’t, you just end right back where you were at” (18-year-old male). One caregiver and 3 children advised families do as the doctors say, whether that be taking the medicine on time, keeping their hands clean, or staying away from sick people, “just basically follow the rules of the doctors” (14-year-old boy). Lastly, 3 caregivers and 1 child expressed the importance of the medical team fostering an open environment, “If you communicate in a certain way with your patient, they’ll be honest and then you can deal with it – just making them feel comfortable, to be honest with you” (mother of a 15-year-old girl).
Practical strategies to maneuver post-HCT treatment
When asked to offer advice to other families and providers, caregivers and children also shared practical strategies for handling life post-transplant: (1) remain hopeful, (2) be active, (3) stay busy indoors, (4) focus on other stuff, (5) make it a game, (6) rest, (7) trust, (8) find support, and (9) stay committed. Three children (no caregivers) expressed the importance of remaining hopeful, knowing normalcy would eventually return, and realizing “it will be over before you know it, and it could be way worse” (14-year-old boy). Two children and 1 caregiver advised finding ways to stay entertained indoors and be active, “don’t just sit there and make time just waste by” (15-year-old boy), even if that means you must wear a mask, “If I could have gone back, I would have worn a mask in public if I could’ve hung out with them. I would think they were judging me, but they really weren’t” (16-year-old boy). Additionally, 1 child (no caregivers) advised focusing on something else and making it a game, like “who can wear a mask and gloves longest” (9-year-old girl). Lastly, 1 child (no caregivers) expressed that rest is helpful, because “sometimes physical therapy and all the other stuff, really doesn’t help anymore and the only thing you want to do is rest” (14-year-old boy), and trust is important because “it makes me feel better when it is someone I trust” (9-year-old girl). Three caregivers (no children) advised families to find support and accept help, such as joining support groups on Facebook, relying on school resources, or welcoming help from family and friends. One caregiver (no children) advised sticking with the treatment even when it is challenging. When asked to give advice to future families, caregivers and children also provided suggestions that were previously addressed as common adherence facilitators: 6 caregivers (no children) said to maintain an organized routine, 2 children (no caregivers) said to discover a successful medication administration method, and 1 caregiver and 2 children said to manage the number/bad taste of medications and have assistance from the medical team regarding at-home medication administration.
Discussion
This study uniquely examines pediatric HCT adherence, highlighting the multifaceted nature of adherence, beyond medication. The interviews revealed families found adherence success by having an organized medication system and finding practical ways to navigate life post-HCT. Families reported challenges with maintaining a structured routine, staying organized, and adapting to life post-HCT. Additionally, families shared valuable advice regarding the importance of communication and strategies to maneuver HCT treatment. Families also discussed the difficulties of post-HCT restrictions and interviews revealed children’s involvement. The child’s perspective also validates the need for social support from their medical staff, family, and friends post-HCT (Butow et al. Reference Butow, Palmer and Pai2010; Nørskov et al. Reference Nørskov, Yi and Crouch2021). This study provides concrete suggestions from children and their caregivers on navigating the restrictive HCT process, adhering to medical regimens, and making the most out of life post-HCT.
The first theme, family navigation and self-management of post-HCT medications and restrictions, addresses the first study aim by highlighting barriers, facilitators, and restrictions that families face post-HCT. The reported facilitators of medication adherence post-HCT were consistent with findings from previous studies. For instance, maintaining routines and understanding the benefits of the medications were reported facilitators (Hoegy et al. Reference Hoegy, Bleyzac and Rochet2019). Additionally, families shared specific adherence strategies, including using an alarm system, medication chart, and unique methods of medication administration. Consistent with previous literature, the most frequently reported barriers included the number of medications (Hoegy et al. Reference Hoegy, Bleyzac and Rochet2019; Chardon et al. Reference Chardon, Klages and Joffe2022; Amonoo et al. Reference Amonoo, Deary and Wang2023), medication distaste, method of medication administration (Chardon et al.), complex medication schedule, and medication side effects (Amonoo et al. Reference Amonoo, Deary and Wang2023). Beyond the expected medical and pharmacological aspects, psychosocial, familial, and healthcare system factors play a significant role in adherence challenges. The dynamic interplay of these factors is emphasized through the nuanced narratives from the children and their caregivers and highlight a need for holistic, individualized approaches.
The second theme, advice from families on navigating post-HCT care, addresses the second aim by highlighting collaborative advice and communication between the child, medical team, and caregiver. While few differences emerged between caregiver and child reports within themes, the individual perspectives from the children present unique information about their communication preferences, feelings about transplant, and strategies for managing life post-HCT. Additionally, individual findings from caregivers reveal the treatment responsibility between caregivers and their child. Half of caregivers reported the child was responsible for making sure they took their medications and just under half of the children were responsible for knowing when to take the medication. However, it is notable that the level of responsibility and involvement the child had with their medications (i.e., was there supervision?) remains unclear. In literature, caregivers report difficulties managing medication responsibility with their partners and assuming full responsibility for the medication regimen post-HCT (Chardon et al.). Additionally, adolescents with positive family relationships, open communication, and strong social support have better adherence and fewer complications (Nørskov et al. Reference Nørskov, Yi and Crouch2021), whereas poor relationships have been associated with adherence challenges (Butow et al. Reference Butow, Palmer and Pai2010). Therefore, literature has begun to shed light on the unique child-caregiver dynamics related to medication responsibility post-HCT and associated barriers and/or facilitators; this study illuminates that reality as the results include shared medication responsibility and emphasizes communication. The involvement of the child in medication responsibilities underscores the importance of communication throughout the transplant process and when considering future interventions.
Limitations
While this study provides valuable insights, certain limitations merit acknowledgment. The single-center nature of the study and the potential for recall bias are important considerations. The diversity in caregivers was limited as they were primarily female, White, and well-educated, and child diversity was limited by race. The interview guides targeted medication management and post-HCT restrictions/guidelines, not family dynamics, a common topic that emerged. Additionally, the study was conducted during the COVID-19 pandemic, which could have made the families’ experiences handling the treatment regimens and restrictions (i.e., avoiding crowds, wearing masks) easier than other times. Therefore, prospective mixed-method studies are needed to confirm findings. Despite the aforementioned limitations, the sample had diverse representation of socioeconomic statuses, included non-parental caregivers, met saturation, and ample information was provided to evaluate study aims. Future research should explore the generalizability of these findings across healthcare settings, delve into the implications of shared child-caregiver medication responsibility, and consider the multifaceted aspects of adherence. Additionally, education, employment, marital, sibling, and socioeconomic status of families in relation to their adherence should be examined.
Conclusion and clinical implications
Findings underscore the importance of adopting a comprehensive and patient-centered approach in pediatric HCT care due to the complexity of navigating treatment and life post-HCT. All individuals involved should be attuned to the child’s needs and support system. Healthcare providers should know the family’s psychosocial structure, incorporate family-centered strategies, and enhance communication. For instance, providers can facilitate regular family meetings to explore family concerns, clarify roles, and set realistic self-management goals. Interdisciplinary team members can play specific roles in supporting families: nurses can provide education and assess family readiness; social workers can address emotional barriers for effective self-management; dietitians can involve families in culturally-tailored nutrition planning. These practices can promote family engagement to improve HCT outcomes.
Acknowledgments
The study team extends heartfelt gratitude to the patients and families who generously dedicated their time and effort to participate in this study. We also sincerely thank the nursing team for their dedication in conducting this study in the clinic, in particular Mindy Bibart, Alyssa Baker, and Amber Pruett for their leadership. Finally, we acknowledge the DAISY Foundation for their invaluable funding support, which made this work possible.
Funding
Funding for this study was provided to Dr. Skeens by a grant from the DAISY Foundation: grant number: JPB-2019-439.
Open access
