Content and Response-process Validation of the Parent-reported CDKL5 Clinical Severity Assessment
Abstract number :
1.081
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2022
Submission ID :
2205123
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
Scott Demarest, MD, MSCS – University of Colorado; Sonja Ziniel, PhD – University of Colorado; Alexandra Mackie, BS – University of Colorado; Jacinta Saldaris, PhD – Telethon Kids Institute, Perth, Western Australia, Australia; Leonard Helen, MBChB, MPH – Telethon Kids Institute, Perth, Western Australia, Australia; Peter Jacoby, MSc – Telethon Kids Institute, Perth, Western Australia, Australia; Eric Marsh, MD, PhD – Children’s Hospital of Philadelphia, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Bernhard Suter, MD – Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA; Elia Pestana Knight, MD – CCLMC, Cleveland, Ohio; Heather Olson, MD MS – Boston Children’s Hospital, Boston, MA, USA; Dana Price, MD – NYU Langone Health, New York, NY, USA; Judith Weisenberg, MD – Washington University of St. Louis, St. Louis, Missouri, USA; Raj Rajaraman, MD – UCLA Mattel Children’s Hospital, Los Angeles, CA, USA; Gina VanderVeen, MS – University of Colorado; Tim Benke, MD, PhD – University of Colorado; Jenny Downs, BApplSci, GradCertPubHlth, MSc, PhD – Telethon Kids Institute, Perth, Western Australia, Australia
Rationale: CDKL5 Deficiency Disorder (CDD) is a severe x-linked developmental and epileptic encephalopathy characterized by seizure onset in the first weeks of life. Few children with CDD attain independent walking or even less speak words. Existing developmental outcome measures have floor effects and fail to capture pertinent symptoms for this disorder. A novel parent-reported CDD clinical severity assessment (CCSA) was therefore recently developed and assessed regarding content and response-process validity.
Methods: The parent-reported CCSA was developed through iterative rounds of cognitive interviews or “think aloud” with parent caregivers of patients with CDD. The scope of the “think aloud” pertained to developmental domains and comorbidities such as epilepsy, behavior, autonomic and gastrointestinal symptoms. During interviews, parents completed the initial CCSA and were asked to “think aloud” and discuss their understanding and concerns regarding the understandability and appropriateness of both questions and answer options. Three “think aloud” rounds were completed with 15 caregivers total. Interviewees’ challenges were identified in each round and items were adjusted, expanded, removed, and added based on the themes from that round. The wording of items and questionnaire structure were iterated several times to ensure questions were understood as intended. The review and decisions were made by the qualitative interviewer, a survey methodologist and two child neurologists with expertise in CDD. In the fourth-round, 11 parents were invited to self-complete the survey online or with the interviewer present. The interviewer requested feedback only at the end in this round. Those who self-completed the survey provided a free text assessment of the overall survey. Finally, 10 CDD clinician experts also provided qualitative feedback on the appropriateness of the items and the instrument content.
Results: The parent-reported initial CCSA was refined and divided during the validation into two parent-report measures (Figure 1): (1) the CDD Developmental Questionnaire – Parent (CDQ-P) focused on developmental milestones attained and the attainment consistency, and (2) the CDKL5 Clinical Severity Assessment – Parent/Caregiver focused on patient symptom severity over the past month (CDQ-P). The final CDQ-P had five domains (fine and gross motor skills, receptive and expressive communication, social/cognitive skills) with 16, 18, 4, 20, and 8 items, respectively. The final CCSA-P had three subdomains (epilepsy, cognition/behavior/vision, and autonomic symptoms) with 23, 9, and 15 items, respectively. An initial data set (n=11) suggested no clear floor effects (Figure 2).
Conclusions: This study refined the parental portion of the initial CCSA and provided evidence for its content and response process validity. These validation steps are essential before field testing and further psychometric validation. Future work is focusing on psychometric validation of these measures in a multi-site study, so that this outcome measure can then be advanced toward clinical trial readiness.
Funding: NIH/NINDS U01NS114312 (Benke/PD), International Foundation for CDKL5 Research
Translational Research