Background
Methods
Data source and search strategy
Study selection and data extraction
Results
Generic and specific HrQoL instruments in IMDs pediatric and adult populations
Instrument Name | Sub-scales | Item number | Target Group (years) | IMDs |
---|---|---|---|---|
Adolescent- and adult-oriented instruments | ||||
General | ||||
15D | Mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort, depression, distress, vitality, sexual activity | 15 | > 16 | Familial hypercholesterolemia [95] |
AQOL-4D | Independent living (self-care, household tasks and mobility), relationships (friendships, isolation and family role), mental health (sleeping, worrying and pain) and senses (seeing, hearing and communication) | 12 | 15–19 (norm) | Hereditary haemochromatosis [144] |
EQ-5D | Mobility, self-care, usual activities, pain/discomfort, anxiety/depression | 5 plus the VAS | > 18 | |
EQ-5D-5 L | 5 plus the VAS | |||
EQ-5D-3 L | 5 plus the VAS | |||
EQ-5 VAS | 1 | |||
NHP | Energy level, pain, emotional reaction, sleep, social isolation, physical abilities, work, house tasks, social functioning, sex life, interests and hobbies, vacations. | 45 | > 16 | Pompe disease [119] |
PGWBI | Anxiety, depression, positive well-being, self-control, general health, vitality | 22 | > 18 | PKU [133] |
PLC | Emotional, practical and social impact, disease-specific symptoms, diet and therapeutic impact | 40 | Adolescents and adults | |
SIP-136 | Sleep and rest, eating, work, home management, recreation and pastimes, ambulation, mobility, body care and movement, social interaction, alertness behavior, emotional behavior, communication | 136 | Adolescents, adults and elderly | MELAS [69] |
SIP-68 | Somatic autonomy, mobility control, mobility range, social behaviour, emotional stability, psychological autonomy/communication | 68 | Adolescents, adults and elderly | Niemann-Pick disease type C [72] |
SF-36 | Physical functioning, role limitations due to physical health, body pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. | 36 | > 14 | Acute porphyrias [68], carnitine palmitoyltransferase II deficiency [158], cystinuria [143], Fabry disease [52‐57, 87, 92, 107‐111, 132, 141, 145, 147, 159‐162], familial hypercholesterolemia [95, 112], Gaucher disease [60, 61, 98, 99, 113, 114, 128, 163, 164], GSD type I [137], hereditary hemochromatosis [67, 155, 165], mevalonate kinase deficiency [66] McArdle disease [70, 100, 101], MELAS [69], MPS [35], MPS IV [71, 115], Niemann-Pick type B [47] and type C [72], PKU [89, 94, 166], Pompe disease [62‐65, 102‐105, 118, 167‐169], Wilson disease [116, 140, 170], X-linked hypophosphatemia [73] |
SF-36-6D | Physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. | 11 | Pompe disease [131] | |
SF-12 | Physical functioning, role limitations, social functioning, pain, mental health, vitality | 12 | > 12 | |
TAAQOL | Gross motor functioning, fine motor functioning, cognition, sleep, pain, social contacts, daily activities, sex, vitality, happiness, depressive mood, anger | 45 | > 16 | |
WHOQOL-100 | Vitality, psychological well-being, relationship with friends, leisure activities, relationship with parents, physical well-being, relationship with teachers, school, body image, relationship with medical staff. | 100 | > 18 | |
WHOQOL-BREF | Physical health, psychological health, social relationships, and environment | 26 | > 18 | |
Specific | ||||
PKU-QOL Adult version | PKU symptoms, PKU in general (emotional, practical, social and overall impact), administration of Phe-free protein supplements, dietary protein restriction | 65 | > 18 | PKU [89] |
Pediatric instruments | ||||
General | ||||
CHQ | General health, physical functioning, role limitations due to emotional problems, role limitations due to physical health, body pain, behaviour, global behaviour, mental health, self-esteem, general health perceptions, emotional parental impact, time parental impact, family activities, family cohesion. | 5–18 | ||
CHQ-CF87 | 87 | 5–18 | ||
CHQ-PF28 | 28 | 5–18 | PKU [89] | |
CHQ-PF50 | 50 | 5–18 | ||
DISABKIDS-37 | Independence, emotion, inclusion, exclusion, limitations, treatment | 37 | Children and adolescents with chronic diseases | PKU [46] |
HUI 2 | Sensation, mobility, emotion, cognition, self-care, pain, fertility | 15 (self) | > 5 | Fabry disease [40] |
HUI 3 | Vision, hearing, speech, ambulation, dexterity, emotion, cognition, pain | 15 (self) | > 5 | |
KIDSCREEN-27 | Walking/standing, Reach/grip, Sleeping, School/work, Activities and Breathing; and a satisfaction-with-function and a botheredness-with-function domains | 27 | 8–18 | MPS II [77] |
KINDL | Physical well-being, psychological well-being, autonomy and parents, peers & social support, school environment | 4–16 | PKU [44, 45], carbohydrate metabolism disorders including GSD, galactosemia, and fructose-1,6-bisphosphatase deficiency; OAs including MMA, PA, MSUD, 3-methylcrotonyl CoA carboxylase deficiency and 3-hydroxy-2-methylglutaryl CoA lyase deficiency; and amino acid metabolism disorders including PKU, alkaptonuria, homocystinuria and tyrosinemia [24] | |
KiddyKINDL | 12: self 46: proxy | 4–6 or their parents | Propionic acidemia [97] | |
KidKINDL | 24 | 7–13 or their parents | ||
KiddoKINDL | 24 | 14–17 or their parents | ||
PedsQL | Physical, emotional, social and school functioning | 23 | 5–18 | |
PedsQL parent version | 23 | Parents of 2–18 years old patients | Batten disease [31], citrin deficiency [51], Fabry disease [83], GSD type I [39], MMA [34], MPS [35], MSUD [48], PKU [43, 46, 84], OAs, including MMA, PA, IVA, GA1; UCDs, including CPS1 deficiency, citrullinemia type I, ASL deficiency, HHH syndrome, OTC deficiency [50] and inborn errors of metabolism in general [33] | |
PODCI | Upper extremity function, transfers and mobility, physical function and sports, comfort (lack of pain), happiness, satisfaction, and expectations | 42 | 2–18 | MPS IVa [115] |
SF-10 | Physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role emotional and mental health | 10 | 5–18 children’s parents | LC-FAOD [38] |
TACQOL | General physical functioning, motor functioning, autonomy, cognition, social contacts, positive mood, negative mood | 56 | 6–11 or their parents (parent form) | |
TAPQOL | Stomach problems, skin problems, lung problems, sleeping problems, appetite, problem behaviour, positive mood, anxiety, liveliness, social functioning*, motor functioning* and communication* | 43 | Parents of 9 months-6 years children | Galactosemia [89] MPS VI [49] |
VSP-Ae | Gross motor functioning, fine motor functioning, cognition, sleep, pain, social contacts, daily activities, sex, vitality, happiness, depressive mood, anger | 38 | 8–10 | OAs, UCDs, MSUD [41] |
VSP-A | Physical functioning, motor functioning, autonomy, cognitive functioning, social functioning, positive and negative emotional functioning | 39 | 11–17 | OAs, UCDs, MSUD [41] |
VSP-Ap | Symptoms, sleeping, appetite, motor functioning, behaviour, social functioning, communication, positive and negative emotional functioning | 37 | Parents of patients of all ages | OAs, UCDs, MSUD [41] |
Specific | ||||
PKU-QOL | PKU symptoms, PKU in general (emotional, practical, social and overall impact), administration of Phe-free protein supplements, dietary protein restriction | PKU [89] | ||
Child | 40 | 9–11 | ||
Adolescent | 58 | 12–17 | ||
Parent | 54 | PKU patients’ parents | ||
PKU-QOLQ | Impact, worries, satisfaction, support, well-being | NA | 10–18 | PKU [124] |
QoL Scale for Metabolic Diseases – Parent Form | Impact of disease, attention, perception of disease, physical function, stigmatization, social support, school status, and health perception | 28 | Parents of children (1–15) with a metabolic disorder treated with restrictive diet for at least 1 year | Carbohydrate metabolism disorders, including GSD, galactosemia, fructose-1,6-bisphosphatase deficiency; OA including MMA, PA, MSUD, 3- methylcrotonyl CoA carboxylase deficiency, 3-hydroxy-2-methylglutaryl CoA lyase deficiency; amino acid metabolism disorders including PKU, alkaptonuria, homocystinuria, tyrosinemia [24] |
Proxy-reports to complement self-reports
HrQoL is generally impaired in IMDs
HrQoL tools detect changes upon treatment in IMD
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. | |
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 | [74] | |
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. | [128] | |
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 | [49] |
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 | |
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] |
Critical appraisal and main limitations of HrQoL studies
Discussion
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qualitative interviews with patients, their families and caregivers;
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patient registries, which also motivate patient enrolment in research projects and clinical trials [10]. The fact that Fabry disease is the condition with higher HrQoL assessment, is likely to be a direct consequence of the successful establishment of two patient registries - the Fabry Outcome Survey (NCT03289065) and the Fabry Registry (NCT00196742). Both include periodic HrQoL evaluations as a clinical outcome;
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clinical trials networks that facilitate data sharing and collaborations, ultimately improving access to the available information [153].