Suggestions from adolescents, young adults, and parents for improving informed consent in phase 1 pediatric oncology trials


  • We thank the parents and patients involved in the research for sharing their insights and Deborah Gibson, MA, and Sabahat Hizlan, BA, BS, for their contributions to the data analysis. Dr. Eric Kodish had full access to study data and takes responsibility for the integrity and accuracy of data analysis.



Informed consent for a pediatric oncology phase 1 trial is a delicate process, and is made more complex by the difficulty of the information and the requirement for parental consent, and patient assent when applicable. This analysis identifies suggestions for improving the informed consent process received from parents and adolescent and young adult patients (aged 14 years-21 years) who had the option of participating in a phase 1 pediatric oncology trial.


A total of 57 parents and 20 patients completed interviews as part of a multisite, prospective, descriptive study. These transcribed interviews were studied using established content analysis methods.


Parent and patient responses contained 220 suggestions and 54 suggestions, respectively. A total of 21 unique suggestions for improvement emerged in 3 main themes: 1) provision of more information; 2) structure and presentation of the informed consent process, and 3) suggestions for physicians conducting the process. Common suggestions included providing more specific information about the trial, allowing more time for decision-making, and using different methods to deliver information.


Participants involved in the informed consent process for a phase 1 trial provided specific recommendations to research teams to enhance the process. Physician/investigators should be informed of these recommendations and develop and test interventions incorporating them. Cancer 2013;119:4154–4161. © 2013 American Cancer Society.


The informed consent process (ICP) for research trials is a complex activity that occurs in multiple stages and involves many aspects of communication and decision-making. Phase 1 cancer trials are designed to determine the initial safety profile and the maximum tolerated dose of an experimental agent for later use in phase 2 and 3 trials. They offer little to no therapeutic benefit to the patient and carry possible toxic side effects. This creates challenges for physicians communicating the goals of phase 1 trials to families, especially given the inclusion of vulnerable high-risk populations and the dual role of the physician/investigator. The literature comments extensively on problematic aspects of the ICP, including a lack of participant understanding of drug trials, persistence of “therapeutic misconception” (ie, belief that the primary goal of research is to benefit the participant),[1] the high literacy level required to understand the information being presented, and many other concerns.[1-3]

The ICP can be particularly difficult in a pediatric context, given the elements of parental consent and patient assent, rather than autonomous patient consent.[4, 5] In fact, the ICP for a pediatric phase 1 clinical trial is arguably one of the most complex because the trial uses an experimental agent, involves a minor, and is often considered during a difficult time (ie, at the time of a patient's disease recurrence or progression).[6, 7] The search for options after cancer recurrence may lead a family to work with an unfamiliar oncologist and medical team and, occasionally, an unfamiliar institution. Families are usually provided vast amounts of information and the time frame for decision-making is often short.[7] Furthermore, adolescents and older children want to be included in the decision-making process and often have strong opinions about their health care,[8-10] but to the best of our knowledge, these opinions have not been investigated in the phase 1 context.

We previously reported physicians' suggestions for improving the ICP for phase 1 trials.[8] Although patients/participants and their families have provided feedback regarding improving the ICP for oncology trials,[11-13] suggestions specific to phase 1 trials remain largely unexplored despite frequent pediatric patient/participant involvement.[14]


The purpose of the current study was to identify specific suggestions of parents and of adolescent and young adult (AYA) patients/participants for improving the quality of the ICP for phase 1 trials. This was achieved via a secondary analysis of data taken from a larger study conducted at 6 US pediatric cancer centers that assessed physician-parent communication and parental understanding of the scientific purpose of pediatric phase 1 cancer trials.[15] Prior analyses of data from this study revealed significant deficiencies in parental understanding of the primary goals of the phase 1 trial[15] and differences in AYA patient/participant perspectives on, and understanding of, a phase 1 trial.[14]

Approval for the overarching study was obtained from the Institutional Review Boards of all study sites, and all participants provided informed consent. A total of 85 families considering enrollment on a variety of open phase 1 trials were recruited by site research assistants, and their informed consent conferences (ICCs) were audiotaped. Suggestions presented in the current study come from the participation of parents and their eligible children (AYA patients/participants) in optional semistructured interviews completed after the ICC. AYA patients/participants were eligible for the interview if they were aged 14 years to 21 years and present during the audiotaped ICC, and parental permission was obtained for adolescents (those aged 14 years-17 years). Young adults (those aged 18 years-21 years) were approached directly. One AYA patient/participant (aged 21 years) was interviewed with no parental involvement in the ICC or the interview. During the interviews, 1 question specifically asked for suggestions about the ICP: “In your opinion, how can we make the process of decision-making about the (phase 1 clinical trial) better?”

Responses were analyzed using semantic content analysis, an established qualitative method.[7, 16] Each answer to the primary question was reviewed for the presence of “mutually exclusive and exhaustive”[16] reasonably clinically actionable themes related to the interview/research question. Four trained study team members (J.B., A.L., H.S., and D.G.) with experience enrolling patients in clinical trials and performing qualitative analysis[15] independently examined the transcripts and developed codes for common themes. Through repeated discussions, the team refined each code's definition and came to consensus regarding its applicability to the ICP in the context of a phase 1 trial. To illustrate the relative importance of each theme to either the parents or the AYA patient/participant, the frequencies of each code were calculated for both groups. To compensate for a specific individual's repeated discussion of a particular concern, percentages of total respondents who had mentioned a theme were also calculated. Interview transcripts were then reviewed in their entirety to identify additional unique recommendations that were not included in responses to the direct question asking for suggestions.


In total, 57 parents (72% of whom were female, with a mean age of 41.1 years) and 20 eligible AYA patients/participants (75% of whom were male, with a mean age of 17.8 years) completed interviews (Table 1).[17] A total of 220 parents and 54 AYA patients/participants offered overlapping suggestions that were collapsed into 21 unique codes (Table 2). Mean interrater reliability was 92.6% for parent responses and 91% for patient/participant responses. The most common suggestions included providing more information about the specific study; offering straightforward, honest communication without medical jargon; and individualizing the ICP to meet patient and family needs (Table 2). Recommendations identified in other sections of the interviews are listed in Table 3.

Table 1. Patient and Parent Demographics and Clinical Data
CharacteristicNo. (%) or Mean (SD; Range)
  1. Abbreviations: CNS, central nervous system; ICC, informed consent conference; SD, standard deviation.

  2. a

    Lower scores indicate higher socioeconomic status[17]; parent data were missing for one adolescent and young adult patient/participant.

Patients (n = 20)
Age, y17.8 (2.35; 14 y-21 y)
Male15 (75%)
Female5 (25%)
Cancer diagnosis 
Bone and soft tissue11 (55%)
Brain/CNS7 (35%)
Leukemia1 (5%)
Sertoli-Leydig cell tumor1 (5%)
Y from cancer diagnosis to phase 1 ICC2.93 (2.68; 0.27 y-12.29 y)
Parents (n = 57)
Age, y41.1 (7.9; 23 y-66 y)
Female41 (71.9%)
Male16 (28.1%)
Non-Hispanic white48 (84.2%)
Other9 (15.8%)
Index of social positioninga 
1-219 (33.3%)
319 (33.3%)
4-519 (33.3%)
Child's age, y12.16 (5.4; 2 y-21 y)
Child's cancer diagnosis 
Bone and soft tissue18 (31.6%)
Neuroblastoma13 (22.8%)
Brain/CNS18 (31.6%)
Other5 (8.8%)
Leukemia (blood)3 (5.3%)
Y from child's cancer diagnosis to phase 1 ICC3.04 (2.53; 0.27 y-12.29 y)
Table 2. Suggestions of Parents and AYA Patients/Participants
Suggestion (Code Definition)Total No. (%) Expressing Code, Parent N=57Total No. (%) Expressing Code, Patient N=20Example Quotations
  1. Abbreviations: AYA, adolescent and young adult; FDA, US Food and Drug Administration.

Provide more information: 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.24 (42.1)6 (30)Patient: “Gather more information on it…have more data for people to take in…the more data you have, the better your decision will be.”
Give it to us straight: be straightforward and honest; avoid medical jargon, hide nothing-even bad news.16 (28.1)5 (25)Parent: “Just be honest, like they were. Honesty is probably the most–the best way to explain…”
Things went well: family was satisfied with the process.18 (31.6)7 (35)Parent: “I think you're doing more than enough to help us to make it through this time and this process easier.”
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.18 (31.6)3 (15)Patient: “Explain it a lot better. Or explain it to people that aren't going to quite understand it. They might only pick out little bits of what they want to hear, and they are not going to hear the whole story. I would emphasize the…the bad parts of it more than the good parts.”
Allow enough time: provide adequate time for patients and families to discuss options; let them know they do not need to decide “right now.”14 (24.6)1 (5)Patient: “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.”
Use multiple methods of delivery: offer a variety of alternatives for sharing information and recognize that many people are visually oriented in their learning.5 (8.8)3 (15)Parent: “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.”
Tell us our options: let patients and families know the phase 1 trial is one possible option and is voluntary; provide information about all available trials and treatment options, including when they may become available.7 (12.3)5 (25)Patient: “Then just make sure that the patient is willing or knows about the other options. That's what I would make sure you guys get that point across–that you don't have to take this thing, but there's other options.”
Ensure all questions are answered: ensure that concerns have been addressed, and have someone regularly available to address questions and any issues regarding the study.8 (14)2 (10)Patient: “I think he did a good job, the way he described everything, the decision-making process, he opened it up for questions and everything, explained all of it really well.”
Recognize that this is difficult: understand that enrolling in a phase 1 trial is a difficult and stressful event.9 (15.8)2 (10)Parent: “You don't really feel like you have any control over what the study is either so you get hit in the side of the head with the study.”
Tell us how different types of trials work: provide information about general goals, objectives, and logistical issues involved in phase 1 trials, like the differences between clinical trials and the standard of care.4 (7)0 (0)Parent: “…maybe knowing a little bit more about the whole structure of FDA approval for medications and things like that and what a phase 1 and a phase 2 and a phase 3 trial is.”
Provide information about the risks and benefits: explain what you expect our child to experience, and let us know about other possible risks/benefits.5 (8.8)1 (5)Patient: “I walked out of the meeting knowing what was likely to happen to me and realizing that even though what's likely to happen to me and what isn't likely to happen to me, there might even be something else that we don't even know that could happen to me.”
Give us information beforehand: provide information (including consent form) to families for consideration before the meeting.6 (10.5)0 (0)Parent: “They give it to you beforehand so that way you have time to read over and go through and highlight important facts, or if you have questions about a particular area you'll already, you know, be on top of it and you won't go in there blindsided.”
Let us know this trial may help other children: the team should be explicit about altruism as a goal and how the study may help other children and benefit future science.4 (7)1 (5)Patient: “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.”
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.6 (10.5)1 (5)Patient: “Like how well did it work? Or even the other 6 patients that are doing the same thing, did it work for them? Even though they can't give that information out, it would be a lot nicer to make my decision if I knew that it worked for them.”
Give us regular study updates: provide timely information after enrollment about how the trial is progressing and future steps for the drug.5 (8.8)0 (0)Parent: “What really helped us with the decision-making was that it is going to be checked regularly, and that's one of the reasons that we were excited to come because we knew that when the ball got rolling…it was going to continue to roll, and we were going to see or hear something.”
Help us make the decision: make a recommendation, and explain your rationale; work with families to ensure that study goals do not conflict with the patient's and family's goals.4 (7)1 (5)Patient: “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.”
Provide user-friendly consent forms: make improvements to the informed consent form by making it shorter, more to the point, with more understandable language; highlighting key aspects of the trial, while accentuating risks/benefits.3 (5.3)3 (15)Patient: “Maybe not put it in big packages of paper. I know it has to be written but…it takes forever to read.”
Let us know you care: take a caring, compassionate approach to the informed consent discussion.3 (5.3)0 (0)Parent: “… the way she presented it really made me think of [patient] as a lab rat. I don't think it made a difference to my husband, and like I said, different personalities are gonna react differently. But I just want that personal effect that this is really about your child.”
Make sure you understand the trial: convey confidence that you understand the background and rationale for the phase 1 trial being discussed.2 (3.5)0 (0)Parent: “I felt the doctors were very, very well prepared in explaining the choices and answering our questions–not with ‘yes' or ‘no' or short answers, but with detailed information that did help make our decision easier.”
Consider multiple meetings: have 2 meetings for the discussion, one for information and one for enrolling on the trial.1 (1.8)0 (0)Parent: “…then obviously we went to the second meeting where we decided what we were going to do. And my wife and I made it (decision) quickly.”
Have discussion in a comfortable area: provide a comfortable place (preferably not the examination room) for the family to talk and make the decision.1 (1.8)0 (0)Parent: “It would be kind of nice to be in a room where you're talking to each other across the table instead of on an examination table or something.”
Table 3. Additional Suggestions From Interview Content
SuggestionParticipant Quotation
Use good bedside manner and interpersonal skills“I mean they're very good at explaining it. So I don't know that there was anything about that, but it's just very easy to talk to [doctor]…her interpersonal skills…it's just you know, she has a good way of dealing with patients.”
Ensure accessibility of research team members“You know, I have her [doctor's] e-mail address, we've been you know, e-mailing one another. So is there anything she did?Yeah. She made herself accessible.”
Include the patient in the conversation“He [doctor] asked questions, he listened, and we talked back and forth, and he made sure that [patient] participated in that discussion.”
Use fewer acronyms or clearly define them“If she would have told me that or broken the word down. C something. ABC, spell it out to me. It was just an emotional thing going on…less acronyms.”
Give the option to do things close to home“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.”
Make a recommendation“It was very difficult initially because we didn't have a lot of direction as to which way to go, so not being a medical professional was very hard on us because as parents we sat there and we thought, you know, what if we make the wrong decision? You know, we were just, I think, hoping that our doctors would give us more of a recommendation.”
Encourage questions“She made it clear that I can ask any questions that I wanted to. She was also very encouraging as I was asking questions, telling me that they were good questions and if I had any more.”
Check for understanding“I think also, there were a couple of times when, obviously he doesn't understand or know us well enough to know what level of understanding we have, so if he used a word like, you know-polymorphism or you know, he kind of checked to make sure and if not he would explain what that meant.”
Use the whole team to support the informed consent process“…overall it was nice to have the whole team in the room.”
Explain the study multiple times“He kind of went over it 3 times, and every time they went over it, they asked if we had any questions.”
Review the consent document in its entirety“Going over the paperwork. Before, a doctor would just give it to me. He'd say read it and then ask questions. She [new doctor] would actually do it step by step, and that made it a lot easier to understand.”
Summarize the treatment course and why the trial is being offered“Well I think [doctor] generally does a good job sort of summarizing where we've been and where we are and options about where we need to go…”

More Information: Content and Methods of Delivery

Parents and AYA patients/participants most frequently suggested that providing more information would be helpful. Specifically, they wanted additional information regarding the following: the risks, benefits, and goals of the study; the scientific background of the experimental agent; and objectives and logistical issues specific to phase 1 trials (ie, the need for inpatient admission or additional tests). Families also wanted to know about all their options and how their participation in the trial would help future patients. They also requested that the physician/investigator present a summary of the patient/participant's medical history. Furthermore, 6 parents and 1 AYA patient/participant suggested providing the clinical status of other trial participants.

Parents and AYA patients/participants frequently made recommendations about the IC document and associated educational material. Many families highlighted the need to receive this information in writing but also via audio and visual methods, suggesting the use of graphs, figures, videos, DVDs, fast facts (ie, 1-page summaries of clinical and research issues), podcasts, Internet content, electronic slide presentations, and CDs. Most interviewees indicated preferring more than 1 way to receive information, particularly at different times in the consent process.

Informed Consent Process: Structure and Presentation

Patients/participants and families also voiced concerns about having enough time and being adequately prepared to make their decision. Many suggested providing information in advance of the ICC, including general information about clinical trials and details of the trials the family and AYA patient/participant could consider. Specifically, families suggested sending protocol summaries and/or actual consent forms in advance.

Parents and AYA patients/participants also suggested explaining the study multiple times, stopping periodically to ensure their understanding, and having a follow-up meeting to allow the family to discuss their options before making a final decision. They also noted the importance of the physical environment and recommended providing a comfortable space rather than an examination room for the ICC.

Physician/Investigator-Specific Suggestions: Communication Style and Strategy

Participants in the current study preferred that information be provided in a straightforward and honest manner, tailored to their needs and learning styles, while ensuring that all of their questions were answered. An explicit recommendation from study participants was to have a physician or a medical team member regularly available to respond to questions and concerns.

The participants' responses indicated that they would like physicians to guide their decisions about enrollment in a phase 1 trial. They want clinicians to explore the family's goals and values and then provide expertise and a transparent explanation of his or her values when providing an opinion regarding trial participation. In other words, families would like to know how an expert in the field would make a decision about trial participation if the expert shared the family's goals and values.

Participants also suggested that other members of the interdisciplinary team, such as registered nurses, nurse practitioners, social workers, psychologists, and chaplains, could be included in the decision-making process to provide a sounding board for parents as they work through the ramifications of their possible choices.


Enrollment in a phase 1 trial is among the most difficult decisions that the parents of a child with cancer must make.[18, 19] Parents and AYA patients/participants emphasized their need for physicians to recognize this struggle and to demonstrate a compassionate, personal, and involved approach to the ICP. High-quality physician communication is associated with a greater likelihood of parents being comfortable with their preferred decision-making role.[20] The majority of parents of children with cancer prefer to share the responsibility for decision-making with the physician. Shared medical decision-making includes careful consideration of which options best promote the patient's interests, and minimizes harm to the patient and family, while ensuring that all options represent responsible therapeutics.[21] Parents and AYA patients/participants depend on physician/investigators to demonstrate these values during the phase 1 ICP and to provide guidance in the decision-making process. Given their dual role as both health care provider and researcher, physician/investigators must remain aware of their influence over patients and their families and the associated problems it may cause ethically and scientifically.[22]

Parents and AYA patients/participants in the current study recommended improvements in communication similar to those already reported.[23, 24] We suggest that physician/investigators evaluate their communication throughout the ICP, especially in relation to the goals and objectives of phase 1 trials. Physician/investigators must better communicate the goals and objectives of the trial under consideration, and the most effective ways of delivering this information should be studied. The literature further supports the use of an interdisciplinary team, because the availability of psychosocial resources has been linked to decreased decisional regret and improved bereavement outcomes.[21]

The responses of the interviewees in the current study clearly demonstrated that information should be tailored to the needs and learning styles of ICP participants. Physicians could accomplish this by organizing a short meeting in which, through a brief question-and-answer session, they ascertain what kinds of information the family and patient desire and how best they understand information. This method would allow physicians, who may be unacquainted with the family and patient, to better understand their needs and to tailor their presentation of more difficult subject matter to the learning styles of the family/patient. Researchers should also consider the increased use of a variety of visual and auditory formats when presenting phase 1 studies. Multimedia methods designed with the input of research participants have proven feasible in the phase 3 clinical trial ICP.[13] Although to the best of our knowledge no such data exist for phase 1 trials, we hope to use and assess a similar methodology to help create interventions to improve the phase 1 ICP. This approach may enhance the understanding of treatment options, thereby helping families to make better-informed decisions, especially during the emotionally and mentally taxing time that a cancer recurrence brings. Requests for more information regarding the clinical status of other trial participants may have reflected the persistence of a therapeutic misconception in the minds of interviewees. Moreover, it would be difficult to accommodate the request due to the typical use of blinded outcome data and the right to protect confidentiality. This suggests a need to carefully revisit the goals of phase 1 trials and that potential participants may be seeking information about the trial drug's efficacy and potential side effects on which to base their decisions.

Suggestions for more than one ICC are consistent with the findings of a study by our group that demonstrated that an approach comprising 2 meetings and regularly stopping to check for understanding was helpful in improving parents' and patients' understanding of phase 3 trials.[13] This approach, as well as integrating interdisciplinary teams, could help to recognize and address concerning issues such as therapeutic misconception exhibited by parents and/or AYA patients/participants.

Study Limitations

All participants in the current study elected to enroll in the phase 1 trial being presented; therefore, families who declined enrollment were not represented. In the entire study sample, only 2 families declined enrollment after the ICP and did not participate in subsequent study interviews. In addition, most suggestions originated from an ICP experience that patients and families found satisfactory. Participants pointed to helpful practices by the research team as the basis for their suggestions. Future research should examine the experiences of those families who choose not to enroll in a phase 1 trial to understand more clearly the reasons for their refusal. In addition, these responses largely represent answers to a single question within a larger interview, and our method may not have been the best way to identify recommendations. Further suggestions may have resulted if a greater emphasis on the topic had prompted additional probing during the interview itself. Another limitation is that the small sample size limited the statistical comparison of suggestions between AYA patients/participants and their parents. Providing age-appropriate support to AYA patients is needed, and larger mixed-methods studies could focus more specifically on the differences in the perception of AYA patients and their parents regarding the goals, risks, and benefits of phase 1 trial participation, leading to more effectively tailored interventions. Failing to evaluate the impact of obtaining assent rather than consent in AYA patients/participants is also a study limitation. Assent of patients aged < 18 years and the consent of older patients may have differentially affected their experience of the ICP, thereby influencing their response when prompted for suggestions.


In the current study, parents and AYA patients/participants provided specific, clinically relevant recommendations to research teams on the basis of their ICP experience. This report begins to give voice to AYA patients/participants in phase 1 trials and to prepare physician/investigators for their increasing role in the health care of these individuals. Interview responses highlight patients' and parents' needs for information about the phase 1 trial and development of the experimental agent, appreciation of the individual needs of families, and more time for decision-making that maximizes the families' ability to consider participation and make the most informed decision possible. Physician/investigators should incorporate these recommendations into the phase 1 ICP. We plan to build on this work by inviting parents who participated in the study and agreed to future contact to help develop more specific improvements of the phase 1 trial ICP.


Supported by National Institutes of Health grant R01CA122217 and the American Lebanese Syrian Associated Charities (ALSAC).


The authors made no disclosures.