Procedures and measurements
Participants were recruited through MLD patient advocacy groups and screened by researchers at Magnolia Innovation. The study sponsor was blinded to the identity of the participants. The study included a 60-minute quantitative telephone-assisted web survey and a 30-minute follow-up qualitative phone interview, during which the EQ-5D-5L questionnaire to measure health status was administered. Moderators administered the surveys, interviews and questionnaires in native languages for caregivers in Germany and France, respectively, and in English for all other countries.
This paper presents the quantitative findings from the survey and EQ-5D-5L. The content of the survey was validated by MLD clinical experts and national representatives of MLD patient advocacy groups. The main sections of the survey included caregiver and patient demographics, and questions on the disease management burden, time investment, and the social, emotional, psychological, and financial impacts of MLD. Where applicable, the survey captured information regarding the previous 4-week and 12-month periods.
Caregivers answered a series of “yes” or “no” questions and provided estimates regarding the time involved in daily caregiving duties, as well as for the stem cell transplant procedure (where appropriate). Caregivers also provided estimates for the number of times that their children with MLD had outpatient and inpatient hospital visits. Outpatient visits were defined as any medical care received that did not require an overnight hospital stay including doctor’s office, urgent care, or follow-up appointments outside the hospital setting, and inpatient hospital visits were defined as any medical care received where the child with MLD was admitted overnight.
To measure the emotional impact of providing care for a child with MLD, the caregivers were asked to select the frequency of the positive and negative emotions that they felt in the previous 4-week period, on a Likert scale with six options (all of the time, most of the time, a good bit of the time, some of the time, a little of the time, or none of the time).
The social impact of MLD was evaluated by asking the caregivers to indicate the extent to which they agreed or disagreed with a series of statements regarding their social lives since their child’s diagnosis. There were seven categories of responses: strongly disagree, disagree, somewhat disagree, neither agree nor disagree, somewhat agree, agree, or strongly agree. The caregivers were also asked how often they could keep up with their family responsibilities and social commitments in the previous 4-week period, with the following response options: never, rarely, sometimes, often, or always.
The effects of MLD on familial relationships was determined through caregiver responses to the level at which key relationships had been negatively impacted, based on the following options: not at all, little, moderate, somewhat, significantly, extremely, or not applicable.
The caregivers answered “yes” or “no” to a series of questions related to their professional lives and financial situations. Additionally, there were questions about the amount of nursing assistance received and if they paid for the services themselves.
While all participants were administered the same survey, the question about the hours spent as a caregiver was asked differently for caregivers in France versus the caregivers in all other countries due to differences in interpretation. In France, the caregivers were asked “How many additional hours do you spend caring for your child with MLD, outside the hours you would normally spend caregiving for a child?”, while caregivers in all other countries were asked “How many hours in total do you spend caregiving for your child with MLD?”. Therefore, these responses were evaluated separately for the caregivers in France and for caregivers in all other countries combined.
Participants completed the EQ-5D-5L questionnaire  following the quantitative survey. The spouses or live-in partners of the participants were invited to complete the EQ-5D-5L questionnaire if they also provided care for the individual with MLD. The EQ-5D-5L measured the quality of life (health status) of caregivers across five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression at five levels (no problems, slight problems, moderate problems, severe problems, unable). The scores of the five dimensions were also converted to EQ-5D utility index scores for caregivers in the US, Germany, UK, and France using the EuroQol EQ-5D-5L Crosswalk Index Value Calculator [11, 12], as limited national EQ-5D-5L value sets are currently available. The utility index scores ranged from 0 to 1, where 0 indicated death and 1 indicated perfect health. The questionnaire included a visual analogue scale (VAS), which asked respondents to rate the overall current state of their health on a scale of 0 to 100, where 0 represented the worst imaginable health and 100 represented the best imaginable health. The utility index and VAS scores for caregivers in the US, Germany, UK and France were compared to the general population norms in each country .
Unless otherwise noted, the analysis included the responses of caregivers in the all the survey countries, namely US, Germany, UK, France, Norway and Belgium. Due to the relatively small sample of caregivers in Norway and Belgium, the responses of these caregivers were described separately only where appropriate.
Subgroup analyses aimed to evaluate outcomes for the caregivers of patients diagnosed with late infantile onset MLD compared to those diagnosed with juvenile onset MLD. Additionally, the impact of time since diagnosis, which was calculated only for the MLD patients alive at the time of interview, was evaluated by comparing outcomes of caregivers whose children had been diagnosed within the past two years (Group A) at the time of the survey, caregivers whose children had been diagnosed more than two years but less than six years (Group B) at the time of the survey, and caregivers whose children had been diagnosed six or more years ago (Group C). Lastly, outcomes were compared for the caregivers of patients who had received stem cell transplant for MLD to those who have only received palliative treatments for MLD. These subgroup analyses specifically focused on the differences in time investment, and social and familial impact.