Background
Methods
Sample and recruitment
CE interviews
Development of the draft CGI-C and CaGI-C
CD interviews
Analysis of interviews
Finalizing CGI-C and CaGI-C
Ethical approval
Results
CE sample: Participant demographics
Demographic | CE sample | CD sample |
---|---|---|
Total no. of clinicians (n = 9) | Total no. of clinicians (n = 9) | |
Job title, n (%) | ||
Neurologist | 3 (33.3%) | 5 (55.6%) |
Pediatric neurologist | 6 (66.7%) | 4 (44.4%) |
Time in role, n (%) | ||
Range (years) | 6–25 | 8–30 |
Less than 10 years | 3 (33.3%) | 2 (22.2%) |
10–15 years | 1 (11.1%) | 1 (11.1%) |
Over 15 years | 5 (55.6%) | 6 (66.7%) |
Years treating individuals with Duchenne, n (%) | ||
Range (years) | 8–30 | 8–30 |
Less than 10 years | 1 (11.1%) | 1 (11.1%) |
10–15 years | 3 (33.3%) | 3 (33.3%) |
Over 15 years | 5 (55.6%) | 5 (55.6%) |
Individuals currently managing with Duchenne, n (%) | ||
0–25 individuals | 3 (33.3%) | 5 (55.6%) |
26–50 individuals | 5 (55.6%) | 3 (33.3%) |
51–75 individuals | 0 | 0 |
76–100 individuals | 1 (11.1%) | 1 (11.1%) |
Demographic | CE sample | CD sample |
---|---|---|
Total no. of caregivers (n = 7) | Total no. of caregivers (n = 8) | |
Gender, n (%) | ||
Male | 1 (14.3%) | 1 (12.5%) |
Female | 6 (85.7%) | 7 (87.5%) |
Age of individual with Duchenne cared for n, (%) | ||
6–7 years | 2 (28.6%) | 3 (37.5%) |
8–9 years | 2 (28.6%) | 3 (37.5%) |
10 years | 3 (42.8%) | 2 (25.0%) |
Caregiver race, n (%) | ||
White | 6 (85.7%) | 6 (75.0%) |
Asian | 0 | 1 (12.5%) |
Hindu* | 1 (14.3%) | 1 (12.5%) |
Relationship with individual cared for, n (%) | ||
Parent/guardian | 7 (100.0%) | 8 (100.0%) |
Work status, n (%) | ||
Working full time | 6 (85.7%) | 5 (62.5%) |
Working part time | 1 (14.3%) | 1 (12.5%) |
Full-time homemaker | 0 | 1 (12.5%) |
Occasional consultancy work | 0 | 1 (12.5%) |
Level of education | ||
High school diploma | 1 (14.3%) | 1 (12.5%) |
Some years of college | 2 (28.6%) | 3 (37.5%) |
Cert program | 1 (14.3%) | 0 (0%) |
College or university | 2 (28.6%) | 1 (12.5%) |
Graduate or professional degree | 1 (14.3%) | 3 (37.5%) |
Demographic | CE sample |
---|---|
Total no. of individuals interviewed (n = 7*) | |
Age of individual with Duchenne (%) | |
6–7 years | 2 (28.6%) |
8–9 years | 2 (28.6%) |
10 years | 3 (42.8%) |
Age diagnosed with Duchenne, n (%) | |
Under 5 years old | 4 (57.1%) |
Between 6 and 10 years old | 3 (42.9%) |
Age experienced symptoms of Duchenne, n (%) | |
0–5 years old | 5 (71.4%) |
6–10 years old | 2 (28.6%) |
Can the individual with Duchenne walk? n (%) | |
Yes | 7 (100.0%) |
No | 0 |
CD sample: Participant demographics
CE interviews
Concept | Supporting quote on meaningful improvement | Supporting quote on meaningful worsening |
---|---|---|
Washing | “It would be an improvement for him to be able to do it all by himself, the whole, the whole get in, wash up, and get out and get dressed would be a big improvement.” (caregiver) | “Not being able to stand in the shower that would be way worse.” (caregiver) |
Dressing | “Well he can do it, just—doing it with less struggle.” (caregiver) | “So a worsening would be that he can’t stand up to do it comfortably.” (caregiver) |
“Figuring out how to keep him independent and able to get changed himself.” (caregiver) | “When he’s not able to lift his arms at all to kind of help me get his shirt on.” (caregiver) | |
Eating and drinking | “Probably being more effective at cutting up his own food.” (caregiver) | “I suppose that sort of gradual change, you know, when he can't actually cut any food at all.” (caregiver) |
Drafts of the CGI-C and CaGI-C
Section of CGI-C | Feature of detailed training document | Feature of top line item/instruction document | CE content that informed section | Key CE findings | CD content that informed section | Key CD findings |
---|---|---|---|---|---|---|
Title and purpose of CGI-C instruction document | ✓ | ✓ | N/A: title and purpose based on existing CGI-C principles [15] | Assessed understanding of the title, instructions and the relevance of a Duchenne-specific CGI-C | All clinicians (9/9) understood the title and 8/9 understood the purpose of the CGI-C All clinicians (9/9) considered the content relevant All clinicians (9/9) reported that the inclusion of information in the training document relating to how the CGI-C instructions had been developed (i.e. involving individuals, caregivers and neurologists) was informative and supported its credibility | |
Duchenne CGI-C definition and CGI-C items and response options | ✓ | ✓ | N/A: definition based on existing CGI-C principles [15] | N/A: definition based on existing CGI-C principles [15] | All clinicians (9/9) understood the Duchenne CGI-C definition and 7/8 considered the focus on symptoms and functional ability as relevant to the assessment of ‘overall health’ Several clinicians (4/9) advocated the use of the phrase ‘clinical status’ to represent symptoms and functional ability over the phrase ‘overall health’ as the latter was considered too broad The majority of clinicians asked (5/7) understood the Duchenne CGI-C item wording and 4/5 asked thought it was easy to complete | |
Information to consider when completing the CGI-C | ✓ | ✓ | Symptoms, physical functioning and ability to perform ADL were the key themes that arose as core to Duchenne in the CE clinician data | 10 symptoms raised (muscle weakness, fatigue cardiac symptoms, enlarged calves, respiratory problems, muscle stiffness/tightness, contractures, pain, scoliosis and gastro-intestinal issues) 15 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, difficulties with upper limb functioning) Five ADL difficulties were raised (bathing/showering, toileting, dressing, brushing hair, brushing teeth) | Assessed understanding of the instructions | The majority of clinicians (7/8) understood the ‘information to consider’ section Several of the clinicians asked (4/8) reported that they would improve the clarity of the ‘symptom’ domain in the ‘information to consider’ section by including key symptoms in addition to muscle weakness. The symptoms pain and fatigue were added to this section. |
CGI-C determining change in response category descriptions | ✓ | ✓ | Descriptions of change category information was informed by the CE data where there was a focus on any change being meaningful | Meaningful improvement and worsening focused on symptoms and functional ability;a key theme was that any loss or gain of independence that led to changes in the need or level of assistance was important. In addition, the following themes emerged: Change in level of effort and confidence when carrying our activities Changes in speed, endurance and quality of movements | Assessed understanding of the instructions and item including descriptions | The majority of clinicians asked understood the descriptions of each level of change: ‘very much worse’ (9/9), ‘much worse’ (8/9), ‘minimally worse’ (9/9), ‘no change’ (8/8), ‘minimally improved’ (8/8), ‘much improved’ (7/7), ‘very much improved’ (6/6) |
CGI-C determining change response category example | ✓ | ✗ | The examples were based on the themes raised by clinicians in the CE interviews and focused on symptoms such as muscle weakness, pain and physical functioning, as well as the amount of assistance or time required to complete a task | Assessed understanding of the instructions, domains and the relevance of the level of change descriptions and examples | The majority of clinicians asked considered the descriptions of each level of change to be relevant: ‘very much worse’ (8/9), ‘much worse’ (9/9), ‘minimally worse’ (5/5), ‘no change’ (7/8), ‘minimally improved’ (5/5), ‘much improved’ (5/5), ‘very much improved (4/5) All of the clinicians asked understood the examples of each level of change: ‘very much
worse’ (9/9), ‘much worse’ (9/9), ‘minimally worse’ (9/9), ‘no change’ (6/6), ‘minimally improved’ (8/8), ‘much improved’ (6/6), ‘very much improved’ (5/5) The majority of clinicians asked consider the examples for each level of change to be relevant: ‘very much worse’ (8/9), ‘much worse’ (9/9), ‘minimally worse’ (8/9), ‘no change’ (7/8), ‘minimally improved’ (5/5), ‘much improved’ (8/8), ‘very much improved’ (4/5) | |
Example of CGI-C score vignettes | ✓ | ✗ | The vignettes were informed by the CE data. Changes in standing up from sitting and walking and the associated consequences in daily life of improving or worsening on these functions, informed the creation of the vignettes | Standing up from sitting on the floor and walking were of key importance clinically and thus chosen for the vignettes (see Additional file 1) | Assessed understanding of the vignettes | The majority of clinicians asked (6/7) thought the vignettes were useful, agreed with the assigned level of change rating (3/5) and considered the treatment notes relevant to Duchenne (2/2) |
Section of CaGI-C | Feature of item/instruction document | CE content that informed section | Key CE findings | CD content that informed section | Key CD findings | |
---|---|---|---|---|---|---|
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) |