The Rett Syndrome Behavior Questionnaire’s implementation as global outcome measure in FDA-approved trials was the result of its comprehensive nature since it includes behavior-related symptom questions as well as questions for regular behaviors.
Recently, Anavex Life Sciences announced the publication of a peer-reviewed study in the American Journal on Intellectual and Developmental Disabilities in which investigators recommended some additional evaluations and improvements to the Rett Syndrome Behavior Questionnaire (RSBQ), an assessment developed for pediatric Rett observational studies.1 The reports from this psychometric study provide additional support for the use of the RSBQ among studies for children and adults as well as reference values and revised subscales for how to improve its use.2
Authors evaluated the RSBQ's psychometric properties in 6 pediatric (n = 323) and 5 adult (n = 309) datasets. All told, Total and General Mood subscale scores had good reliability while clinical severity demonstrated no influence on RSBQ scores. Analyses for exploratory and confirmatory factor yielded 6 pediatric and 7 adult clinically relevant and psychometrically strong factors, including the original Breathing Problems and Fear/Anxiety subscales and the novel Emotional and Disruptive Behavior subscale.
“This paper is a further demonstration of Anavex’s involvement as part of the team of clinicians and commitment to the rare disease and especially to the Rett syndrome community,” Christopher U Missling, PhD, president and chief executive officer at Anavex said in a statement.1
Led by senior author Walter E. Kaufmann, MD, adjunct professor of human genetics at Emory University School of Medicine and chief science officer at Anavex Life Sciences, and colleagues, the study reported the distribution of scores and other statistical features of the RSBQ from more than 600 children and adults living with Rett syndrome. Investigators also re-examined the structure of the questionnaire, specifically the grouping of questions into different subscales. Following the analysis, the researchers then proposed some changes to the organization of the questions such as revised subscales.
"When the measure was developed, and that process began about 1998, that was about 15 years after the modern recognition of Rett syndrome. Before, Rett syndrome had been known as a very pediatric disorder that decreased life expectancy, there wasn't much known about adults. The life expectancy has improved dramatically, so now life expectancy in the US is 50 years or more than that," Kaufmann told NeurologyLive®. "With that, more and more adults have been diagnosed with Rett syndrome. This study was the first one to have massive data on adults, we published data on 300 patients in the world, which is a pretty substantial number. This couldn't have been possible at the time when the original paper was published in 2002, there wasn't that population."
The study, representing the largest analysis on the RSBQ and the first report of the instrument in adults with Rett Syndrome, was produced with an international collaboration including anonymized databases from the United States, Australia, United Kingdom, and Denmark. The final goal of the analysis was to give reference values and other metrics of the RSBQ for its clinical application and implementation in studies.
"It's also shows where the field of neurodevelopmental disorder is going since we have made advances in the quality of life and life expectancy. Now we have a different population, we have adults with developmental disorders who pose a different set of challenges for most of us who train in the pediatric field. Now, we have to worry about these patients developing the typical diseases of adults such as chronic disorders like hypertension, diabetes, and cancer surveillance. The field is changing and this paper reflects that change 20 years later," Kaufmann told.
The RSBQ, developed by a British team of clinicians and researchers, aimed to better delineate behavioral problems among children with Rett syndrome. Over 2 decades, use of the RSBQ has expanded to observational studies in adults with Rett syndrome and efficacy assessments. The RSBQ’s implementation as global outcome measure in clinical trials is because of its comprehensive nature, including questions not only for behaviors but also for behavior-related symptoms.
"This is an example of international collaboration and in rare diseases, you need that. Even though in the United States, where we can probably do our own study, we benefit more from having collaboration with other countries because they have data for these rare diseases, and sharing data is so important," Kaufmann told.
Recently in June 2023, Anavex Life Sciences announced that all participants had been dosed in the placebo-controlled phase 2/3 EXCELLENCE (NCT04304482) study assessing blarcamesine, a small-molecule activator of sigma-1 receptor, in pediatric patients with Rett syndrome.3 The trial, which features 92 pediatric patients with Rett syndrome, aged 5 to 17 years old, is a multi-center, double-blind trial assessing the safety, tolerability, and efficacy of the therapy, otherwise known as ANAVEX 2-73.
After discussions with the FDA, EXCELLENCE plans to use the RSBQ total score and CGI-I as coprimary end points. Effects on these end points will be calculated through a statistical analysis plan that includes specified linear mixed-effects models for repeated measures. "We are looking forward to the topline data from the EXCELLENCE phase 2/3 ANAVEX2-73-RS-003 Rett syndrome pediatric clinical trial in the second half of 2023,” Missling said in a statement.1