Development of a Clinical Global Impression of Change (CGI-C) and a Caregiver Global Impression of Change (CaGI-C) measure for ambulant individuals with Duchenne muscular dystrophy

Hannah Staunton, Claire Trennery, Rob Arbuckle, Maitea Guridi, Elena Zhuravleva, Pat Furlong, Ryan Fischer, Rebecca Hall, Hannah Staunton, Claire Trennery, Rob Arbuckle, Maitea Guridi, Elena Zhuravleva, Pat Furlong, Ryan Fischer, Rebecca Hall

Abstract

Background: In clinical trials for rare diseases, such as Duchenne muscular dystrophy, clinical outcome assessments (COA) used to assess treatment benefit are often generic and may not be sensitive enough to detect change in specific patient populations. Thus, there is a need for disease specific COAs that track meaningful change among individuals. When developing such measures, input from clinicians, caregivers and patients is critical for assessing clinically relevant concepts and ensuring validity of the measure.

Method: The aim of this study was to develop two Duchenne-specific global impression items for use in clinical trials. The development of the Duchenne Clinical Global Impression of Change (CGI-C) and Caregiver Global Impression of Change (CaGI-C) was informed by findings from concept elicitation (CE) interviews with clinicians, caregivers and individuals with Duchenne. Through cognitive debriefing (CD) interviews, clinicians and caregivers evaluated draft CGI-C and CaGI-C items to ensure relevance and understanding of the items and instructions. Suggestions made during the CD interviews were incorporated into the finalized CGI-C and CaGI-C measures.

Results: The symptoms most frequently reported by clinicians, caregivers and individuals with Duchenne were muscle weakness, fatigue, cardiac difficulties and pain. Regarding physical functioning, all three populations noted that small changes in functional ability were meaningful, particularly when independence was impacted. Caregivers and clinicians reported that changes in speed, endurance and quality of movement were important, as was improvement in the ability of individuals to keep up with their peers. A change in the ability to complete everyday activities was also significant to families. These results were used to create two global impression of change items and instruction documents for use by clinicians (CGI-C) and caregivers (CaGI-C). Overall, both items were well understood by participants. The descriptions and examples developed from the CE interviews were reported to be relevant and appropriate for illustrating different levels of meaningful change in patients with Duchenne. Modifications were made based on caregiver and clinician CD feedback .

Conclusions: As part of a holistic measurement strategy, such COA can be incorporated into the clinical trial setting to assess global changes in relevant symptoms and functional impacts associated with Duchenne.

Keywords: Adolescent; Children; Clinical outcome assessment; Duchenne muscular dystrophy; Quality of life.

Conflict of interest statement

Hannah Staunton is an employee and shareholder of Roche Products Ltd. Maitea Guirdi is an employee of F. Hoffman La Roche. Elena Zhuravleva is an employee and shareholder of F. Hoffman La Roche. Rob Arbuckle and Rebecca Hall are employees of Adelphi Values who were commissioned by Roche to conduct this study. Claire Trennery was an employee at Adelphi Values at the time this study was conducted and is now an employee of GlaxoSmithKline. Pat Furlong and Ryan Fisher are employees of PPMD. PPMD has received grant and consultancy service fees from Roche outside of the work described.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Overview of the development of CGI-C and CaGI-C items. CaGI-C, Caregiver Global Impression of Change; CGI-C, Clinical Global Impression of Change
Fig. 2
Fig. 2
Overview of the concept elicitation (CE, a) and cognitive debriefing (CD, b) sample
Fig. 3
Fig. 3
Maintenance of current functioning would be a meaningful treatment goal, from the perspective of caregivers and clinicians as reported in the concept elicitation interviews

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