Measuring Patient Experiences in Fabry Disease
Measuring Patient Experiences in Fabry Disease
Introduction: Common symptoms for children with Anderson-Fabry Disease (FD) such as acroparaesthesia and gastrointestinal manifestations can only be objectively assessed in patients using a valid instrument. To date, no such instrument exists.
Methods: A preliminary 40-item measure of symptoms and experience with FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was developed, but lacked a formal assessment of its measurement properties. The FPHPQ was used in the Fabry Outcome Survey (FOS), a registry for all patients with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are treatment naïve and who are managed by physicians participating in FOS. After an item analysis to explore how items performed and combined into domains, a battery of psychometric analyses was performed to assess the measurement properties of this new instrument.
Results: Eighty-seven children (ages 4–18 years) completed the questionnaire. Twenty-three items in three subscales of the questionnaire emerged: pain associated with heat or exertion, pain associated with cold, and abdominal pain and fatigue symptoms. Internal consistency reliability for all three subscales was good (Cronbach alpha ≥ 0.84). Reliability was equally high for all age groups (4–7, 8–12, and 13–18). Test-retest reliability was high for all three subscales (intraclass correlation coefficient ≥ 0.74). Construct validity was demonstrated by moderate correlation with brief pain inventory (BPI), KINDL, and EQ-5D. Known group validity showed all subscales were able to discriminate between Fabry disease severity groups as classified by above or below median of the FOS MSSI (Mainz Severity Score Index) grade. The heat or exertion subscale was responsive to change in symptoms between responders and non-responders as defined by change in EQ-5D index scores between the first and second visit.
Conclusions: Preliminary results indicate that the measurement properties of FPHPQ are valid and reliable for assessing patient-reported symptoms of FD. The questionnaire could be a useful tool for clinicians to understand the progression of disease and monitor treatment effects. FPHPQ will be further validated and refined as the FOS registry is continuously adding more patients.
Anderson-Fabry disease (FD) is a rare condition, but the second most common among the lysosomal storage diseases (LSD) and the only X-linked sphingolipidosis. It is an inherited disorder caused by a deficiency of alpha-galactosidase A (GLA) that results in a slowly progressive disease with premature death in adult males and some females due to cardiac, renal or central-nerve-system (CNS) events. FD is rare with an estimated incidence of 1 in 40,000 to 60,000 males, with clinical heterogeneity in female patients. The disease typically begins in childhood and can be diagnosed by measuring the level of alpha-galactosidase activity; however, this may be misleading in female heterozygotes probably due to the random nature of X-inactivation. Molecular analysis of the GLA gene is the most accurate method of diagnosis, and many mutations which cause the disease have been noted.
Characteristic features of FD include episodes of neuropathic pain. Other symptoms may include fatigue, nausea, dizziness, gastrointestinal symptoms such as diarrhoea, a decreased ability to sweat, angiokeratoma, cornea verticillata and hearing impairment may also occur in childhood.
In rare conditions such as FD, close and prospective monitoring of as many patients as possible is important to gain a better understanding of the natural history of the disease and the rate of disease progression. Additionally, to assess the impact of treatments such as enzyme replacement therapy (ERT), a valid disease-specific measure is required. Because no instrument to assess the typical manifestations of the disease existed, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was developed and has been used to address the most commonly reported symptoms experienced by children with FD followed in a Fabry registry – the Fabry Outcome Survey (FOS; sponsored by Shire Human Genetics Therapies).
The preliminary FPHPQ was a 40-item questionnaire on children's symptoms and experience with FD developed by the FOS Paediatric Working Group - an international group of dedicated and experienced clinicians. The FOS Paediatric Working Group set out to develop a tool that would both identify disease burden in children that affected their quality of life but also in the future once validated, could be used to monitor treatment effects. The questions were specifically chosen based on what the clinical experts knew at the time of the subjective early clinical manifestations of FD.
FOS is the world's most comprehensive database on medical outcomes of patients with FD. FOS is designed as an international multi-centre, open-label registry. It is open to all patients on, or candidates for ERT with agalsidase alfa. Patients with FD entered into the database but not receiving ERT are also followed in order to gain insight into the natural history of the condition. The principal aim of FOS is to collect and disseminate information about the long-term course of the disease, especially in patients treated with agalsidase alfa. In order to guide treatment, relevant data recorded on the FOS database are being made available to the treating physician on an individual patient basis. Questions to the database aimed at helping FOS physicians in their routine clinical practice and patient management to be handled swiftly.
The purpose of this study is to present the psychometric validation of the FPHPQ, as well as to explore the underlying concepts measured and their dimensionality.
Abstract and Introduction
Abstract
Introduction: Common symptoms for children with Anderson-Fabry Disease (FD) such as acroparaesthesia and gastrointestinal manifestations can only be objectively assessed in patients using a valid instrument. To date, no such instrument exists.
Methods: A preliminary 40-item measure of symptoms and experience with FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was developed, but lacked a formal assessment of its measurement properties. The FPHPQ was used in the Fabry Outcome Survey (FOS), a registry for all patients with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are treatment naïve and who are managed by physicians participating in FOS. After an item analysis to explore how items performed and combined into domains, a battery of psychometric analyses was performed to assess the measurement properties of this new instrument.
Results: Eighty-seven children (ages 4–18 years) completed the questionnaire. Twenty-three items in three subscales of the questionnaire emerged: pain associated with heat or exertion, pain associated with cold, and abdominal pain and fatigue symptoms. Internal consistency reliability for all three subscales was good (Cronbach alpha ≥ 0.84). Reliability was equally high for all age groups (4–7, 8–12, and 13–18). Test-retest reliability was high for all three subscales (intraclass correlation coefficient ≥ 0.74). Construct validity was demonstrated by moderate correlation with brief pain inventory (BPI), KINDL, and EQ-5D. Known group validity showed all subscales were able to discriminate between Fabry disease severity groups as classified by above or below median of the FOS MSSI (Mainz Severity Score Index) grade. The heat or exertion subscale was responsive to change in symptoms between responders and non-responders as defined by change in EQ-5D index scores between the first and second visit.
Conclusions: Preliminary results indicate that the measurement properties of FPHPQ are valid and reliable for assessing patient-reported symptoms of FD. The questionnaire could be a useful tool for clinicians to understand the progression of disease and monitor treatment effects. FPHPQ will be further validated and refined as the FOS registry is continuously adding more patients.
Introduction
Anderson-Fabry disease (FD) is a rare condition, but the second most common among the lysosomal storage diseases (LSD) and the only X-linked sphingolipidosis. It is an inherited disorder caused by a deficiency of alpha-galactosidase A (GLA) that results in a slowly progressive disease with premature death in adult males and some females due to cardiac, renal or central-nerve-system (CNS) events. FD is rare with an estimated incidence of 1 in 40,000 to 60,000 males, with clinical heterogeneity in female patients. The disease typically begins in childhood and can be diagnosed by measuring the level of alpha-galactosidase activity; however, this may be misleading in female heterozygotes probably due to the random nature of X-inactivation. Molecular analysis of the GLA gene is the most accurate method of diagnosis, and many mutations which cause the disease have been noted.
Characteristic features of FD include episodes of neuropathic pain. Other symptoms may include fatigue, nausea, dizziness, gastrointestinal symptoms such as diarrhoea, a decreased ability to sweat, angiokeratoma, cornea verticillata and hearing impairment may also occur in childhood.
In rare conditions such as FD, close and prospective monitoring of as many patients as possible is important to gain a better understanding of the natural history of the disease and the rate of disease progression. Additionally, to assess the impact of treatments such as enzyme replacement therapy (ERT), a valid disease-specific measure is required. Because no instrument to assess the typical manifestations of the disease existed, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was developed and has been used to address the most commonly reported symptoms experienced by children with FD followed in a Fabry registry – the Fabry Outcome Survey (FOS; sponsored by Shire Human Genetics Therapies).
The preliminary FPHPQ was a 40-item questionnaire on children's symptoms and experience with FD developed by the FOS Paediatric Working Group - an international group of dedicated and experienced clinicians. The FOS Paediatric Working Group set out to develop a tool that would both identify disease burden in children that affected their quality of life but also in the future once validated, could be used to monitor treatment effects. The questions were specifically chosen based on what the clinical experts knew at the time of the subjective early clinical manifestations of FD.
FOS is the world's most comprehensive database on medical outcomes of patients with FD. FOS is designed as an international multi-centre, open-label registry. It is open to all patients on, or candidates for ERT with agalsidase alfa. Patients with FD entered into the database but not receiving ERT are also followed in order to gain insight into the natural history of the condition. The principal aim of FOS is to collect and disseminate information about the long-term course of the disease, especially in patients treated with agalsidase alfa. In order to guide treatment, relevant data recorded on the FOS database are being made available to the treating physician on an individual patient basis. Questions to the database aimed at helping FOS physicians in their routine clinical practice and patient management to be handled swiftly.
The purpose of this study is to present the psychometric validation of the FPHPQ, as well as to explore the underlying concepts measured and their dimensionality.
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