Skip to main content

Table 2 PROMs/ObsROMs HrQoL instruments used across IMDs to evaluate therapeutic benefit in clinical studies

From: Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review

IMD Sample (age in years) Treatment/Therapy Follow up time HrQoL tool Effects on HrQoL and major findings Ref.
Carnitine palmitoyl transferase II deficiency Adults Bezafibrate 6 months SF-36 - ↑ HrQoL in all domains, specially role limitations due to physical health and body pain [158]
  Children and adults (10–55) Anaplerotic diet therapy 7–61 months SF-36 - ↑ HrQoL in the physical component score [106]
Fabry disease Male adults (16–48) Agalsidase-β 10 days-20 weeks SF-36 - Phase 1/2 trial that proved the efficiency and safety of Fabrazyme including an ↑ HrQoL, namely regarding bodily pain, general health, vitality, physical role and emotional role domains. Placebo effects were noticed. [107, 108]
Adults and adolescents (> 14) Agalsidase-β 3 years SF-36 - ↑ HrQoL more pronounced in men [109]
Adults (41.4, mean) Agalsidase-β 2 years SF-36 - Ns changes in HrQoL [141]
Male adults (16–34) Agalsidase-β 20 weeks SF-36 - ↑ HrQoL with significant changes in the general health and the mental component score [110]
Adults Agalsidade-α 2 years EQ-5D - Significant ↑ HrQoL [120]
Adults Agalsidase-α 2 years EQ-5D - Significant ↑ HrQoL which negatively correlates with pain [122]
Adults (39.2 ± 12.3, mean) Agalsidase-α 5 years EuroQoL - Significant ↑ HrQoL [121]
Adults (males: 44.25 ± 11; females: 52.3 ± 10.5, means) Agalsidase-α 4 weeks EQ-5D - Ns differences in HrQoL in the 3 dose regimens. (NCT01218659) [129]
Heterozygous females (20–66) Agalsidase-α 55 weeks SF-36 - Phase 3 study that proved the agalsidase-α safety and efficacy in heterozygous females with significant ↑ HrQoL, mostly in the physical domain. [111]
Children (7–18) Agalsidase-α 55 weeks HUI, CHQ - Phase 2 study that showed the efficiency and safety of agalsidase-α, however HrQoL remained unchanged. (NCT01363492) [40]
Adults (42.5 ± 12.5, mean) ERT 6.1 ± 2.5 years EQ-5D - ↑ HrQoL in severely affected males
- Unchanged HrQoL in women
- Annual ↓ in HrQol in non-classical patients
Adults (26–68) ERT 4–7 years SF-36 - Stable HrQoL except for the social functioning score. [161]
Children (6–18) ERT PedsQL - Children on ERT had higher scores that approached significance. [83]
Adults (16–74) Migalastat 2 years SF-36 - Results did not reveal any clinical benefit (NCT00925301 and NCT01458119) [162]
Familial hypercholesterolemia Children and adults (9–57) LDL apheresis NA SF-36 - ↑ HrQoL in 2 patients with baseline data [112]
Gaucher disease type I Children and adults (12–70) Imiglucerase 4 years SF-36 - Significant ↑ HrQoL in the physical component score and, particularly, the physical functioning, physical role limitations and bodily pain subscores. (NCT00365131) [60]
Adults (18–82) Imiglucerase 2 years SF-36 - Since baseline HrQoL approached those of the general population, there was no space for improvements and ns changes were observed. [164]
Adults (17–69) Miglustat 6–24 months SF-36 - Miglustat administration significantly ↑ HrQoL, while imiglucerase or combination of both reduced HrQoL [113]
Adults (35.2 ± 10.2, mean at start) Miglustat 12–48 months SF-36 - Similar improvements in HrQoL between miglustat and ERT-treated patients. [114]
Adults (18–66) ERT 2 years SF-36 - Self-perception of global health, physical activity and social functioning improved with ERT. [61]
Children and adults (> 5) ERT or SRT 10 years (mean) SF-36 - 65 patients achieved the therapeutic goal for HrQoL but differences between treated and untreated patients were ns. [99]
Children and adults (> 12) (one type 3 Gaucher disease patient) ERT 8.5 years (mean) SF-36 - Bodily pain was significantly decreased in ERT-naïve patients but physical functioning, role physical, general health, social functioning and role emotional scores showed clinical meaningful impairments too.
- Gaucher disease patients receiving ERT have significant higher scores than Fabry disease patients also receiving ERT.
Hereditary hemochromatosis Adults (55 ± 9.0, mean) Erythrocytaphe-resis 2 years SF-36 - There is no benefit in terms of HrQoL of erythrocytapheresis over phlebotomy. (NCT01398644) [155]
MPS IH Children and adults (2–25) Hematopoietic cell transplant 9 years (mean) CHQ-PF50 - Higher age at transplant correlates with poor physical scores [36]
LC-FAOD Children and adults (12.06 ± 13.2, mean) Triheptanoin (UX007) 24 weeks SF-12, SF-10 - Significant ↑ HrQoL in the physical and mental domains for adults but not for children. (NCT01886378) [38]
MPS VI Children and adults (5–21) Arylsulfatase B 1.3–5-4 years TAPQOL, TACQOL - ↑ HrQoL regarding lung problems, sleeping, liveliness, positive mood, social functioning and communication
- ↓ HRQoL in the anxiety and negative emotions domains
McArdle’s disease Adults (18–60) Ramipril 3 months SF-36 -↑ HrQoL in the emotional status and social role in both ramipril and placebo groups [100, 101]
MPS IV Children and adults (9.8–42.2) Elosulfase-α 48–96 weeks SF-36, PODCI - Stable HrQoL, except in 1 child with ↓ HrQoL (NCT01697319) [115]
Nephropathic cystinosis Children and adolescents (6–21) Delayed-release cysteamine birtrate 2 years PedsQL - Significant ↑ HrQoL particularly in social, school and total function. [123]
Pompe disease Adults (41–42) Alglucosidase-α 2 years SF-36 - ↑ HrQoL, particularly in the bodily pain domain [102]
Adults (28–62) Alglucosidase-α 52 weeks SF-36 - 3/5 patients improved both physical and mental scores while 1/5 improved only the mental or the physical score [103]
Late onset adults (27–73) Alglucosidase-α 36 months SF-36 - Ns differences from baseline [117]
Late onset adults (21–69) Alglucosidase-α 1 year SF-36 - Ns differences from baseline [118]
Adults (24–76, at start) ERT 4 years (median) SF-36 - Significant ↑ HrQoL in the physical functioning, role physical, general health, vitality and mental health subscores, after 2 years. After 4 years, the bodily pain domain significantly worsened. [64]
Adult (65) L-alanine 6 months SF-36 - ↓ HrQoL, mainly the physical domain due to worsening of muscle function. ↑ HrQoL during placebo interval reflecting the optimism of entering a trial. [104]
Adults (20–71) Exercise program 12 weeks SF-36 - Borderline ↑ HrQoL at the mental component [105]
Late onset adults (35.5–60.7) Inspiratory muscle training program 8 weeks NHP - Significant ↑ HrQoL exclusively in the social isolation subscore [119]
PKU Children and adults (4–44) BH4 1 year PedsQL, TAAQOL - Unchanged HrQoL and similar between responsive and non-responsive patients [46]
Children and adolescents (6.6–18.7) BH4 6 months KINDL - Unchanged HrQoL and similar between responsive and non-responsive patients [44]
Children and adults (10–49) BH4 1 year PKU-QOLQ - ↑ HrQoL in responders, provisional responders and non-responders in terms of impact, satisfaction [124]
Wilson disease Children and adults (8–41) Orthotopic liver transplantation 97 months (mean) SF-36 - Ns difference between norm-based scores and patients who underwent transplantation [116]
Adults (36.6 ± 12.9) D-penicillamine, trientine, zinc 8.1–12.6 years (mean) SF-36 - D-penicillamine-treated patients had the highest HrQoL scores compared to trientine- or zinc-treated patients. [140]
  1. Abbreviations: AQOL-4D Assessment of Quality of Life 4D, CHQ Child Health Questionnaire, HUI Health Utilities Index, LDL Low-density lipoprotein, NA non available, NHP Nottingham Health Profile, Ns No significant, PedsQL Pediatric Quality of Life Inventory, PGWBI Psychological General Well-Being Index, PLC Profile for the Chronically Ill, PODCI Pediatric Outcomes Data Collection Instrument, PKU-QOL Phenylketonuria-Quality of Life, SF-36 36-Item Short Form Survey, TAAQOL TNO-AZL questionnaire for Adult’s HrQoL, TACQOL TNO-AZL Questionnaire for Children’s HrQoL, TAPQOL TNOAZL Questionnaire for Preschool Children’s HrQoL, VSP-A Vécu et Santé Percue de l’Adolescent, WHOQOL World Health Organization Quality of Life