Parents’ Insights into Pediatric Oncology Phase I Clinical Trials: Experiences from Their Child's Participation
Introduction
Although the incidence of cancer in children and adolescents is slowly increasing, survival rates continue to improve due to advances in therapies and supportive care and high levels of participation in pediatric oncology clinical trials.1, 2, 3, 4 Clinical trials are the research studies that are conducted in people to evaluate the effectiveness of novel therapies. There are four stages of clinical trials: Phase 1, Phase 2, Phase 3, and Phase 4.5 Phase 1 clinical trials (P1Ts) are the first stage of trials. They seek to establish the recommended dose, administration schedule, and most frequent side effects of a novel therapy. The unique aspect of P1Ts is that the proper dose and the potential side effects of the therapy are not well-defined in advance. As a result, participants are enrolled in small groups of three to six patients at a time. If the patients tolerate the therapy at the given dose, another group of patients may enroll at a higher dose (or the same dose) until the recommended dose is established. Phase 2 clinical trials seek to determine if the novel therapy is effective in people with a particular condition. Phase 3 clinical trials further evaluate the effectiveness of the novel therapy by comparing it against current treatments, in different populations, and in different combinations with other drugs. Phase 4 clinical trials are conducted after Food and Drug Administration (FDA) approval is obtained for a novel therapy and involve continued evaluation of the safety and efficacy of the novel therapy in broader populations.
P1Ts are essential in drug development to determine proper dosing and to characterize the safety of new therapies in patients.4,6, 7, 8 Because of the unknown efficacy of novel therapies, children with cancer are eligible to participate in P1Ts only when no known curative therapy options are available. Children enrolled in a pediatric oncology P1T have a median life expectancy of 3.6 to 6.4 months.7,9,10 Understanding the experiences of the children and families who participate in P1Ts is particularly salient to help ensure that participants’ well-being is adequately supported.
Although research regarding the informed consent process for P1Ts has been conducted,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 little is known about the experiences and perceptions of children who participate in these trials and that of their parents.22 The authors conducted a qualitative, phenomenological study that described the meaning of the experience for the parents of children with cancer who participated in a P1T.23 This qualitative study found that parents at times embraced the P1T and all its unknowns, felt special for being asked or chosen to participate, were fearful of unknowns and potential toxicities, and deemed the P1T as more burdensome than other medical treatments.23 Specific burdens identified by parents included additional medical procedures, toxicities, and appointments; having to wait to start P1T therapy; and a sense of their lives revolving around meeting the P1T requirements.23 Despite these burdens, parents’ experiences during P1Ts were primarily positive.23 One parent reported, “the trial itself . . . could not have been better” [parent of a 12-year-old with osteosarcoma]. Another said, “I have nothing negative to say about it whatsoever” [parent of a 17-year-old with Ewing sarcoma]. Regardless of their child's outcomes, parents did not regret their child's participation and would recommend participation to other parents of children with cancer.23 Most parents described the decision to participate in a P1T as easy, and many had a sense that the P1T plan “just fell into place” [parent of a 12-year-old with osteosarcoma]. Altruism and a desire to be part of cutting-edge cancer research contributed significantly to children's and parents’ decision to participate in a P1T. One parent described how her child “would get so excited . . . knowing that maybe there is something out there that she is going to be a part of that is going to help out another child” [parent of a 16-year-old with spindle cell sarcoma].
What was not included in the primary publication of the qualitative study results,23 nor is well-described in the literature, is parents’ insights into the processes and procedures that occur as part of participation in a pediatric oncology P1T. The purpose of this article is to explore the specific aspects of pediatric oncology P1Ts that parents found particularly challenging, thereby offering an opportunity for nurses, other clinicians, and researchers to learn from those experiences and consider strategies to lessen the burden associated with P1T participation.
Section snippets
Methods
We used an adapted version of Colaizzi's method to conduct this descriptive, qualitative, and empirical phenomenological study.24,25 Phenomenological research is used to describe commonalities in the lived experiences of people in similar life situations.26, 27, 28 We used Colaizzi's method because the systematically derived products—the exhaustive description and the essential structure of the experience—are rich sources of information. The methods are described in greater detail in the
Description of Accrued Sample
Twelve parents were recruited to participate in this qualitative study. The response rates to recruitment attempts at the two medical centers were 35.3% (6 of 17 approached parents) and 33.3% (3 of 9 approached parents), respectively. Because this was a retrospective qualitative study, the response rates were substantially reduced by the unavailability of current contact information for parents, particularly for parents of deceased children. All eligible parents (100%, n = 2) recruited through
Discussion
P1Ts are essential to the development of novel therapies for childhood cancers; however, they raise ethical concerns about balancing the need for the trials with maintaining the well-being of the participating children and their families. P1T experiences were found to be primarily positive in this qualitative study, although P1T processes and procedures posed some challenges.23 Many of these challenges are inherent in the complexities of P1T protocols and may be present in all phases of
Conclusion
In this qualitative study, parents identified P1T processes and procedures that are particularly challenging, thereby providing an opportunity for nurses, other clinicians, and researchers to learn from their experiences. Although parents’ overall P1T experiences were positive, some aspects of participation negatively impacted children's and parents’ experiences. Enhancing the education provided to families during recruitment and minimizing the logistical issues associated with P1T requirements
Funding
Research reported in this publication was supported by the National Institute of Nursing Research under award [F31 NR015393 and T32 NR007066]; the National Cancer Institute under award [T32 CA117865]; the American Cancer Society under grant [DSCN-13-267-01-SCN and DSCNR-15-081-03-SCN]; an Oncology Nursing Society Foundation Dissertation Research Grant; and a Midwest Nursing Research Society Founder's Circle Endowment Grant. The content is solely the responsibility of the authors and does not
Conflicts of Interests
JMC (institutional principal investigator), JE (research nurse), and JW (clinical research professional) are actively involved with the conduct and management of phase 1 clinical trials through the Children's Oncology Group Pediatric Early Phase Clinical Trial Network. The authors do not have any financial or other conflicts of interest to declare with respect to the research, authorship, and/or publication of this article.
Acknowledgments
The authors thank the parents for participating in this study and sharing stories of their child's experiences. In addition, we would like to acknowledge the generous support of Casey Hooke, PhD, RN, PCNS, CPON, from University of Minnesota School of Nursing and Melissa Lee, CCRP, from Riley Hospital of Children, without which the study could not have been completed.
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