Table 6 Summary of key sections across the CaGI-C item/instruction document and associated CE/CD data

Title and purpose of CaGI-C instruction document

✓

N/A: Title and purpose based on existing CGI-C principles [15]

Assessed understanding of the instructions and the relevance of a Duchenne-specific CaGI-C

The majority of caregivers (5/7) understood the title and purpose of the CaGI-C

All caregivers (7/7) reported that the inclusion of information relating to how the CaGI-C had been developed was relevant and informative

One caregiver reported that the title and ‘purpose of the instructions’ section could be simplified to improve clarity, specifically relating to the time period over which changes should be considered (e.g. since the start of the clinical trial)

CaGI-C change response category descriptions (i.e. very much improved to very much worse)

✓

Selected domains chosen based on CE themes (symptoms, physical ability, ability to perform daily activities, social life, emotions and mental wellbeing and overall health)

Descriptions of change category was informed by CE data indicating the meaning of improvement/worsening

Five symptoms raised (muscle weakness, fatigue, pain, muscle stiffness/tightness, constipation)

17 physical functioning activities raised (standing still, standing on heels, standing on one leg, standing up from a chair, standing up from lying on the floor, standing up from sitting on the floor, lifting head, walking, stepping onto box, stepping off of box, hopping, jumping, running, climbing stairs, bending over, exercise, difficulties with upper limb functioning)

10 ADL difficulties were raised (washing, dressing, eating/drinking, toileting, getting in/out of car, getting in/out of bed, brushing hair, brushing teeth, stretching and drawing/writing)

10 emotional concepts (feeling different to peers, reduced independence/autonomy, sadness/depression, worry/anxiety, feeling self-conscious/embarrassed, anger/frustration, reduced confidence, stress, maladaptive thoughts, irritability)

Six social concepts (difficulties participating in social activities, difficulties during breaks/recess, need for modified activities/lessons, missed activities/school due to illness/medical appointments, limited mobility and obstacles outside of the home, marginalization/bullying)

Three cognitive concepts raised but not included as a domain due to lack of relevance

One behavior and one sleep concept raised but not included as domains due to lack of relevance

A key theme was that any loss or gain of independence that led to changes in assistance was important. In addition, the following themes emerged:

Change in level of effort and confidence

Changes in speed, endurance and quality of movements

Improvements in abilities associated with keeping up with  peers

Assessed understanding of the change categories and response categories and the relevance of the descriptions

All the caregivers (7/7/) understood the description of each level of change (‘very much worse’, ‘much worse’, ‘minimally worse’, ‘no change’, ‘minimally improved’ and ‘very much improved)

The majority of caregivers considered the descriptions of each level of change to be relevant: ‘very much worse’ (7/7), ‘much worse’ (6/7), ‘minimally worse (7/7), ‘no change’ (6/7), ‘minimally improved’ (6/7), ‘much improved’ (7/7/) and ‘very much improved’ (7/7)

Duchenne

CaGI-C items and response options

✓

Selected domains selected based on CE themes (symptoms, physical ability, ability to perform daily activities, social life, emotions and mental wellbeing and overall health)

Assessed understanding of the instructions and items, domains and the relevance of the examples

All caregivers (7/7) understood the original global question (i.e. taking into account all of the individuals’ DMD symptoms and overall quality of life, how would you rate the change in his overall health since the start of this clinical trial? Please select one response only)

Two caregivers indicated this question would be difficult to answer, leading to thinking about Duchenne in its entirety. This led to the creation of domain-level items, thus narrowing the concepts caregivers had to think about in relation to each item

Updated domain CaGI-C: the final caregiver understood all items and assisted with the modification of the examples to ensure relevance (e.g. including strength as an example in symptoms)