November 2008 ⅐ Vol. 10 ⅐ No. 11 article A pilot assessment of parental practices and attitudes regarding risk disclosure and clinical research involving children in Huntington disease families Leon S. Dure, MD1, Kimberly Quaid, PhD2, and T. Mark Beasley, PhD3 Purpose: To characterize parental practices of informing children of risk for Huntington disease (HD), and to understand the attitudes of parents concerning childhood participation in HD research. Methods: An anonymous Internet survey was accessed by individuals of HD families. The survey probed for data regarding individual risk for HD, as well as when or if children had been informed of the disease. Respondents expressed their attitudes concerning childhood participation in HD clinical research. Results: Two hundred forty-nine individuals responded (ϳ80% female), and 84% had never participated in an HD clinical trial. Seventy-five percent of respondents were parents; nearly two thirds of them had provided some information about HD to their children. There was overwhelming support for affected, at-risk, and unaffected adults in terms of HD research participation, but there was a statistically significant disparity by gene status, with gene negative and symptomatic gene positive adults being more inclined to participate than at-risk or asymptomatic/gene positive adults. More than 50% of respon- dents supported childhood participation, but typically in late adolescence (15–18 years). Gene negative and symptomatic adults were statistically more likely to agree with childhood inclusion than at-risk or asymptomatic/ gene positive adults. Conclusion: These results serve as pilot data for further investigations to address childhood participation in HD research. In addition, these findings will inform ongoing studies as to appropriate practices to undertake to include minors. Genet Med 2008:10(11):811–819. Key Words: Huntington disease, clinical research, childhood participation, genetic epidemiology, informed consent, assent Huntington disease (HD) is an autosomal dominant disor- The Huntington Study Group (HSG) is an international or- der characterized by the appearance in midlife of chorea, inco- ganization of clinical investigators dedicated to developing ordination, and a gait abnormality.1 It is caused by an ex- clinical trial initiatives with the stated goal of discovering an panded trinucleotide repeat of cytosine, adenine, and guanine effective treatment for the disease. A number of trials have been carried out, yet no clearly effective treatment modalities (CAGn) in the Huntington gene on the short arm of chromo- some 4, and affects approximately 4–10 people per 100,000 of have been identified.6,7 A recent initiative undertaken by the the general population. Because of its somewhat late appear- HSG is the Cooperative Huntington Observational Research ance, individuals who carry the gene for Huntington disease Trial (COHORT), involving sites in the United States, Canada, often have already begun their families before the onset of and Australia. The study objective is “to collect prospective symptoms. The disorder is progressive, with no effective cure. data from individuals who are part of an HD family, in order to Recent work suggests that there may be a prodrome of behav- relate phenotypes between individuals and families with each other and genetic factors in order to learn more about HD, ioral and psychiatric pathologies that antedates the motor syn- develop potential treatments for HD, and to plan for future drome, and this remains an ongoing area of investigation.2–5 research studies of experimental drugs aimed at slowing or postponing the onset and progression of HD,” (I Shoulson et al., personal communication). Inclusion criteria are directed at 1 From the Departments of Pediatrics and Neurology, The University of Alabama at Birming- individuals who have clinically diagnosed Huntington disease, ham School of Medicine, Alabama; 2Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana; 3Department of Biostatistics, School of Public Health, or are at risk for the disorder. First-degree relatives including The University of Alabama at Birmingham, Alabama. parents, siblings, and children are eligible for recruitment. In Leon S. Dure, MD, 1600 7th Avenue South, 314 CH, Birmingham, AL 35233. E-mail: addition, family members with no risk of Huntington disease [email protected]. are encouraged to participate, in an attempt to develop a co- Disclosure: The authors declare no conflict of interest. hort of unaffected individuals. Submitted for publication June 7, 2008. As part of the study, individuals will be seen on a regular Accepted for publication August 14, 2008. basis, and at each visit undergo a neurologic examination, as DOI: 10.1097/GIM.0b013e31818adb01 well as an interview regarding family and medical history. Each Genetics IN Medicine 811 Dure et al. participant will provide a blood specimen, an aliquot of which the activities in a particular study may be received by potential will be analyzed for CAG repeat length, and the remaining participants. In a study of parental attitudes regarding child- stored in a central facility, a biobank, which will serve as a hood participation in a genetic study of hearing loss, Gillam et repository for basic science research. To date, over 1000 indi- al.14 were able to illustrate particular issues relating to genetic viduals have been enrolled. literacy and competence of parents, as well as to identify atti- During the planning stages for this study up to the present tudes affecting consent. While serving to provide some insight time, there have been a number of discussions revolving into how a particular clinical trial may need to be structured for around the enrollment of minor children. Currently, only the inclusion of children, we have adopted a modification of symptomatic children have been enrolled, but there is a scien- this type of effort to access parental attitudes regarding child- tific basis to encourage the participation of unaffected and at- hood participation in HD clinical research. Using an anony- risk minors. This includes the fact that Huntington disease is in mous Internet survey structured in such a way as to obtain all likelihood a disorder with a definable phenotype that pre- basic demographic and historical information, we have de- dates the appearance of motor symptomatology.2,4,5,8 In addi- rived pilot data regarding parental practices of informing their tion, it is as yet unclear as to why individuals with identical children of the presence of HD in the family. Our results sug- mutations may have quite variable ages of onset. These varia- gest a variety of mechanisms with which COHORT may be tions are felt to be due to either other genetic or environmental adapted to ethically enroll minors, and to be sensitive to paren- factors. Because it is reasonable to suppose that interventional tal attitudes regarding juvenile inclusion. In addition, this pilot trials would have the most impact earlier in the course of the has also prompted a number of other investigations which will disease, thorough and early characterization of individuals is be necessary to fully capture juvenile participation in HD clin- warranted. Thus, the inclusion of minor children in COHORT ical research. Indeed, this mechanism could serve as a template may not only help to illuminate early signs of HD, but also for other genetic observational studies. assist in understanding what at some point may be a distinct study population. Despite the intent to include children, there have been con- METHODS cerns raised regarding the processes of enrollment, particularly the issue of consent. Although parents may be considered as a The Internet survey was created on Survey Monkey (www. proxy for a child’s participation in clinical research, there is a surveymonkey.com), and was reviewed and approved by the consensus that assent of a child should be obtained if that child Institutional Review Board of the University of Alabama at is to participate in clinical research,9–11 and US federal regula- Birmingham. The survey was linked to two Web sites, that of tions require such assent.12 Although the provision for child- the Huntington Disease Society of America (HDSA) and the hood assent is currently in widespread use in a variety of clin- HSG. The link was active from May 2007 to October 2007 (150 ical trial initiatives, the application is somewhat problematic days). No respondents were included in the data set after that for Huntington disease. One reason for this relates to the fact time, when the links were removed. that before the recruitment of a child into an HD study such as Consent for participation was implied by completion of the COHORT, the child must know why he/she is eligible for in- survey. Other than gender, age, and HD-related information, clusion. Currently, little is known how HD families process no personal information was obtained. There were 251 respon- information regarding risk, making it difficult to assess a likely dents to the survey. Periodic review of completed surveys was age at which a child would be capable of assent. In addition, performed by one of the authors (LSD) to gauge activity and there are concerns regarding the disposition of biobank mate- response totals. Upon completion of data collection, the data- rial, specifically relating to confidentiality and the determina- set was downloaded from the survey site in a spreadsheet for- tion of the presence or absence of the HD mutation.13 Parental mat for review and analysis. attitudes toward participation are not currently known, nor is The survey was designed in multiple parts. There was no there a good understanding of when children in HD families attempt to force completion of any particular question in the learn of their risk for disease. Finally, the impact of participa- survey. However, upon completion of certain questions, the tion by children remains an open question. Clearly, these issues survey would direct the respondent to a particular set of ques- will need to be resolved to satisfy both regulatory and social tions (see Fig.