Portal de Periódicos da CAPES

Conceptual Model and Clinical Outcomes Assessments for Angelman’s Syndrome: Utilizing Pragmatic Methods in Rare Diseases

2016; Elsevier BV; Volume: 19; Issue: 7 Linguagem: Inglês

10.1016/j.jval.2016.09.225

1524-4733

Linda Abetz-Webb, Raquel Cabo, Joseph C. Grieco, Amit Rakhit, M J During,

Genetic Syndromes and Imprinting

Remaining patient--centered when developing a COA strategy in rare diseases can be challenging. Angelman Syndrome (AS) is a rare (1/15,000) neurogenetic disorder characterized by happy demeanor and significant delay across developmental milestones. While there are currently no therapeutics to treat AS and no AS-specific COAs, recent research led to the discovery of potential therapies. This study used pragmatic methods to select relevant and valid measures for AS, without delaying a therapeutic trial. Review of AS published research and caregiver blogs, and discussions with clinical experts, advocacy groups and parents of children with AS aided in the development of an AS conceptual model. Using this model, we performed a literature review searching for COAs that meet FDA COA guidelines. FDA /EMA websites, clinicaltrials.gov, Pubmed and Google were searched for relevant instruments used in AS or in diseases with similar neurodevelopmental profiles. Comparisons of instrument content validity and psychometrics were made. Key concepts identified included: developmental delay (including motor, cognition and speech), behavior and sleep and other physical problems (e.g. seizures), impact on patients and caregivers, and possible mediators. We evaluated 88 AS-specific and 149 related-neurodevelopmental disease articles and 56 instruments (18 Behavior, 12 motor, 7 cognition, 7 communication, 6 sleep and 6 caregiver impact). No instruments, other than one for sleep, were specifically developed for AS. We will present the comparison of instruments’ content validity and psychometrics. Our research yielded an AS conceptual model and measures for potential use in clinical trials, though validation in AS is required. Pre-existing specific measures in rare diseases, such as AS, represent high unmet need. Methods need to be appropriately robust and pragmatic, to ensure that treatments are not delayed, or even dismissed, due to lack of measurement strategies for rare disease populations. When successfully implemented, all stakeholders benefit, and most importantly, the patients themselves.