An expansion in the availability of clinical drug trials for genetic neurodevelopmental conditions is underway. Delineating patient priorities is key to the success of drug development and clinical trial design. There is a lack of evidence about parent decision-making in the context of clinical drug trials for genetic neurodevelopmental conditions. We assessed parents’ priorities when making a decision whether to enroll their child with fragile X syndrome (FXS) in a clinical drug trial. An online survey included a best–worst scaling method for parents to prioritize motivating and discouraging factors for child enrollment. Parents were recruited through the National Fragile X Foundation and FRAXA. Sequential best–worst with conditional logit analysis was used to determine how parents prioritize motivating and discouraging factors about trial enrollment decisions. Respondents (N = 354) were largely biological mothers (83%) of an individual with FXS who ranged in age from under 5 to over 21 years. The highest motivating factor was a trial to test a drug targeting the underlying FXS mechanism (coeff = 3.28, p < 0.001), followed by the potential of the drug to help many people (coeff = 3.03, p < 0.001). Respondents rated requirement of blood draws (coeff = −3.09, p < 0.001), loss of access to the drug post trial (coeff = −3.01, p < 0.001), and drug side effects (coeff = −2.96, p < 0.001) as most discouraging. The priorities defined by parents can be incorporated into evidence-based trial design and execution to enhance the enrollment process.
Subscribe to Journal
Get full journal access for 1 year
only $33.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Tărlungeanu DC, Novarino G. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Exp Mol Med. 2018;50:1–7.
Bailey DB, Raspa M, Bishop E, Olmsted M, Mallya UG, Berry-Kravis E. Medication utilization for targeted symptoms in children and adults with fragile X syndrome: US survey. J Dev Behav Pediatr. 2012;33:62–9.
U.S. Food and Drug Administration. Learn about FDA patient engagement. U.S. Food and Drug Administration; 2020. https://www.fda.gov/patients/learn-about-fda-patient-engagement.
Berry-Kravis EM, Lindemann L, Jønch AE, Apostol G, Bear MF, Carpenter RL, et al. Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome. Nat Rev Drug Discov. 2018;17:280–99.
Reiss AL, Hall SS. Fragile X syndrome: assessment and treatment implications. Child Adolesc Psychiatr Clin N Am. 2007;16:663–75.
Hall SS, Lightbody AA, Reiss AL. Compulsive, self-injurious, and autistic behavior in children and adolescents with fragile X syndrome. Am J Ment Retard. 2008;113:44–53.
Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A, et al. Advances in the treatment of fragile X syndrome. Pediatrics. 2009;123:378–90.
U.S. National Library of Medicine. ClinicalTrials.gov. U.S. National Library of Medicine; 2020. https://clinicaltrials.gov/.
Fisher HR, McKevitt C, Boaz A. Why do parents enrol their children in research: a narrative synthesis. J Med Ethics. 2011;37:544–51.
Truong TH, Weeks JC, Cook EF, Joffe S. Altruism among participants in cancer clinical trials. Clin Trials. 2011;8:616–23.
de Vries MC, Houtlosser M, Wit JM, Engberts DP, Bresters D, Kaspers GJ, et al. Ethical issues at the interface of clinical care and research practice in pediatric oncology: a narrative review of parents’ and physicians’ experiences. BMC Med Ethics. 2011;12:1–11.
Mason SA, Allmark PJ, Group ES. Obtaining informed consent to neonatal randomised controlled trials: interviews with parents and clinicians in the Euricon study. Lancet. 2000;356:2045–51.
Becerra TA, Massolo ML, Yau VM, Owen-Smith AA, Lynch FL, Crawford PM, et al. A survey of parents with children on the autism spectrum: experience with services and treatments. Perm J. 2017;21:16–009.
Paquette E, Shukla A, Davidson J, Rychlik K, Davis M. Burden or opportunity? Parent experiences when approached for research in a pediatric intensive care unit. J Ethics Hum Res. 2019;41:2–12.
Johnson FR, Beusterien K, Özdemir S, Wilson L. Giving patients a meaningful voice in United States regulatory decision making: the role for health preference research. Patient. 2017;10:523–6.
Moultrie RR, Lewis MA, Paquin RS, Lucas A, Jarecki J, Peay HL. An evidence-based, community-engaged approach to develop an interactive deliberation tool for pediatric neuromuscular trials. J Genet Couns. 2018;27:416–25.
D’Amanda C, Peay H, Wheeler A, Turbitt E, Biesecker BB. Fragile X syndrome clinical trials: exploring parental decision making. J Intellect Disabil Res. 2019;63:926–35.
Peay H, Tibben A, Fisher T, Brenna E, Biesecker B. Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy. Clin Trials. 2013;11:77–85.
Richstein J, Cohen J, Hardiman B. Fragile X research from a parental perspective. In: Fragile X syndrome. Elsevier; 2017. p. 457–70.
Landy DC, Brinich MA, Colten ME, Horn EJ, Terry SF, Sharp RR. How disease advocacy organizations participate in clinical research: a survey of genetic organizations. Genet Med. 2012;14:223–8.
Cascio MA, Weiss JA, Racine E. Person-oriented research ethics to address the needs of participants on the autism spectrum. Ethics Hum Res. 2020;42:2–16.
Özalp Gerçeker G, Ayar D, Özdemir EZ, Bektaş M. Effects of virtual reality on pain, fear and anxiety during blood draw in children aged 5–12 years old: a randomised controlled study. J Clin Nurs. 2020;29:1151–61.
Nicholas DB, Zwaigenbaum L, Ing S, MacCulloch R, Roberts W, McKeever P, et al. “Live it to understand it” the experiences of mothers of children with autism spectrum disorder. Qual Health Res. 2016;26:921–34.
Bombard Y, Hayeems RZ. How digital tools can advance quality and equity in genomic medicine. Nat Rev Genet. 2020;21:505–6.
Gillies K, Cotton SC, Brehaut JC, Politi MC, Skea Z. Decision aids for people considering taking part in clinical trials. Cochrane Database Syst Rev. 2015. https://doi.org/10.1002/14651858.CD009736.pub2.
Cheung KL, Wijnen BF, Hollin IL, Janssen EM, Bridges JF, Evers SM, et al. Using best–worst scaling to investigate preferences in health care. Pharmacoeconomics. 2016;34:1195–209.
Louviere J, Lings I, Islam T, Gudergan S, Flynn T. An introduction to the application of (case 1) best–worst scaling in marketing research. Int J Res Mark. 2013;30:292–303.
Louviere J, Flynn TN. Using best-worst scaling choice experiments to measure public perceptions and preferences for healthcare reform in Australia. Patient. 2010;3:275–83.
Bridges JF, Oakes AH, Reinhart CA, Voyard E, O’Donoghue B. Developing and piloting an instrument to prioritize the worries of patients with acute myeloid leukemia. Patient Prefer Adherence. 2018;12:647–55.
Tromp K, Zwaan CM, van de Vathorst S. Motivations of children and their parents to participate in drug research: a systematic review. Eur J Pediatr. 2016;175:599–612.
Ryan M, Watson V, Entwistle V. Rationalising the ‘irrational’: a think aloud study of discrete choice experiment responses. Health Econ. 2009;18:321–36.
Louviere JJ, Flynn TN, Marley AAJ. Best-worst scaling: theory, methods and applications. Cambridge University Press, Cambridge; 2015.
Flynn TN. Valuing citizen and patient preferences in health: recent developments in three types of best–worst scaling. Expert Rev Pharm Outcomes Res. 2014;10:259–67.
Flynn TN, Louviere JJ, Peters TJ, Coast J. Using discrete choice experiments to understand preferences for quality of life. Variance-scale heterogeneity matters. Soc Sci Med. 2010;70:1957–65.
McFadden D. Conditional logit analysis of qualitative choice behavior. In: Frontiers in econometrics. Academic Press; 1973. p. 105–42.
Tait AR, Voepel-Lewis T, Malviya S. Participation of children in clinical research factors that influence a parent’s decision to consent. J Am Soc Anesthesiol. 2003;99:819–25.
Caldwell PH, Butow PN, Craig JC. Parents’ attitudes to children’s participation in randomized controlled trials. J Pediatr. 2003;142:554–9.
The authors would like to thank the parents and caregivers who provided responses to the survey and those who helped with survey development. The authors are grateful to Dr Philip Shaw at the National Human Genome Research Institute for recruitment support. The authors would like to thank the National Fragile X Foundation and FRAXA for their help advertising our study.
This research study was funded by the National Human Genome Research Institute Intramural Research Program, National Institutes of Health.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Turbitt, E., D’Amanda, C., Hyman, S. et al. Parent clinical trial priorities for fragile X syndrome: a best–worst scaling. Eur J Hum Genet (2021). https://doi.org/10.1038/s41431-021-00922-w