CONTEXT:

Children with incurable cancer may participate in research studies at the end of life (EOL). These studies create knowledge that can improve the care of future patients.

OBJECTIVE:

To describe stakeholder perspectives regarding research studies involving children with cancer at the EOL by conduct of a systematic review.

DATA SOURCES:

We used the following data sources: Ovid Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science, and ProQuest (inception until August 2020).

STUDY SELECTION:

We selected 24 articles published in English that examined perceptions or experiences of research participation for children with cancer at the EOL from the perspectives of children, parents, and health professionals (HPs).

DATA EXTRACTION:

Two authors independently extracted data, assessed study quality, and performed thematic analysis and synthesis.

RESULTS:

Eight themes were identified: (1) seeking control; (2) faith, hope, and uncertainty; (3) being a good parent; (4) helping others; (5) barriers and facilitators; (6) information and understanding; (7) the role of HPs in consent and beyond; and (8) involvement of the child in decision-making.

LIMITATIONS:

Study designs were heterogeneous. Only one study discussed palliative care research.

CONCLUSIONS:

Some families participate in EOL research seeking to gain control and sustain hope, despite uncertainty. Other families choose against research, prioritizing quality of life. Parents may perceive research participation as the role of a “good parent” and hope to help others. HPs have positive views of EOL research but fear that parents lack understanding of the purpose of studies and the likelihood of benefit. We identified barriers to research participation and informed consent.

Despite improvements in survival rates, ∼20% of children with cancer still die of their disease or its treatment.1  Some of these children and their families are offered to participate, and consider participating, in early-phase (phase I or II) research studies toward the end of life (EOL).2  In these studies, new chemotherapeutic agents are usually tested.3,4  Objectives of these studies include to identify maximum tolerated drug doses and potentially to provide initial information on efficacy to inform future research.5  Children with cancer may also be eligible to participate in palliative and EOL research studies. Delivering palliative care in pediatric oncology can be challenging because of the complexity of symptoms and the sensitivity of dealing with difficult decisions.611  However, there is a paucity of evidence available to guide practice and a lack of research studies performed to address this evidence gap.9,1215  Although participants may benefit from enrollment in both early-phase or palliative care studies, the primary intention is to produce generalizable knowledge that will benefit future patients.3,4 

Concerns are often expressed regarding the vulnerability of children and families nearing the EOL, the burdens that research may place on them, and the ethics of research in this context.16,17  Research ethics boards may hesitate to approve any type of study involving these patients, and health professionals (HPs) may hesitate to suggest enrollment.18  Regarding early-phase studies, further concerns have been expressed relating to therapeutic misconception: despite the purpose of these trials being to benefit future patients, patients may enroll believing that they are designed primarily to benefit current research participants.1921 

Although it is important to understand the views of stakeholders in pediatric oncology research at the EOL, including children, parents, and HPs, this area has been relatively under-explored. A number of reviews have been published on the subject of EOL decision-making in pediatric oncology, but none include a detailed discussion on decisions relating to research enrollment.22,23 

Studying the decision-making process around EOL research is important because it will allow HPs to understand how families make the challenging decisions for their children to participate in research and will guide HPs in counseling families around research enrollment. Furthermore, allowing HPs to understand families’ perspectives may help manage differences in opinions around research participation between medical teams and families. Researchers will benefit from understanding families’ and HPs’ experiences, which will assist them in designing studies that are acceptable to families and HPs as well as inform the recruitment process.

In this review, we set out to answer the following research questions: What are the perceptions and experiences of children with cancer, their parents, and the HPs who treat them on the enrollment of children with cancer in phase I or other research studies at the EOL? How do the perceptions of these stakeholders compare with each other in regard to research enrollment?

A protocol was developed a priori, following the Enhancing Transparency in Reporting the Synthesis of Qualitative Research and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements.24,25  A literature search was designed and conducted with the aid of a health librarian by using Ovid Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science, and ProQuest (inception to August 19, 2020). The search strategy (Supplemental Tables 5 and 6) included subject headings and keywords for the following concepts: (1) children and adolescents, (2) cancer, (3) clinical trials, and (4) terms relating to perceptions, understanding, and decision-making.

Included studies were focused on perceptions or experiences of research participation for children and adolescents with cancer at the EOL from the perspectives of pediatric patients with cancer (<21 years), their parents or guardians, or HPs involved in caring for this population. EOL research participation was defined as the enrollment in research studies by children whose cancer was no longer thought to be curable by standard treatments within what was thought to be the last few months of life. This encompassed any type of research, including palliative care and symptom management studies as well as studies of anticancer treatments. For studies to be included, there needed to be a discussion explicitly about research enrollment and not just the broader topic of EOL decision-making. Exclusion criteria were as follows: (1) studies that were not fully published peer-reviewed studies (conference proceeding or gray literature), (2) review articles or editorials, (3) studies that were not published in the English language, (4) duplicate publications, (5) studies that included adult patients in which results relating to patients <21 years of age could not be extracted separately, (6) studies that included non-EOL research in which results related to EOL research could not be extracted separately, and (7) studies that were focused on EOL decision-making in general without an explicit discussion on decision-making about EOL research. The search was supplemented by examining the bibliographies of included studies. Two authors (F.H. and L.W.) independently screened titles and abstracts to identify potentially eligible studies. The full text was retrieved for these studies and evaluated for eligibility by the same 2 reviewers who applied the eligibility criteria.

Two investigators (F.H. and L.W.) independently extracted data and appraised studies using piloted forms. Studies were classified as qualitative or quantitative (survey-based or retrospective case series). Relevant criteria from 3 tools were used for study appraisal: the Consolidated Criteria for the Reporting of Qualitative Evidence checklist for qualitative studies,26  the British Medical Journal Critical Appraisal Checklist for a Questionnaire Study27  for survey-based studies, and the Joanna Briggs Institute Critical Appraisal Checklist for Case Series.28  No study was excluded because of quality.

Two investigators (F.H. and L.W.) inductively coded the text included in the results section of each (qualitative or quantitative) article line by line. Thematic synthesis was performed by first grouping codes into descriptive and then analytic themes, with translation of themes across studies.29  The authors independently performed initial analyses, then developed the synthesis together through iterative discussion.

Any disagreements in study selection, data extraction, quality assessment, and synthesis were resolved by discussion. Conflicts in study selection and other review procedures were resolved through discussion with a third reviewer (K.W.).

A total of 15 203 articles were identified, of which 24 were included for analysis (Fig 1). One of the 24 included articles was categorized as a palliative care research study, whereas the remaining 23 studies were categorized as phase I anticancer treatment studies. Qualitative methods were used in 11 articles, whereas quantitative methods were used in 13 articles, 11 of which were surveys and 2 of which were retrospective case series (Tables 1–3). These 24 studies included 1787 participants (162 patients aged 6–21 years old, 904 parents, and 721 HPs). One study included 2 surveys, but the number and type of individuals participating in the second survey were not reported.14  Similarly, the authors of a retrospective case series reported the perspectives of HPs without stating how many HPs’ views were described.30 

FIGURE 1

Flow of information through the phases of the review: search process and results. a The views of at least 1787 individuals are represented in the 24 studies included in the review.

FIGURE 1

Flow of information through the phases of the review: search process and results. a The views of at least 1787 individuals are represented in the 24 studies included in the review.

Close modal
TABLE 1

Description of Included Qualitative Studies

Study, SettingMethodologyQualitative Data Collection MethodData Analysis MethodParticipantsResearch Topic
Type (n)Male/Female RatioMean Age (Range), y
Baker et al,52  United States Qualitative Secondary analysis of semistructured interviews performed for a prospective descriptive study68  Semantic content analysis Patients (20) 15:5 17.8 (14–21) Informed consent for phase I pediatric oncology trials 
Parents (57) 16:41 41.1 (23–66) 
Barrera et al,47  Canada Qualitative Individual semistructured interviews Qualitative analyses Patients (3) 3:0 NS (7–15) Reasons for participation in phase I trials 
Parents (9) 7:2 NS 
Béranger et al39  Qualitative, multiple methods Individual semistructured interviews Qualitative analysis by using a validated code framework Patients (37) 19:18 13.2a (11–15) Understanding of and decision-making relating to phase I research 
Logistic regression to identify correlates of understanding Parents (119) NS NS 
Crane et al,40  United States Qualitative (phenomenology) Individual unstructured interviews Adapted phenomenological analysis as per Colaizzi82  Parents (12) 10:2 NS Parents’ experiences of their children’s participation in phase I research 
Deatrick et al,36  United States Qualitative Secondary analysis of interview data collected for a prospective descriptive study6  Qualitative analyses Parents (21) 19:2 NS Parents’ perceptions of their children’s participation in phase I research 
Schröder Håkansson et al,49  Sweden Qualitative (grounded theory) Individual unstructured interviews Grounded theory, constant comparison HPs (12) 2:12 NS HPs’ experiences of the informed consent process for oncology research, including phase I research 
Hinds et al,38  United States Qualitative, multiple methods Semistructured interviews and questionnaire Content analysis, logistic regression to relate questionnaire data to qualitative data Parents (39) 18:19 NS Treatment decisions faced by parents of children with cancer, including phase I participation, and factors influencing decision-making 
HPs (21) NS NS 
Hinds et al,7  Australia and United States Qualitative Semistructured interviews Semantic content analysis Patients (20) 6:14 17.3, 10–21 EOL care preferences of children with cancer, parents, and HPs, including phase I participation 
Parents (19) 6:13 NS 
HPs (14) 12:2 NS 
Johnson et al,42  United States Qualitative Parent advisory group discussion of data from previous studies34,35,52  NS Parents (8) 1:7 42.3 (NS) Informed consent process for phase I pediatric oncology trials 
Maurer et al,37  United States Qualitative Secondary analysis of semistructured interviews performed for a prospective descriptive study83  Semantic content analysis Parents (62) NS 38.2 (NS) Rationale for EOL decision-making, including phase I participation 
Miller et al,35  United States Qualitative Semistructured interviews NS Patients (20) 15:5 17.8 (14–21) Adolescents’ perspectives on their understanding and decision-making regarding phase I trials 
Study, SettingMethodologyQualitative Data Collection MethodData Analysis MethodParticipantsResearch Topic
Type (n)Male/Female RatioMean Age (Range), y
Baker et al,52  United States Qualitative Secondary analysis of semistructured interviews performed for a prospective descriptive study68  Semantic content analysis Patients (20) 15:5 17.8 (14–21) Informed consent for phase I pediatric oncology trials 
Parents (57) 16:41 41.1 (23–66) 
Barrera et al,47  Canada Qualitative Individual semistructured interviews Qualitative analyses Patients (3) 3:0 NS (7–15) Reasons for participation in phase I trials 
Parents (9) 7:2 NS 
Béranger et al39  Qualitative, multiple methods Individual semistructured interviews Qualitative analysis by using a validated code framework Patients (37) 19:18 13.2a (11–15) Understanding of and decision-making relating to phase I research 
Logistic regression to identify correlates of understanding Parents (119) NS NS 
Crane et al,40  United States Qualitative (phenomenology) Individual unstructured interviews Adapted phenomenological analysis as per Colaizzi82  Parents (12) 10:2 NS Parents’ experiences of their children’s participation in phase I research 
Deatrick et al,36  United States Qualitative Secondary analysis of interview data collected for a prospective descriptive study6  Qualitative analyses Parents (21) 19:2 NS Parents’ perceptions of their children’s participation in phase I research 
Schröder Håkansson et al,49  Sweden Qualitative (grounded theory) Individual unstructured interviews Grounded theory, constant comparison HPs (12) 2:12 NS HPs’ experiences of the informed consent process for oncology research, including phase I research 
Hinds et al,38  United States Qualitative, multiple methods Semistructured interviews and questionnaire Content analysis, logistic regression to relate questionnaire data to qualitative data Parents (39) 18:19 NS Treatment decisions faced by parents of children with cancer, including phase I participation, and factors influencing decision-making 
HPs (21) NS NS 
Hinds et al,7  Australia and United States Qualitative Semistructured interviews Semantic content analysis Patients (20) 6:14 17.3, 10–21 EOL care preferences of children with cancer, parents, and HPs, including phase I participation 
Parents (19) 6:13 NS 
HPs (14) 12:2 NS 
Johnson et al,42  United States Qualitative Parent advisory group discussion of data from previous studies34,35,52  NS Parents (8) 1:7 42.3 (NS) Informed consent process for phase I pediatric oncology trials 
Maurer et al,37  United States Qualitative Secondary analysis of semistructured interviews performed for a prospective descriptive study83  Semantic content analysis Parents (62) NS 38.2 (NS) Rationale for EOL decision-making, including phase I participation 
Miller et al,35  United States Qualitative Semistructured interviews NS Patients (20) 15:5 17.8 (14–21) Adolescents’ perspectives on their understanding and decision-making regarding phase I trials 

Unless otherwise stated, no qualitative methodology was provided beyond “qualitative” or “descriptive.” n, number of participants; NS, not stated.

a

Median.

TABLE 2

Description of Included Survey-Based Studies

Study, SettingParticipantsDistribution MethodResearch Topic
Type (n), %Male/Female RatioMean Age (Range), y
Barnes et al,32  United States MDs (94), 25 52:42 45.6 (NS) E-mail + Web-based survey + follow-up reminder Comparison of physicians and nurses working in pediatric oncology centers of phase I studies 
Nurses (122), 44 1:121 40.7, NS 
Berg et al,50  United States Patients (12), NS NS NS NS Attitudes of participants in phase I trials toward optional pharmacokinetic studies 
Parents (38), NS NS NS NS 
Chang,44  Canada Nurses (43), 45 NS NS NS Nurses’ perceptions of phase I studies 
Dussel et al,14  United States Survey 1: patients (7); parents (87), 65a NS NS Survey 1: administered in hospital or mailed Survey 1: reasons for enrolment (or not) in an oncology palliative care randomized controlled trial 
Survey 2: (46), 45b NS NS Survey 2: NS Survey 2: reasons for ongoing participation in the same 
Estlin et al,41  United Kingdom and United States MDs (131), 26 NS NS Mailed + reminder Comparison of perspectives of UK and US pediatric oncologists regarding phase I studies 
Gilliam et al,31  United States MDs (94), 25 NS NS E-mail + Web-based survey Comparison of perspectives of oncologists in phase I participating institutions with those of oncologists in nonparticipating institutions regarding phase I studies 
Kamps et al,48  Netherlands Parents (168), 82 NS NS Permission requested to send survey (by phone call from MD or letter to be returned) + survey mailed if permission given Perspectives of parents of childhood cancer survivors on the involvement of children in decisions about phase I or II study participation 
Mack et al,51 United States Parents (141), 64 24:117 43.4c (NS) Interviews by telephone Perspectives of bereaved parents on cancer-directed treatment of children with incurable cancer 
Robertson et al,33  Australia and New Zealand MDs (44), NS All participants (N = 69): 25:44 All participants (N = 58): 43.8 (28–74) E-mail + Web-based survey or handout at a conference (NS how paper questionnaires were returned) Perspectives of HPs working in pediatric oncology regarding phase I studies 
Nurses (24), NS NS NS 
Other HPs (19), NS NS NS 
van der Geest et al,43  Netherlands Parents (24), 35 10:14 46 (25–53) NS Rationale for participation in oncology studies at the EOL and whether this was perceived to be a burden; survey part of a larger study examining parental perspectives of pediatric palliative care84  
Yap et al,34  United States MDs (103), 71 51:52 42 (NS) NS Pediatric oncologists’ opinions about the consent process for phase I studies; part of a larger study examining consent for phase I studies68  
Study, SettingParticipantsDistribution MethodResearch Topic
Type (n), %Male/Female RatioMean Age (Range), y
Barnes et al,32  United States MDs (94), 25 52:42 45.6 (NS) E-mail + Web-based survey + follow-up reminder Comparison of physicians and nurses working in pediatric oncology centers of phase I studies 
Nurses (122), 44 1:121 40.7, NS 
Berg et al,50  United States Patients (12), NS NS NS NS Attitudes of participants in phase I trials toward optional pharmacokinetic studies 
Parents (38), NS NS NS NS 
Chang,44  Canada Nurses (43), 45 NS NS NS Nurses’ perceptions of phase I studies 
Dussel et al,14  United States Survey 1: patients (7); parents (87), 65a NS NS Survey 1: administered in hospital or mailed Survey 1: reasons for enrolment (or not) in an oncology palliative care randomized controlled trial 
Survey 2: (46), 45b NS NS Survey 2: NS Survey 2: reasons for ongoing participation in the same 
Estlin et al,41  United Kingdom and United States MDs (131), 26 NS NS Mailed + reminder Comparison of perspectives of UK and US pediatric oncologists regarding phase I studies 
Gilliam et al,31  United States MDs (94), 25 NS NS E-mail + Web-based survey Comparison of perspectives of oncologists in phase I participating institutions with those of oncologists in nonparticipating institutions regarding phase I studies 
Kamps et al,48  Netherlands Parents (168), 82 NS NS Permission requested to send survey (by phone call from MD or letter to be returned) + survey mailed if permission given Perspectives of parents of childhood cancer survivors on the involvement of children in decisions about phase I or II study participation 
Mack et al,51 United States Parents (141), 64 24:117 43.4c (NS) Interviews by telephone Perspectives of bereaved parents on cancer-directed treatment of children with incurable cancer 
Robertson et al,33  Australia and New Zealand MDs (44), NS All participants (N = 69): 25:44 All participants (N = 58): 43.8 (28–74) E-mail + Web-based survey or handout at a conference (NS how paper questionnaires were returned) Perspectives of HPs working in pediatric oncology regarding phase I studies 
Nurses (24), NS NS NS 
Other HPs (19), NS NS NS 
van der Geest et al,43  Netherlands Parents (24), 35 10:14 46 (25–53) NS Rationale for participation in oncology studies at the EOL and whether this was perceived to be a burden; survey part of a larger study examining parental perspectives of pediatric palliative care84  
Yap et al,34  United States MDs (103), 71 51:52 42 (NS) NS Pediatric oncologists’ opinions about the consent process for phase I studies; part of a larger study examining consent for phase I studies68  

n, number of participants; NS, not stated; %, response rate.

a

Overall response rate.

b

Participant type not stated.

c

Median.

TABLE 3

Description of Included Retrospective Case Series

Study, SettingParticipantsResearch Topic
Type (n)Male/Female RatioMean Age (Range), y
Nitschke et al45  and Nitschke et al,46  United States Patients (43) NS NS (6–20) Children’s reasons for their decision to participate or not in phase II studies for end-stage cancer 
Surun et al,30  France Parents (100)a; HPs (NS) NS NS Reasons for HPs’ decision not to offer or parents’ refusal to accept phase I study enrollment for children with progressive cancer 
Study, SettingParticipantsResearch Topic
Type (n)Male/Female RatioMean Age (Range), y
Nitschke et al45  and Nitschke et al,46  United States Patients (43) NS NS (6–20) Children’s reasons for their decision to participate or not in phase II studies for end-stage cancer 
Surun et al,30  France Parents (100)a; HPs (NS) NS NS Reasons for HPs’ decision not to offer or parents’ refusal to accept phase I study enrollment for children with progressive cancer 

n, number of participants; NS, not stated.

a

The charts of 100 patients were reviewed, and the perspectives of their parents are reflected in the results. The exact number of parents whose perspectives are reflected is not stated in the publication.

The 11 included qualitative studies met between 10 and 22 of the 32 items on the Consolidated Criteria for the Reporting of Qualitative Evidence checklist (Supplemental Table 7).26  Four of the survey-based studies included some qualitative findings; thus, 26 quality criteria in the British Medical Journal checklist were relevant, and 11 to 14 were met (Supplemental Table 8).27  The remaining 7 survey-based studies were purely quantitative and met 7 to 21 of 24 relevant criteria. Survey instruments were only available for review from 4 studies.3134  In all the studies, a new survey or a preexisting, unvalidated survey was used or a previously validated survey was adapted without revalidation. The 2 case series met 2 to 7 of 7 quality criteria in the Joanna Briggs Institute checklist (Supplemental Table 9).28 

Eight themes were identified (Fig 2, Table 4).

FIGURE 2

Thematic schema: results of the thematic analysis.

FIGURE 2

Thematic schema: results of the thematic analysis.

Close modal
TABLE 4

Illustrative Quotations

Theme and ParticipantsSource TextRef No(s).
Seeking control   
 Wanting choices (child, parent, HP) “Because it’s a different opportunity—it’s a different treatment and I’ve pretty much exhausted most other treatments.…” (child)35  7,33,3540  
 “Thirteen of the parents said that they did not have any choice in their situation. They knew that they signed a consent form, but, they didn’t think of it as a decision. These parents described ‘choice’ in terms of the promise of potentially ‘curative’ treatment, not in terms of providing comfort or palliation. ‘There wasn’t really a choice in my mind because if I chose to not do anything then I would have been choosing to let her go and I’m not ready for that.’” (parent)36   
 “Nobody ever really counseled us on that. I also had this stigma about hospice services because I thought that was giving up, but it turns out [hospice services] was a very good decision.” (parent)40   
 Trying anything (child, parent, HP) “You have to try everything…keep fighting to keep her here with me. You have to do what you have to do.” (parent)36  7,3234,36,37,40,41,43,44  
 “The family continues to believe there is a chance for cure, and they expect the staff to support their desire for continued therapy.” (parent)37   
 Awareness of poor prognosis (parent) “For the parent, the [enrollment] decision is a ‘head versus heart’ struggle. The head knows that survival is unlikely, but the heart needs to believe there is hope.” (parent)42  7,3638,40,42  
 “[W]ith these studies…we aren’t even looking for the cancer to shrink; we’re just looking for it to stay at bay.” (parent)40   
Faith, hope, and uncertainty   
 Hope (child, parent, HP) “Hopefully, it will uh, make it longer. Before this I was only like given 6 months to live. And then now I think this will help.” (child)35  7,3137,4049  
 “Some parents were hoping for a cure or a miracle, whereas others stated that this was not their expectation. Many admitted that they wanted a miracle, but that they might not get one.” (parent)36   
 “I am…prolonging the inevitable until a cure comes along…I want her to be healed. I keep telling her to hold on.…” (parent)7   
 “No matter how you phrase it, families are going to perceive it as something that will potentially help their child. At least get some quality of life if not cure.” (HP)42   
 “The participants discussed whether an early/middle development study could hinder the child from receiving good palliative care or give the family unrealistic hopes of cure.” (HP)49   
 Uncertainty (child, parent) “No one knows,…because it’s, again, undetermined how much benefit it will have.” (child)35  35,36,40,47  
 “Nothing’s ever a given. Even in medicine that’s been proven…we knew that…everything was a ticking time bomb.… We just knew that certain things would not work….it just seemed like [the P1T] was the one that offered the most hope. And, I don’t know if that was a tangible hope or not.” (parent)40   
 Faith (child, parent) “Half (n. 10) of participants indicated that faith was important to the decision, primarily because it gave them strength to make decisions.” (child)35  7,35,36,40,45,46  
 “I don’t care what you want to call it, my belief had a lot to do with believing that there is something better out there for her.” (parent)7   
Being a good parent   
 Fulfilling a “good parent” role (parent) “Considering the facts, explanations, opinions, and preferences of experts and others (eg, family members, ill child, and other bereaved parents) and then choosing the option most consonant with an internal definition of a caring, competent protector of their child.” (parent)7  7,3638,40,42  
 “On some level, every one of the 21 parents continued to view their role as parent and their human need to keep trying.…” (parent)36   
 “I knew all about this trial, I knew the details, everything on this trial before I walked into that consent. I had a stack every week of at least 5–10 different trials going on that I plowed through with my doctor.…” (parent)42   
 “It’s all on our shoulders.” (parent)40   
 Acting in the child’s best interest (parent) “[E]very decision we have had to make, we considered what is best for her.” (parent)37  7,37,40,43  
Helping others   
 Altruism (child, parent, HP) “Doctors could lay out all the options if you’ve gone through the best and nothing’s really worked then emphasize how this could maybe help, and if not, it does help other people in years to come, hopefully.” (child)52  7,14,3237,4046,48,50,52  
 “After having postponed the administration of a phase II drug for several weeks, he finally stated that he did not want the therapy but had agreed to it to please the physicians, who needed more information about the drug.” (child)45,46   
 “If it’s not going to help my child, if it’s going to save some other child from going through this or some other parent going through this then yes, I would do my child. I mean, it’s not hurting her any worse than what…the end result was going to be the same. It’s not hurting her to try.” (parent)42   
 “[W]ith medical benefit, altruism, and hope of cure being identified as reasons parents agree to enter their children onto a phase I study.” (HP)41   
 Legacy (parent, HP) “We feel that if he would die in a useful manner, it would kind of help cleanse us of the burden…give it a little bit of meaning.… Whereas going home and dying on the bed to us is very meaningless and very frustrating, and just very damaging in every sense of the word.… It’s family dealing with death in a very real [way].… At least we have made the effort…and enhanced some type of ongoing study…that would be my son’s legacy.” (parent)36  36,37,40,41  
Barriers and facilitators   
 Access to trials (parent, HP) “It was like whoever had the fastest finger is the one that got on the trial.” (parent)42  36,40,42  
 “[T]iming was an important issue in their decision. They could get into a trial right now in their present treatment facility and if that trial failed, they could go to the other institution as backup.” (parent)36   
 “[I]t’s important that…the people that are involved in this feels comfortable enough to openly include these things because if you are afraid that you are going to be kicked off the trial because you’re on a medicine, you’re not going to say something.” (parent)42   
 “‘Him being sick right now…we’re trying not to give him any Tylenol or anything that could whack his body out.’ This resulted from an overriding fear that additional medications could exacerbate toxicities…and cause the child’s premature removal from the trial.” (parent)40   
 “Clinicians should address parents’ fear that unless they make a rapid decision they risk losing their child’s ‘spot’ in a trial.” (HP)42   
 Burden of participation (child, parent, HP) “I know I will go to heaven. I want to be close to home.” (child)45,46  7,14,30,31,33,3537,4048,50  
 “This would have meant extra days in the hospital…injections at home…probably less time off between treatments. He might not get the time to recuperate in between.” (parent)7   
 “Disadvantages included…a sense of their lives revolving around the P1T.” (parent)40   
 “The patient factor ‘avoiding adverse events,’ the parent factor ‘avoiding negative outcomes,’ and the physician factor ‘wanting to avoid harm’ (68.4% to 78.6% of each group) reflected a common desire to prevent or reduce suffering or clinical deterioration.” (child, parent, HP)7   
 Familiarity and convenience (child, parent, HP) “They’re being very good about giving me the option of doing stuff at our home hospital if needed versus having to travel up here, which I think is great.” (child)52  7,14,36,37,44,48,50,52  
 “The parent desires better and smoother transmittal of information between providers and between clinics; they do not like having to repeat things to multiple new people.…” (parent)37   
 “[T]he opportunity to participate in research and/or receive a treatment that was familiar to the parent made the option even more attractive.…” (parent)37   
Information and understanding   
 Practicalities of consent (child, parent) “I definitely think—not that you or the doctor did anything wrong, but that I kind of felt that I wanted to just talk about it with my mom first, and I hadn’t really got the chance to.” (child)52  7,42,52  
 “You know…a little video presentation or something talking about ‘getting ready for your phase 1 trial’ or something like that. And utilizing the Internet…because people assimilate their information in all sorts of different ways and some people need diagrams and flowcharts and other people need explanations in words and things like that.” (parent)52   
 Honest, clear, communication (child, parent, HP) “Individualize your approach: recognize families are different; provide information in a manner individualized to the needs/preferences of the particular child and family, including tailoring the amount of information they want.” (child, parent)42  7,14,31,32,34,42,44,52  
 “There is a lot of concepts going on, we’re talking about dose escalation, toxicity, and I realize that a lot of these that the physicians are melding it…it’s almost like teaching people to talk in paragraphs.” (parent)42   
 “The informed consent documents are currently often 30 pages long. There is so much required language that points unique to that person are lost in the repetitive language. Consents could be simplified to improve patient understanding.” (HP)42   
 Specific information needs (child, parent) “[R]eported the following staff behaviors as helpful: ‘explained everything to me/gave us written information,…answered my questions and gave me time to think,…told me about how other patients did.…’” (child)7  7,35,36,38,52  
 “Provide more information about the specific phase 1 trial being considered, including detailed information regarding the mechanism, science, development, and side effects of the study drug.” (child, parent)52   
 “Let us know about other kids on the trial: provide an update about [enrollment] and current patient status in advance of the decision to enroll on the trial.” (parent)52   
 Participant understanding (child, parent, HP) “When asked specifically whether most patients who participate in phase I trials receive medical benefit, 30% (n. 6) said ‘yes,’ 20% (n. 4) said ‘no,’ and 50% (n. 10) said ‘don’t know.’… When asked about their own chances of getting medical benefit, 13 (65%) participants answered ‘don’t know’ or did not provide a percentage, while seven provided percentages ranging from 5% to 100% (M. 55.71%; SD. 37.13). Participants rated the information that was given to them as easy to understand.” (child)35  3235,39,42,44,52  
 “The understanding by the parents of the purpose of the trial and of the potential individual benefits was poor.…” (parent)39   
 “[A] large proportion of the nurses in this study (47%) felt that patients and families did not understand the goals of phase I clinical trials.” (HP)44   
 HP beliefs and understanding (HP) “Physicians were more likely to correctly identify the main goals of phase 1 studies including testing the safety, determining the maximum tolerated dose, and identifying the dose-limiting toxicity of an experimental drug. In addition to being less likely to correctly identify the main goals of phase 1 trials, nurses were more likely to incorrectly endorse goals including determining the efficacy of a drug for a specific disease and extending the life span of a patient. No providers endorsed curing patients as a goal of phase 1 therapy.” (HP)32  31,32,41,44  
Role of HPs in consent and beyond   
 Trust, support, Reassurance, and guidance (child, parent, HP) “So I asked for his opinion on whether I should do it or not, and he very carefully answered that it depends on what I value and whether I’m willing to take the risks and whether I’m looking for quality of life or looking for a treatment that works or how I view the situation, and that was good.” (child)52  7,31,34,3638,4042,49,52  
 “Parents would like staff to accept them, to advocate and be there for their child, to provide comfort, and to treat the child the same as before the decision was made.” (parent)37   
 “What made it so hard for me is that I’m not a doctor, and he was so well-educated. He usually guides me well with decisions, but he couldn’t tell me what to do here, and it made me feel so helpless.… I wanted so much to have someone else tell me that I had made the right decision, but there isn’t anyone who can tell me that.” (parent)36   
 “I am grateful…no one is giving up on us.” (parent)37   
 “We were just prayerful that we were being pushed in this direction [to the P1T] for good reasons.” (parent)40   
 “HCPs expressed the concept of being on both sides when they were conscious of their dual role. On the one hand, they were HCPs, building close relationships with parents and children, and on the other they were researchers/investigators, with responsibility for introducing and conducting clinical trials.” (HP)49   
 Training to take consent (HP) “HCPs reported having received either informal training through the observation of mentors (52.3%, n = 45) or self-directed learning (via conferences and literature) (37.2%, n = 32), with few having undergone a formal training programme (17.4%, n = 15).” (HP)33  33,34,42  
 Impact on HPs (HP) “22 nurses (51%) in this study reported that they experienced ethical or moral conflict with the oncologists’ decision to offer phase I clinical trials to families and, to a lesser degree (15%), with the families’ decision to enroll in phase I clinical trials.” (HP)44  7,31,41,44,49  
 “Physicians reported the following reasons for feeling okay about their part in a phase I decision: ‘consistent with my ethical standards.…’” (HP)7   
 “[E]arly and middle development studies (phase I/II) brought up more ethical challenges particularly whether participating in the trial was of benefit to the child.” (HP)49   
Involvement of the child in decision-making   
 Involvement of the child in decision-making (child, parent, HP) “Younger children were ‘too young to really have any conversations about what it [the cancer] meant’ and to ask tough questions, and did not remember any other way of living.” (parent)40  7,14,3135,3740,43,44,48  
 “If I don’t take it, my family would support me, but they don’t want me to quit. Grandpa said he would worry himself to death if I don’t try it. My boyfriend wants me to take it for him. I don’t want to do it but for my family.” (child)7   
 “The doctor gave us the facts and told us how serious this is, and we told our daughter. But the choice part has not been difficult for us.… It’s never been a question for us because she has plans, and we are going to do everything we can to see that those plans are able to be made and, if not, then she knows and we know that we have done everything we can.” (parent)7   
Theme and ParticipantsSource TextRef No(s).
Seeking control   
 Wanting choices (child, parent, HP) “Because it’s a different opportunity—it’s a different treatment and I’ve pretty much exhausted most other treatments.…” (child)35  7,33,3540  
 “Thirteen of the parents said that they did not have any choice in their situation. They knew that they signed a consent form, but, they didn’t think of it as a decision. These parents described ‘choice’ in terms of the promise of potentially ‘curative’ treatment, not in terms of providing comfort or palliation. ‘There wasn’t really a choice in my mind because if I chose to not do anything then I would have been choosing to let her go and I’m not ready for that.’” (parent)36   
 “Nobody ever really counseled us on that. I also had this stigma about hospice services because I thought that was giving up, but it turns out [hospice services] was a very good decision.” (parent)40   
 Trying anything (child, parent, HP) “You have to try everything…keep fighting to keep her here with me. You have to do what you have to do.” (parent)36  7,3234,36,37,40,41,43,44  
 “The family continues to believe there is a chance for cure, and they expect the staff to support their desire for continued therapy.” (parent)37   
 Awareness of poor prognosis (parent) “For the parent, the [enrollment] decision is a ‘head versus heart’ struggle. The head knows that survival is unlikely, but the heart needs to believe there is hope.” (parent)42  7,3638,40,42  
 “[W]ith these studies…we aren’t even looking for the cancer to shrink; we’re just looking for it to stay at bay.” (parent)40   
Faith, hope, and uncertainty   
 Hope (child, parent, HP) “Hopefully, it will uh, make it longer. Before this I was only like given 6 months to live. And then now I think this will help.” (child)35  7,3137,4049  
 “Some parents were hoping for a cure or a miracle, whereas others stated that this was not their expectation. Many admitted that they wanted a miracle, but that they might not get one.” (parent)36   
 “I am…prolonging the inevitable until a cure comes along…I want her to be healed. I keep telling her to hold on.…” (parent)7   
 “No matter how you phrase it, families are going to perceive it as something that will potentially help their child. At least get some quality of life if not cure.” (HP)42   
 “The participants discussed whether an early/middle development study could hinder the child from receiving good palliative care or give the family unrealistic hopes of cure.” (HP)49   
 Uncertainty (child, parent) “No one knows,…because it’s, again, undetermined how much benefit it will have.” (child)35  35,36,40,47  
 “Nothing’s ever a given. Even in medicine that’s been proven…we knew that…everything was a ticking time bomb.… We just knew that certain things would not work….it just seemed like [the P1T] was the one that offered the most hope. And, I don’t know if that was a tangible hope or not.” (parent)40   
 Faith (child, parent) “Half (n. 10) of participants indicated that faith was important to the decision, primarily because it gave them strength to make decisions.” (child)35  7,35,36,40,45,46  
 “I don’t care what you want to call it, my belief had a lot to do with believing that there is something better out there for her.” (parent)7   
Being a good parent   
 Fulfilling a “good parent” role (parent) “Considering the facts, explanations, opinions, and preferences of experts and others (eg, family members, ill child, and other bereaved parents) and then choosing the option most consonant with an internal definition of a caring, competent protector of their child.” (parent)7  7,3638,40,42  
 “On some level, every one of the 21 parents continued to view their role as parent and their human need to keep trying.…” (parent)36   
 “I knew all about this trial, I knew the details, everything on this trial before I walked into that consent. I had a stack every week of at least 5–10 different trials going on that I plowed through with my doctor.…” (parent)42   
 “It’s all on our shoulders.” (parent)40   
 Acting in the child’s best interest (parent) “[E]very decision we have had to make, we considered what is best for her.” (parent)37  7,37,40,43  
Helping others   
 Altruism (child, parent, HP) “Doctors could lay out all the options if you’ve gone through the best and nothing’s really worked then emphasize how this could maybe help, and if not, it does help other people in years to come, hopefully.” (child)52  7,14,3237,4046,48,50,52  
 “After having postponed the administration of a phase II drug for several weeks, he finally stated that he did not want the therapy but had agreed to it to please the physicians, who needed more information about the drug.” (child)45,46   
 “If it’s not going to help my child, if it’s going to save some other child from going through this or some other parent going through this then yes, I would do my child. I mean, it’s not hurting her any worse than what…the end result was going to be the same. It’s not hurting her to try.” (parent)42   
 “[W]ith medical benefit, altruism, and hope of cure being identified as reasons parents agree to enter their children onto a phase I study.” (HP)41   
 Legacy (parent, HP) “We feel that if he would die in a useful manner, it would kind of help cleanse us of the burden…give it a little bit of meaning.… Whereas going home and dying on the bed to us is very meaningless and very frustrating, and just very damaging in every sense of the word.… It’s family dealing with death in a very real [way].… At least we have made the effort…and enhanced some type of ongoing study…that would be my son’s legacy.” (parent)36  36,37,40,41  
Barriers and facilitators   
 Access to trials (parent, HP) “It was like whoever had the fastest finger is the one that got on the trial.” (parent)42  36,40,42  
 “[T]iming was an important issue in their decision. They could get into a trial right now in their present treatment facility and if that trial failed, they could go to the other institution as backup.” (parent)36   
 “[I]t’s important that…the people that are involved in this feels comfortable enough to openly include these things because if you are afraid that you are going to be kicked off the trial because you’re on a medicine, you’re not going to say something.” (parent)42   
 “‘Him being sick right now…we’re trying not to give him any Tylenol or anything that could whack his body out.’ This resulted from an overriding fear that additional medications could exacerbate toxicities…and cause the child’s premature removal from the trial.” (parent)40   
 “Clinicians should address parents’ fear that unless they make a rapid decision they risk losing their child’s ‘spot’ in a trial.” (HP)42   
 Burden of participation (child, parent, HP) “I know I will go to heaven. I want to be close to home.” (child)45,46  7,14,30,31,33,3537,4048,50  
 “This would have meant extra days in the hospital…injections at home…probably less time off between treatments. He might not get the time to recuperate in between.” (parent)7   
 “Disadvantages included…a sense of their lives revolving around the P1T.” (parent)40   
 “The patient factor ‘avoiding adverse events,’ the parent factor ‘avoiding negative outcomes,’ and the physician factor ‘wanting to avoid harm’ (68.4% to 78.6% of each group) reflected a common desire to prevent or reduce suffering or clinical deterioration.” (child, parent, HP)7   
 Familiarity and convenience (child, parent, HP) “They’re being very good about giving me the option of doing stuff at our home hospital if needed versus having to travel up here, which I think is great.” (child)52  7,14,36,37,44,48,50,52  
 “The parent desires better and smoother transmittal of information between providers and between clinics; they do not like having to repeat things to multiple new people.…” (parent)37   
 “[T]he opportunity to participate in research and/or receive a treatment that was familiar to the parent made the option even more attractive.…” (parent)37   
Information and understanding   
 Practicalities of consent (child, parent) “I definitely think—not that you or the doctor did anything wrong, but that I kind of felt that I wanted to just talk about it with my mom first, and I hadn’t really got the chance to.” (child)52  7,42,52  
 “You know…a little video presentation or something talking about ‘getting ready for your phase 1 trial’ or something like that. And utilizing the Internet…because people assimilate their information in all sorts of different ways and some people need diagrams and flowcharts and other people need explanations in words and things like that.” (parent)52   
 Honest, clear, communication (child, parent, HP) “Individualize your approach: recognize families are different; provide information in a manner individualized to the needs/preferences of the particular child and family, including tailoring the amount of information they want.” (child, parent)42  7,14,31,32,34,42,44,52  
 “There is a lot of concepts going on, we’re talking about dose escalation, toxicity, and I realize that a lot of these that the physicians are melding it…it’s almost like teaching people to talk in paragraphs.” (parent)42   
 “The informed consent documents are currently often 30 pages long. There is so much required language that points unique to that person are lost in the repetitive language. Consents could be simplified to improve patient understanding.” (HP)42   
 Specific information needs (child, parent) “[R]eported the following staff behaviors as helpful: ‘explained everything to me/gave us written information,…answered my questions and gave me time to think,…told me about how other patients did.…’” (child)7  7,35,36,38,52  
 “Provide more information about the specific phase 1 trial being considered, including detailed information regarding the mechanism, science, development, and side effects of the study drug.” (child, parent)52   
 “Let us know about other kids on the trial: provide an update about [enrollment] and current patient status in advance of the decision to enroll on the trial.” (parent)52   
 Participant understanding (child, parent, HP) “When asked specifically whether most patients who participate in phase I trials receive medical benefit, 30% (n. 6) said ‘yes,’ 20% (n. 4) said ‘no,’ and 50% (n. 10) said ‘don’t know.’… When asked about their own chances of getting medical benefit, 13 (65%) participants answered ‘don’t know’ or did not provide a percentage, while seven provided percentages ranging from 5% to 100% (M. 55.71%; SD. 37.13). Participants rated the information that was given to them as easy to understand.” (child)35  3235,39,42,44,52  
 “The understanding by the parents of the purpose of the trial and of the potential individual benefits was poor.…” (parent)39   
 “[A] large proportion of the nurses in this study (47%) felt that patients and families did not understand the goals of phase I clinical trials.” (HP)44   
 HP beliefs and understanding (HP) “Physicians were more likely to correctly identify the main goals of phase 1 studies including testing the safety, determining the maximum tolerated dose, and identifying the dose-limiting toxicity of an experimental drug. In addition to being less likely to correctly identify the main goals of phase 1 trials, nurses were more likely to incorrectly endorse goals including determining the efficacy of a drug for a specific disease and extending the life span of a patient. No providers endorsed curing patients as a goal of phase 1 therapy.” (HP)32  31,32,41,44  
Role of HPs in consent and beyond   
 Trust, support, Reassurance, and guidance (child, parent, HP) “So I asked for his opinion on whether I should do it or not, and he very carefully answered that it depends on what I value and whether I’m willing to take the risks and whether I’m looking for quality of life or looking for a treatment that works or how I view the situation, and that was good.” (child)52  7,31,34,3638,4042,49,52  
 “Parents would like staff to accept them, to advocate and be there for their child, to provide comfort, and to treat the child the same as before the decision was made.” (parent)37   
 “What made it so hard for me is that I’m not a doctor, and he was so well-educated. He usually guides me well with decisions, but he couldn’t tell me what to do here, and it made me feel so helpless.… I wanted so much to have someone else tell me that I had made the right decision, but there isn’t anyone who can tell me that.” (parent)36   
 “I am grateful…no one is giving up on us.” (parent)37   
 “We were just prayerful that we were being pushed in this direction [to the P1T] for good reasons.” (parent)40   
 “HCPs expressed the concept of being on both sides when they were conscious of their dual role. On the one hand, they were HCPs, building close relationships with parents and children, and on the other they were researchers/investigators, with responsibility for introducing and conducting clinical trials.” (HP)49   
 Training to take consent (HP) “HCPs reported having received either informal training through the observation of mentors (52.3%, n = 45) or self-directed learning (via conferences and literature) (37.2%, n = 32), with few having undergone a formal training programme (17.4%, n = 15).” (HP)33  33,34,42  
 Impact on HPs (HP) “22 nurses (51%) in this study reported that they experienced ethical or moral conflict with the oncologists’ decision to offer phase I clinical trials to families and, to a lesser degree (15%), with the families’ decision to enroll in phase I clinical trials.” (HP)44  7,31,41,44,49  
 “Physicians reported the following reasons for feeling okay about their part in a phase I decision: ‘consistent with my ethical standards.…’” (HP)7   
 “[E]arly and middle development studies (phase I/II) brought up more ethical challenges particularly whether participating in the trial was of benefit to the child.” (HP)49   
Involvement of the child in decision-making   
 Involvement of the child in decision-making (child, parent, HP) “Younger children were ‘too young to really have any conversations about what it [the cancer] meant’ and to ask tough questions, and did not remember any other way of living.” (parent)40  7,14,3135,3740,43,44,48  
 “If I don’t take it, my family would support me, but they don’t want me to quit. Grandpa said he would worry himself to death if I don’t try it. My boyfriend wants me to take it for him. I don’t want to do it but for my family.” (child)7   
 “The doctor gave us the facts and told us how serious this is, and we told our daughter. But the choice part has not been difficult for us.… It’s never been a question for us because she has plans, and we are going to do everything we can to see that those plans are able to be made and, if not, then she knows and we know that we have done everything we can.” (parent)7   

Themes represent the perspectives of children, parents, or HPs. HCP, health care practitioner; P1T, phase I trial.

Wanting Choices

Many parents and patients considering phase I studies actively searched for cancer treatment options but believed that these options were increasingly limited (or nonexistent).7,3540  They had exhausted any curative treatments and now perceived the decision to be “phase I or nothing.”7,36,39,40  In contrast, HPs did not espouse the idea that families participated because of a lack of choice and talked of presenting families with options, including palliative care.7,33,34,38,41,42  Despite this, many families did not feel that palliative care alone was a viable alternative.39,40 

Trying Anything

Parents and patients participated in phase I trials to access treatment with even a remote chance of keeping the child alive.7,36,42,43  Regardless of the final outcome, they needed to know that they had not given up.7,36,37,43  HPs were conscious of families’ desires to try anything,7,3234,40,41,43,44  perceiving it to be a significant barrier to informed consent.34 

Awareness of Poor Prognosis

Many parents and patients alluded to expected poor outcomes.7,3638,40,42  Some talked of miracles while recognizing that the chances of a cure were low.36  Other parents only questioned their research participation after they saw their child decline or fail to improve on study.36 

Hope

For many patients and parents, the desire to try anything was motivated by optimism; predominantly hope for a cure.7,3537,40,42,43,45,46  Others knew that currently available trials were unlikely to offer a cure but participated in the hope that their child might survive until a cure became available.35,36,47  For a smaller number of parents and children across multiple studies, participation was motivated by other desires, such as hopes for prolonging life7,3537,40,43,48  or improving symptoms.7,36 

HPs commonly described symptom improvement as a reason to enroll children in trials31,41,42,44  but did not discuss longer life or a cure as a potential benefit.34  However, HPs were aware of families’ desires to maintain hope for a cure through research participation.7,3134,41,42,44  A minor theme expressed by HPs across several studies was the ethical concern that offering families phase I trials may encourage false or unrealistic hope.31,32,41,44,49  These HPs identified difficulties in ensuring realistic expectations, particularly when obtaining consent for research participation.33,34  Some HPs talked of encouraging families to focus on more achievable goals than a cure, for example, symptom relief or a peaceful death.42 

Uncertainty

Despite hoping to benefit from trial participation, many parents and children expressed concern about whether participation was ultimately the right decision for them and about the possible outcomes.35,36,40,47 

Faith

A small number of parents and children, but not HPs, discussed the role of religion and spirituality in guiding decisions and sustaining hope.7,35,36,40,45,46 

Fulfilling a “Good Parent” Role

This theme was discussed only by parents. According to some participants, a “good parent” was an expert on their child: extensively researching potential treatments and protecting and advocating for their child while considering the opinions of others, including their child, family, and HPs.7,36,37,40,42  Many parents perceived the ongoing quest for a cure to be a fundamental aspect of this role, only considering noncurative options once a cure seemed impossible.36,38 

Acting in the Child’s Best Interest

Again, this concept was only described by parents. Parents talked of “doing right” by their child: considering the facts and making decisions that put the child first.7,37,40,43  In particular, although many parents had altruistic goals for research participation, they prioritized their child’s well-being.7,37,43 

Altruism

Many children and parents hoped to help others through research participation.* Some families stated expressly that it was acceptable for HPs to mention possible benefits for other families and participated with this intention.48  Some wished to prevent others from experiencing the suffering they had lived through.43  They valued research and sometimes hoped to help HPs out of gratitude.14,45,46,50  In contrast, HPs believed that families made decisions in their own child’s interest, with benevolence playing a minor role.32,41  Many HPs avoided discussing this topic with families altogether.33,34 

Legacy

A minority of parents talked about helping others through research participation as a way of finding meaning in their experience, particularly after their child’s death.7,36,37,40  In contrast, HPs rarely discussed meaning or considered it to be a benefit of participation.41 

Access to Trials

Parents discussed time pressures inherent in phase I enrollment: limited spaces in trials necessitated quick decisions, constraining their ability to consider the options.36,42  Other fears included their child’s possible deterioration before receiving trial medications or failure to meet study requirements, losing their place.36,40,42  Some parents coped by making one or more contingency plans.36  HPs were aware of this parental urgency.42 

Burden of Participation

All 3 types of participants considered the possible effects of studies on quality of life (QoL). Some chose research participation hoping to improve QoL,7,35,36,38  whereas others tolerated possible temporarily decreased QoL to allow study involvement.7,35  Still others chose not to participate, fearing reduced QoL due to side effects, invasive procedures, or psychological suffering.7,30,37,4548,50  Families considered their children’s current state of health and ability to tolerate further treatment, sometimes deciding against study enrollment for children who were unwell or symptomatic.7,14,36,51  HPs perceived that potential toxicity was a common reason for families not wanting to participate.6,31 

Familiarity and Convenience

Parents, and to a lesser extent, children and HPs, referred to practical facilitators of enrollment.36,37,44,52  Parents felt comfortable with their children receiving treatments they had previously been given in hospitals known to them.36,37  Transferring care to another medical team to facilitate research participation meant having to retell their story, establish new relationships, and deal with possible miscommunication between teams.14  Time spent in the hospital7,14,48,50  (particularly at short notice), traveling to receive treatment,36,50,52  and interruptions to family life50  were other barriers to enrollment.

Practicalities of Consent

Parents and children appreciated receiving study information before discussions with HPs.52  They valued the opportunity for multiple meetings33,34,42,52  in comfortable locations52  and having time for decision-making.7,42,52  Families welcomed having easy access to HPs when questions arose.52 

Honest, Clear Communication

Parents and children described consent as involving large amounts of complex oral and written information.42,52  They preferred succinct, forthright language that was tailored to their needs in quantity and complexity.42,52  Families appreciated receiving multiple forms of information (eg, verbal, pictorial, and written) to suit different learning styles.52  HPs agreed that consent processes, specifically paperwork, were lengthy and complex, in part because of regulatory requirements.31,32,34,44 

Specific Information Needs

Families appreciated that HPs discussed certain issues during the consent process: summarizing the child’s previous treatment and current status,38,52  clarifying the options,36,52  and providing details about individual trials,35,38,52  particularly about how other participants had fared.7,35,36,52  After consenting to participate, families desired regular, timely trial updates.52 

Participant Understanding

HPs believed that parents grasped basic aspects of phase I studies, such as confidentiality, the right to withdraw, potential toxicity, and alternative options.34  However, they perceived that parents misunderstood complex concepts, such as dose escalation.33,34  Many HPs believed that families overestimated the likelihood of their children benefiting from participation31,44  and failed to comprehend the goals of phase I studies.32,34,44  Consistent with this belief, in one study, adolescents participating in phase I research claimed to understand study information but overestimated their chances of benefiting from participation.35  In another study, parents showed poor understanding of risks, benefits, and alternative options.39 

HP Beliefs and Understanding

In general, HPs were aware of the goals of studies,31,32,41,44  but HPs working in different settings held different perspectives about phase I trials. Nurses were less likely than physicians to accurately perceive study goals and the probability of benefit or toxicity.32,44  HPs working in phase I consortium centers were more confident than those working outside these centers that trials benefited participants without causing false hope.31  British oncologists expressed greater ethical concerns regarding phase I trials than US oncologists.41 

Trust, Support, Reassurance, and Guidance

Many families looked to HPs7,38  for advice that was consistent with their values.36,42,52  Often parents sought validation of their choices for fear of making wrong decisions.7,36  Many parents who chose experimental therapy, hoping for a cure, expected the backing of their HPs.7,36,37  Regardless of their choice, parents sought assurances that their child would receive the same standard of ongoing care.7,37,38  Some parents stated that HPs had previously provided treatment recommendations, and so they wanted advice, but these HPs felt parents should make the choice in this situation.36,42,52  HPs referred to families’ needs for general multidisciplinary care but, despite parents’ desires for direction, preferred to avoid making specific recommendations.31,34,41  Some parents and HPs described physicians as holding simultaneous roles as clinicians and researchers.40,49  Both groups were aware of a potential role conflict, but parents hoped that HPs would prioritize their child despite their own research interests.40 

Training to Take Consent

Most HPs had only received informal instruction on taking informed consent for research participation, generally by observing senior colleagues.33,34  Many HPs believed that formal education would be beneficial.33,34 

Impact on HPs

HPs generally had positive perceptions of phase I research, believing that it was appropriate to respect family preferences to participate.31,41,44  A minority described ethical concerns, including the lack of benefit for participants, families’ unrealistic expectations, and misunderstanding of the purpose of studies.41,44  Few HPs described experiencing moral distress secondary to patients’ involvement in phase I studies.44  Any impact of the tension HPs felt between clinical and research roles was rarely discussed.40 

The child’s role in the research consent process was a common theme. Parents and HPs talked of graded participation,34,39,40,46  with parents making choices on behalf of the youngest children,34,39,40,46,48  considering older children’s preferences,7,14,31,3740,43  and allowing the oldest children to choose for themselves.32,35,39,44,48  Many HPs suggested that although children could decide, often it was parents who did decide33,34  or the children deferred to parental preferences.44  Decision-making conflict was infrequently discussed,45,48  although parents in one study were more willing to accept their child’s request to participate in research against parental wishes than their refusal.48 

This review brings together patient, parent, and HP perspectives on the topic of EOL research in pediatric oncology, with the intention of providing clinically relevant guidance to these groups.

Parents of children with incurable cancer and the HPs who treat them may find it helpful to discuss how other families make decisions about EOL research. We found that many parents sought a sense of control at the EOL by making choices but experienced a somewhat contradictory position as the choices available to them increasingly diminished. Despite sometimes being presented with several choices, many parents only considered options that were associated with a chance of a cure, however small. The implication is that for many parents, palliative care without anticancer treatment was not a worthwhile choice.

Families making decisions about EOL research may also benefit from hearing of other families in our review who considered the practical inconveniences of research and potential interference in QoL and chose not to participate.

At times, differences of opinion arise in clinical practice as to whether research participation is in the interest of a particular child. We sought to identify differences in views of EOL research between children, parents, and HPs because understanding divergent perspectives may help HPs to manage conflict. One area of difference was perceptions of hope. Hope for a cure was commonly cited by families searching for any available treatment option. However, other hopes were also described and valued, such as hope for symptom relief. These findings echoed the results of other studies revealing the importance of hope in promoting resilience for families of children with cancer.5356  In contrast, a small proportion of HPs in our review were concerned about familial hope. These HPs feared that consent could never be truly informed when participants were so determined to access treatment. Fewer HPs worried that hope could be false and that families may be acting under therapeutic misconception.19,57 

These differences in families’ and HPs’ conceptions of hope are reflected in the broader literature.5860  Whereas families may experience different types of hope, HPs typically focus on a limited vision of hope, such as hope for a cure.58,59  When a cure is unlikely, HPs may worry that hopeful families are unrealistic and will pursue aggressive treatments at the EOL, leading to children suffering.53,5861  It may help HPs to understand that for many parents, hope and the ongoing trial of new treatments was a key aspect of being a “good parent.” This is consistent with related studies, notably the ethnographic study by Bluebond-Langer et al62  in which parents felt driven to pursue further treatment up until days before their child’s death.53,54  Similarly, in the study by Tomlinson et al,53,54  parents of children with incurable cancer were more willing than HPs to accept chemotherapy for children at the EOL, even if treatment compromised QoL. Although there is some literature that demonstrates an association between hope, delayed prognostic understanding, and aggressive EOL care, the findings of our and other studies suggest that parents can simultaneously be hopeful but also understand the prognosis.59,60 

We also identified differences in the ways that families and HPs approached altruism and legacy. While prioritizing their child’s interests, families found meaning and legacy in altruism. This is consistent with previous studies in adult and pediatric oncology.63  In contrast, we found that HPs were reluctant to discuss altruistic motivations for research participation, despite the primary intent of research studies to benefit future patients.64  Similarly, HPs avoided guiding parental decision-making, although many parents desired guidance and support. It may be that HPs hesitate to influence parents or to discuss altruism for fear of coercion.65,66  However, the nature of phase I research means that discussions about altruism could be considered to be a critical aspect of informed consent and may help to avoid therapeutic misconception.66,67 

Lastly, we explored the perceptions of families and HPs regarding EOL research so that researchers may use this information to guide study processes and design. Children, parents, and HPs all found informed consent processes for phase I trials to be challenging because of the requirement to transmit large amounts of complex information, often in short periods of time. Unsurprisingly, this was associated with a perceived lack of research participant understanding. These findings are supported by the broader literature on understanding in participants across adult and pediatric research.6871  We identified several possible improvements to the informed consent process, including the need for formal training of HPs in taking research consent.70  More research is needed on the child’s role in the consent process.

Although we hoped to provide guidance that was grounded in child and adolescent perspectives of EOL research, it is important to note that a majority of participants in the included studies were parents and HPs. Therefore, the perspectives of patients were under-represented. It may be that researchers hesitated to approach young people about a potentially sensitive topic. However, our findings indicate that children and adolescents played an increasing role in decision-making with age and that many were willing to discuss their perspectives in studies included in this review. We would suggest that future researchers should investigate these perspectives further.

A particular strength of this review is the inclusion of data from a broad range of perspectives, permitting comparison of the views of a range of stakeholders and identifying areas for practice improvement.

Despite conduct of a broad and systematic search, we only identified 1 study in which palliative care research was evaluated. This may be due to a lack of both palliative care research and studies in which stakeholder perceptions of it are examined. Our findings therefore relate primarily to phase I studies. Although many HPs were included, this was usually in survey-based studies, limiting the depth to which their opinions were explored. Although qualitative methods were used in several included studies, they usually provided only thin descriptions and limited data.72,73  The inclusion of heterogeneous data presented a challenge for synthesis.

Children with cancer, their parents, and the HPs who treat them hold a broad range of perspectives regarding EOL research participation. Considering these perspectives and how they differ can help guide clinical and research practice. More research is needed to understand how these stakeholders, particularly the children themselves, view palliative care and other EOL research studies.

We thank Tamsin Adams-Webber and Quenby Mahood for designing and performing the literature search. We also thank Dr Angela Punnett for advice on the conduct of the study and for reviewing the manuscript.

Dr Hasan conceptualized and designed the study protocol, performed study selection, data extraction, quality appraisal, and thematic analysis and synthesis, drafted the initial manuscript, and reviewed and revised the manuscript; Dr Wheaton performed study selection, data extraction, quality appraisal, and thematic analysis and synthesis and reviewed and revised the manuscript; Dr Widger contributed to the design of the study, supervised conduct of the study, critically reviewed and revised the manuscript for important intellectual content, was the third reviewer, and contributed to discussions regarding study selection; Dr Sung contributed to the design of the study, supervised conduct of the study, and critically reviewed and revised the manuscript for important intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

*

Refs 7,14,3537,40,42,43,45,46,48,50,52.

Refs 7,14,30,31,33,3537,4148,50.

FUNDING: Dr Hasan is funded by the Garron Family Cancer Centre at The Hospital for Sick Children. Dr Widger is supported by a Tier 2 Canada Research Chair in Pediatric Palliative Care. Dr Sung is supported by a Canada Research Chair in Pediatric Oncology Supportive Care. Dr Wheaton received no external funding.

     
  • EOL

    end of life

  •  
  • HP

    health professional

  •  
  • QoL

    quality of life

1
American Cancer Society
.
Cancer Facts & Figures 2019
.
Atlanta, GA
:
American Cancer Society
;
2019
2
Schechter
T
,
Grant
R
.
The complexity of consenting to clinical research in phase I pediatric cancer studies
.
Paediatr Drugs
.
2015
;
17
(
1
):
77
81
3
Lee
DP
,
Skolnik
JM
,
Adamson
PC
.
Pediatric phase I trials in oncology: an analysis of study conduct efficiency
.
J Clin Oncol
.
2005
;
23
(
33
):
8431
8441
4
Ackerman
TF
.
The ethics of phase I pediatric oncology trials
.
IRB
.
1995
;
17
(
1
):
1
5
5
Weber
JS
,
Levit
LA
,
Adamson
PC
, et al
.
American Society of Clinical Oncology policy statement update: the critical role of phase I trials in cancer research and treatment
.
J Clin Oncol
.
2015
;
33
(
3
):
278
284
6
Hinds
PS
,
Oakes
L
,
Furman
W
, et al
.
End-of-life decision making by adolescents, parents, and healthcare providers in pediatric oncology: research to evidence-based practice guidelines
.
Cancer Nurs
.
2001
;
24
(
2
):
122
134, NaN–136
7
Hinds
PS
,
Drew
D
,
Oakes
LL
, et al
.
End-of-life care preferences of pediatric patients with cancer
.
J Clin Oncol
.
2005
;
23
(
36
):
9146
9154
8
Jalmsell
L
,
Kreicbergs
U
,
Onelöv
E
,
Steineck
G
,
Henter
JI
.
Symptoms affecting children with malignancies during the last month of life: a nationwide follow-up
.
Pediatrics
.
2006
;
117
(
4
):
1314
1320
9
Hilden
JM
,
Himelstein
BP
,
Freyer
DR
,
Friebert
S
,
Kane
JR
. End-of-Life Care: Special Issues in Pediatric Oncology. In:
Foley
KM
,
Gelband
H
, eds.
Improving Palliative Care for Cancer
.
Washington, DC
:
National Academies Press
;
2001
10
Waldman
E
,
Wolfe
J
.
Palliative care for children with cancer
.
Nat Rev Clin Oncol
.
10
(
2
):
100
107
11
Sung
L
,
Regier
DA
.
Decision making in pediatric oncology: evaluation and incorporation of patient and parent preferences
.
Pediatr Blood Cancer
.
2013
;
60
(
4
):
558
563
12
Cooley
C
,
Adeodu
S
,
Aldred
H
,
Beesley
S
,
Leung
A
,
Thacker
L
.
Paediatric palliative care: a lack of research-based evidence
.
Int J Palliat Nurs
.
2000
;
6
(
7
):
346
351
13
Steele
R
,
Bosma
H
,
Johnston
MF
, et al
.
Research priorities in pediatric palliative care: a Delphi study
.
J Palliat Care
.
2008
;
24
(
4
):
229
239
14
Dussel
V
,
Orellana
L
,
Soto
N
, et al
.
Feasibility of conducting a palliative care randomized controlled trial in children with advanced cancer: assessment of the PediQUEST study
.
J Pain Symptom Manage
.
2015
;
49
(
6
):
1059
1069
15
Hinds
PS
,
Pritchard
M
,
Harper
J
.
End-of-life research as a priority for pediatric oncology
.
J Pediatr Oncol Nurs
.
2004
;
21
(
3
):
175
179
16
Joffe
S
,
Miller
FG
.
Rethinking risk-benefit assessment for phase I cancer trials
.
J Clin Oncol
.
2006
;
24
(
19
):
2987
2990
17
Kodish
E
.
Pediatric ethics and early-phase childhood cancer research: conflicted goals and the prospect of benefit
.
Account Res
.
2003
;
10
(
1
):
17
25
18
Kodish
E
,
Stocking
C
,
Ratain
MJ
,
Kohrman
A
,
Siegler
M
.
Ethical issues in phase I oncology research: a comparison of investigators and institutional review board chairpersons
.
J Clin Oncol
.
1992
;
10
(
11
):
1810
1816
19
Appelbaum
PS
,
Roth
LH
,
Lidz
C
.
The therapeutic misconception: informed consent in psychiatric research
.
Int J Law Psychiatry
.
1982
;
5
(
3–4
):
319
329
20
Horng
S
,
Grady
C
.
Misunderstanding in clinical research: distinguishing therapeutic misconception, therapeutic misestimation, and therapeutic optimism
.
IRB
.
2003
;
25
(
1
):
11
16
21
Glannon
W
.
Phase I oncology trials: why the therapeutic misconception will not go away
.
J Med Ethics
.
2006
;
32
(
5
):
252
255
22
Valdez-Martinez
E
,
Noyes
J
,
Bedolla
M
.
When to stop? Decision-making when children’s cancer treatment is no longer curative: a mixed-method systematic review
.
BMC Pediatr
.
2014
;
14
:
124
23
Heinze
KE
,
Nolan
MT
.
Parental decision making for children with cancer at the end of life: a meta-ethnography
.
J Pediatr Oncol Nurs
.
2012
;
29
(
6
):
337
345
24
Tong
A
,
Flemming
K
,
McInnes
E
,
Oliver
S
,
Craig
J
.
Enhancing transparency in reporting the synthesis of qualitative research: ENTREQ
.
BMC Med Res Methodol
.
2012
;
12
:
181
25
Moher
D
,
Liberati
A
,
Tetzlaff
J
,
Altman
DG
;
PRISMA Group
.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
.
PLoS Med
.
2009
;
6
(
7
):
e1000097
26
Tong
A
,
Sainsbury
P
,
Craig
J
.
Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups
.
Int J Qual Health Care
.
2007
;
19
(
6
):
349
357
27
Boynton
PM
,
Greenhalgh
T
.
Selecting, designing, and developing your questionnaire
.
BMJ
.
2004
;
328
(
7451
):
1312
1315
28
Munn
Z
,
Barker
TH
,
Moola
S
, et al
.
Methodological quality of case series studies: an introduction to the JBI critical appraisal tool
.
JBI Evid Synth
.
2020
;
18
(
10
):
2127
2133
29
Thomas
J
,
Harden
A
.
Methods for the thematic synthesis of qualitative research in systematic reviews
.
BMC Med Res Methodol
.
2008
;
8
:
45
30
Surun
A
,
Dujaric
,
Aerts
I
, et al
.
Enrollment in early-phase clinical trials in pediatric oncology: the experience at Institut Curie
.
Pediatr Blood Cancer
.
2018
;
65
(
5
):
e26916
31
Gilliam
MB
,
Madan-Swain
A
,
Adams
JM
,
Pressey
JG
.
Physician perceptions and beliefs of phase I trials in pediatric oncology
.
Pediatr Blood Cancer
.
2013
;
60
(
8
):
E67
E69
32
Barnes
MJ
,
Pressey
J
,
Adams
J
,
Hensler
MA
,
Madan-Swain
A
.
Physician and nurse beliefs of phase 1 trials in pediatric oncology
.
Cancer Nurs
.
2014
;
37
(
5
):
E48
E52
33
Robertson
EG
,
Mitchell
R
,
Wakefield
CE
, et al
.
Enrolment in paediatric oncology early-phase clinical trials: the health-care professionals’ perspective
.
J Paediatr Child Health
.
2019
;
55
(
5
):
561
566
34
Yap
TY
,
Yamokoski
AD
,
Hizlan
S
, et al.;
Phase I Informed Consent (POIC) Research Team
.
Informed consent for pediatric phase 1 cancer trials: physicians’ perspectives
.
Cancer
.
2010
;
116
(
13
):
3244
3250
35
Miller
VA
,
Baker
JN
,
Leek
AC
, et al
.
Adolescent perspectives on phase I cancer research
.
Pediatr Blood Cancer
.
2013
;
60
(
5
):
873
878
36
Deatrick
JA
,
Angst
DB
,
Moore
C
.
Parents’ views of their children’s participation in phase I oncology clinical trials
.
J Pediatr Oncol Nurs
.
2002
;
19
(
4
):
114
121
37
Maurer
SH
,
Hinds
PS
,
Spunt
SL
,
Furman
WL
,
Kane
JR
,
Baker
JN
.
Decision making by parents of children with incurable cancer who opt for enrollment on a phase I trial compared with choosing a do not resuscitate/terminal care option
.
J Clin Oncol
.
2010
;
28
(
20
):
3292
3298
38
Hinds
PS
,
Oakes
L
,
Furman
W
, et al
.
Decision making by parents and healthcare professionals when considering continued care for pediatric patients with cancer
.
Oncol Nurs Forum
.
1997
;
24
(
9
):
1523
1528
39
Béranger
A
,
Bouazza
N
,
de Haut de Sigy
A
, et al
.
Parents’ and children’s comprehension and decision in a paediatric early phase oncology trial: a prospective study
.
Arch Dis Child
.
2019
;
104
(
10
):
947
952
40
Crane
S
,
Haase
JE
,
Hickman
SE
.
Parental experiences of child participation in a phase I pediatric oncology clinical trial: “we don’t have time to waste”
.
Qual Health Res
.
2019
;
29
(
5
):
632
644
41
Estlin
EJ
,
Cotterill
S
,
Pratt
CB
,
Pearson
AD
,
Bernstein
M
.
Phase I trials in pediatric oncology: perceptions of pediatricians from the United Kingdom Children’s Cancer Study Group and the Pediatric Oncology Group
.
J Clin Oncol
.
2000
;
18
(
9
):
1900
1905
42
Johnson
LM
,
Leek
AC
,
Drotar
D
, et al
.
Practical communication guidance to improve phase 1 informed consent conversations and decision-making in pediatric oncology
.
Cancer
.
2015
;
121
(
14
):
2439
2448
43
van der Geest
IMM
,
van den Heuvel-Eibrink
MM
,
Zwaan
CM
,
Pieters
R
,
Passchier
J
,
Darlington
ASE
.
Participation in a clinical trial for a child with cancer is burdensome for a minority of children
.
Acta Paediatr
.
2016
;
105
(
9
):
1100
1104
44
Chang
A
.
An exploratory survey of nurses’ perceptions of phase I clinical trials in pediatric oncology
.
J Pediatr Oncol Nurs
.
2008
;
25
(
1
):
14
23
45
Nitschke
R
,
Humphrey
GB
,
Sexauer
CL
,
Catron
B
,
Wunder
S
,
Jay
S
.
Therapeutic choices made by patients with end-stage cancer
.
J Pediatr
.
1982
;
101
(
3
):
471
476
46
Nitschke
R
,
Wunder
S
,
Sexauer
CL
,
Humphrey
GB
.
The final-stage conference: the patient’s decision on research drugs in pediatric oncology
.
J Pediatr Psychol
.
1977
;
2
(
2
):
58
64
47
Barrera
M
,
D’Agostino
N
,
Gammon
J
,
Spencer
L
,
Baruchel
S
.
Health-related quality of life and enrollment in phase 1 trials in children with incurable cancer
.
Palliat Support Care
.
2005
;
3
(
3
):
191
196
48
Kamps
WA
,
Akkerboom
JC
,
Kingma
A
,
Humphrey
GB
.
Experimental chemotherapy in children with cancer–a parent’s view
.
Pediatr Hematol Oncol
.
1987
;
4
(
2
):
117
124
49
Schröder Håkansson
A
,
Pergert
P
,
Abrahamsson
J
,
Stenmarker
M
.
Balancing values and obligations when obtaining informed consent: healthcare professionals’ experiences in Swedish paediatric oncology
.
Acta Paediatr
.
2020
;
109
(
5
):
1040
1048
50
Berg
SL
,
Winick
N
,
Ingle
AM
,
Adamson
PC
,
Blaney
SM
.
Reasons for participation in optional pharmacokinetic studies in children with cancer: a Children’s Oncology Group phase 1 consortium study
.
Pediatr Blood Cancer
.
2010
;
55
(
1
):
119
122
51
Mack
JW
,
Joffe
S
,
Hilden
JM
, et al
.
Parents’ views of cancer-directed therapy for children with no realistic chance for cure
.
J Clin Oncol
.
2008
;
26
(
29
):
4759
4764
52
Baker
JN
,
Leek
AC
,
Salas
HS
, et al
.
Suggestions from adolescents, young adults, and parents for improving informed consent in phase 1 pediatric oncology trials
.
Cancer
.
2013
;
119
(
23
):
4154
4161
53
Tomlinson
D
,
Bartels
U
,
Gammon
J
, et al
.
Chemotherapy versus supportive care alone in pediatric palliative care for cancer: comparing the preferences of parents and health care professionals
.
CMAJ
.
2011
;
183
(
17
):
E1252
E1258
54
Tomlinson
D
,
Bartels
U
,
Hendershot
E
,
Maloney
AM
,
Ethier
MC
,
Sung
L
.
Factors affecting treatment choices in paediatric palliative care: comparing parents and health professionals
.
Eur J Cancer
.
2011
;
47
(
14
):
2182
2187
55
Fletcher
PC
,
Schneider
MA
,
Harry
RJ
.
How do I cope? Factors affecting mothers’ abilities to cope with pediatric cancer
.
J Pediatr Oncol Nurs
.
2010
;
27
(
5
):
285
298
56
McCubbin
M
,
Balling
K
,
Possin
P
,
Frierdich
S
,
Bryne
B
.
Family resiliency in childhood cancer
.
Fam Relat
.
2002
;
51
(
2
):
103
111
57
Lidz
CW
,
Appelbaum
PS
,
Grisso
T
,
Renaud
M
.
Therapeutic misconception and the appreciation of risks in clinical trials
.
Soc Sci Med
.
2004
;
58
(
9
):
1689
1697
58
Feudtner
C
.
The breadth of hopes
.
N Engl J Med
.
2009
;
361
(
24
):
2306
2307
59
Roscigno
CI
,
Savage
TA
,
Kavanaugh
K
, et al
.
Divergent views of hope influencing communications between parents and hospital providers
.
Qual Health Res
.
2012
;
22
(
9
):
1232
1246
60
Reder
EA
,
Serwint
JR
.
Until the last breath: exploring the concept of hope for parents and health care professionals during a child’s serious illness
.
Arch Pediatr Adolesc Med
.
2009
;
163
(
7
):
653
657
61
Wolfe
J
,
Klar
N
,
Grier
HE
, et al
.
Understanding of prognosis among parents of children who died of cancer: impact on treatment goals and integration of palliative care
.
JAMA
.
2000
;
284
(
19
):
2469
2475
62
Bluebond-Langner
M
,
Belasco
JB
,
Goldman
A
,
Belasco
C
.
Understanding parents’ approaches to care and treatment of children with cancer when standard therapy has failed
.
J Clin Oncol
.
2007
;
25
(
17
):
2414
2419
63
Truong
TH
,
Weeks
JC
,
Cook
EF
,
Joffe
S
.
Altruism among participants in cancer clinical trials
.
Clin Trials
.
2011
;
8
(
5
):
616
623
64
National Bioethics Advisory Commission
.
Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries
.
Bethesda, MD
:
National Bioethics Advisory Commission
;
2001
65
Ladd
RE
,
Forman
E
.
Altruistic motives reconsidered
.
Am J Bioeth
.
2006
;
6
(
5
):
55
56
66
Hester
DM
,
Hackler
C
.
Improving medicine through research and the constitutive nature of altruism
.
Am J Bioeth
.
2006
;
6
(
5
):
51
52
67
Joffe
S
.
Altruistic discourse and therapeutic misconception in research informed consent
.
Am J Bioeth
.
2006
;
6
(
5
):
53
54
68
Cousino
MK
,
Zyzanski
SJ
,
Yamokoski
AD
, et al
.
Communicating and understanding the purpose of pediatric phase I cancer trials
.
J Clin Oncol
.
2012
;
30
(
35
):
4367
4372
69
Kodish
E
,
Eder
M
,
Noll
RB
, et al
.
Communication of randomization in childhood leukemia trials
.
JAMA
.
2004
;
291
(
4
):
470
475
70
Simon
C
,
Eder
M
,
Raiz
P
,
Zyzanski
S
,
Pentz
R
,
Kodish
ED
.
Informed consent for pediatric leukemia research: clinician perspectives
.
Cancer
.
2001
;
92
(
3
):
691
700
71
Kass
N
,
Taylor
H
,
Fogarty
L
, et al
.
Purpose and benefits of early phase cancer trials: what do oncologists say? What do patients hear?
J Empir Res Hum Res Ethics
.
2008
;
3
(
3
):
57
68
72
Bryman
A
. The Nature of Qualitative Research. In:
Quantity and Quality in Social Research
, 1st ed.
London, United Kingdom
:
Routledge
;
1988
:
62
63
73
Green
J
,
Thorogood
N
. Flexible Research Strategies. In:
Qualitative Methods for Health Research
, 3rd ed.
London, United Kingdom
:
SAGE Publications
;
2014
:
25
27
74
Chappuy
H
,
Baruchel
A
,
Leverger
G
, et al
.
Parental comprehension and satisfaction in informed consent in paediatric clinical trials: a prospective study on childhood leukaemia
.
Arch Dis Child
.
2010
;
95
(
10
):
800
804
75
Chappuy
H
,
Doz
F
,
Blanche
S
,
Gentet
JC
,
Pons
G
,
Tréluyer
JM
.
Parental consent in paediatric clinical research
.
Arch Dis Child
.
2006
;
91
(
2
):
112
116
76
Chappuy
H
,
Bouazza
N
,
Minard-Colin
V
, et al
.
Parental comprehension of the benefits/risks of first-line randomised clinical trials in children with solid tumours: a two-stage cross-sectional interview study
.
BMJ Open
.
2013
;
3
(
5
):
e002733
77
Tait
AR
,
Voepel-Lewis
T
,
Malviya
S
.
Participation of children in clinical research: factors that influence a parent’s decision to consent
.
Anesthesiology
.
2003
;
99
(
4
):
819
825
78
Janson
SL
,
Alioto
ME
,
Boushey
HA
;
Asthma Clinical Trials Network
.
Attrition and retention of ethnically diverse subjects in a multicenter randomized controlled research trial
.
Control Clin Trials
.
2001
;
22
(
suppl 6
):
236S
243S
79
Wolfe
J
,
Grier
HE
,
Klar
N
, et al
.
Symptoms and suffering at the end of life in children with cancer
.
N Engl J Med
.
2000
;
342
(
5
):
326
333
80
Mack
JW
,
Hilden
JM
,
Watterson
J
, et al
.
Parent and physician perspectives on quality of care at the end of life in children with cancer
.
J Clin Oncol
.
2005
;
23
(
36
):
9155
9161
81
Kodish
ED
,
Pentz
RD
,
Noll
RB
,
Ruccione
K
,
Buckley
J
,
Lange
BJ
.
Informed consent in the Childrens Cancer Group: results of preliminary research
.
Cancer
.
1998
;
82
(
12
):
2467
2481
82
Colaizzi
PF
. Psychological Research as the Phenomenologist Views It. In:
Valle
RS
,
King
M
, eds.
Existential-Phenomenological Alternatives for Psychology
.
New York, NY
:
Oxford University Press
;
1978
:
48
71
83
Hinds
PS
,
Oakes
LL
,
Hicks
J
, et al
.
“Trying to be a good parent” as defined by interviews with parents who made phase I, terminal care, and resuscitation decisions for their children
.
J Clin Oncol
.
2009
;
27
(
35
):
5979
5985
84
van der Geest
IMM
,
Darlington
ASE
,
Streng
IC
,
Michiels
EM
,
Pieters
R
,
van den Heuvel-Eibrink
MM
.
Parents’ experiences of pediatric palliative care and the impact on long-term parental grief
.
J Pain Symptom Manage
.
2014
;
47
(
6
):
1043
1053

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

Supplementary data