Table 1 PICOS eligibility criteria
Eligibility criteria | Inclusion criteria |
|---|---|
Population | Patients with MLDa • Late-infantile MLD • Juvenile MLD • Adult MLD |
Interventions | Any or none |
Comparators | Any or none |
Outcomes | Natural history evidence • Association between GMFC-MLD at baseline or phenotype and outcomes in the future, especially progression-related • To include evidence for which an association has already been tested and evidence that could later be used for statistical testing (e.g., any longitudinal data) • Specific question: does treatmentb give longer time in a more severe disease state? Clinical outcomes • Treatment options (best supportive care, HSCT, gene therapy, etc.), associated clinical outcomes in different disease stages, and variability across key markets •Disease progression (including but not limited to): • gross motor function • cognitive function  • difficulty in eating and drinking • difficulty in breathing • Morbidity and mortality associated with different treatment options stratified by:     • clinical subtype (late-infantile, juvenile, or adult MLD)     • disease stages      • time period  •  Treatment efficacy and/or effectiveness, treatment safety    • Response and change from baseline evaluated using GMFC-MLD, including time to unreversed decline    • Response and change from baseline evaluated using GMFM-88, including total score decline    • Change from baseline in expressive language evaluated using ELFC-MLD    • Change from baseline in CSF sulfatide levels    • Change from baseline in proton MRS metabolite level of N-acetylaspartate/creatine    • Change from baseline in Eichler MLD MRI severity score    • TEAEs    • AEs (grade > 3)    • Pharmacokinetic measurements    • HRQoL and patient-reported outcomes (LQLA; Vineland Adaptive Behavior Scales; PedsQL Family Impact Module, EQ-5D-5L, and EQ-5D-Y), COMFORT   •Association between benefit for patient subgroups and types of treatments (especially HSCT) • Humanistic and economic burden of illness evidence • Healthcare resource use and costs (by clinical subtype and phenotype if reported)  •Direct healthcare-related resource use (e.g., number of hospital admissions, days per admission) • Cost of treatments • Indirect healthcare cost (e.g., home modifications, wheelchairs, transportation, cost of care) • Societal resource use (e.g., days that the caregivers take off work, percentage of people who quit their jobs) •Economic evaluations • Quality-adjusted life-years gained  •Progression-free life-years gained • Life-years gained •Health state utilities • Treatment patterns by geography (especially use of HSCT) |
Study design | Natural history • Real-world observational/non-interventional studies • Clinical evidence • RCTs, single-arm trials and real-world observational/non-interventional studies • Humanistic and economic burden of illness evidence • Not limited by study type • All evidence • SLRs and meta-analysesc • Animal/in vitro studies and case reports will be excluded; case series will be included |
Date restrictions | •No limit |
Publication type | • All primary publications and SLRsc • Non-SLRs, editorials, notes, and letters will be excluded |
Country and language | • All countries if English language |