Adolescents’ preferences regarding disclosure of incidental findings in genomic sequencing that are not medically actionable in childhood

INTRODUCTION

The development of less expensive genomic sequencing and its increased clinical use has renewed the debate about predictive genetic testing in asymptomatic minors for conditions that are not medically actionable in childhood.

When the test for Huntington disease (HD), one of the first predictive genetic tests in clinical practice, was developed, a consensus formed that predictive testing should not be performed on asymptomatic minors [International Huntington Association and the World Federation of Neurology Research Group on Huntington's Chorea, 1990]. Arguments against testing focused on potential harms including decreasing self-esteem, increasing anxiety, and limiting future choices [Malpas, 2006; Mand et al., 2012]. As this test was used in clinical practice, the predictions of severe negative psychological consequences were not fulfilled [Duncan and Delatycki, 2006; Wade et al., 2010], and arguments regarding potential psychological and social benefits developed, for example, decreasing anxiety, and facilitating family and career planning [Malpas, 2008; Mand et al., 2012]. Later policy statements from professional organizations articulated a presumption against, rather than a prohibition of, testing [Ross et al., 2013].

With improvements in technology, genomic sequencing has become less expensive than serially testing of single genes or testing panels of genes in some clinical contexts. Sequencing's potential uses in pediatrics, including clinical management in neonatal intensive care and alternative approaches to newborn screening, are currently being investigated [National Institutes of Health, 2013]. Genomic sequencing has the potential to identify variants in genes not associated with the phenotype that prompted the testing or to be used as a screening test [Burke et al., 2013]. For example, when sequencing is performed on minors with intellectual impairment, incidental findings could be identified in genes for adult onset conditions for which no medical interventions are available in childhood, for example, BRCA1 or BRCA2, genes with known predisposition to hereditary breast and ovarian cancer.

This new technology as renewed the ethical debate. The American College of Medical Genetics and Genomics’ (ACMG's) initial policy on incidental findings stated that medically actionable incidental findings should be sought and returned in panel of 57 (later revised to 56) genes irrespective of patients’ preference or age. The College argues that, given parents do not currently have easy access to low cost sequencing, this information may indirectly benefit children because their parents might otherwise be unaware of their risks [Green et al., 2013]. The policy engendered significant controversy [Burke et al., 2013; Wolf et al., 2013]. While much of the attention has focused on adults’ ability to decline incidental findings, some have discussed the testing of minors [Ross et al., 2013]. While some of the older arguments are not applicable to this context (testing is generally done in the absence of a positive family history and, therefore, anticipatory anxiety is decreased) and there are some new arguments (it is not feasible for laboratories to mask analysis of specific genes), many of the issues are similar.

In analyzing this issue, there is limited empirical data regarding parents’ and adolescents’ preferences for the return of incidental findings that are not medically actionable in childhood. Fernandez et al. [2014] surveyed parents of children at risk for genetic abnormalities. Eighty-three percent desired to receive incidental findings even if there were no preventive or therapeutic options. Kleiderman et al. [2014] also found that most parents felt that they should be aware of such findings despite potential negative consequences. In the research context, Hens et al. [2009] report teenagers desire the return of medically important information and trust parental decisions.

The goal of this study is to determine adolescents’ views regarding the disclosure of incidental findings for adult onset conditions that are not medically actionable in childhood, to examine which arguments they find most and least compelling, and to characterize whether they wish to participate in the decision making process.

MATERIALS AND METHODS

We conducted a cross-sectional study of 7–12th graders attending public school in Cincinnati, Ohio. We developed a scripted educational presentation that addressed genetics and genetic testing, the nature, and potential uses of whole exome sequencing (WES), and the arguments for and against returning incidental findings that are not medically actionable in childhood (Online Supplemental Materials: Educational Presentation). We developed a survey to assess the students’ preferences regarding knowledge and participation and the rationales supporting these preferences. Reasons for and against disclosing incidental findings were adapted from Mand et al.'s [2012] literature review to reflect the differences between older forms of predictive genetic testing and genomic sequencing. Equal numbers of reasons for and against were presented to reduce bias. The survey was implemented in GoogleDocs, an application used in the school district and familiar to the students (Online Supplemental Materials: Survey). The presentation was approximately 8 min long and the survey took approximately 6 min to complete. Both the presentation and survey were written at the 7th grade reading level. The presentation and survey were evaluated for face validity by genetics clinicians and pilot tested on a convenience sample of adolescents. The students’ teachers also reviewed these tools to promote the use of familiar language and terms.

We identified three schools within the Cincinnati public school system with varied socioeconomic status, that is, the percentage of students on Aid for Dependent Children, the percentage who qualify for free or reduced-priced lunches, and median family income [2012]. The district required that the individual schools not be identified. The presentation and survey were conducted in 7–12th grade biology and life sciences classes. The students were provided an opt-out consent form that they were instructed to take home to their parents or guardians.

Cincinnati Children's Hospital Medical Center's Institutional Review Board and Cincinnati Public School's Research Board approved this study.

RESULTS

DISCUSSION

The results of this study demonstrate that the majority of adolescents surveyed desire to have access to incidental findings and to participate in health care decisions. Adolescents who wanted this information most frequently endorse the justification that knowing this information would enable them to plan for their futures. The majority of adolescents believed that they, together with their parents or by themselves, should be able to make decisions about receiving this information. Younger adolescents were less likely than older adolescents to want to know incidental findings and more likely to believe that neither parents nor adolescents should have access to this information.

The strong desire of adolescents in this study to receive incidental findings is consistent with the available information regarding adults’ preferences for themselves and their children. As previously mentioned, Fernandez et al. [2014] found that the majority of parents of children at risk for genetic abnormalities desired to receive incidental findings in WES even if there were no preventive or therapeutic options available in childhood. Kleiderman et al. [2014] also found that most parents felt that they should be aware of such findings despite potential negative consequences.

A major argument against presymptomatic predictive testing is preserving minors’ ability to make this decision for themselves as adults absent medical benefits of testing in childhood. The available data suggest minors are able to understand the potential benefits and risks of testing [Wiggins et al., 1992; Broadstock et al., 2000]. Duncan et al. [2008], for example, found that minors were able to state the arguments for and against predictive testing that had been described in the literature. Younger adolescents may have the ability to understand the risks, benefits, and alternatives, while older adolescents may have a more mature ability to appreciate and evaluate the information and make a voluntary decision [Silber, 2011]. The majority of participants in our study believed themselves capable of making decisions about incidental findings.

We found that adolescents endorsed relatively similar patterns of reasons for and against disclosure. This would suggest that rather than identifying different reasons, these individuals weigh the same reasons differently; some place greater emphasis on potential benefits and others on potential risks.

While there was not a statistically significant trend with age, there was a difference between 12-year olds and older adolescents in the rates of wanting disclosure, who should be the decision maker, and whether parents having the right to make the decision for children younger than 12. It is likely that the lower desire for disclosure may contribute to the differences in the decision maker and parental rights when children are under 12. Twelve-year olds’ lower rate of desiring disclosure may be influenced by their assessment of their own decision making capacity. Further research is needed to determine if this finding is reproducible and, if so, the reason(s) for it.

The ACMG has asserted that incidental findings should be disclosed regardless of age [Green et al., 2013]. The participants in this study would support access to these results. While the ACMG initially argued that adolescent assent should be sought for testing, it argued that return of incidental findings to the ordering clinician is intrinsic to testing and, therefore, if one did not wish the clinicians to receive the incidental findings, one should forego testing altogether [Green et al., 2013]. Our results support the College's revised policy allowing individuals to “opt-out” of ordering these additional results but not necessarily the recommendation that the decision apply to the entire list of genes [ACMG Board of Directors, 2015]. Contrary to the College's justification, many laboratories offer a variety of secondary results options [Hufnagel and Antommaria, 2014].

While this study has a number of strengths, it also has several limitations. Strengths include the study's high response rate: all students who attended class on the day of the presentation completed the survey. The study also includes the views of roughly equal numbers of males and females, as well as of a large number of African Americans; males and African Americans are often underrepresented in other studies [Garrison et al., 2015]. A major limitation is the fact that the study was conducted in a single school district, and therefore may have limited generalizability. Other limitations include the low participation of other racial groups and those of Hispanic ethnicity. The presentation could also inadvertently have introduced bias. The survey was not validated and did not assess understanding. Another limitation is that the survey questions were hypothetical; the participants were not actually undergoing WES. Their preferences regarding actual testing may differ.

The majority of adolescents in this study wished to receive incidental findings in clinical WES even if they were not medically actionable in childhood and the participants most commonly endorsed the justification that it may help them plan for their futures. The participants also wished to participate in decisions regarding testing and receiving results. Twelve-year olds were less likely than older adolescents to want to know incidental findings and believe that neither parents nor adolescents should have access to this information. This study provides preliminary information about these stakeholders’ view and should be considered in policy development.