Thanks to almost 900 PWS families who completed multiple surveys in the Global PWS Registry, a new study examining sleep disorders, seizures, and psychiatric behaviors provides a great deal of valuable data and new insights into the relationship between these important aspects of PWS.
Many PWS caregivers report that among the most challenging aspects of the syndrome are the symptoms of anxiousness and associated distress expressed by those with PWS. Caregiver-reported data from the Global PWS Registry indicates that anxiety is a significant problem for almost half of individuals with PWS ages 10 and above. However, to date, there are very few treatments that target these symptoms in PWS, despite the fact that both caregivers and individuals with PWS have identified this as one of the most pressing needs (Tsai et al 2018; Dykens et al 2021).
One limiting factor has been the lack of assessment tools for measuring the symptoms of anxiousness and distress in PWS. Currently available assessments, used for the general population, are not appropriate for individuals with PWS and don’t measure key aspects of anxiousness observed in PWS (e.g., worries about schedules, food and possible changes in routines).
To facilitate the development of new therapies for PWS, a group of researchers from Levo Therapeutics, Research Triangle Institute (RTI) and FPWR, with input from the members of the PWS-Clinical Trials Consortium (PWS-CTC), collaborated to develop a measure to capture the unique aspects of anxiousness and distress in PWS. The results of this study were recently published in the journal, Value in Health: The Prader-Willi Syndrome Anxiousness and Distress Behaviors Questionnaire (PADQ): Development and Psychometric Validation.
The final version of the “PADQ” is described in the paper and consists of 15-items, answered by a caregiver (usually a parent), assessing observable behaviors of anxiousness and distress in PWS. The PADQ is now available for use as a clinical outcome assessment for researchers and pharmaceutical companies interested in measuring how behaviors of anxiousness and distress change with new treatments.
Development of the PADQ:
After reviewing available measures of anxiety and determining that they did not capture unique aspects of anxiousness in PWS, the working group developed a list of possible questionnaire items reflecting observable behaviors of anxiousness and distress in PWS. Members of the PWS-CTC Behavior Outcomes working group, comprised of behavior and mental health experts in PWS, reviewed the list of possible items for the PADQ and provided comments and suggestions. To further support the development of the PADQ, in-depth qualitative interviews were conducted with caregivers of children with PWS who were identified as having challenges with anxiousness. The qualitative data from these interviews showed that caregivers consistently endorsed the items on the PADQ and were confident that the items accurately captured their observations of anxiousness in their loved one with PWS. The development process for the PADQ followed guidelines set out by the FDA Division of Clinical Outcome Assessment (COA) for the development of new instruments for use in clinical trials.
As part of the validation process, the PADQ was then administered to 403 PWS caregivers through the Global PWS Registry (thank you to everyone who contributed their data to this effort!) The range of ages for the individuals with PWS in this sample was 3 years to 30+ years. No significant differences were found between mean scores on the PADQ for PWS age groups, PWS gender, or PWS genetic subtype. As expected, the mean PADQ scores were significantly higher in individuals who had reported an anxiety disorder.
Additional analyses were conducted to evaluate the overall reliability and validity of the PADQ. In order for a questionnaire to be useable in research it must have good reliability, which refers to the consistency of a measure over time, i.e., will you get the same results again if the conditions are the same, and validity, which refers to the accuracy of a measure, i.e., do the results reflect what the researchers are trying to measure.
104 PWS caregivers completed the PADQ at a second timepoint to provide test-retest reliability data, which was shown to be very good for this new measure. Validity was assessed by examining correlations between PADQ and global ratings of anxiousness severity and the impact of the symptoms on the person with PWS; these correlations also demonstrated good validity for the PADQ. Finally, the PADQ was used as a secondary outcome measure in Levo Therapeutic’s CARE-PWS Phase 3 Trial. Significant reductions in scores on the PADQ were seen between the treatment (LV-101: Carbetocin) vs. placebo groups, showing that the PADQ is sensitive to changes with treatment.
The items on the PADQ reflect anxiousness and distress as they are uniquely expressed in PWS, and this questionnaire captures a constellation of behaviors that are important to persons with PWS and their families. The PADQ provides a new, valid, and reliable assessment of anxiousness in PWS, which can be used to understand the impact of new treatments for these challenging PWS behaviors. The PADQ is now available for researchers in the field to use to monitor symptoms of anxiousness and test new treatments that can help to reduce anxiousness experienced by individuals with PWS, thus helping them move towards improved quality of life.
Researchers can contact firstname.lastname@example.org for more information and for permission to use the PADQ.
We are grateful to Levo Therapeutics & Sara Cotter for leading this effort to create an assessment tool for anxiousness in PWS, and for generously donating the PADQ to FPWR, so it can be widely used across the PWS research community!