Caregivers’ Experience of Medication Adherence Barriers during Pediatric Hematopoietic Stem Cell Transplant: A Qualitative Study

Abstract

Objective

Medications are critical for reducing morbidity and mortality risk in pediatric hematopoietic stem cell transplant (HCT). Nonetheless, medication adherence is suboptimal in this population. Identifying and managing barriers to medication management (i.e., medication barriers) is a key component of supporting medication adherence. However, understanding how medication barriers uniquely impact the pediatric HCT population and which barriers characterize each treatment stage remain unclear. Therefore, this study examined caregiver-perceived medication barriers over the course of pediatric HCT.

Methods

Semi-structured qualitative interviews and demographic questionnaires were completed by 29 caregivers of children (≤12 years) who had received an HCT in the past 24 months and were either still admitted to, or had been discharged from, the hospital.

Results

Grounded methodology revealed 21 qualitative themes grouped into 6 hierarchical categories. Findings reflected barriers to be present across HCT treatment but to differ based on treatment stage with only child medication refusal being a consistent barrier across all stages. Barriers were particularly prevalent after hospital discharge post-HCT when caregivers assumed full responsibility for medication management. In addition, families approaching hospital discharge often lacked insight about these post-discharge barriers such that they did not report anticipating the range of barriers described by caregivers who had already been discharged from the hospital and taken on full responsibility for medication management.

Conclusions

Findings support the benefit of medication barrier assessment across HCT treatment. These results suggest that families may benefit from intervention to address the specific barriers they experience around medication adherence especially during the post-HCT outpatient period.

Introduction

Hematopoietic stem cell transplant (HCT) is an intensive, potentially curative treatment for rare pediatric malignancies, bone marrow failure conditions, and immune deficiencies (Fraint et al., 2020). Survival and the mitigation of life-threatening complications depend, in part, on the child and caregiver’s adherence to a complex daily medication regimen (Pai et al., 2018). Nonetheless, the few studies evaluating medication adherence in this population show suboptimal adherence rates ranging from 52% to 73% (Morrison et al., 2017; Pai et al., 2018; Phipps & DeCuir-Whalley, 1990). Both caregivers and medical providers identify poor medication adherence as a primary concern after pediatric HCT (Hoegy et al., 2019; Skeens et al., 2020).

Factors that make medication adherence challenging (i.e., adherence barriers) are strong predictors of medication adherence and can be conceptualized by the Pediatric Self-Management Model (Modi et al., 2012). This model shows medication barriers to fall into four domains: individual, family, community, and healthcare system (Modi et al., 2012). Barriers within each of these domains can further be classified as either modifiable or non-modifiable. Barriers vary depending on the specific treatment demands and characteristics of a pediatric population (Varnell et al., 2021). Therefore, understanding the unique adherence barriers, particularly those that are potentially modifiable, is critical to informing efforts to support adherence.

Very little is known regarding medication barriers over the pediatric HCT treatment course. Characteristics of HCT treatment likely make medication adherence particularly challenging for children and caregivers. For instance, the post-HCT medication regimen typically includes a high number of medications with complex dosing schedules (e.g., daily immunosuppressant medication, prophylactic antibiotics 3 days per week) that are frequently changed to accommodate titration or to address unexpected medical complications. Caregivers are also tasked with administering additional medication as needed to address treatment side effects (e.g., nausea, pain). This is concerning as greater medication regimen complexity and illness severity are associated with worse medication adherence within pediatric medical populations (Chandwani et al., 2012; Coleman et al., 2012). In addition, caregivers must abruptly assume responsibility for managing this complex regimen upon discharge as medications are primarily managed by the child’s HCT medical team during the initial hospitalization. This rapid shift requires caregivers to quickly develop the skills necessary to integrate medication management into their daily routines.

To date, only two studies have directly examined medication barriers in pediatric HCT and have reflected barriers in the healthcare domain (i.e., large number of medications, dosing changes). They also revealed some barriers in the individual domain (e.g., anxiety, depression, side effects). However, both these studies focused on youth within the first 4 months after discharge. Given the evidence for medication adherence gradually worsening over the outpatient period, it may be that medication barriers differ across HCT treatment stages. Thus, a deeper understanding of medication barriers could inform the timing and content of screening tools and interventions. Furthermore, while there are several validated measures of medication adherence, this study chose to employ qualitative methods given the goal of observing the nuanced evolution of barriers over time and these inductive methods may allow for a more unbiased and rich source of information about caregiver experiences.

Thus, this study aimed to qualitatively evaluate perceived medication barriers over the HCT treatment course in a sample of caregivers of children ages 0–12 years, the peak age range for pediatric HCTs (Health Resources and Services Administration, 2018). Given the exploratory nature of this study, inductive grounded theory and thematic analytic methods were used to limit potential bias placed by a priori hypotheses (Charmaz et al., 2018).

Methods

Participants and Procedures

A recruitment goal of 25–50 caregivers was chosen based on previous grounded theory studies (Loades et al., 2020; MacLeod et al., 2003). Thirty caregivers were recruited from a Midwest children’s hospital in the United States between April and July 2020. One caregiver withdrew from the study before completing study procedures for a total sample of 29 caregivers. Study staff identified potentially eligible caregivers via electronic medical record review. Caregivers were eligible if they (a) spoke English, (b) were the primary caregiver for a child (≤12 years) who had received an HCT within the last 2 years, and (c) their child was (or would be) prescribed an outpatient medication. Caregivers were ineligible if their cognitive status precluded their ability to complete study procedures. Two groups were included to capture families’ perceptions over the full HCT treatment course: (a) caregivers of children in the hospital post-HCT who were approaching discharge (inpatient cohort) and (b) caregivers of children post-HCT who had been discharged (post-discharge cohort). Eligible caregivers were contacted by study staff via telephone and completed a brief screener to confirm their eligibility. Informed consent was then completed via telephone and their semi-structured telephone interview was scheduled. After completing the interview, caregivers completed measures via RedCap or paper forms. All study procedures were approved by the Institutional Review Board. Caregivers were compensated for their time. Further details regarding recruitment and study procedures have been published in Chardon et al. (2021).

Individual semi-structured interviews were conducted over the telephone by the first author (M. Chardon). A topic guide was used during the interview, which consisted of open-ended questions designed to elicit caregivers’ responses about their and their families’ experiences with medication management during their child’s HCT treatment (see Appendix). Open-ended questions for the topic guide were generated from a review of the literature and in collaboration with two experts in pediatric HCT medication adherence. When warranted, additional prompts were used to elicit more detailed responses (e.g., “Can you tell me more about that?”). Semi-structured interviews lasted 29–84 min. Interviews were audio-recorded and transcribed verbatim by an HIPPA-compliant transcription service. Transcripts were reviewed for accuracy by study staff and were uploaded into NVivo (Version 13) for analysis.

Measures

Demographic and Clinical Variables

Child clinical data (age, sex, diagnosis, and HCT treatment information) were collected via medical record review. Caregivers provided additional demographic information on a demographic form (caregiver age, sex, and income) and on select items from the Psychosocial Assessment Tool-Hematopoietic Cell Transplant (child/caregiver race, caregiver/child ethnicity, and caregiver marital status; Pai et al., 2019).

Data Analysis

Transcripts were coded in NVivo (Version 13) using inductive thematic analytic methods (Attride-Stirling, 2001). Coding occurred in stages. First, M. Chardon and A. Pai independently completed line-by-line coding of one inpatient and two post-discharge transcripts to ensure that the themes were inductively built, reducing the risk of investigator bias on data interpretation. M. Chardon and A. Pai then compared independently generated codes to create an initial coding dictionary to guide further analysis. M. Chardon was the master coder and trained K. Klages on all procedures by coding four interview transcripts together before independently coding interview transcripts and reconciling coding differences after completing each transcript. Once 80% agreement was achieved (n = 5), M. Chardon coded the remaining 20 transcripts. M. Chardon and K. Klages met weekly to review coded transcripts. All discrepancies in coding or amendments to the coding dictionary were discussed between M. Chardon and K. Klages. A. Pai was consulted to resolve discrepancies between coders and reviewed coding dictionary amendments. Additional codes were added to the coding dictionary until saturation was reached (i.e., no new codes being generated from subsequent transcripts). Interview transcripts that were coded prior to the addition of new codes were recoded as necessary to accommodate the coding dictionary amendments. Dimensional (i.e., consolidating codes with similar properties) and axial (i.e., organizing codes into hierarchical categories) coding, informed by the Pediatric Self-Management Model (Modi et al., 2012), were then used to organize and consolidate codes into themes.

This coding process resulted in 21 saturated themes specific to medication barriers (see Table I) that were organized into six hierarchical categories: anticipated, child, caregiver, family, medication and medical, and medical team barriers. Time specifiers were then added to coded statements to indicate when the barrier occurred during the treatment course; barriers that were present before the HCT hospital admission, during the HCT hospital admission, or after discharge from the hospital post-HCT were given the specifier of pre-admission, inpatient, or post-discharge, respectively, within a given theme. Statements were coded as a “global or unspecified” when the time period was either unclear, or the caregiver reported that the barrier was present across HCT treatment stages.

Table I.

Medication Barrier Themes Definitions and Rates of Endorsement by Caregivers Across HCT Treatment Stages

Medication Barrier Themes	Operational Definition of Barrier	Barrier Endorsement Frequency
		Totala  n (%)	Global or Unspecifieda  n	Pre-admissiona  n	Inpatienta  n	Post-Dischargeb  N
Hierarchical category: anticipated barriersc		9	—	—	—	—
Anticipated barriers		9	—	—	—	—
Hierarchical category: child factors		29	12	13	20	16
Medication refusal	Problems with child acting out or refusing to take medication (e.g., tantrum, spitting out medication)	22 (76%)	9	6	12	6
Side effects	Challenges with child physical side effects (e.g., nausea, vomiting, mouth sores, taste changes)	20 (69%)	5	6	14	6
Child emotions	Difficulty with child negative emotions about taking medications (e.g., burn-out, frustration, anger)	12 (41%)	5	2	5	3
Pill swallowing problems	Child struggling to swallow pills	7 (24%)	0	0	4	3
Sleep	Child’s sleep schedule interfering with medication administration	6 (21%)	0	1	0	6
Hierarchical category: caregiver factors		27	11	11	8	21
Caregiver emotions	Difficulty with caregiver negative emotions about medication management	22 (75%)	6	5	1	15
Forgetting	Problems with caregiver forgetting (or being fearful of forgetting) to administer medication	15 (52%)	1	1	4	12
Lack of medication knowledge or experience	Challenges due to caregivers lacking information about medication or not having previous medication/medical experience	15 (52%)	4	8	6	6
Challenges with multiple caregivers	Difficulty coordinating medication administration responsibilities across multiple caregivers	9 (31%)	3	2	1	5
Hierarchical category: family factors		16	3	3	2	11
Daily life, responsibilities, and stressors	Activities outside of daily routine, other responsibilities (e.g., sibling care), and/or stressors (e.g., financial stress) making medication adherence difficult	16 (55%)	3	3	2	11
Hierarchical category: medication factors		27	20	11	12	18
Taste	Problems with medication tasting bad	16 (55%)	3	3	7	7
Medication number or schedule	Difficulty managing the medication amount/frequency, rigid administration windows, or non-daily medications	17 (59%)	0	8	3	12
Medication names and the amount of information	Difficulty learning names of medications, large quantity of information to understand or remember	12 (41%)	3	2	5	5
Accessing or refilling medications	Challenges with physically getting medications (e.g., insurance issues, transportation difficulties, germ fears at pharmacy, availability of medication at pharmacy)	10 (34%)	0	1	0	9
Medication delivery modality	Challenges manipulating the medication modality including problems with tools (e.g., syringes), size of pill or quantity of liquid, oral versus feeding tube	10 (34%)	0	5	1	10
Other self-management tasks	Difficulty balancing medication management with non-medication self-management tasks (e.g., tube feedings)	10 (34%)	0	0	0	10
Frequently changing medications	Challenges with frequent changes in medication dose or schedule	6 (21%)	0	0	1	6
Safety concerns	Coordinating medication management with safety concerns (e.g., placing medications in a cabinet that young siblings cannot access)	4 (14%)	0	0	0	4
Hierarchical category: medical team factors		10	1	1	6	4
Communication challenges	Difficulties with unclear, inconsistent, or jargon-filled communication about medications between caregivers and medical teams	8 (28%)	1	1	5	4
Power dynamic	Caregiver concern about power differential between themselves and medical providers	4 (14%)	0	0	2	3

Note. Barriers present before the HCT hospital admission, during the HCT hospital admission, or after discharge from the hospital post-HCT were given the specifiers of pre-admission, inpatient, or post-discharge, respectively, within that barrier theme. Statements where the time period was unclear or the caregivers indicated that the barrier was present across HCT treatment stages were coded in the global or unspecified specifier. The total column reflects the total number of caregivers who described that barrier at any point during the interview. The sum of specifier column counts may be greater than the count within the total column as caregivers were included in multiple specifier columns if they indicated that same barrier being present at multiple time points (e.g., both in pre-HCT and post-HCT columns for taste). HCT = hematopoietic stem cell transplant.

^aAll 29 caregivers could provide responses to these time periods.

^bOnly the 20 caregivers in the post-discharge group could provide responses for barriers in the post-discharge period.

^cOnly the nine caregivers in the inpatient group could provide responses for anticipated barriers.

Results

Participant Characteristics

Twenty-nine participants (9 in the inpatient group and 20 in the post-discharge group) completed interviews and were included in the results. Caregivers (M_age = 36.2 years, SD = 8.6) were predominantly female (n = 25; 86.2%), non-Hispanic (n = 28; 96.6%), and married or partnered (n = 21; 72.4%). Caregivers identified their race as White (n = 24; 82.8%), Black/African American (n = 3; 10.4%), Asian (n = 1; 3.4%), and “others” (n = 1; 3.4%). The median household income was $60,000–$69,000 (range from <$9,000 to >$200,000). Children (M_age = 5.8 years, SD = 6.0) were mostly male (n = 18; 62.1%) and non-Hispanic (n = 27; 93.1%). Child race was identified as White (n = 24; 82.8%), Black/African American (n = 3; 10.4%), multi-racial (n = 1; 3.4%), and “others” (n = 1; 3.4%). The most common HCT associated diagnosis category was bone marrow failure (n = 13; 44.8%), followed by malignancy (n = 9; 31.0%), immune deficiency (n = 5; 24.1%), hematological disorder (n = 1; 3.4%), and metabolic syndrome (n = 1; 3.4%). Twenty-five (86%) children received an allogeneic transplant and 4 (14%) received an autologous transplant. Time from discharge to study completion for the outpatient group were <6 months (n = 9), 6–12 months (n = 4), 12–18 months (n = 3), and 18–24 months (n = 4). Additional details regarding participant demographics are reported in Chardon et al. (2021).

Qualitative Results

Anticipated Barriers

The theme, anticipated barriers, included statements made by caregivers in the inpatient group (n = 9) about the challenges they expected related to medication management after discharge. Three caregivers were unsure of, or had not yet thought about, what to expect in regard to medication management. Four caregivers expected that the large number of medications and complexity of the dosing schedules would make it challenging to establish an organizational system and ensure administration within the prescribed window. Two caregivers expressed concerns about nausea or vomiting impairing medication administration, with one mother who was employed in the pharmaceutical field expressing particular concern that if nausea resulted in too many re-administrations, her insurance company may refuse to cover medication refills. Other medication barriers anticipated by caregivers prior to discharge included: child behavior (e.g., medication refusal; n = 3), inability to use a pillbox due to the liquid formulation of medications (n = 1), safety concerns (e.g., storing medication in a place inaccessible to children; n = 1), and balancing medication management with other demands (e.g., tube feedings; n = 1).

Child Factors

Five child-related barriers emerged from qualitative interviews. Medication refusal was the most common, reported by 76% of caregivers. Caregivers expressed that their child’s resistance to taking medication (e.g., refusing to open mouth, spitting medication out) made administration difficult. A mother of a 10-year-old reported that “getting a child that has an opinion and an attitude to take all those meds is a nightmare.” This theme was present across all treatment stages but was described as varying day-to-day depending on the child’s emotional or physical state. One mother indicated that if her 2-year-old son “feels good, he’ll go with the flow, take medicine, do whatever. If he doesn’t feel well, then it is like, ‘No. I don’t want to do that.’ So sometimes getting him to take meds wasn’t always pleasant.” Caregivers note that two additional barriers contributed to medication refusal: side effects and child emotions.

Side effects (e.g., nausea, vomiting, loss of appetite, mouth sores, and taste changes) was reported as a medication barrier theme by 69% of caregivers. It was present at all stages of treatment but increased during inpatient admission (n = 14) and often persisted into the early months after discharge (n = 6). During the inpatient period, medical teams were described as being primarily responsible for ensuring adequate medication dosing despite nausea (often via intravenous therapy or nasogastric tubes). Post-discharge, caregivers reported being responsible for managing this and struggling with how and when to re-dose medications if their child vomited shortly after administration.

“You had to watch the clock. If [she threw up] before 15 minutes, you re-give it. And sometimes I would have to call. Like, it was almost 15 minutes, she only puked a little bit, and then it’s like ‘Do I give her half?’ Because cyclosporine [a commonly prescribed immunosuppressant] is an important medicine. So that was a little difficult at times. Especially trying to get her to keep from throwing it up” (mother, 2-year-old female).

Regarding taste changes, a mother of an 8-year-old girl stated, “She refused to take [cyclosporine] at some point when she was in the hospital. Because of the chemo, her taste buds changed completely, and she wouldn’t take a lot of things.” Caregivers also reported that their child’s loss of appetite made it harder to manage their nausea as they struggled to get their child to eat before administering medications despite their eating before medication administration helping to alleviate medication-related nausea.

Child emotions, especially treatment-related burnout and anxiety, was another commonly cited barrier across all treatment stages (n = 12). For example, a mother of a 5-year-old boy described burnout developing early in treatment: “Within a few weeks, it got old … He was starting to become resistant … After they’ve been forced to take these medications so many times they’re kind of like, ‘No, I don’t want to do that anymore.’”

Pill swallowing problems were reported during the hospital admission (n = 4) and after discharge (n = 3). Three caregivers who described pill swallowing difficulty in the hospital attributed it to the size of the chemotherapy pills. Post-discharge, pill swallowing difficulties arose when families tried to avoid the aversive taste of liquid cyclosporine by transitioning to the pill form before the child mastered pill swallowing skills.

Six caregivers reported sleep as another challenging medication barrier post-discharge with doses either being delayed or missed due to the child waking up late in the morning or falling asleep too early at night. “I know they’re supposed to be given within an hour … I would try our best to keep to that. But there are sometimes, like if she is sleeping, I’m gonna let her sleep” (mother, 5-year-old daughter). Two caregivers illustrated the nuanced decision-making caregivers sometimes engaged in indicating that they were more likely to wake the child to administer cyclosporine than other medications they viewed as less important.

Caregiver Factors

Four themes pertaining to caregiver-related barriers emerged. The most common, Caregiver emotions, was endorsed by 75% of caregivers at some point in treatment. This barrier was primarily reported in outpatient settings (pre-HCT admission n = 5 and post-discharge n = 15) when caregivers were responsible for medication management. Pre-HCT admission, caregivers’ emotional barriers included fear of administering injectable medications, feeling overwhelmed with the amount of information to learn, and difficulty processing their child’s diagnosis. Fifteen of the 20 post-discharge group caregivers reported that negative emotions made it difficult to administer medications, particularly during the acute period when they were transitioning home from the hospital. Caregivers expressed feeling overwhelmed by the amount of information they had to learn and the amount of responsibility they abruptly assumed for their child’s medical care during this period. A mother of a 5-year-old male reported that it was “exhausting going home, getting him out the door, being up all night giving the medications, and then, as soon as we get home, they’re delivering medical supplies … It was just overwhelming … you can’t really absorb any of that information.” A mother with a 10-year-old daughter felt intimidated during the transition home, stating that when they were inpatient, “there was a nurse or sometimes even two … in her room all day just to care for her. So, it’s intimidating to think like, ‘Okay, she needed this amount of care, but now this is on me.’”

Forgetting was endorsed by more than half of caregivers (n = 15). During the inpatient admission, four caregivers described forgetting information about the medication (e.g., name, purpose). Most caregivers described forgetting (or a fear of forgetting) to administer medications shortly after discharge from the hospital (n = 12). Caregivers attributed forgetting or the fear of forgetting to the novelty of medication management and the large number of prescribed medications during this transition period. Caregivers also reported being more likely to forget to administer non-daily medications or on days when their family was out of their typical routine.

Over half of caregivers (n = 15) indicated that lacking knowledge or experience about the medications (i.e., not knowing the medication’s purpose, its common side effects, or potential flexibility in dosing schedule) made it challenging to optimally administer them. Caregivers also described often feeling unsure of what questions to ask the medical team to facilitate medication management. “We didn’t even know what question to ask because we were so overwhelmed with all this information… The doctors would ask us, ‘Do you have any questions?’ I’m like, ‘I don’t know. What questions should we have?’” (mother, 7-year-old daughter).

Finally, nine caregivers reported challenges coordinating across caregivers at some point in treatment. This barrier was most commonly reported for the post-discharge period (n = 5) when multiple caregivers were involved and, therefore, they needed to establish new or more effective communication strategies around medication administration and dosing changes.

Family Factors

One family-related barrier was identified: daily life, responsibilities, and stressors. This barrier was endorsed by 55% of caregivers and was most salient during outpatient treatment stages (pre-admission n = 3; post-discharge n = 11). Caregivers described how, particularly shortly after discharge, having to attend to other demands/responsibilities of daily life (e.g., caring for siblings, transitioning back to work, and financial stressors) made medication administration difficult. A mother of an 8-year-old female explained that the transition to the outpatient setting was “overwhelming in the sense of, ‘Okay, what has to be done?’ I have other kids too. So … trying to figure out everything and how we’re gonna do things was hard.” Eight caregivers also reported that medication doses were more likely to be skipped or delayed on days when the family was out of their typical routine (e.g., sports games, family functions).

Medication Factors

Eight medication and medical factors emerged as barriers. Over half of caregivers (55%) reported that their child struggled to take medication (often liquid cyclosporine) due to its taste. Taste was a persistent barrier during the inpatient admission (n = 7) and acutely after discharge (n = 7) before gradually ameliorating over the post-discharge period.

Medication number or schedule was identified as a medication barrier by 60% of the 20 caregivers who had discharged home post-HCT. It was particularly hard for caregivers to keep track of the large number of medications in the early weeks following discharge. They noted that medications that needed to be given at a specific time (e.g., cyclosporine) were particularly stressful. Children also struggled with taking such a large number of medications, so caregivers described needing to space out medication administrations, thus taking up large portions of their day. A mother of a 9-year-old boy stated that giving medications “can be exhausting. It can take me an hour to give his medications in the morning and then an hour again in the evenings … I spend a lot of the day giving medication.” While caregivers were able to establish routines to support optimal administration of daily medications, four caregivers reported difficulty remembering to administer non-daily medicines or knowing when to administer as-needed medications. For example, a mother of a 7-year-old girl described difficulties judging when she should administer as-needed medications. “‘Does she need to wean off the appetite stimulant or is it nausea? … Do I add another anti-nausea one?’ Or just like pain meds, ‘Ok, when do I give her this?’” Fortunately, caregivers noted that this barrier decreased over time with practice and a gradual reduction of prescribed medications.

Similarly, 41% of caregivers found learning medication names and the amount of information challenging, particularly early in the HCT course. A mother of a 5-year-old girl stated that at the beginning, “you feel like your head’s spinning. There’s so much information coming at you and basically all you can do is smile and nod.” Difficulty learning names and the large quantity of information about medications frequently started during the inpatient admission (n = 5) and persisted post-discharge (n = 5). While inpatient, caregivers predominantly had trouble remembering the names and purpose of their child’s medications, resulting in them frequently asking medical providers to repeat information. Once home, caregivers expressed difficulty remembering medication purposes and administration processes. However, caregivers described medication administration as getting easier as familiarity with the medications increased.

Almost half of the caregivers in the post-discharge group (n = 9) identified accessing or refilling medications as a significant barrier after leaving the hospital. Only two caregivers reported that refill barriers led to missed doses. However, all nine caregivers described the refill process as stressful due to the insurance companies denying refills until the medication was almost out, number of pharmacy trips required, lack of reliable transportation, concerns about germ exposure at the pharmacy, and difficulty identifying pharmacies that dispense liquid medications. Frequently changing medications was a barrier reported during (n = 1) and after (n = 6) the hospital admission. After discharge, caregivers described dose changes often occurring between clinic visits, requiring them to independently track the changes and, at times, resulting in medications running out.

Medication delivery modality was endorsed as a barrier by half of the post-discharge caregivers (n = 10). Caregivers highlighted issues associated with liquid medication including the large quantity of liquid medication their child needed to ingest, difficulty transporting it when traveling away from the home, and dosing issues related to washing/cleaning dosing syringes.

Four caregivers of younger children (<8 years) or with toddler siblings identified medication safety as a barrier. They expressed concerns about younger children getting access to the medications such that they placed medications in locked cabinets or high-up locations (e.g., on top of the fridge). This was particularly challenging for families who first discharged to temporary housing (e.g., Ronald McDonald house) as they were confined to a single room.

Finally, half of the post-discharge caregivers (n = 10) reported difficulty managing medications after hospital discharge due to the demands of other self-management tasks (e.g., medical appointments, managing feeds via feeding tubes, central line care, and ensuring adequate water consumption). For example, a mother described caring for her 7-year-old daughter as “a full-time job because her medication, she has a central line, and she also had to do feedings through her feeding tube.”

Medical Team Factors

Caregivers reported two medical team-associated barriers: communication challenges and power dynamic. Communication challenges with the medical team was endorsed as a medication barrier by 28% of caregivers (n = 8) across treatment stages. This barrier was most salient during the inpatient admission (n = 5) when caregivers described having difficulty grasping the information being communicated by the medical team.

“Doctors and nurses walk in with their book of knowledge and… their big words. I instantly get confused. I’m like ‘What?… Can you break it down?’… I’m not saying that they’re all speaking above me or anything, but not every one of them knows how to break it down a certain way for people like me” (mother, 1-year-old male).

Communication challenges also contributed to confusion about prescribed outpatient medications and dosing schedules during hospital discharge (n = 2) as well as about which medical team to contact with questions or concerns when transitioning to local care (n = 2).

The power dynamic between caregivers and the medical team was noted as a barrier during the hospital admission (n = 2) and after discharge (n = 3). Caregivers reported concern or anxiety about how the medical team would perceive and/or respond to them following treatment-related questions (e.g., fearing sounding entitled or difficult). One mother explained that medical providers approached her as she was preparing for her 7-year-old son to be discharged from the hospital and said “Here’s what you’re going to be able to do, right? This is not that complex; you can handle it.” She further explained, “I think we’re setting them [caregivers] up for a little bit of failure because if they don’t feel comfortable with doing it … So maybe we have people leaving on medications they’re really not comfortable giving because they didn’t want to speak up.”

Discussion

Medication adherence is suboptimal within the pediatric HCT population (McGrady et al., 2014; Morrison et al., 2017; Phipps & DeCuir-Whalley, 1990), particularly once families transition home post-HCT (Pai et al., 2018). Caregivers within this population abruptly assume responsibility for their child’s medically critical and complex medication regimen upon hospital discharge; thus, understanding medication barriers families anticipate and experience post-HCT is imperative to guiding assessment and intervention efforts to improve medication adherence in this population. These exploratory results reflected child refusal of medications to be the most pervasive and persistent medication barrier, which was observed across all treatment stages. The findings also suggest that barriers within this population are consistent with the Pediatric Self-Management Model (Modi et al., 2012); individual (e.g., medication refusal, pill swallowing difficulties and child mood), family (e.g., caregiver psychological distress, lack of knowledge about the regimen and distractions of daily family life), and healthcare systems (e.g., quality of communication from medical providers) factors were all reported by caregivers. Notably, the salience of medication barriers differed based on the child’s treatment stage (particularly, if they were inpatient or outpatient), with the largest number of barriers being present after hospital discharge post-HCT.

Pre-HCT Admission Medication Barriers

A unique medication barrier before the HCT hospital admission was caregivers having difficulty adjusting to their child’s diagnosis or need for medications. Children refusing medications was also a salient barrier during this period. Before the HCT admission, the majority of caregivers perceived this barrier to result from their child’s frustration with their medication regimen. Targeted screening of caregiver and child adjustment to the child’s health status may be particularly important during this stage of treatment. In addition, parent behavior management may be beneficial as early as is feasible in the HCT course. Prior to HCT admission was also when caregivers were most unfamiliar with the medical system and administering medications, which was described as contributing to medication administration challenges. Consequently, families in this treatment stage (particularly, those with little medical experience) may benefit from support and instruction to bolster their ability to effectively navigate the medical system and learn how to manage their child’s medication regimen.

HCT Hospital Admission Medication Barriers

Child medication refusal was the most common barrier during the HCT hospital admission as well, but caregivers in this sample described are as varying day-to-day depending on the child’s emotional and physical state. The frequency and severity of this barrier may reflect how the behavioral challenges, such as medication refusal, that characterize this period often coincide with the secondary factors (i.e., side effects) of this intensive treatment. Results suggest that caregivers may benefit from anticipatory guidance about the impact of treatment and its side effects on child behaviors, as well as strategies for effectively managing both. Children may also benefit from psychosocial support to help them cope with emotional and physical symptoms (e.g., psychology, child life). Caregivers reported that, despite medical providers giving them information about their child’s medications while in the hospital, they still struggled to retain the information given difficulties with patient–provider communication, challenging medication names, and complex (and often changing) medication regimens. Given that caregivers of children with a history of HCT or cancer have previously identified effective collaboration with providers and clear communication about medication information as promoting medication adherence (Hoegy et al., 2019; Lambert et al., 2019), these results suggest that identifying methods to deliver medication information to already overwhelmed caregivers is needed to better match their preferences.

Post-HCT Hospital Discharge Medication Barriers Versus Anticipated Medication Barriers

Consistent with previous research (Hoegy et al., 2019), caregivers in this study described medication management to be the most challenging when transitioning home from the hospital. This period is when children are prescribed the largest number of medications and caregivers are still learning their child’s treatment regimen. During this period, caregivers expressed feeling overwhelmed by the large amount of medication information and skills they needed to learn (i.e., medication characteristics, schedule, administration requirements), while integrating medication administration into daily life. Notably, challenges with taste, administration modality, and accessing refills persisted throughout the discharge period. Fortunately, most caregivers perceived barriers generally to decrease over time.

Interestingly, caregivers approaching hospital discharge were often relatively unaware of the medication barriers that they were likely to face after discharge. Unsurprisingly, the barriers they anticipated were those that they had already encountered before or during their HCT admission (e.g., the large number of medications, nausea/vomiting, and medication refusal). Caregivers rarely anticipated barriers that were unique to the post-discharge period (e.g., feeling overwhelmed with independently managing the medication regimen, difficulty accessing refills, and integrating medication management into daily life). Barriers also often changed, developed, or evolved post-HCT discharge. These findings suggest that it may be beneficial to reinforce the role caregivers have in their child’s care throughout their hospitalization as well as provide suggestions about the amount and type of support families should be offered after discharge.

Limitations and Future Directions

While the qualitative nature of this study provided the opportunity to collect rich data while limiting researcher biases, our sample was small and was primarily comprised of White, non-Hispanic, married, or partnered female caregivers at a single institution. While this sample was representative of the patient population in our institution, structural racism within the healthcare system may have important implications on how caregivers from minoritized ethnic and racial groups perceive medication barriers after pediatric HCT. For instance, the experienced power differential between caregivers and the medical team may be a more salient barrier for caregivers from minoritized ethnic and racial backgrounds. It will be important for future studies to measure and evaluate how structural racism and issues related to diversity, equity, and inclusion are associated with caregiver-perceived medication barriers. This study also focused on medication barriers given their robust association with medication adherence and outcomes within pediatric medical populations (Modi et al., 2012; Varnell et al., 2021). However, barriers were retrospectively reported, which makes our results vulnerable to retrospective bias. In addition, information about caregiver experience with medications prior to their child’s HCT treatment was not systematically collected in this sample. Subsequent studies are needed to evaluate how prior experience and other medical history factors (e.g., previous medical treatment, autologous versus allogeneic HCT) impact perceived barriers and facilitators of adherence to inform future intervention approaches. While caregivers primarily manage medications in children aged ≦12 years, future studies may also consider a multi-informant or mixed-methods design (e.g., inclusion of quantitative measures such as the Parent Medication Barriers Scale; Tackett et al., 2016) to capture similarities and differences in perceptions of medication self-management across stakeholders (e.g., children, doctors, home care nurses, and pharmacists; Hoegy et al., 2019) as well as their association with objective measures of adherence. Finally, data for this study were collected during the COVID-19 pandemic, which may have impacted caregiver and child emotional functioning and self-management experiences. The impact of COVID-19 on caregiver and family adjustment during pediatric HCT is discussed in Chardon et al. (2021).

Conclusions

The rich and detailed findings from this qualitative study show how medication barriers are present throughout HCT but vary between treatment stages and families. Prior to discharge, families had limited insight into potential barriers related to managing medications outpatient. However, medication barriers became particularly salient after hospital discharge and changed over the post-discharge period. These results suggest that ongoing systematic assessment of barriers may be beneficial at all treatment stages, particularly during the initial months following discharge, in order to provide timely, targeted, and appropriate medication adherence promoting interventions.

Appendix 1: Medication Adherence Barriers Topic Guide

Questions asked of all caregivers about medication barriers pre-HCT:

• What was your family's pre-HCT medication regimen

• Was anything challenging about administering medications pre-HCT? If so, what?

• What was the hardest part of administering medications prior to HCT?

• Did the challenges stay consistent or change over time?

Questions asked only of caregivers in the inpatient group about medication barriers during their current hospital admission and anticipated barriers after discharge:

• What has your family's experience managing your child's medications in the hospital been like so far?

• Has anything been challenging about medication administration in the hospital setting?

• What do you expect managing your child's medications will be like after you leave the hospital?

• Is there anything that you expect will be challenging about managing your child's medications once you discharge?

Questions asked only of caregivers in the post-discharge group about medication barriers both during and after their HCT hospital admission:

• What was your family's experience managing your child's medications while admitted to the hospital?

• Was anything challenging about medication administration in the hospital setting?

• What has your family's experience managing your child's medications been like since discharge from the hospital?

• Has anything been difficult or gotten in the way of administrating medications? If yes, what?

• Have difficulties with medication administration changed since you first left the hospital? If yes, how so?