Parent clinical trial priorities for fragile X syndrome: a best–worst scaling

Abstract

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 decisionmaking 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.

Community views on medication use in fragile X syndrome

“…There therefore appears to be a clear appetite within the FXS community for medication trials to take place and highlights the need for trials to be well advertised, so that those who would like to take part can be given the opportunity. The reasons for not wanting to take part in trials were mainly not being aware of any, travel, concern about coming off current medication and side effects, ndings which are similar to previous studies carried out in this area (10,14,15) Anxiety and ability to learn were the two most frequently endorsed priorities highlighted for targeting by future trials, with language, attention and social behaviour also highlighted by more than half of participants. It is interesting that two of these ve priorities (anxiety and attention) are areas for which medications already exist but, as mentioned above, there is a lack of strong evidence for their use in fragile X syndrome (16).…”

Best-Worst Scaling Survey of Inpatients’ Preferences in Medical Decision-Making Participation in China

“…Kaya Pezük et al explored the rankings of COVID-19 vaccines' side effects with a soft decisionmaking approach and summarized the strengths and weaknesses of MCDM methods [43]. Turbitt established parents' priorities when deciding whether to let children with fragile X syndrome participate in clinical drug trials [44]. Paquin et al determined rankings of factors affecting health workers' and patients' participation in early-phase gene therapy trials for Duchenne muscular dystrophy with the BWS method [45].…”

GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy

“… 87 The importance of partnering with families and advocacy groups to establish priorities and select meaningful endpoints and to inform considerate trial design is becoming increasingly recognized and is central to ultimate regulatory approval. 88 …”