Key principles and tenets from ethical guidelines (stream 1)
Eight guidelines about decision-making towards the end-of-life, in children and young people with cancer, were purposively sampled, reviewed and then summarized [16–23] (Table 3) in order to determine what constitutes best practice in accordance with commonly accepted medico-legal and ethical guidelines. The guidelines selected include the most comprehensive documents on the substantive rights and obligations to protect the child patient’s vulnerability. Many medical societies worldwide, including the British Medical Association, are bound to them by international law.
What constitutes best practice in legal and ethical guidelines?
Children age 16 to 18 years are presumed to be competent to give consent to medical treatment as if they were adult (age 18 years in the UK). However, if both the parents and their child refuse treatment, the court can override the refusal if it is in the best interest of the child to do so [4–6]. Children under 16 lack ordinary legal authority to make binding medical decisions, yet they could in specific circumstances meet functional criteria and be declared competent to do so. In such situations legal arguments support giving decisional authority to the minor patient [16–18, 20–23]. In this group of children, the best interest of the child is always a primary consideration (Table 3). Whilst the guidelines outline consistent ethical principles, there is however an absence of guidance on the application to real life clinical scenarios.
Actor perspectives and decision-making towards the end-of-life (streams 2 and 3)
Quantitative studies on actor perspectives included cross-sectional structured interviews with parents [24–26, 30–34] and with paediatric oncologists [25, 26, 34], a mailed survey with paediatric oncologists , one in depth history audit of medical records ; and a review of medical charts . Most of the studies [26, 30–34] included bereaved parents 0.6 to 5 years after their child’s death.
Qualitative studies included semi-structured interviews with parents [35–39, 41] and with parents/children/oncologists , one ethnographic study , and one focus group . Only three studies [34, 38, 39] included bereaved parents with 1 to 3 years after their child’s death.
Synthesis of 18 included studies identified six overarching themes: (i) the flow of information to inform decision-making; (ii) disclosure of prognosis; (iii) the process by which doctor-child/parent relationships were developed; (iv) biomedical aspects and child/family preferences; (v) alternatives of treatment, preferences, and objectives and goals of their preferences, and (vi) barriers and facilitators to decision-making.
Information exchange (type, amount, and direction of information flow processes)
All parents recognized that they had assisted in making a treatment-related decision on behalf on their child [24, 27, 32, 35–41]. Hinds  and Steward  reported that all US parents willingly assumed the burden because they considered that it was their job and they never considered shirking this critical responsibility. However, in a cross-cultural study (US, Australia and Hong Kong) Hinds  found that all five Hong Kong parents were “feeling forced” to participate in the decision-making process, thereby showing that cultural context is an important consideration.
The type and amount of information exchanged between clinicians and parents, and whether information flow was really two ways, was not reported. However, nearly all parents described an interactive process between themselves and the healthcare team, mostly with their child’s primary oncologist [26–28, 32, 35, 36, 40, 41]. Some parents reported that their child’s primary nurse, or the psychosocial clinician [26, 32], or another doctor , were involved at some point in the discussions about whether their child had no realistic chance of being cured. Only few parents denied having discussed this with the clinical team [28, 32]. In a few of these cases, it was reported that a conflict existed involving disagreement between clinicians and parent(s), with the parent(s) not yet ready to agree to a change in ‘do not resuscitate’ status .
Some studies [26, 28, 30, 36, 40, 41] clearly identified whether or not the children and young people were included in the discussion regarding treatment. There was variability in the degree to which parents elected to involve their child in the decision-making process. Mack  and Steward  reported that some parents deliberately excluded their child, either because they felt their child was too young to participate or to spare even older children from the burden of participating in the decision. Among children who were not perceived (by their parents) to be too young (median age 10 years, range 3—17 years), the majority received information via direct communication from the doctor [26, 30, 36, 41]. In contrast, according to the US parents interviewed, the child’s preference was of high importance in end-of-life care decision-making irrespective of the child’s age [24, 26, 35, 36, 38, 39, 41]. The children’s ages of this group of parents ranged from 0.6 to 21.6 years, with a median of 13.5 years. The studies did not organise findings by children’s age to shed more light on age-related decision-making processes and assent and consent issues. Only one study  reported to have interviewed directly a sample of children to identify the factors that influenced their end-of-life care decisions, the child participants in this study were aged 10-20 years.
Disclosure of prognosis
For parents and young people, disclosure of prognosis and the process by which doctor-child/parent relationships were developed were important when making judgements and decisions towards the end-of-life in children and young people with cancer. For oncologists, biomedical aspects (child prognosis and comorbid conditions) and child/family preferences regarding the options that respond to the problem frame figured most importantly in their decision-making.
Terminal care was defined as cessation of cancer-directed treatment, which may or may not continue with aggressive symptom management [24, 36, 37]. The term palliative care was used to make reference to the initiation of palliative measures when there was no longer a reasonable hope of cure, or to refer to supportive care [27, 38, 40]. The terminal stage was reached when, according to child’s primary oncologist, standard therapy had failed and cure was no longer a possibility [24–28, 30, 31, 37, 38, 40]. The terminal stage involved the prediction and evaluation of outcomes, which were usually probable rather than certain. The trajectory to death of those who had reached this stage was lower than or slightly longer than 3 months [26, 28, 31, 38, 40], or in one study less than 6 months . Some clinicians initiated disclosures when cancer had recurred and it had less than 30% chance of cure [25, 38, 40]. End-of-life period was defined as the time before death and it was related to incurable cancer and its terminal stage. End-of-life discussions more likely occurred in the last 7 days of life,  or late in treatment .
Parents and mostly proxy reports of children’s views showed that irrespective of context they wanted their doctors to appear interested, listen well, explain clearly, be open to discussion and achieve verbal agreement with them [24, 27, 30, 32, 34–38, 40]. Time to allow other possibilities like a second opinion and/or alternative therapies [27, 35, 40] were important during the end-of-life period. Other factors impacted on the effectiveness of end-of-life communication, such as the need for hopeful messages about a possibility for cure, or longer life expectancy, or related to short term visions of the future, or continued care, or an indication that the clinician had not given up (children) and, that they had not given up on their child (parents) [24–28, 31, 36–38, 40]. The single study conducted with children and young people  showed that they preferred to be informed even when the prognosis was poor or treatment was no longer curative.
The process by which doctor-child/parent relationships was developed
Trust was the single most important factor in the decision-making process and there was variation in trust afforded by parents to doctors. Trust was in part a product of clinician behaviour. Several parents looked for medical facts that included the trustworthy doctor’s expertise (clear and understandable information about their child’s condition) or medical knowledge obtained through research [24, 30, 32, 34–38, 41]. Many parents reported a need to believe that clinicians were giving to their child the best possible clinical care and that they (parents) could count on clinicians to guide the decision-making [34–38, 40, 41].
A few parents acknowledged that they really had no choice but to trust in individual caregivers and in the profession of medicine (paediatric oncology specifically) given their child’s situation . For these parents, trusting doctors and medical knowledge eased the pressure they felt to make the right decision . Only one parent articulated a lack of trust in her child’s clinical team, specifically voicing scepticism about the doctor’s motives for presenting a clinical trial in a positive light in order to enrol her child. The scepticism towards the motives of the doctor intensified the difficulty of the decision-making process for parents .
Whilst the evidence suggests that variation in trust is associated with clinician behaviour, the variation may be highly individual and reflect a parent’s own health beliefs concerning the appropriateness of experimental or ‘rescue’ therapies or their individual ability to trust others that predates the child’s illness. The same clinician behaviour that is perceived as collaborative and in the best interest of their child by one parent may be perceived as intrusive, threatening or experimental treatment by another. Parents also stressed the importance of needing to be treated as individuals. Parental assessments of doctor attributes rested, largely, on their perceptions of the doctor’s ability and willingness to contextualize the decision-making process by framing the end-of-life discussion in terms of each child’s unique background, characteristics and life experience [24, 35, 36, 41]. From the parent’s perspective the expectation was always that the doctor would facilitate this process. Both groups (parents and children)  desired that staff should continue to provide thoughtful care, including emotional care. Parents cited actions, for example: honesty, caring, sensitivity, and treating each child uniquely [30, 37, 38]. There was a noticeable lack of evidence concerning the wider complexities of decision-making and the complex beliefs and experiences of parents that could help or hinder the process of developing trusting relationships with clinicians.
Biomedical aspects and child/family preferences
To all oncologists, the child’s prognosis and comorbid conditions were among the central considerations of their decision-making [25, 26, 29, 34, 36]. This evidenced their desire to avoid harm and to lessen suffering in the absence of effective therapy. A survey of 52 paediatric oncologists and 144 parents showed that the highest doctors’ ratings of quality of end-of-life care were characterized by ‘little pain’ and ‘minimal time in the hospital in the last month of life’, whereas parents’ highest ratings were ‘clear information, given in a sensitive caring manner, about what to expect in the end-of-life-period’ . No association was found between parent and doctor ratings of quality of end-of-life care . All participating doctors also marked child/family preferences as important [25, 26, 29, 34, 36].
Treatment alternatives, child and family and clinician preferences and goals
Parents and children typically faced one of two alternative decisions: doing something or doing nothing. The first was a choice of cancer-directed treatment, randomized or non-randomized controlled trial, or terminal care (end-of-life palliative care) with or without palliative chemotherapy. The second included the choice of withdrawal or withholding treatment and the decision to not resuscitate. The selection of an option was based on the decision-maker’s goals and objectives.
Parents with inaccurate perceptions of the prognosis or unrealistic expectations for cure were more likely to choose aggressive therapies, including cancer-directed treatment to overcome disease and promote recovery, than parents with more realistic expectations. The decision for cancer-directed treatment in the end-of-life care period occurred more frequently in those parents who had not had a discussion with the clinical team on the topic beforehand [27, 32] or when trust was not apparent or shared in the decision-making process . There were also parents who recognized that cure was unlikely, and even then they elected to continue cancer curative treatment. These parents pursued different goals, such as: to keep hoping [26, 27, 33, 40]; to ensure that everything had been done [26, 33]; to have more time with their child ; or life expectancy extension [26, 33]. Few parents reported that the primary goal of cancer-directed treatment during this period was to lessen suffering [26, 31]. In contrast, oncologists in surveys mentioned ‘the family choices’ as a primary goal [26, 34].
Recruitment to clinical trials
Parents saw their primary goal as advocating for their child the best chance for a cure [24, 36, 41]. Deciding to enrol their child in a trial of experimental treatment was commonly interpreted by parents as being offered a chance for cure, albeit sometimes a very slim or even highly unlikely chance of cure depending on the type of trial. Within this decision-making scenario parents also weighed up and considered secondary goals such as preserving the child’s present and future quality of life . Another parental goal included the desire to help others by means of cancer research [33, 36, 41]. Young people reported that for them, their goals were to extend their life expectancy ―specifically to cure, and to want to help others by means of cancer research . In the same study, doctors declared that their goal was wanting to benefit their patients and others, thereby indicating a dual purpose in wanting to do the best for individual children, but also to use their knowledge and clinical experience of treating individuals, to advance the care and treatment for children with cancer generally (ie a greater good) .
All parents that chose terminal care without palliative chemotherapy (supportive care alone) voiced many reasons, but the most common goal was to pursue their child’s quality of life, by diminishing the suffering of their child [24, 34–36, 38]. The following considerations were influential factors in their decision-making: valuing time left [36, 38], nothing more left to do [24, 35, 36, 38], believing that nothing else could really help the child , thinking the child would never get better . The primary goal for those parents who chose terminal care with palliative chemotherapy was also their child’s quality of life, and as a secondary goal to create a sense of hope for a cure and an extension of life expectancy [25, 38]. The decision to opt for terminal care in the end-of-life period occurred more frequently in those parents who had held a discussion with the clinical team on the topic [24, 32, 34, 35]. The goals typically mentioned by young people were also focused on their quality of their life, the avoidance of cancer-directed treatment adverse effects, the belief that further treatment is futile, the feeling of being ready to die or the experience of having seen someone else die . Oncologists saw as their primary goal to avoid harm when there was no other option or the absence of effective therapy [29, 34, 36].
Withdrawal, withholding, and do not resuscitate
Young people, parents and clinicians pursued the same terminal care goals, that is to improve life conditions with good symptom control and quality of death in this group of children [24, 32, 34–37]. A few families considered the financial cost of further treatment for their child as a factor that facilitated their decision to forgo any further active treatment .
Place of death
Most children and young people died from disease progression in a hospital setting [27, 28, 31, 32, 39]. The parents’ goal was to be in control at the time their child’s death . More than a third of 228 paediatric oncologists surveyed in the US, Canada and UK stated that the lack of a readily available and easy-to-use palliative care team or pain service made the delivery of good terminal care difficult .
Barriers and facilitators to decision-making
One study identified the barriers and facilitators to end-of-life care . Five studies identified the actions from staff that helped or did not help in the decision-making process [24, 34–36, 38].
The barriers identified most often according to parents included: the fondness that staff members showed their child that made it more difficult (for parents) to make a decision to stop cancer-directed treatment , feeling forced to decide from alternative care pathway options , not having written information about the drug in a trial , and financial burden . For young people, the barriers related to the possible toxicities of the experimental drug being tested in a trial . In contrast, for oncologists, the barriers were commonly the family having unrealistic expectations for cure , family denial of the illness as terminal , and internal family conflicts .
The facilitators most often identified by parents were: the provision of thoughtful care by staff [24, 34–36, 38], trusting the staff [24, 34, 35], getting clear information from the clinical team throughout the entire process of decision-making [34–36], and the support to them/their child from the clinical team [24, 34, 36]. For young people, facilitators included: the provision of thoughtful care by staff , getting clear information from the clinical team , and receiving support from the clinical team . For oncologists, facilitators included: staff agreement on option chosen [34, 36], and ability of the child and family to understand and accept the situation [34, 36].
Overarching narrative synthesis of the entire dataset and development of a theoretical framework
The overarching narrative synthesis focused on moving beyond the thematic analysis to mapping ideas and generating and interrogating relationships in the synthesised body of evidence with Howard’s model in order to develop a theoretical framework of the positive and negative influences on the decision-making process when the treatment is no longer curative. The process began with privileging factors influencing decision-making from the perspective of the relevant actors as outlined in Figure 3, which were then used as a basis for developing a theoretical framework (Figure 4). The logic of the theoretical framework (Figure 4) is described in the following paragraphs.
Evidence suggests that when doctors believe that their work is to cure disease or maximize medical outcomes, the doctor’s clinical role in decision-making is restricted to giving the parents/children all relevant research evidence on the benefits and risks of various treatment options so that they will be able to make an informed decision alone. In the Figure 4 this notion is depicted in the left-hand circle, at the centre of the figure. Child prognosis and comorbid conditions - when treatment is no longer curative - were the predominant motivations in the doctors’ decision. The right-hand circle represents, theoretically, the subjective realm of health and illness. Both circles ought to be inextricably joined. Yet, the evidence showed that doctors did not generally dig deeper to explore wider life-course determinants that may impact on a parent’s ability to trust them. This superficial level of doctor involvement in the relationship with the children’s parents resulted in either lack of parental trust, or meant that parents made substantial errors when judging their child’s prognosis. Hence, for many parents, participating in decision-making represented a high burden and emotional distress, conflict with the clinical team, and the constant searching for cancer directed treatments. This resulted in children and young people who did not experience a clear and timely shift in the goals of care, from curative to palliative, over time.
Whereas, when doctors established a collaborative relationship with the child and their parents, and showed loyalty to what parents and their children were demanding of them (to be attentive to all the evidence, understand the evidence intelligently, rationally judge whether their understanding was correct, and act at the right time based on what has been understood correctly), parents felt understood and treated as persons. They trusted their doctors and clinical team, thereby decreasing the emotional distress, and their children experienced a timely and clear transition from therapeutic care to palliation.
Whilst showing a trajectory of positive and negative outcomes, it is likely that families will move along a continuum depending on the decision, the illness trajectory and the varying perspectives of different clinicians that they encounter. Parents’ role as protectors and their desire to prevent harm in combination with the variety of treatment options, outcomes and prognosis makes decision-making very hard and some are likely to waver or alter their decisions over time.