Content Validation of Clinician-Reported Items for a Severity Measure for CDKL5 Deficiency Disorder

Abstract

CDKL5 deficiency disorder (CDD) results in early-onset seizures and severe developmental impairments. A CDD clinical severity assessment (CCSA) was previously developed with clinician and parent-report items to capture information on a range of domains. Consistent with US Food and Drug Administration (FDA) guidelines, content validation is the first step in evaluating the psychometric properties of an outcome measure. The aim of this study was to validate the content of the clinician-reported items in the CCSA (CCSA-Clinician). Eight neurologists leading the USA CDD Center of Excellence clinics were interviewed using the "think aloud" technique to critique 26 clinician-reported items. Common themes were aggregated, and a literature search of related assessments informed item modifications. The clinicians then participated in 2 consensus meetings to review themes and finalize the items. A consensus was achieved for the content of the CCSA-Clinician. Eight of the original items were omitted, 11 items were added, and the remaining 18 items were revised. The final 29 items were classified into 2 domains: functioning and neurologic impairments. This study enabled refinement of the CCSA-Clinician and provided evidence for its content validity. This preliminary validation is essential before field testing and further validation, in order to advance the instrument toward clinical trial readiness.

Keywords: CDKL5 deficiency disorder; clinical severity; content validity; outcome measure; think aloud.

Conflict of interest statement

Declaration of conflicting interests:

Dr. Downs and Dr. Leonard: Consultancy for Avexis, Anavex, GW, Newron and Marinus. Any remuneration has been made to Telethon Kids Institute.

Dr. Demarest: Consultancy for Upsher-Smith, Biomarin and Neurogene, Marinus and Ovid Therapeutics on an unrelated subject matter.

Dr. Benke: Consultancy for AveXis, Ovid, GW Pharmaceuticals, International Rett Syndrome Foundation, Takeda, and Marinus; Clinical Trials with Acadia, Ovid, GW Pharmaceuticals, Marinus and RSRT; All remuneration has been made to his department.

Dr. Marsh: Consultancy for Stoke therapeutics, Cipla pharmaceuticals. Clinical trials with Acadia, GW pharma, Marinus, RSRT, Biopharm, Stoke therapeutics, Zogenix Pharmaceuticals.

Dr. Weisenberg: Participating in clinical trials sponsored by Marinus and Acadia pharmaceuticals as a local investigator. All remuneration is to Washington University.

Dr Olson: Received consulting fees from Takeda Pharmaceuticals regarding clinical trial design and for Ovid Therapeutics for review of clinical trial data; this study involves identification of an outcome measure potentially relevant for future clinical trials.

Dr. Devinsky: Consultant and a member of advisory boards for Privateer Holdings/Tilray, Egg Rock/Papa & Barkley, Receptor Life Sciences, Empatica, Tevard, Engage, Rettco, Pairnomix/ Q-state, Zogenix, and GW Pharmaceuticals.

Dr. Rajaraman: Consultant for Marinus Pharmaceuticals.

Each of these disclosures relate to subject matter not contained in this manuscript.

All other authors have no conflicts to disclose.

Figures

Figure 1:

CDKL5 Deficiency Disorder (CDD) Clinician Clinical Severity Assessment (CCSA-Clinician) development process including preliminary concepts, content validation and further psychometric testing towards a final measure suitable for clinical trials. The parent reported CCSA (CCSA-Parent) will undergo the same process and combine with the CCSA-Clinician for use in clinical evaluation and trials.