Patient advocacy group perspectives on treatment priorities and clinical trials for the rare neurodevelopmental condition, Prader-Willi syndrome.

backgroundUsing Prader-Willi syndrome (PWS) as an example, this position statement focuses on supporting the development and evaluation of new treatments for rare neurodevelopmental disorders. As members of two patient advocacy organisations we have drawn on published research and the experience of participants, parents, paid care providers, and clinicians to make recommendations to improve the translational process from drug discovery to treatment approval and availability. MAIN TEXT: PWS is a rare complex genetically-determined neurodevelopmental condition. Severe hypotonia and failure to thrive are apparent at birth, followed by an atypical pattern of development associated with variable but characteristic physical and neuropsychiatric phenotypes. Like other neurodevelopmental conditions, atypical brain development results in intellectual and cognitive impairments. Relative growth and sex hormone deficiencies, the onset of hyperphagia in early childhood, and other phenotypic characteristics are a consequence of impaired hypothalamic function. Although growth hormone treatment for children with PWS has improved the phenotype of PWS, treatments for other features of the disorder are needed given their severe impact on the lives of people with PWS and their families. We identified factors that have delayed the development and evaluation of new treatments including: a limited understanding of causal mechanisms; additional measures required due to the participants’ intellectual and cognitive impairments potentially impacting on consent, compliance, and requiring informant rather than participant-based outcome measures; high risk for co-morbidities; and recruitment from a small population; and over-restrictive inclusion/exclusion criteria.

conclusionsClinical trials can be performed in PWS but the associated complexities requires an understanding of the challenges and a more flexible approach to recruitment and trial design. The identification of biomarkers to screen new agents and for prediction of efficacy and outcome are warranted. Novel statistical methods for small numbers and/or qualitative methodologies, may be necessary and appropriate. Robust and meaningful engagement of those living with PWS and their families, advocacy groups and expert clinicians is critical to the successful clinical trial completion. Given the example of the variable availability and affordability internationally of growth hormone to people with PWS, we express concern about the availability of new treatments globally.