Anxiousness and distress are common and challenging aspects of PWS. Worry about schedules, food, changes in routine, or other aspects of daily life can lead to significant distress and can affect the entire family.
The Global PWS Registry indicates that anxiousness is a significant problem for almost half of individuals with PWS aged 10 and above.
Despite the fact that both caregivers and individuals with PWS have identified this as one of the most pressing needs, there are very few treatments that target these symptoms in PWS.
For researchers developing new treatments, this creates an important challenge: How do you measure whether a treatment actually improves these behaviors?
The Prader-Willi Syndrome Anxiousness and Distress Behaviors Questionnaire (PADQ) was developed to help answer that question.
Why do we need a PWS-specific measure?
Many questionnaires used to measure anxiety were developed for the general population and do not fully capture the ways anxiousness and distress are expressed in people with PWS. For example, anxiousness in PWS may be closely connected to concerns about schedules, routines, and food.
Some people with PWS also have difficulty describing their internal feelings, making observable behaviors an important part of assessing anxiousness and distress.
Researchers and clinicians therefore needed a tool designed specifically for PWS—one that could capture behaviors that caregivers recognize and be used to measure changes during clinical trials.
What is the PADQ?
The Prader-Willi Syndrome Anxiousness and Distress Behaviors Questionnaire (PADQ) is a 15-item questionnaire completed by a caregiver, usually a parent or other person who knows the individual well.
The PADQ focuses on observable behaviors associated with anxiousness and distress in people with PWS. Rather than asking someone to describe an internal feeling of anxiety, the questionnaire asks caregivers to report on behaviors they can observe.
The PADQ is designed as a clinical outcome assessment for research. It is not a diagnostic test for an anxiety disorder and does not replace an evaluation by a healthcare professional.
How was the PADQ developed?
The PADQ was developed in collaboration by Levo Therapeutics, the Research Triangle Institute (RTI) and FPWR with input from the members of the PWS-Clinical Trials Consortium (PWS-CTC) and the PWS community.
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.
Conclusions
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 theresa.strong@fpwr.org for more information and for permission to use the PADQ.
Learn More
The PADQ is available as a clinical outcome assessment for researchers and pharmaceutical companies interested in measuring anxiousness and distress behaviors in PWS.
Learn more about the PADQ: “The Prader-Willi Syndrome Anxiousness and Distress Behaviors Questionnaire: Development and Psychometric Validation” →