OBJECTIVE: Critics argue that pediatric research without the potential for clinical benefit is unethical because it treats children as mere means, exposing those who cannot consent to risks for the benefit of others. The present survey was designed to assess whether this claim is consistent with the views of adolescents who actually participate in research, or their parents.
METHODS: Interviews were conducted with adolescents participating in research at the NIH Clinical Center or Seattle Children's Hospital, and their parents, from June 2008 through April 2010.
RESULTS: Interviews were completed with 177 of 186 adolescent/parent pairs (response rate= 95.2%). Overall, 90% of the adolescents and parents were willing to have the adolescent undergo a few extra blood draws, and 65% were willing to have the adolescent undergo an extra skin biopsy, for research purposes. The vast majority felt that the adolescents were making an important contribution to help others, and 80.8% of the adolescents felt proud to be doing so. Respondents overall were equally willing to have the adolescent face risks to help others in a research study or in a charitable activity.
CONCLUSIONS: The views and experiences of these respondents do not support the claim that pediatric research without the potential for clinical benefit treats subjects as mere means. Instead, the findings provide proof of principle for the claim that non-beneficial pediatric research involves a type of charitable activity which offers children the opportunity to contribute to a valuable project to help others.
- NIH —
- National Institutes of Health
What’s Known on This Subject:
Critics argue that pediatric research without the potential for clinical benefit treats children as mere means to benefit others. Yet, there are no data to assess whether adolescents who participate in research, or their parents, agree with this view.
What This Study Adds:
Respondents felt that by participating in research the adolescents were making important contributions to help others, and the adolescents felt proud to be doing so. These findings support the view that nonbeneficial pediatric research involves a type of charitable activity.
Clinical research frequently exposes children to risky procedures to collect data that might benefit future patients.1,2 This occurs in studies that pose risks but do not offer any potential for clinical benefit, such as phase 1 studies in healthy volunteers. It also occurs in studies that offer the potential for clinical benefit but include purely research procedures, such as research blood draws and research imaging scans.
Because children are not competent to consent, these “nonbeneficial” studies and procedures raise important ethical concerns.3,4 Some critics argue that nonbeneficial pediatric research is unethical because it treats nonconsenting children as mere means to benefit others.5–7 This view is endorsed by many commentators,8 as well as pediatricians9 and chairs of ethics committees.10 In the only US court case to explicitly address nonbeneficial pediatric research, the Grimes court argued that it is unethical to enroll children in research that offers subjects a “negative” risk/benefit profile.11 This view, if widely endorsed, could undermine research needed to improve pediatric medical care.12
The present study evaluated this view by assessing to what extent it is consistent with the views or experiences of adolescents who participate in research, or their parents. What do adolescent subjects and their parents think about the practice of exposing children to research risks for the benefit of others? What is it like for adolescents to participate in research studies that perform risky procedures on them to collect information to benefit others?
Two draft survey instruments, one for adolescents and one for their parents, were developed using an iterative process that began with a comprehensive literature review and included numerous rounds of revision based on input from statisticians, experts on the ethics of pediatric research, and survey professionals at Research Triangle Institute. Several questions were adapted from a previous survey.13
The draft surveys underwent successive rounds of cognitive pretesting with adolescents at the National Institutes of Health (NIH) Clinical Center who met the eligibility criteria for the study, and their parents. The cognitive pretests used a “think-aloud’ approach that allows investigators to assess whether eligible respondents understand the questions in the way the investigators intend them. For example, cognitive pretest respondents were asked to describe their understanding of the draft question regarding their willingness to undergo (allow their child to undergo) a research biopsy. The draft question was revised until respondents understood that the research biopsy posed some risks to the child and offered no potential for clinical benefit. Cognitive pretesting and instrument revision were continued until respondents consistently understood all the draft questions.
The final draft instruments then underwent behavioral pretesting. During this stage, the survey was completed with eligible respondents in the same way that was planned for the actual study. Behavioral pretesting allowed for evaluation of the implementation and impact of the survey and ensured that it could be completed in the allotted time (30 minutes). The final English versions were translated into Spanish, pretested with Spanish-speaking adolescent-parent pairs, and revised accordingly.
The final surveys evaluated 4 domains: (1) consent/assent, (2) motivations, (3) decision-making, and (4) attitudes regarding pediatric research. This article describes the results from the fourth domain. The questions in the fourth domain were multiple choice, with the exception of 2 questions that asked respondents to explain their previous answer (see Supplemental Information for verbatim questions).
The surveys were conducted in person by interviewers who were specifically trained for this study and who were independent of the clinical trials in which the adolescent respondents were enrolled. The adolescents and their parents were interviewed concurrently and separately. The interviews lasted ∼30 minutes on average. The interviewers read the questions and recorded respondents’ verbatim answers. Respondents were provided with a copy of the survey so that they could read along while the questions were being read to them.
Adolescents were eligible if (1) they were 13 to 17 years of age, (2) had enrolled in the previous 6 months in a research study for any disorder or as healthy controls at the NIH Clinical Center or Seattle Children’s Hospital, (3) spoke English or Spanish, and (4) had a parent or guardian who agreed to be interviewed. Adults were eligible if (1) they were the parent or guardian of an eligible adolescent who agreed to be interviewed and (2) spoke English or Spanish. Previous experience suggested that most adolescents would be accompanied by their mothers. Thus, when both parents were present, the father was invited to participate.
To ensure broad representation of studies and illnesses, we attempted to invite all eligible adolescents who came to the 2 sites during the study period. Investigators of all studies open to children at the NIH were contacted regularly during the study period and asked to refer any potentially eligible adolescents. In addition, advertisements were placed in the pediatric units so potential respondents could self refer. At Seattle Children’s, a research coordinator contacted investigators who were studying cancer, diabetes, or hepatitis on a regular basis and asked them to refer any potentially eligible adolescents. Participating adolescents received a gift card worth $20; parents were not compensated.
This study was approved by the institutional review boards for the National Institute of Child Health and Human Development, Seattle Children’s Hospital, and Research Triangle Institute. Written parental permission and written adolescent assent were obtained before all interviews. The adolescents and their parents were informed that participation was voluntary and that refusal to participate would not affect the adolescent’s care or research participation in any way. Respondents were also informed that their answers would remain confidential.
This is the first study of which we are aware to evaluate the views and experiences of adolescents with respect to nonbeneficial pediatric research. Thus, rather than attempt to test unsubstantiated a priori hypotheses, we conducted an exploratory analysis to evaluate whether any of 13 potentially relevant, dichotomized variables were significant: study site (NIH vs Seattle Children’s), adolescent’s age (13–15 vs 16–17 years), parent’s age (<45 vs ≥45 years), household income (<$50,000 vs ≥$50,000), adolescent’s gender (male vs female), parent’s gender (male vs female), parent’s self-reported race/ethnicity (white and non-Hispanic vs all others), parent’s education level (some college or less vs completed college or graduate school), adolescent’s health (ill vs healthy), impact of illness on adolescent (can do few or no activities vs can do most or all activities), time since diagnosis (≤6 months vs >6 months), home location (city or suburb vs town or rural area), adolescent’s birth order (middle or youngest vs oldest or only child). Individual χ2 tests were used to evaluate associations among these 13 dichotomized variables and the questions in the fourth domain. All P values reported are unadjusted for multiple comparisons. If a variable is not mentioned in the Results section, it was not significant. Because we evaluated multiple variables, it is possible that some of the significant findings are due to chance alone.
For the 2 open-ended, follow-up questions, 1 author (DW) created a list of response categories based on assessment of a random sample of 10 surveys. This list was refined by a second author (LW) based on assessment of an additional 10 surveys. The 2 authors then independently coded the open-ended responses using these categories. Disagreements were discussed, and any remaining disagreements were settled by a third author (CG).
Overall, 177 of 186 adolescent-parent pairs who were approached completed the survey, 147 at the NIH Clinical Center and 30 at Seattle Children’s (Table 1). This represents a response rate of 95.2%, although it is not possible to determine whether any potential respondents decided not to participate after reading the advertisements or after discussing the survey with their primary research team.
Of the adolescents, 51.4% were girls; 72.3% had a significant illness, and 20.9% were healthy. Mean age was 15.1 years (Table 1). Based on self-report, 69.5% of the adolescents were white, 14.7% were African American, and 12.4% were Hispanic. Of the adults, 76.3% were women, and mean age was 45.3 years; 173 were the parent of the participating child, 4 were the legal guardian. The self-reported race and ethnicity of the parents and guardians was similar to that of the adolescents.
Overall, 59.9% of the adolescents were participating in a study that did not offer the prospect of clinical benefit and included nonbeneficial research procedures (Table 1). In addition, 33.3% were participating in a study that offered the prospect of clinical benefit but included nonbeneficial procedures, such as purely research biopsies, imagining scans, or blood draws.
Views of Current Research Participation
Overall, 84.7% of the adolescents and 87.1% of their parents indicated that “helping find better treatments for others who are ill” was “pretty important” or “very important” to their decision to enroll (the adolescent) in research (data not shown). When asked “How much do you think you are (your child is) helping others by being in your (his/her) current research study?” 68.9% of the adolescents and 78.0% of the parents felt the adolescent was “helping a moderate amount” or “helping a lot” (data not shown).
When asked “How does it make you feel to be in a medical research study that is collecting information from you to help future patients?” 80.8% of the adolescents indicated that they felt “proud,” 5.7% indicated that they felt like a “guinea pig,” and 8.5% indicated that they felt both ways (Fig 1). Based on χ2 statistics with 1 degree of freedom, comparing adolescents who answered “proud” to adolescents who answered either that they felt “like a guinea pig” or that they felt both proud and like a guinea pig, adolescents whose parents earned ≥$50 000 per year were significantly more likely to report feeling like a guinea pig compared with children whose parents earned <$50 000 per year (5.02, P = .03). Similarly, adolescents who lived in an urban or suburban area were significantly more likely to report feeling like a guinea pig compared with children who lived in a town or rural area (7.04, P = .01).
Adolescents who stated that participating in research to help others made them feel like a “guinea pig” were asked to explain why they felt this way. The responses suggest that many of the adolescents do not regard feeling like a guinea pig as necessarily problematic (Fig 1). For example, one adolescent stated that he felt “very proud, being a guinea pig not bad.”
Willingness to Face Research Risks to Help Others
Overall, 90.4% of the adolescents and 91.6% of the parents were “definitely” or “probably” willing to allow the research staff to “draw your (your child’s) blood a couple of extra times if it would not help you (your child) but would help them learn something that might help others” (Fig 2). Similarly, 64.4% of the adolescents and 65.5% of the parents were “definitely” or “probably” willing to allow the adolescent to undergo “an extra skin biopsy, where the doctor takes a small piece of your (your child’s) skin to examine it? It might hurt and might leave a tiny scar, but has very little risk.”
On the basis of a χ2 statistic with 1 degree of freedom, comparing only adolescents who answered “definitely willing” or “probably willing” to those who answered “definitely not willing” or “probably not willing,” adolescents who had been diagnosed >6 months earlier were significantly more likely to be willing to undergo the skin biopsy compared with adolescents who had been diagnosed within the previous 6 months (4.90, P = .03).
Finally, to compare respondents’ attitudes toward nonbeneficial pediatric research studies versus charitable activities, they were asked: “If there was the same risk of spraining your ankle in both activities, would you be more willing to (allow your child to) help others by volunteering for a medical research study or by volunteering for a charity after school?” Overall, 67.2% of the adolescents and 80.2% of their parents were equally willing to have the adolescent participate in both activities, 14.7% of the adolescents and 5.5% of their parents preferred participation in research, and 11.9% of the adolescents and 3.4% of the parents preferred that the adolescent participate in a charitable activity (Fig 3).
Critics argue that pediatric research studies and procedures that do not offer the potential for clinical benefit treat nonconsenting children as mere means to benefit others. This view casts ethical doubt on most pediatric research and, if widely endorsed, could undermine society’s ability to improve pediatric medical care.
The views of respondents to this survey were not consistent with this view. The vast majority stated that by participating in research, the adolescent was making an important contribution to help others, and the vast majority of the adolescents felt proud to be doing so. These findings are noteworthy given that 93.2% of the adolescent respondents were participating in studies that included nonbeneficial research procedures.
These findings highlight an important mistake in critics’ arguments against nonbeneficial pediatric research. Critics rightly point out that children are not competent to consent to research. Yet critics miss the fact that children who are not competent to consent can nonetheless make important contributions to help others and can personally value the opportunity to do so. This possibility provides proof of principle for a novel way to assess the ethics of pediatric research that do not offer the potential for clinical benefit. Specifically, the findings provide empirical support for the possibility of regarding nonbeneficial pediatric research studies and procedures as a type of charitable activity in which children face risks for the benefit of others.14 Future research is needed to assess this view in a broader range of children, especially children who have not already agreed to participate in research.
Previous surveys have evaluated children’s and their parent’s views of pediatric research that offers the potential for clinical benefit.15–26 A few studies have attempted to collect empirical data on pediatric research that does not offer the potential for clinical benefit.27 Unfortunately, most of these studies failed to state explicitly that the research in question posed risks.28 For example, one survey found that many parents were willing to allow their child to donate a clipping of hair as part of a research study.29 However, respondents may have assumed that providing a clipping of hair posed no risks.
A previous survey, from which several of the questions in the survey described here were adapted, evaluated the attitudes of children with a mean age of 10.1 years and their parents regarding pediatric research that poses some risks and does not offer any potential for clinical benefit.13 This previous survey found that the majority of respondents considered pediatric research without the potential for clinical benefit to be appropriate. Although these results are important, they are limited to children with cancer or asthma. In addition, empirical data suggest that most children do not begin to develop an adequate understanding of clinical research until 12 to 14 years of age.30,31 To provide a more effective evaluation of critics’ concerns regarding nonbeneficial pediatric research, our study surveyed children aged 13 to 17 years who had a broad range of conditions, as well as healthy volunteers.
The Present Findings
The present findings undermine the claim that pediatric studies and procedures without the potential for clinical benefit inappropriately treat children as mere means to benefit others. First, the vast majority of adolescent respondents and their parents were willing to have the adolescent face research risks for the benefit of others. This finding suggests that respondents consider it appropriate to expose adolescents to some research risks when doing so offers the potential to benefit others.
Second, 8 in 10 respondents indicated that helping to find better treatments for others who are ill was an important reason for them to enroll in research. Third, 93% of respondents were involved in studies that included nonbeneficial research procedures. Most felt that the adolescent was thereby helping others, and 8 in 10 of the adolescents felt proud to be doing so. These findings suggest that the vast majority of the adolescents surveyed found the experience of undergoing research procedures for the benefit of others to be more like that of a valuable contributor, as opposed to a mere means used to benefit others.
Fourth, respondents overall were equally willing to have the adolescent help others by participating in research or by participating in a charitable activity. Assuming that the respondents consider charitable activities for children to be appropriate, this finding suggests that the vast majority also regard nonbeneficial clinical research as an appropriate opportunity for children to help others, even when it poses some risks. Consistent with numerous studies that have found that adults often are motivated to enroll in research to help others,32–34 the current study establishes that adolescents also can be motivated by and embrace the opportunity to help others by participating in research.
A few adolescents stated that participating in clinical research to help others made them feel like guinea pigs. Future research is needed to evaluate what factors are associated with pediatric subjects feeling like important contributors, and what factors are associated with their feeling that they are being treated as mere means to benefit others. In the present survey, the term ‘guinea pig’ had positive connotations for some respondents, and negative connotations for others. Hence, use of the term ‘guinea pig’ alone may not be sufficient to identify individuals who feel that they are being inappropriately treated as mere means.
US regulations allow institutional review boards to approve pediatric research that does not offer the “prospect of direct benefit” only when the risks are “minimal” or a “minor increase” over minimal.35,36 The examples used in the present survey were intended to evaluate respondents’ views of research that poses these levels of risk. Specifically, the example of several blood draws was intended to represent a “minimal risk” procedure; the skin biopsy was intended to represent a procedure that poses a “minor increase” over minimal risk. The fact that the majority of adolescent and parent respondents were willing to have the adolescent undergo these procedures suggests that they endorse nonbeneficial pediatric research when it falls within these risk limits.
We found that adolescents who had been diagnosed >6 months earlier were significantly more likely to be willing to undergo a research skin biopsy compared with adolescents who had been diagnosed within the previous 6 months. Future research is needed to confirm and explain this finding. Although not addressed by the data, it seems plausible to assume that individuals who are recently diagnosed will be more focused on obtaining treatment, whereas individuals who have been diagnosed in the past will be more willing to help others who are ill. A second possibility is that time since diagnosis may correlate with type of disease, which may influence individuals’ willingness to participate in nonbeneficial research. Third, time since diagnosis may be positively correlated with length of time spent in research. If so, individuals who have spent more time in research may have increased trust in researchers, increased comfort with research procedures, and/or increased recognition of the value of research.
These findings are subject to at least 4 important limitations. First, to evaluate adolescents’ experiences with nonbeneficial research, we surveyed adolescents and their parents who had already agreed to enroll the adolescent in research. Future research is needed to assess the extent to which our findings are consistent with the views of adolescents and parents who have not been involved in research. Second, participants were enrolled at only 2 sites. Future research is needed to assess the views of children and parents at other sites. Third, although 95.2% of those who were approached agreed to participate, it is not possible to determine how many potential respondents might have decided not to participate after reading an advertisement or discussing the study with their primary research team. Fourth, while the percentages of respondents in different racial and ethnic groups was similar to that of the US population in general in terms of absolute numbers, relatively few respondents were from minority groups.
Critics argue that pediatric research studies and procedures without the potential for clinical benefit are unethical because they treat nonconsenting children as mere means used to benefit others. The vast majority of respondents to the present survey did not endorse this view. They felt that by participating in nonbeneficial clinical research, the adolescents were making a valuable contribution to help others, and the vast majority of the adolescents felt proud to be doing so.
These findings provide proof of principle for a novel way to assess the acceptability of pediatric research studies and procedures that do not offer the potential for clinical benefit. Specifically, the findings provide empirical support for the view that participation in nonbeneficial research, like involvement in charitable activities, offers children the opportunity to make important contributions to help others. This view suggests that nonbeneficial pediatric research studies and procedures, like charitable activities, can be appropriate when parents give their permission, the children assent, the risks are low, and the activity offers the potential to benefit others in important ways.
We thank the respondents for their time and effort. Statistics Collaborative provided the statistical tabulations. Susan Hilsensbeck, PhD, provided statistical guidance. Research Triangle Institute provided study organization and data entry. Statistics Collaborative and Research Triangle Institute received payment for their contributions.
- Accepted June 4, 2012.
- Address correspondence to David Wendler, PhD, Department of Bioethics, NIH Clinical Center, Building 10, Room 1C118, Bethesda, MD 20892. E-mail:
All authors contributed to the manuscript and approve of its being submitted for publication. Drs Grady and Wendler conceived of the project. Drs Grady, Wiener, and Wendler, and Ms Abdoler designed the survey; Drs Grady, Wiener, and Wendler, and Ms. Abdoler collected the data; Dr Wendler wrote the first draft; Drs Grady, Wiener, and Wendler, and Ms. Abdoler revised the manuscript for important intellectual content; and Drs Wendler and Grady had full access to the data.
This work was completed as part of the authors’ official duties as employees of the National Institutes of Health Clinical Center. The opinions expressed are the authors’ own. They do not represent the position or policy of the US National Institutes of Health, Public Health Service, or Department of Health and Human Services.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: This work was supported by the Intramural Research Program at the National Institutes of Health Clinical Center and National Institutes of Health Program Evaluation Funds. The Clinical Center and the Evaluation Program had no role in the analysis of the data, writing of the manuscript, or the decision to submit the manuscript for publication. Funded by the National Institutes of Health (NIH).
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- Copyright © 2012 by the American Academy of Pediatrics