Abstract
Background
The rare genetic disease Duchenne muscular dystrophy (DMD) mostly affects males, impacting mobility and pulmonary/cardiac function from childhood. This study explored non-professional caregiving in DMD, comparing burden across regions and by care recipients’ ambulatory status.
Methods
Data were from the Adelphi Real World Disease Specific Programme™, a cross-sectional survey in Europe (France, Germany, Spain), the United States of America (USA), and Japan from October 2022–November 2023. Caregivers reported health status (their own and that of dependents with DMD) via the EQ-5D-5L, and their own productivity via the Work Productivity and Impairment Index (WPAI).
Results
Of 216 individuals with DMD, 45.8%, 41.7% and 12.5% were from Europe, USA and Japan, respectively; 54.4% were ambulatory, 68.4%, 52.2% and 11.1% in Europe, USA and Japan, respectively. Individuals with DMDs’ mean (standard deviation; SD) EQ-5D-5L index value was 0.19 (0.27), with no significant difference across regions, but was higher in ambulatory than non-ambulatory individuals (p < 0.0001). Individuals with DMDs’ mean (SD) EQ-VAS score was 24.3 (27.9), differed across regions (p < 0.0001), but did not differ by ambulatory status. In the USA, Europe and Japan, 38.9%, 23.5% and 7.4% of caregivers, respectively, worked full-time (p = 0.0020). Caregiver employment did not differ significantly between ambulatory/non-ambulatory dependents. Mean caregiver absenteeism, presenteeism and overall work impairment were 9.7%, 37.8% and 42.4%, respectively, with no significant differences between regions or ambulatory/non-ambulatory dependents. Mean activity impairment was 49.0%, (Japan: 67.6%, Europe: 49.4%, USA: 43.4%; p = 0.0002), and higher in caregivers of non-ambulatory than ambulatory dependents (p < 0.0001). Most caregivers reported no problems with their own mobility, self-care, usual activities, or pain/discomfort. The severity of anxiety/depression varied across regions (p < 0.0001), with no significant difference by dependents’ ambulatory status. Mean (SD) caregivers’ EQ-VAS score and index value were 26.9% (30.3%) and 0.83 (0.23), respectively. EQ-VAS score differed significantly across regions (USA: 52.1% [33.3%], Europe: 8.9% [1.7%], Japan: 8.9% [1.7%]; p < 0.0001), but not by dependents’ ambulatory status. EQ-5D-5L index value did not differ significantly across regions or with dependents’ ambulatory status.
Conclusions
Non-professional caregiving in DMD presented a substantial burden, varying across regions, and greater for those caring for non-ambulatory than ambulatory dependents.
Keywords: Caregiver, Duchenne muscular dystrophy, Employment, Productivity, Real-world
Background
Duchenne muscular dystrophy (DMD) is a rare inherited disease in which mutations or other genetic rearrangements in the dystrophin gene result in a lack of the protein dystrophin [1]. Due to the X-linked recessive genetic cause of DMD, it is much more prevalent in males than females, although females may be carriers with few or no disease manifestations [1].
Pathological changes result from dysfunctional dystrophin-deficient myocytes, with progressive deterioration of skeletal muscle causing mobility issues, cardiomyopathy, and pulmonary dysfunction [2]. DMD is usually diagnosed in early childhood due to delays in walking and unsteady gait [3] and is generally life-limiting due to its impact on the heart and lungs [2–4].
The majority of day-to-day caregiving in DMD is provided by non-professional, informal caregivers – most often family members [5–7]. Two systematic literature reviews [5, 8] of caregiver burden concluded that caregiving in DMD is frequently associated with poor health-related quality of life (HRQoL) and psychological well-being, sexual dysfunction, and lower self-esteem. This is further compounded by a considerable impact on working life and productivity, placing an increased financial burden on the family [5, 8]. A USA web-based survey reported that the parents of children with DMD had worse mental health and had more employment challenges than a control group of parents of children who did not have DMD [9].
Most of the studies summarized in the two systematic reviews described in the previous paragraph [5, 8] were from single countries and had small sample sizes, with very few including a well-recognized HRQoL measure, and none including a recognized measure of productivity and activity impairment. The objective of the study described in this paper was to describe and quantify the burden of caring for dependents with DMD across a large, international cohort of non-professional caregivers. We also aimed to compare caregiver burden in different geographical regions (Europe, the USA and Japan), and between those caring for ambulatory and non-ambulatory dependents with DMD.
Methods
Study design and data source
Data were drawn from the Adelphi Real World DMD Disease Specific Programme (DSP)™, a survey with cross-sectional and retrospective elements of data collection, in Europe (France, Germany, and Spain), the USA, and Japan between October 2022 and November 2023. The DSP was administered to physicians treating patients with DMD, who then invited the non-professional caregivers of their patients to participate.
To increase the sample size for analysis, some additional caregivers in the USA completed a separate caregiver survey, which was administered directly to them, rather than via a physician. These caregivers were initially contacted during in-person patient events or via patient advocacy and support groups. They were enrolled into an independent panel via a rigorous vetting process before being invited to participate in the DMD caregiver survey.
Vetting involved manual checking of answers to questions about the condition and treatment, technological checking that contact information matched independent sources and that IP addresses were unique, and the use of tools such as Research Defender to help ensure overall authenticity.
The DSP methodology has been previously described [10, 11], validated [12] and demonstrated to be representative and consistent over time [13].
Study participants and eligibility criteria
For data collected via the DSP:
The physicians who invited DMD caregivers to participate were required to be neurologists or pediatric neurologists (or internists in France), and to be directly involved in treatment decisions and management for at least one patient with DMD in a typical month. Physicians confirmed their patients’ DMD diagnosis and ambulatory status.
To be eligible for inclusion, non-professional caregivers (i.e. not paid to provide care, such as a parent or other family member) who provided care for a dependent with a physician-confirmed diagnosis of DMD who was not enrolled in a clinical trial were invited by the recruiting physician to participate in the DSP.
For data collected via the USA caregiver survey:
To be eligible for inclusion, caregivers had to be non-professional (i.e. not paid to provide care, such as a parent or other family member) and had been vetted to confirm that they provided care for a dependent with DMD; however, there was no physician confirmed diagnosis of the dependent’s DMD.
Study procedures and data collected
All caregivers enrolled via the DSP were asked to fill out a caregiver self-completion (CSC) form. Caregivers enrolled in the USA caregiver survey completed a survey form. The survey form and the CSC were identical, and data collected via these two sources were merged.
Caregivers reported demographics, disease history, ambulation status, health insurance coverage, cost of DMD-related prescribed medication, and cost to manage DMD, for the dependent with DMD they cared for. They also provided patient HRQoL data via the EQ-5D-5L. Caregivers also self-reported data on demographics, relationship to the dependent they cared for, employment data, HRQoL via the EQ-5D-5L, and work productivity and activity impairment data via the Work Productivity and Activity Impairment questionnaire (WPAI).
The EQ-5D-5L assesses health status across five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) rated on five severity levels, providing a single health utility index value. Index values range from perfect health (1) to states worse than death (< 0) [14, 15]. The EQ-5D-5L also includes a visual analog scale (VAS) which assesses self-perceived health state on a scale from 0 (worst imaginable health) to 100 (best imaginable health).
The Work Productivity and Activity Impairment questionnaire (WPAI) assesses productivity and activity during the past seven days [16]. The WPAI assesses percentage impairment for absenteeism, presenteeism, overall work impairment and total activity impairment. The version used assessed impairment due to a specific health problem (DMD), with the wording in data collection materials reflecting this.
Analyses
Data were stratified by country/region (Europe [France, Germany, Spain], USA or Japan) and according to the person with DMD’s ambulatory status (ambulatory or non-ambulatory). Continuous variables were described as mean, standard deviation (SD) and range. Categorical variables were described as percentage.
The USA value set (tariff) was utilized when deriving EQ-5D-5L index values [15] as the largest cohort of people with DMD was from the USA.
Comparisons between countries/regions, and ambulatory versus non-ambulatory status, were carried out using analysis of variance, Fisher’s exact test, Student's t-test, Kruskal–Wallis test, and Mann–Whitney U test [17]. Analyses were performed using Stata 17 [18].
Results
Study participants
A total of 216 caregivers provided data, of whom 61 from the USA provided data via the DMD caregiver survey. The largest cohort of participants (45.8%) was from Europe, with 41.7% from the USA and 12.5% from Japan.
Characteristics of people with DMD
The characteristics for the total sample of people with DMD, stratified by geographical region and ambulatory status, are shown in Table 1.
Table 1.
Demographics of people with DMD
| Total (n= 216) |
Europe (n = 99) |
USA (n = 90) |
Japan (n = 27) |
p-value | Non-ambulatory (n = 98) | Ambulatory (n = 117) |
p>-value | |
|---|---|---|---|---|---|---|---|---|
| Age, years |
< 0.0001 (AN) |
< 0.0001 (TT) |
||||||
|
n Mean (SD) Range |
216 13.98 (7.40) 0.83, 30.00 |
99 12.87 (8.00) 1.08, 29.00 |
90 13.52 (6.30) 0.83, 30.00 |
27 19.56 (6.23) 6.00, 30.00 |
98 19.10 (5.03) 7.00, 30.00 |
117 9.55 (6.05) 0.83, 22.00 |
||
| Age at DMD symptom onset, years |
0.0039 (AN) |
0.0161 (TT) |
||||||
|
n Mean (SD) Range |
194 4.20 (4.07) 0.08, 20.00 |
93 5.21 (4.82) 0.50, 20.00 |
80 3.29 (3.15) 0.08, 16.00 |
21 3.24 (2.10) 1.00, 9.00 |
88 3.44 (3.13) 0.08, 18.00 |
106 4.84 (4.62) 0.08, 20.00 |
||
| Age at DMD diagnosis, years | ||||||||
|
n Mean (SD) Range |
208 5.25 (4.57) 0.00, 24.00 |
95 6.07 (5.57) 1.00, 24.00 |
86 4.93 (3.58) 0.08, 18.00 |
27 3.36 (2.47) 0.00, 9.00 |
0.0167 (AN) |
93 4.75 (3.70) 0.75, 20.00 |
114 5.50 (4.88) 0.00, 21.00 |
0.2241 (TT) |
| Ambulatory status, n (%) |
< 0.0001 (KW) |
< 0.0001 (MW) |
||||||
|
n Early ambulatory Late ambulatory Early non- ambulatory/Transfer Late non- ambulatory |
215 76 (35.4) 41 (19.1) 33 (15.4) 65 (30.2) |
98 47 (48.0) 20 (20.4) 12 (12.2) 19 (19.4) |
90 26 (28.9) 21 (23.3) 20 (22.2) 23 (25.6) |
27 3 (11.1) 0 (0.0) 1 (3.7) 23 (85.2) |
98 0 (0.0) 0 (0.0) 33 (33.7) 65 (66.3) |
117 76 (65.0) 41 (35.0) 0 (0.0) 0 (0.0) |
Europe = France, Germany and Spain
AN analysis of variance, DMD Duchenne muscular dystrophy, KW Kruskal–Wallis test, MW Mann–Whitney U test, SD standard deviation, TT Student’s t-test, USA United States of America
Of the 215 people with DMD whose ambulatory status was known, 54.4% were ambulatory (still able to walk independently) and 45.6% were non-ambulatory (unable to walk independently). The age of people with DMD differed across regions (p < 0.0001), with the mean age lowest in Europe and highest in Japan, and those with non-ambulatory DMD were older than those with ambulatory DMD (p < 0.0001). There was a significant difference in age at DMD symptom onset across the regions (p = 0.0039); the mean age at symptom onset was highest in Europe. People with ambulatory DMD at the time of the survey were significantly older at symptom onset than those who were non-ambulatory (p = 0.0161). The age at diagnosis of DMD differed across regions (p = 0.0167), with mean age lowest in Japan and highest in Europe, and no difference between those with ambulatory and non-ambulatory DMD (p = 0.2241).
At the time of the survey, more ambulatory people with DMD were at the early than the late ambulatory stage, and more non-ambulatory people with DMD were at the late than the early non-ambulatory stage. There was a significant difference in ambulatory status between regions (p < 0.0001), with 68.4%, 52.2% and 11.1% of people with DMD from Europe, the USA and Japan, respectively, ambulatory at the time of the survey.
Health status of people with DMD as reported by caregivers
The health status of people with DMD, based on caregivers’ proxy responses on the EQ-5D-5L, is shown in Table 2.
Table 2.
Caregiver-reported proxy health status of people with DMD (dimensions of the EQ-5D-5L)
| Total (n = 216) |
Europe (n= 99) |
USA (n = 90) |
Japan (n = 27) |
p-value | Non-ambulatory (n = 98) | Ambulatory (n = 117) |
p-value | |
|---|---|---|---|---|---|---|---|---|
| Mobility, n (%) |
0.0052 (KW) |
< 0.0001 (MW) | ||||||
|
n I have no problems in walking about I have slight problems in walking about I have moderate problems in walking about I have severe problems in walking about I am unable to walk about |
108 1 (0.9) 9 (8.3) 8 (7.4) 9 (8.3) 81 (75.0) |
35 0 (0.0) 2 (5.7) 2 (5.7) 5 (14.3) 26 (74.3) |
51 1 (2.0) 7 (13.7) 6 (11.8) 4 (7.8) 33 (64.7) |
22 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 22 (100.0) |
82 0 (0.0) 0 (0.0) 0 (0.0) 2 (2.4) 80 (97.6) |
25 1 (4.0) 9 (36.0) 8 (32.0) 7 (28.0) 0 (0.0) |
||
| Self-Care, n (%) |
< 0.0001 (KW) |
< 0.0001 (MW) | ||||||
|
n I have no problems washing/dressing myself I have slight problems washing/dressing myself I have moderate problems washing/dressing myself I have severe problems washing/dressing myself I am unable to wash or dress myself |
108 4 (3.7) 11 (10.2) 15 (13.9) 19 (17.6) 59 (54.6) |
35 0 (0.0) 4 (11.4) 3 (8.6) 9 (25.7) 19 (54.3) |
51 4 (7.8) 7 (13.7) 12 (23.5) 9 (17.7) 19 (37.3) |
22 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.6) 21 (95.5) |
81 0 (0.0) 2 (2.5) 7 (8.6) 14 (17.3) 58 (71.6) |
26 4 (15.4) 9 (34.6) 8 (30.8) 4 (15.4) 1 (3.9) |
||
| Usual Activities, n (%) |
< 0.0001 (KW) |
< 0.0001 (MW) | ||||||
|
n I have no problems doing my usual activities I have slight problems doing my usual activities I have moderate problems doing my usual activities I have severe problems doing my usual activities I am unable to do my usual activities |
109 3 (2.8) 14 (12.8) 27 (24.8) 19 (17.4) 46 (42.2) |
36 0 (0.0) 4 (11.1) 4 (11.1) 7 (19.4) 21 (58.3) |
51 3 (5.9) 7 (13.7) 23 (45.1) 10 (19.6) 8 (15.7) |
22 0 (0.0) 3 (13.6) 0 (0.0) 2 (9.1) 17 (77.3) |
82 1 (1.2) 5 (6.1) 16 (19.5) 15 (18.3) 45 (54.9) |
26 2 (7.7) 9 (34.6) 11 (42.3) 3 (11.5) 1 (3.9) |
||
| Pain/Discomfort, n (%) |
0.0012 (KW) |
0.4938 (MW) | ||||||
|
n I have no pain or discomfort I have slight pain or discomfort I have moderate pain or discomfort I have severe pain or discomfort I have extreme pain or discomfort |
109 17 (15.6) 48 (44.0) 37 (33.9) 2 (1.8) 5 (4.6) |
36 1 (2.8) 19 (52.8) 13 (36.1) 0 (0.0) 3 (8.3) |
51 6 (11.8) 21 (41.2) 20 (39.2) 2 (3.9) 2 (3.9) |
22 10 (45.5) 8 (36.4) 4 (18.2) 0 (0.0) 0 (0.0) |
82 16 (19.5) 29 (35.4) 30 (36.6) 2 (2.4) 5 (6.1) |
26 1 (3.9) 18 (69.2) 7 (26.9) 0 (0.0) 0 (0.0) |
||
| Anxiety/Depression, n (%) |
< 0.0001 (KW) |
0.6040 (MW) | ||||||
|
n I am not anxious or depressed I am slightly anxious or depressed I am moderately anxious or depressed I am severely anxious or depressed I am extremely anxious or depressed |
108 41 (38.0) 36 (33.3) 27 (25.0) 2 (1.9) 2 (1.9) |
35 14 (40.0) 14 (40.0) 6 (17.1) 1 (2.9) 0 (0.0) |
51 9 (17.7) 20 (39.2) 19 (37.3) 1 (2.0) 2 (3.9) |
22 18 (81.8) 2 (9.1) 2 (9.1) 0 (0.0) 0 (0.0) |
81 31 (38.3) 24 (29.6) 22 (27.2) 2 (2.5) 2 (2.5) |
26 9 (34.6) 12 (46.2) 5 (19.2) 0 (0.0) 0 (0.0) |
Europe = France, Germany and Spain
KW Kruskal–Wallis test, MW Mann–Whitney U test, USA United States of America
Overall, substantial problems were reported with mobility, self-care, and usual activities (defined as people with DMD being unable to walk, unable to wash or dress themselves, and unable to complete their usual activities ─ the worst possible response in each EQ-5D-5L dimension). There were significant differences across the geographical regions in mobility (p = 0.0052), self-care (p < 0.0001), and usual activities (p < 0.0001). The proportions of those with DMD having substantial problems with mobility, self-care, and usual activities were 100%, 95.5% and 77.3%, respectively, in Japan compared with 64.7%, 37.3% and 15.7%, respectively, in the USA. People with non-ambulatory DMD had significantly greater problems than those with ambulatory DMD with mobility, self-care and usual activities (all p < 0.0001).
Overall, the majority of people with DMD had no or slight pain/discomfort and no or slight anxiety/depression. There were significant differences across geographical regions in pain/discomfort (p = 0.0012), with no pain/discomfort reported for only 2.8% of people with DMD in Europe, but 45.5% of those in Japan. Extreme pain/discomfort was not reported for any people with DMD in Japan, but was reported for 8.3% of people in Europe. Significant differences were also seen across regions in anxiety/depression for people with DMD (p < 0.0001). No anxiety/depression was reported for more than 81.8% in Japan but only 17.7%% in the USA, while extreme anxiety/depression was reported for 3.9% of people with DMD in the USA but none of those in Europe or Japan. No significant differences were reported between non-ambulatory and ambulatory DMD in pain/discomfort or anxiety/depression (p = 0.4938 and p = 0.6040, respectively).
Caregiver proxy reported EQ-VAS scores and EQ-5D-5L index values for people with DMD are shown in Fig. 1.
Fig. 1.
Caregiver proxy EQ-VAS and EQ-5D-5L index values of people with DMD. Europe = France, Germany and Spain; USA, United States of America; VAS, visual analog scale. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. SD standard deviation
There was a significant difference across the regions for caregiver proxy reported EQ-VAS score of people with DMD (p < 0.0001), with mean EQ-VAS score highest in the USA. EQ-5D-5L index values were not significantly different across regions (p = 0.0829). No significant differences were reported in EQ-VAS scores between the non-ambulatory and the ambulatory group (p = 0.0975). However, the EQ-5D-5L index value was significantly higher in ambulatory than non-ambulatory patients (p < 0.0001).
Caregiver characteristics
Caregivers’ characteristics for the total sample and stratified by region and their dependent’s DMD ambulatory status are shown in Table 3.
Table 3.
Caregiver demographics and relationship to their dependent with DMD
| Total (n = 216) |
Europe (n = 99) |
USA (n = 90) |
Japan (n = 27) |
p-value | Non-ambulatory (n = 98) | Ambulatory> (n = 117) |
p-value | |
|---|---|---|---|---|---|---|---|---|
| Age, years |
0.0046 (AN) |
< 0.0001 (TT) | ||||||
|
n Mean (SD) Range |
212 44.31 (9.11) 25, 70 |
98 43.97 (9.90) 26, 70 |
88 43.11 (7.98) 25, 62 |
26 49.65 (7.94) 38, 68 |
96 49.94 (7.86) 27, 68 |
115 39.69 (7.30) 25, 70 |
||
| Sex, n (%) |
0.4018 (FE) |
0.3430 (FE) |
||||||
|
n Female Male |
216 183 (84.7) 33 (15.3) |
99 81 (81.8) 18 (18.2) |
90 77 (85.6) 13 (14.4) |
27 25 (92.6) 2 (7.4) |
98 86 (87.8) 12 (12.2) |
117 97 (82.9) 20 (17.1) |
||
| Relationship to patient, n (%) |
0.1386 (FE) |
0.0513 (FE) |
||||||
|
n Parent Sibling Other family member Other Partner/Spouse |
215 198 (92.1) 3 (1.4) 10 (4.7) 3 (1.4) 1 (0.5) |
98 84 (85.7) 2 (2.0) 9 (9.2) 2 (2.0) 1 (1.0) |
90 87 (96.7) 1 (1.1) 1 (1.1) 1 (1.1) 0 (0.0) |
27 27 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) |
98 94 (95.9) 1 (1.0) 1 (1.0) 2 (2.0) 0 (0.0) |
116 104 (89.7) 2 (1.7) 9 (7.8) 1 (0.9) 0 (0.0) |
||
| Employment status, n (%) | ||||||||
| n | 215 | 98 | 90 | 27 | 98 | 116 | ||
|
Homemaker Working full-time Working part-time Unemployed Retired Student Long-term parental leave |
95 (44.2) 60 (27.9) 44 (20.5) 10 (4.7) 3 (1.4) 2 (0.9) 1 (0.5) |
51 (52.0) 23 (23.5) 19 (19.4) 3 (3.1) 1 (1.0) 1 (1.0) 0 (0.0) |
23 (25.6) 35 (38.9) 23 (25.6) 5 (5.6) 2 (2.2) 1 (1.1) 1 (1.1) |
21 (77.8) 2 (7.4) 2 (7.4) 2 (7.4) 0 (0.0) 0 (0.0) 0 (0.0) |
< 0.0001 (FE) 0.0020 (FE) 0.1126 (FE) 0.4348 (FE) 0.7381 (FE) 1.0000 (FE) 0.5442 (FE) |
42 (42.9) 26 (26.5) 22 (22.5) 6 (6.1) 2 (2.0) 0 (0.0) 0 (0.0) |
54 (45.7) 33 (28.5) 22 (19.0) 4 (3.5) 1 (0.9) 2 (1.7) 1 (0.9) |
0.6817 (FE) 0.7617 (FE) 0.6110 (FE) 0.5181 (FE) 0.5941 (FE) 0.5012 (FE) 1.0000 (FE) |
| Change to employment, n (%) | ||||||||
| n | 177 | 79 | 73 | 25 | 86 | 90 | ||
|
Reduced working hours Changed type of work Other changes Work unsocial hours No change |
45 (25.4) 19 (10.7) 19 (10.7) 18 (10.2) 100 (56.5) |
16 (20.3) 0 (0.0) 7 (8.9) 9 (11.4) 51 (64.6) |
28 (38.4) 19 (26.0) 12 (16.4) 9 (12.3) 25 (34.3) |
1 (4.0) 0 (0.0) 0 (0.0) 0 (0.0) 24 (96.0) |
0.0008 (FE) < 0.0001 (FE) 0.0519 (FE) 0.1838 (FE) < 0.0001 (FE) |
26 (30.2) 11 (12.9) 14 (16.3) 8 (9.3) 41 (47.7) |
19 (21.1) 8 (8.9) 5 (5.6) 9 (10.0) 59 (65.6) |
0.1724 (FE) 0.4709 (FE) 0.0282 (FE) 1.0000 (FE) 0.0222 (FE) |
| Change due to DMD, n (%) |
0.0262 (FE) |
0.0064 (FE) |
||||||
|
n Yes No |
166 50 (30.1) 116 (69.9) |
94 25 (26.6) 69 (73.4) |
47 21 (44.7) 26 (55.3) |
25 4 (16.0) 21 (84.0) |
75 31 (41.3) 44 (58.7) |
90 19 (21.1) 71 (78.9) |
Europe = France, Germany and Spain
AN analysis of variance, DMD Duchenne muscular dystrophy, FE Fisher’s exact test, SD standard deviation, TT Student’s t-test, USA United States of America
Overall, caregivers’ age differed significantly across regions (p = 0.0046), with mean age lowest in the USA and highest in Japan. Caregivers of non-ambulatory dependents were older than those caring for ambulatory dependents (p < 0.0001). Most caregivers were female, with no significant difference across regions (p = 0.4018) or between ambulatory and non-ambulatory DMD (p = 0.3430). Most caregivers were the parents of their dependents with DMD. There was no significant difference between regions in the relationship between caregivers and dependents with DMD (p = 0.1386).
Caregiver employment
Details of caregivers’ employment are shown in Table 3 and Fig. 2.
Fig. 2.
Caregiver employment details. Caregivers could report more than one change to employment, so may total > 100%. Europe = France, Germany and Spain; USA, United States of America. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. DMD, Duchenne muscular dystrophy
Employment status was reported by 215 caregivers, of whom almost half were working full- or part-time (Table 3 and Fig. 2a). The number of caregivers working full-time differed significantly across the regions (p = 0.0020), being highest in the USA and lowest in Japan. The number of caregivers who were homemakers differed across the regions (p < 0.0001), and was highest in Japan and lowest in the USA. There were no significant differences in employment status between caregivers for ambulatory and non-ambulatory patients.
A reduction in working hours was the most common type of change in caregiver employment (Table 3). There were significant differences across regions in the number of caregivers reducing working hours (p = 0.0008), with this highest in the USA and lowest in Japan, changing type of work (p < 0.0001), and making no change (p < 0.0001). A higher number of caregivers of people with non-ambulatory DMD than of those with ambulatory DMD made changes to employment other than reducing working hours, changing type of work, or working unsocial hours (p = 0.0282), and a higher number of caregivers of dependents with ambulatory DMD than non-ambulatory DMD made no changes to employment (p = 0.0225).
The proportion of caregivers reporting that changes in their employment were due to caring for a dependent with DMD differed significantly across regions (p = 0.0262), being highest in the USA and lowest in Japan. A higher proportion of caregivers of dependents with non-ambulatory DMD than caregivers of those with ambulatory DMD made changes in employment due to caring for a dependent with DMD (p = 0.0064).
Caregivers’ productivity and activity impairment are shown in Fig. 3.
Fig. 3.
Caregiver work productivity and activity impairment (from WPAI). Europe = France, Germany and Spain; USA, United States of America. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. SD, standard deviation; WPAI, Work Productivity and Activity Impairment questionnaire
No significant differences were seen in absenteeism, presenteeism or overall work impairment due to caregiving based on geographical region or ambulatory status of the patient. Total activity impairment (Fig. 3d) varied significantly across the regions (p = 0.0002), with mean activity impairment highest in Japan and lowest in the USA. Total activity impairment was significantly greater in caregivers of dependents with non-ambulatory DMD compared with those caring for dependents with ambulatory DMD (p < 0.0001).
Caregiver health status
Caregivers’ own health status from their responses on the EQ-5D-5L are shown in Table 4.
Table 4.
Caregiver health status
| Total (n = 216) |
Europe (n = 99) |
USA (n = 90) |
Japan (n = 27) |
p-value | Non-ambulatory (n = 98) | Ambulatory (n = 117) |
p-value | |
|---|---|---|---|---|---|---|---|---|
| Mobility, n (%) |
0.0874 (KW) |
0.7342 (MW) |
||||||
|
n I have no problems in walking about I have slight problems in walking about I have moderate problems in walking about I have severe problems in walking about I am unable to walk about |
216 167 (77.3) 31 (14.4) 7 (3.2) 2 (0.9) 9 (4.2) |
99 80 (80.8) 16 (16.2) 2 (2.0) 1 (1.0) 0 (0.0) |
90 64 (71.1) 12 (13.3) 5 (5.6) 1 (1.1) 8 (8.9) |
27 23 (85.2) 3 (11.1) 0 (0.0) 0 (0.0) 1 (3.7) |
98 78 (79.6) 8 (8.2) 3 (3.1) 0 (0.0) 9 (9.2) |
117 88 (75.2) 23 (19.7) 4 (3.4) 2 (1.7) 0 (0.0) |
||
| Self-Care, n (%) |
0.1357 (KW) |
0.0594 (MW) |
||||||
|
n I have no problems washing/dressing myself I have slight problems washing/dressing myself I have moderate problems washing/dressing myself I have severe problems washing/dressing myself I am unable to wash or dress myself |
216 181 (83.8) 18 (8.3) 7 (3.2) 3 (1.4) 7 (3.2) |
99 83 (83.8) 10 (10.1) 4 (4.0) 2 (2.0) 0 (0.0) |
90 72 (80.0) 8 (8.9) 3 (3.3) 1 (1.1) 6 (6.7) |
27 26 (96.3) 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.7) |
98 88 (89.8) 2 (2.0) 0 (0.0) 1 (1.0) 7 (7.1) |
117 92 (78.63) 16 (13.7) 7 (6.0) 2 (1.7) 0 (0.0) |
||
| Usual Activities, n (%) |
0.1346 (KW) |
0.9067 (MW) |
||||||
|
n I have no problems doing my usual activities I have slight problems doing my usual activities I have moderate problems doing my usual activities I have severe problems doing my usual activities I am unable to do my usual activities |
215 160 (74.4) 33 (15.4) 16 (7.4) 2 (0.9) 4 (1.9) |
98 75 (76.5) 16 (16.3) 7 (7.1) 0 (0.0) 0 (0.0) |
90 62 (68.9) 14 (15.6) 9 (10.0) 2 (2.2) 3 (3.3) |
27 23 (85.2) 3 (11.1) 0 (0.0) 0 (0.0) 1 (3.7) |
98 73 (74.5) 14 (14.3) 5 (5.1) 2 (2.0) 4 (4.1) |
116 86 (74.1) 19 (16.4) 11 (9.5) 0 (0.0) 0 (0.0) |
||
| Pain/Discomfort, n (%) |
0.3365 (KW) |
0.5497 (MW) |
||||||
|
n I have no pain or discomfort I have slight pain or discomfort I have moderate pain or discomfort I have severe pain or discomfort I have extreme pain or discomfort |
215 134 (62.3) 54 (25.1) 21 (9.8) 6 (2.8) 0 (0.0) |
99 65 (65.7) 25 (25.3) 6 (6.1) 3 (3.0) 0 (0.0) |
89 51 (57.3) 23 (25.8) 12 (13.5) 3 (3.4) 0 (0.0) |
27 18 (66.7) 6 (22.2) 3 (11.1) 0 (0.0) 0 (0.0) |
97 58 (59.8) 26 (26.8) 11 (11.3) 2 (2.1) 0 (0.0) |
117 75 (64.1) 28 (23.9) 10 (8.6) 4 (3.4) 0 (0.0) |
||
| Anxiety/Depression, n (%) |
< 0.0001 (KW) |
0.2775 (MW) |
||||||
|
n I am not anxious or depressed I am slightly anxious or depressed I am moderately anxious or depressed I am severely anxious or depressed I am extremely anxious or depressed |
216 92 (42.6) 59 (27.3) 53 (24.5) 9 (4.2) 3 (1.4) |
99 34 (34.3) 23 (23.2) 34 (34.3) 7 (7.1) 1 (1.0) |
90 36 (40.0) 32 (35.6) 18 (20.0) 2 (2.2) 2 (2.2) |
27 22 (81.5) 4 (14.8) 1 (3.7) 0 (0.0) 0 (0.0) |
98 43 (43.9) 32 (32.7) 17 (17.4) 4 (4.1) 2 (2.0) |
117 48 (41.0) 27 (23.1) 36 (30.8) 5 (4.3) 1 (0.9) |
Europe = France, Germany and Spain
KW Kruskal–Wallis test, MW Mann–Whitney U test, USA United States of America
Most caregivers reported no problems with mobility, self-care, usual activities, and pain/discomfort. Very few caregivers were unable to walk about, wash/dress themselves, or complete their usual activities, had severe problems in walking about, washing/dressing themselves or completing their usual activities, or had severe pain/discomfort. There were no differences across the regions in mobility, self-care, usual activities and pain/discomfort (p = 0.0874, p = 0.1357, p = 0.1346, and p = 0.3365, respectively). There were also no differences between caregivers in mobility, self-care, usual activities and pain/discomfort based on the ambulatory status of the dependents with DMD that they cared for (p = 0.7342, p = 0.0594, p = 0.9067, and p = 0.5497, respectively).
Overall, almost 70% of caregivers reported that they were not anxious/depressed or were slightly anxious/depressed. There were significant differences across the regions in anxiety/depression (p < 0.001), with the greatest anxiety/depression reported in Europe and the least in Japan. No differences were reported in anxiety/depression between caregivers for non-ambulatory and ambulatory DMD (p = 0.2775).
Caregiver’s own EQ-VAS scores and EQ-5D-5L index values are shown in Fig. 4.
Fig. 4.
Caregivers’ EQ-VAS and EQ-5D-5L index values. Europe = France, Germany and Spain; USA, United States of America; VAS, visual analog scale. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. SD, standard deviation
There was a significant difference across the regions for caregivers’ EQ-VAS (p < 0.0001), with mean EQ-VAS scores highest in the USA, and identical in Europe and Japan. There was no significant difference in caregivers’ EQ-5D-5L index values across geographical regions (p = 0.0592). No differences were reported between caregivers in the non-ambulatory and the ambulatory group for EQ-VAS scores (p = 0.0867) or EQ-5D-5L index values (p = 0.8520).
Discussion
The early age of onset and severity of symptoms of DMD mean that a caregiver is essential, and that caregiving is likely to be challenging. We aimed to evaluate how providing care for people with DMD impacts non-professional caregivers, and whether this differs across geographical regions or with the ambulatory status of their dependents with DMD. We analyzed survey data from more than 200 caregivers from Europe, the USA and Japan, who were looking after dependents with DMD, almost half of whom were non-ambulatory at the time of the survey. The impact on employment, productivity and activities, together with the impaired health status that we observed, confirmed the substantial burden on caregivers of dependents with DMD.
Within the sample, the characteristics of people with DMD varied across regions, with those in Japan being older and more likely to be non-ambulatory at the time of the survey than those in Europe or the USA. We believe this study is the first to report an age at DMD diagnosis in Japan, where the mean age was 3.4 years, compared with 5.0 years in the USA and 6.1 years in Europe. Age at DMD diagnosis has been reported as 4.9 years in the USA [19], 4.3 years across seven European countries [20] and 3.5 years in Germany [21]. The younger age at diagnosis in Japan might indicate better awareness of the condition in Japan than in the USA and Europe, and potentially higher levels of genetic testing.
Caregiver-reported proxy EQ-5D-5L findings for people with DMD confirmed the major impact of DMD on health states. Not surprisingly, given the severity of the disease, mean proxy EQ-VAS scores of people with DMD in our study, ranging from 7.3 in Japan to 46.9 in the USA, were substantially lower than norms reported for the general population in corresponding countries, which range from 75.0 for Spain to 80.0 for the USA [15]. The values in our study are also lower than the mean EQ-VAS score of 50.5 reported in a cross-sectional European study [22] and in a US study of individuals with DMD aged 12–40 years, in which values ranged from 70.0 to 91.0, depending on disease progression [23]. Similarly, proxy EQ-5D-5L index values for people with DMD in our study ranged from 0.13 in Japan and Europe to 0.25 in the USA, considerably below published population norms, which range from 0.83 for the USA to 0.93 for Japan [15]. The values in our study are also below those reported in the US study, where EQ-5D-5L index values ranged from 0.22 to 0.79, depending on disease status [23]. However, the index values in our study were higher than the values of − 0.05 for non-ambulant patients and 0.51 for ambulant patients reported for the EQ-5D-3L in a cross-sectional study in Portugal [6]. The reasons for the discrepancies in EQ-5D findings between our study and published studies is unclear, although care is needed in interpreting the findings of either of the published studies, due to small sample sizes.
In our study, there were regional differences in problems with mobility, self-care and usual activities reported for people with DMD. The highest proportions of those unable to walk about, wash or dress themselves, and do their usual activities were in Japan, and the lowest proportions in the USA. The findings for Japan align with the higher proportion of non-ambulatory patients in Japan than in other regions and likely reflect differences in the disease stage of DMD between regions. However, a higher proportion of care recipients in the USA than in Europe were non-ambulatory. This apparent disconnect might be explained by regional differences in how health is perceived and reported; the findings of a study by the Organisation for Economic Co-operation and Development reported that people in the USA rated themselves as being in better health than those from the three European countries included in our study [24].
As might be expected, those with ambulatory DMD had significantly fewer problems with mobility, self-care and usual activities than those with non-ambulatory DMD, although no difference was reported between the groups for pain/discomfort or anxiety/depression. The EQ-5D-5L index value was significantly higher for ambulatory than for non-ambulatory DMD, which reflects the fact that the index value is derived from the problems reported in the five dimensions. However, there was no significant difference in EQ-VAS scores between ambulatory and non-ambulatory DMD. The only other study we have identified that has reported EQ-VAS for people with DMD grouped by ambulatory status included small sample sizes and no statistical comparisons were reported between ambulatory and non-ambulatory participants [23]. As the EQ-VAS is a subjective assessment of overall health state, our findings suggest that the overall health of people with non-ambulatory DMD is not perceived to be impaired to a significantly greater extent than that of those with ambulatory DMD. Although this finding might appear unexpected, it must be considered in the context of the multitude of symptoms associated with DMD. In addition to mobility problems, people with DMD experience upper limb issues, pulmonary problems necessitating daytime and nighttime ventilation, fatigue, and cardiomyopathy as the disease progresses. A published study estimating utility values for a range of clinical and functional health states in DMD found that non-ambulatory patients valued their health as far better via a VAS compared to via indirect utility estimates [23], supporting the likelihood that other symptoms might mean that the loss of ambulatory ability is not reflected in a significant reduction in EQ-VAS score.
Most caregivers in our study were parents of their dependents with DMD, as reported in other studies [5, 6, 25]. In our study, under half of caregivers were employed full- or part-time, and almost half of these had made some change to their work. It is highly likely that being a caregiver to an individual with DMD led to the low employment rates among the caregivers in our study; the vast majority of these were mothers, and the employment rate in this group has been reported to be 72% in Europe [26] and the USA [27], and 80% in Japan [28]. In a USA case–control study the employment rate was 57% among DMD caregivers, compared with 73% of parents of children without DMD, with caregivers generally working fewer hours [9]. A reduction in working hours or cessation of work due to caring for DMD patients was also reported by 27%–49% of caregivers in an online survey in Germany, Italy, the UK, and the USA [25]. Our study showed caregivers in the USA to be more likely than those from other regions to be working, supporting findings published previously [25]. This regional difference might reflect the high economic burden of DMD and regional variations in healthcare systems.
As only 48.0% of caregivers in our study were employed, information on absenteeism or presenteeism was available for fewer than half of the caregivers. We were only able to find two publications describing WPAI findings for caregivers in DMD. One of these reported only overall work impairment, which was 20% in Germany and 27% in the USA [25], compared with our findings of 47% in Europe (France, Germany and Spain) and 41% in the USA. The other was a small study in Portugal, which reported mean absenteeism, presenteeism overall work impairment and total activity impairment of 11.1%, 35.8%, 30.5%, and 60.0%, respectively [6], values broadly comparable with those in our study of 9.7%, 37.8%, 42.4%, and 49.0%, respectively. We saw no differences in absenteeism, presenteeism or overall work impairment across geographical regions or based on ambulatory status in our study, possibly due to the relatively low employment rates and sample sizes. Total activity impairment was significantly lower at 42.5% for caregivers of dependents with ambulatory DMD than for caregivers of dependents with non-ambulatory DMD (56.6%); similar finding were reported in the Portuguese study were caregivers of dependents with ambulatory and non-ambulatory DMD reported total activity impairment of 23% and 68%, respectively [6].
Few problems were self-reported by caregivers on four of the five dimensions of the EQ-5D-5L. The mean index value for our DMD caregivers in Europe was 0.83, compared with values ranging between 0.77 and 0.85 (depending on the ambulatory status of the dependent with DMD) reported for a study in Germany, Italy, the UK, and the USA [29] and 0.79 reported for Germany in another study [25] and population norms of 0.87 for France, 0.90 for Germany, and 0.92 for Spain [15]. The mean index value for our DMD caregivers in the USA was 0.80, compared with a value of 0.81 from a published study [25] and a population norm of 0.83 [15], and the mean index value for our DMD caregivers in Japan was 0.91, compared with the population norm of 0.93 [15]. This suggests that health status in the USA and Japan is not adversely affected to a major degree by providing care to a DMD patient. However, caregivers’ mean EQ-VAS score overall was 26.9, compared with population norms in the participating countries ranging from 75.0 for Spain to 80.0 for the USA [15], suggesting substantial impairment of health status due to caregiving. The apparent disconnect between EQ-5D-5L index values and EQ-VAS scores in our study requires consideration. The EQ-5D-5L index value is determined based on responses to the questions for the five dimensions, while the EQ-VAS score is an overall assessment of the respondent’s perceived health; it therefore appears that caregivers generally perceive their health to be poor despite reporting relatively few problems in the dimensions assessed with the EQ-5D-5L. Prior studies have suggested that EQ-VAS scores and index values are not always strongly correlated; in one study, although EQ-VAS scores were broadly associated with EQ-5D index values, variables such as psychological disposition, socio-demographic factors and clinically-important distress contributed to determining EQ-VAS scores [30]. The disparity we observed between EQ-5D-5L index values and EQ-VAS scores might also be linked to caregivers reporting greater problems in anxiety/depression than other dimensions; a published study reported that problems in the anxiety/depression dimension of the EQ-5D had a greater impact on overall health status than other dimensions [31].
Although no differences based on geographical region or ambulatory status of dependents were seen in any of the EQ-5D-5L dimensions or the EQ-5D-5L index values for caregivers, EQ-VAS was significantly different across the regions, with mean EQ-VAS score higher for USA caregivers than for the other two regions, although still lower than the US population norm (52.1 versus 80.0, respectively). Our findings probably reflect regional differences in health perception, with the USA population norm being the highest of any of the countries included in our study [15] and evidence that people in the USA self-rated their health as better than people from the other countries included [24].
Major strengths of this study are the international setting and its basis in real-world clinical practice. We believe our study population to be broadly representative of the wider DMD community; given the mean age of people with DMD included in the study, the ratio of ambulatory to non-ambulatory aligns generally with the findings of a recent systematic review and meta-analysis [32]. There are, however, potential limitations of our study. The DSP is based on a pseudo-random sample of physicians; while minimal inclusion criteria governed the selection of participating physicians, participation was influenced by their willingness to complete the survey. To minimize selection bias, physicians were asked to provide data for a consecutive series of eligible patients. Patient eligibility was based on the judgement of the respondent physician and not on a formalized diagnostic checklist. However, this is representative of the physician’s real-world classification of their patients. Participating patients may not reflect the general DMD population since the DSP only includes patients who are consulting with their physician. This means that patients who consult more frequently have a higher likelihood of being included. The cross-sectional design of this survey prevented any conclusions about causal relationships; however, identification of significant associations was possible. In statistical analyses, no adjustments for multiplicity were made; caution should always be used in interpreting any results. Recall bias, a common limitation of surveys, might also have affected caregivers’ responses. Despite the high numbers of study participants, small sample sizes were available for some variables. Some missing data were to be expected and may have influenced results, although this was not considered a substantial issue. Low response rates for employment-related measures on the WPAI were a result of the low levels of caregivers in paid employment, particularly in Japan. Due to the age and poor health of people with DMD, their health state was assessed by caregivers’ completing the EQ-5D-5L as proxies, rather than by people with DMD themselves. Some studies have shown that parental caregivers of children with dystrophinopathies rate their childrens’ HRQoL as worse than the children rate their own HRQoL [33, 34]. However, an international study of self- or proxy(caregiver)-reported EQ-5D findings concluded it to be a valid and reliable tool for use in people with DMD [35].
Notwithstanding these limitations, this study provides valuable insight into the burden of providing care to people with DMD.
Conclusions
Our findings confirmed the major HRQoL detriment associated with DMD, and how the impact increases with disease progression. Low employment rates with substantial levels of presenteeism, major impairment of activities, and poor perceived health status observed in this study all confirm the considerable burden on caregivers of people with DMD. The caregiving burden appeared to vary across geographical regions, and to be greater when the people with DMD were no longer ambulatory. Further research to better understand the reasons for regional differences might provide insight into potential means to reduce the burden on caregivers.
Acknowledgements
Medical writing support under the guidance of the authors was provided by Carole Evans, PhD, on behalf of Adelphi Real World in accordance with updated Good Publication Practice (GPP) guidelines [36]. The authors acknowledge Susanne Brunner at Pfizer for her contributions to this research study.
Abbreviations
- AN
Analysis of variance
- CSC
Caregiver self-completion
- DMD
Duchenne muscular dystrophy
- DSP
Disease Specific Programme
- FE
Fisher’s exact test
- HRQoL
Health-related quality of life
- KW
Kruskal-Wallis test
- MW
Mann-Whitney U test
- SD
Standard deviation
- TT
Student’s t-test
- UK
United Kingdom
- USA
United States of America
- VAS
Visual analog scale
- WPAI
Work productivity and impairment index
Authors’ contributions
JS, KI, JCC, NP, SX, AT, SD, HI, EC, EM, SW and JdC actively assisted in the study design and interpretation of data, contributed to drafting, review and revision of manuscript; and have provided final approval of the submitted version. HI, EC, EM, SW and JdC were responsible for data acquisition and analyses.
Funding
Data collection was undertaken by Adelphi Real World as part of an independent survey, entitled the Adelphi Real World Duchenne muscular dystrophy DSP. Pfizer did not influence the original survey through either contribution to the design of questionnaires or data collection. The analysis described here used data from the Adelphi Real World Duchenne muscular dystrophy DSP. The DSP is a wholly owned Adelphi Real World product. Pfizer is one of multiple subscribers to the DSP. Publication of survey results was not contingent on the subscriber's approval or censorship of the manuscript. Pfizer funded the analysis and development of the publication.
Data availability
All data, i.e. methodology, materials, data and data analysis that support the findings of this survey are the intellectual property of Adelphi Real World. All requests for access should be addressed directly to Jonathan de Courcy at jonathan.decourcy@omc.com. Jonathan de Courcy is an employee of Adelphi Real World.
Declarations
Ethics approval and consent to participate
The study was performed in accordance with relevant guidelines and followed the principles of the Helsinki Declaration of 1964 and subsequent revisions. The research was submitted to the Pearl Institutional Review Board, study protocol number #22-ADRW-162.
Using a checkbox, caregivers provided informed consent to take part in the survey. Data were collected in such a way that patients, caregivers and physicians could not be identified directly. Data related to physicians, caregivers and people with DMD were pseudo-anonymized. A code was assigned when data were collected. Upon receipt by ARW, data were pseudo-anonymized again to mitigate against tracing them back to the individual. Data were aggregated before being shared with the subscriber and/or for publication.
Consent for publication
Not applicable.
Competing interests
JS is on the advisory board for Sarepta, speaker training for NS Pharma, was PI for Fibrogen pamrevlumab phase 2 trial and currently PI for PTC ataluaren phase 3. JS is also a speaker bureau for Biogen, consultant for UCB and Janssen/Momenta, and PI for Janssen and Alexion. KI received honoraria for speakers bureaus from Nippon Shinyaku Co., Ltd and has an advisory role at Pfizer Japan Inc. JCC and NP are employees and stockholders of Pfizer Inc. SX, AT and SD are employees of Pfizer and may own stocks/shares of the company. EC, EM, SW and JdC are full-time employees of Adelphi Real World, which received funding from Pfizer in connection with the development of this manuscript. HI no longer works for Adelphi Real World but did at the time of writing.
Footnotes
Adelphi Real World, Bollington, United Kingdom is the affiliation when research was conducted.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data, i.e. methodology, materials, data and data analysis that support the findings of this survey are the intellectual property of Adelphi Real World. All requests for access should be addressed directly to Jonathan de Courcy at jonathan.decourcy@omc.com. Jonathan de Courcy is an employee of Adelphi Real World.