1. Introduction
In North America, acute lymphoblastic leukemia (ALL) is the most frequent cancer among children < 14 years old [
1]. The 5-year overall survival is approximately 90% [
2,
3]. This remarkable progress results from the intensification of chemotherapy and the refinement of risk-group stratification [
2,
3]. The regimens of treatment for children newly diagnosed with ALL typically take place in successive phases and include systemic chemotherapy (parenteral and oral) as well as central nervous system-directed therapy (intrathecal chemotherapy ± cranial radiotherapy) [
3,
4]. Corticosteroids (dexamethasone or prednisone) and 6-mercaptopurine (6-MP) are among the mainstay drugs used for preventing ALL relapse [
3,
4,
5]. This requires that children take intermittent or daily doses of corticosteroids and 6-MP prescribed as oral chemotherapy (OC) at home for 2 to 3 years [
3,
4].
The use of these OCs is accompanied with recommendations to ensure their safety and efficacy. For instance, patients are commonly instructed to take 6-MP during the evening on an empty stomach (1 h before or 2 h after meals or snacks), without dairy products, and to handle it with gloves [
6]. Corticosteroids, for their part, have been associated with psychological and physical side effects, including emotional lability, irritability, aggressivity, anxiety, depressed mood [
7,
8], weight gain, hyperglycemia, and hypertension [
9]. Following these administration recommendations and coping with these side effects in the long term can be challenging for children and their parents. A study conducted among 441 children with ALL from diverse ethnicities reported that 43.8% of them did not take at least 95% of their prescribed 6-MP doses [
10]. This study also supports the withdrawal of the 6-MP restrictive recommendations (i.e., taking it in the evening and without food or dairy products) as this did not significantly affect systemic exposure to the drug or increase the risk of relapse but did enhance adherence. The importance of high adherence to 6-MP in pediatric ALL was emphasized in a large study showing that missing ≥5% of the prescribed doses is associated with an increased risk of relapse (hazard ratio, 2.7; 95% confidence interval, 1.3–5.6) [
5]. In a recent study, participants (49 parents and 15 patients with ALL) reported a median of four barriers to 6-MP adherence [
11]. These were multifaceted, being associated with the parents’ and the patient’s capabilities, motivation, and environment. The most frequently reported barriers were to do with finding out what the medications were and meeting with other parents or patients. In a second analysis, these authors found that parents and patients with ALL were favorable to a mobile health intervention to support 6-MP adherence [
12].
Some qualitative studies have provided insights into the journey of families with ALL children [
13,
14,
15,
16,
17], but the specific experiences and needs regarding home-based OC are scarcely documented. One qualitative study focusing specifically on the lived experience with dexamethasone among children with ALL, assessed at two time points during the home-based therapy, indicates that the psychological effects of this treatment are profoundly disturbing for the child and the entire family [
18,
19]. A recent mixed-method study focused on parents’ challenges with OC administration, including 6-MP but excluding dexamethasone, during the maintenance phase [
20]. The difficulties reported in administering the OC were related to their formulation and taste, side effects, required lifestyle adjustments, the child’s cooperation, and the parental burden associated with this new responsibility. A thorough description of the multifaceted experience of families specifically with both the 6-MP and the dexamethasone administered at home is lacking. This qualitative study aimed to describe the parents’ experiences with home-based 6-MP and dexamethasone prescribed to a child diagnosed with ALL.
2. Materials and Methods
2.1. Study Design and Conceptual Framework
We conducted a descriptive, qualitative study to gain an in-depth understanding of the experiences and needs regarding OC from the view of the parents [
21]. The conceptual framework guiding this study was based on the ABC taxonomy of adherence and the Information-Motivation-Behavioral skills (IMB) model [
22,
23]. The ABC taxonomy depicts the components of medication adherence. When applied to home-based OC, these components include the initiation of OC, the implementation (respect for administration recommendations) and persistence for the prescribed duration (approximately 2 years) [
22]. The IMB model conceptualizes factors that could influence the adoption of health-related behaviors such as medication-taking. This model postulates that an individual must know why and how to take the medication
(Information), become motivated to take the medication
(Motivation), and be capable of overcoming barriers and developing strategies (
Behavioral Skills) [
23].
2.2. Study Setting and Population
This study was conducted at the CHU de Québec-Université Laval, a network of teaching hospitals offering health services to the eastern population of Québec (Canada), including specialized and ultra-specialized pediatric care, where about 20 children are annually diagnosed with de novo ALL.
The study was conducted among parents of children <15 years old receiving a first-line pediatric ALL treatment protocol of the Dana-Farber Cancer Institute (ClinicalTrial.gov identifiers: NCT03020030), which globally consists of the following main successive phases: induction, consolidation I, central nervous system therapy, consolidation II, and continuation. Recruitment was performed between June 2019 and August 2019 at the outpatient clinic. To be eligible, parents had to: (1) be directly involved in managing the OC of a child undergoing consolidation or continuation phases (3-week cycles—6-MP taken on days 1 to 14 and dexamethasone taken on days 1 to 5—for approximately 2 years [
3]) and (2) be able to participate in an interview in French. A member of the medical team presented this study as a study on the parents’ experience of OC at home to all eligible parents during a follow-up visit. The research team then explained the study in person or over the telephone and solicited the participation of parents who agreed to be contacted for the study. This study was approved by CHU de Québec-Université Laval Ethics Board (2020-4698). All the participants signed a consent form and received CAD 20 in compensation.
Patients and their caregivers at our institution are provided with education and support from a multidisciplinary team. Oncologists, pharmacists, and nurses are involved in the family’s initial teaching regarding OC. This includes the treatment plan, its aim, and specific information on each OC (e.g., dosing, side effects, and tricks to administer OC). The specific recommendations on OC and the general precautions with chemotherapy are also presented (at time of the study, taking 6-MP during the evening on an empty stomach without dairy products) and limiting potential sources of infection during periods of neutropenia (e.g., avoiding visiting a person with a contagious infection, avoiding large group meetings, and attending schools). Families are provided with written information (e.g., a standardized information sheet on OC, a daily dosing calendar, and a handout summarizing recommendations for the patient). During home-based OC phases, most patients have weekly appointments with the oncologists at the pediatric oncology clinic. They meet with the pharmacists at each of the OC refills, provided free of charge. As required, patients and their caregivers can also contact the nurse navigator and get services from other providers, including social workers, psychologists, nutritionists, physiotherapists, specialized educators, etc.
2.3. Data Collection
We conducted individual semi-structured interviews. The data collection and analysis were performed by a multidisciplinary team interested in pediatric oncology and the optimization of oral anticancer treatments. The interview guide was structured according to our conceptual framework (
Appendix A). The principal investigators (I.L. and S.L.) were present during the first two interviews to ensure the interview guide’s accuracy. As only minor adjustments were made to the guide, these interviews were included in the analysis. The interviews took place at the hospital or by telephone and were audio-recorded and fully transcribed. The data collection was performed by five members of the research team (E.C.-B. and E.N., M.Sc. pharmacy candidates; G.D., psychology student; S.L., Ph.D. trained in social and cultural anthropology and epidemiology; and I.L., Ph.D. and part-time pharmacist at the in-patient pediatric oncology unit). None of the interviewers knew the participants before the study.
2.4. Analyses
The transcripts were thematically analyzed using a codebook developed through a validation process inspired by continuous thematic analysis [
24]. Two research team members (E.C.-B. and E.N.) independently coded one interview using a first version of the codebook. This initial version of the codebook was developed based on the conceptual framework, the interview guide, the notes taken during the interviews, and also what emerged from the data. Based on this first coding experience, a second version of the codebook was produced and used to independently code four interviews by four research team members assembled in pairs (E.C.-B.–G.D., E.N.–G.D., and G.D.–A.B., M.Sc. trained in pediatric medicine and epidemiology). The coding of each pair was compared. Discrepancies were minor, and adjustments were made to the codebook. Using the final codebook, the remaining interviews were coded by two research team members (G.D. and A.B.) using QSR International Pty Ltd. (2018) NVivo Pro (Version 12). Based on the summaries of each code, the team identified emerging themes and their relationships. A professional translator translated the participants’ quotations into English. The participants were not solicited to provide feedback on the findings. As a validation process, to assess the credibility and transferability of our findings, these were shared and discussed with four parents who did not participate in this qualitative study. These parents are involved in managing OC for a child with ALL and are members of an advisory committee guiding our research team in studies of OC in ALL. The parents on this advisory committee met the same eligibility criteria as those in this qualitative study (see
Section 2.2. Study Setting and Population). The advisory committee was presented with the main results of our analysis during a two-hour meeting, and the parents were invited to freely comment on the accuracy of these results based on their own experiences.
4. Discussion
To the best of our knowledge, this is the first qualitative study to specifically describe the subjective parental experience with the concomitant use of home-based 6-MP and dexamethasone, two cornerstone drugs for lasting recovery from ALL. Studying this combination enabled us to capture both the specific difficulties of each drug and their cumulative burden. The findings provide rich and detailed insights into the families’ experiences with home-based OC. The parents felt very responsible for managing the OC at home and were highly motivated to follow the recommendations. They also reported being generally well informed, having gained the required knowledge to take charge of the home-based treatments throughout the treatment course. However, the parents collectively reported that adapting to the consequences of the OC on family daily life was the biggest challenge. The treatment enforced the development and maintenance of a strict family routine, required adapting to changes in the child’s behavior during dexamethasone, and required adapting relationships, both inside and outside the family.
The parents’ motivation toward adhering to 6-MP and dexamethasone recommendations was very high; one parent said that managing the treatment at home correctly was his/her “mission”. This is in direct line with the findings issued from a qualitative study where the parents of 12 children with ALL described their overall journey as “Being there”, meaning “I’ll be there for you” and “Whatever happens, you can count on me, I will never let you down” [
13]. Our findings indicate that the parental role, which may change in the context of a potentially fatal illness such as ALL [
16,
17], also accurately applies to the home-based phase of treatment, when the parents embrace new responsibilities regarding their child’s treatment. Even if highly motivated, entering this new phase was first perceived as a stressful step by some parents. A previous qualitative study also showed that the parents’ representations of the first transition from hospital to home with an ALL child were antagonistic, characterized by both apprehensions and relief [
25]. Thus, this transition may be a critical time when parents need support to adapt to their new responsibilities, including OC management, and to a new family reality.
Despite the amount and the complexity of the information that needed to be assimilated, the parents integrated crucial information in order to self-manage home-based OC. They were generally very satisfied with the information received, as previously documented for the more general type of information received in the context of pediatric cancer [
15,
26]. It is likely that understanding the aim and general mechanisms of the action of 6-MP and dexamethasone contributed to enhancing the parents’ motivation towards initiating, implementing, and persisting with the OC. This may also reinforce the parents’ perception that OCs are just as important as intravenous ones. However, some parents did not clearly understand the purpose of dexamethasone and were unprepared to deal with the emotional and behavioral changes caused by this drug on their child. Specific attention should be paid to dexamethasone, and crucial information regarding its potential impact [
18,
19,
27] should be provided well before the occurrence of side effects.
Being motivated and well-informed does not mean that this step in treatment was easy to live through for the families. Some studies have looked at the overall journey of families with a child diagnosed with cancer, including ALL [
13,
14,
16,
17]. However, our study brings a novel insight into the challenges faced by parents and their children which is specific to integrating the recommendations for the intake of OC at home. The parents’ testimonies reveal that translating the use of this motivation and knowledge into optimal treatment results from constant and daily efforts involving the entire family. The repercussions were felt within the family but go much further as the family’s place within the social network was also affected. Establishing a routine was one of the main strategies used by the parents to integrate the treatment and ensure it was taken appropriately. This strategy, which echoes research on the importance of habit for adherence [
28], was adopted intuitively by the parents. However, developing an automatic habit may be challenging in the context of intermittent OC, especially if the administration precautions are complex. This new routine was also described as constraining, and some parents felt burned-out by following a strict routine. Parents fully embracing the responsibility of administrating OC have also been described in other studies [
20]. Our findings highlight, however, that this responsibility is mainly endorsed by one of the parents, either because they were single parents or because they were afraid to delegate this responsibility, or it made it easier to keep track of the drug administration. The child’s need for seclusion and the changes to the family dynamics because of the routine also contributed to parental fatigue.
One of the biggest challenges encountered by the families was adjusting to the emotional and psychological changes associated with dexamethasone [
18,
19]. The parents, like some of the children, found it profoundly troublesome. Some of the parents modified their parenting style, and the family dynamics changed to accommodate mood changes and minimize their impact [
19,
27]. In addition, this led to seclusion, sometimes initiated by the children themselves to spare others from their difficult behavior during the weeks of dexamethasone. The physical and psychosocial effects of dexamethasone on families have already been studied [
7,
8,
18,
19], and our findings also stress this aspect of the treatment burden from the parents’ perspective. Our results go further by suggesting that, in the context of dexamethasone, social isolation is a family choice that still could cause distress. Again, greater attention needs to be paid to the global lived experience of dexamethasone for intervention development.
Our study has some limitations. Despite relatively high participation (13 of 17 eligible participants), our sample size was limited due to the number of children diagnosed each year with ALL at our hospital (~20 cases). However, the saturation of the main themes was reached as most of the participants shared the same issues. In addition, four parents involved in the management of the OC who are members of our research advisory committee validated that the study findings accurately reflected their own experience. This collective exercise, however, led parents from the advisory committee to emphasize that the preponderance of certain experiences and needs could vary according to the child’s health and age, family structure, and time in the treatment trajectories. The potential impact of these differences on OC experience could not fully be assessed in this study. Our results are more likely to apply to families followed in a specialized hospital with access to a multidisciplinary oncology team. Nevertheless, different pediatric protocols are commonly used to treat ALL, which may differ in 6-MP administration precautions, the use of 6-MP intermittently versus daily therapy, and the frequency of follow-up visits [
3,
4]. This could affect the generalizability of some of our findings, such as the ease of integrating OC in existing routines and the opportunities to obtain advice. Similarly, the education and recommendations provided with OC can also vary between health centers [
10,
29].
Implication for Support Interventions
The needs regarding OC are multifaceted and could be experienced by all family members. We identified three main aspects of the parents’ experiences having direct implications for intervention development. First, taking on the responsibility of self-managing these treatments at home requires integrating complex information. The parents’ testimonies reveal that educational interventions should be delivered gradually using various modes and tools. Offering frequent opportunities to address questions and difficulties as they evolve throughout the treatment trajectory is also crucial. Second, integrating these complex treatments and precautions for two years was very demanding for the whole family. Developing and maintaining a routine was perceived as an essential and effective strategy for managing medication that was also burdensome. The medical team should make accommodations, when possible, in medication intake to ease the integration of the OC into the family’s lifestyle and lessen the burden. Finally, the impact of the treatment goes far beyond drug management, and parents reported some psychosocial needs that were sometimes only partially met for some of them. The neurobehavioural effects of dexamethasone, concerns about parental attitudes to adapting to the child’s changing behavior, parental onus and fatigue, and the social isolation of the child and family were reported as deeply troubling. These difficulties should be monitored and addressed proactively by involving the multidisciplinary team.