A validated disease severity scoring system for Fabry disease

Edward H. Giannini; Atul B. Mehta; Max J. Hilz; Michael Beck; Daniel G. Bichet; Roscoe O. Brady; Michael West; Dominique P. Germain; Christoph Wanner; Stephen Waldek; Joe T.R. Clarke; Eugen Mengel; Jörg M. Strotmann; David G. Warnock; Ales Linhart

doi:10.1016/j.ymgme.2009.10.178

A validated disease severity scoring system for Fabry disease

Edward H. Giannini, Atul B. Mehta, Max J. Hilz, Michael Beck, Daniel G. Bichet, Roscoe O. Brady, Michael West, Dominique P. Germain, Christoph Wanner, Stephen Waldek, Joe T.R. Clarke, Eugen Mengel, Jörg M. Strotmann, David G. Warnock, Ales Linhart

Medicine

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

58 Citas (Scopus)

Resumen

Fabry disease is a lysosomal storage disorder with onset of adverse signs and symptoms usually during childhood and progressive life-threatening decline in organ functions. A validated and feasible Fabry disease severity scoring system (DS3) is needed to reliably quantify the disease burden, monitor disease progression and treatment response, and compare disease status among patient cohorts in clinical studies. We developed a new Fabry DS3 and tested its reliability and validity using a combination of expert consensus formation and statistical techniques. Relevant Fabry disease domains and items were identified, inclusion of items was refined and scaling of scores for individual assessments was optimized to maximize the correlation between the instrument's total score and the assigned clinical global impression of severity (CGI-S scores). Furthermore, the minimum clinically important difference in each of the instrument's domains was estimated and the DS3's quantitative content validity was judged. The current Fabry DS3 working model has 5 domains; 4 clinical domains (Peripheral Nervous System, Renal, and Cardiac, each with 3 items, Central Nervous System with 2 items) and a patient-reported domain (Patient-Reported domain with one item). The domain score is obtained by averaging the scores for all domain items. The Content Validity Index and Feasibility Index were shown to be good; 0.96 and 0.97, respectively. There was no significant inter-rater difference and the level of concordance was high. Correlation with the CGI-S was R² = 0.89 indicating excellent criterion and construct (convergent) validity. In summary, initial estimations of validity, reliability and feasibility for the new Fabry DS3 instrument suggest that it is a feasible and reliable means of assessing disease severity and progression over time and comparing inter-patient severity of Fabry disease. Our results demonstrate that the Fabry DS3 correlates highly with the clinical assessment by Fabry disease experts.

Idioma original	English
Páginas (desde-hasta)	283-290
Número de páginas	8
Publicación	Molecular Genetics and Metabolism
Volumen	99
N.º	3
DOI	https://doi.org/10.1016/j.ymgme.2009.10.178
Estado	Published - mar. 2010

Nota bibliográfica

Funding Information:
The various Fabry DS3 instrument development initiatives, as well as the validation and optimization conferences, were supported by an unrestricted grant from Genzyme Corporation.

Funding Information:
Atul B. Mehta has received unrestricted grants, honoraria and travel support from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Actelion Pharmaceuticals.

Funding Information:
Max J. Hilz received grant support for research, lecture and consultancy fees from Genzyme Corporation, and for a fellowship program at New York University, New York, NY, USA.

Funding Information:
Michael Beck has received unrestricted grants, honoraria and travel support from Genzyme Corporation, Shire Human Genetic Therapies Inc., BioMarin Pharmaceutical Inc. and Actelion Pharmaceuticals.

Funding Information:
Daniel G. Bichet receives occasional honoraria for medical conferences from Genzyme Corporation and his research laboratory is receiving grants from Genzyme Corporation.

Funding Information:
Michael West received honoraria and/or research funding from Amicus Therapeutics Inc., Genzyme Corporation and Shire Human Genetic Therapies Inc.

Funding Information:
Dominique P. Germain has received speaker’s honoraria and research grants from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Amicus Therapeutics Inc.

Funding Information:
Christoph Wanner has received grant support from Genzyme Corporation and lecture fees from Genzyme Corporation and Shire Human Genetic Therapies Inc., as well as honoraria for participation in the Fabry Registry board of advisors.

Funding Information:
Stephen Waldek has received honoraria for participation in the Fabry Registry board of advisors from Genzyme Corporation, and grant support from Genzyme Corporation and Amicus Therapeutics Inc.

Funding Information:
Joe T.R. Clarke has received honoraria and research funding from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Actelion Pharmaceuticals.

Funding Information:
Jörg M. Strotmann has received research grants, speaker’s honoraria and consultant fees from Genzyme Corporation.

Funding Information:
Ales Linhart received speaker‘s honoraria and research support from Shire Human Genetic Therapies Inc. and Genzyme Corporation.

ASJC Scopus Subject Areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Biology
Genetics
Endocrinology

ODS de las Naciones Unidas

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10.1016/j.ymgme.2009.10.178

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Giannini, E. H., Mehta, A. B., Hilz, M. J., Beck, M., Bichet, D. G., Brady, R. O., West, M., Germain, D. P., Wanner, C., Waldek, S., Clarke, J. T. R., Mengel, E., Strotmann, J. M., Warnock, D. G., & Linhart, A. (2010). A validated disease severity scoring system for Fabry disease. Molecular Genetics and Metabolism, 99(3), 283-290. https://doi.org/10.1016/j.ymgme.2009.10.178

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title = "A validated disease severity scoring system for Fabry disease",

abstract = "Fabry disease is a lysosomal storage disorder with onset of adverse signs and symptoms usually during childhood and progressive life-threatening decline in organ functions. A validated and feasible Fabry disease severity scoring system (DS3) is needed to reliably quantify the disease burden, monitor disease progression and treatment response, and compare disease status among patient cohorts in clinical studies. We developed a new Fabry DS3 and tested its reliability and validity using a combination of expert consensus formation and statistical techniques. Relevant Fabry disease domains and items were identified, inclusion of items was refined and scaling of scores for individual assessments was optimized to maximize the correlation between the instrument's total score and the assigned clinical global impression of severity (CGI-S scores). Furthermore, the minimum clinically important difference in each of the instrument's domains was estimated and the DS3's quantitative content validity was judged. The current Fabry DS3 working model has 5 domains; 4 clinical domains (Peripheral Nervous System, Renal, and Cardiac, each with 3 items, Central Nervous System with 2 items) and a patient-reported domain (Patient-Reported domain with one item). The domain score is obtained by averaging the scores for all domain items. The Content Validity Index and Feasibility Index were shown to be good; 0.96 and 0.97, respectively. There was no significant inter-rater difference and the level of concordance was high. Correlation with the CGI-S was R2 = 0.89 indicating excellent criterion and construct (convergent) validity. In summary, initial estimations of validity, reliability and feasibility for the new Fabry DS3 instrument suggest that it is a feasible and reliable means of assessing disease severity and progression over time and comparing inter-patient severity of Fabry disease. Our results demonstrate that the Fabry DS3 correlates highly with the clinical assessment by Fabry disease experts.",

author = "Giannini, {Edward H.} and Mehta, {Atul B.} and Hilz, {Max J.} and Michael Beck and Bichet, {Daniel G.} and Brady, {Roscoe O.} and Michael West and Germain, {Dominique P.} and Christoph Wanner and Stephen Waldek and Clarke, {Joe T.R.} and Eugen Mengel and Strotmann, {J{\"o}rg M.} and Warnock, {David G.} and Ales Linhart",

note = "Funding Information: The various Fabry DS3 instrument development initiatives, as well as the validation and optimization conferences, were supported by an unrestricted grant from Genzyme Corporation. Funding Information: Atul B. Mehta has received unrestricted grants, honoraria and travel support from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Actelion Pharmaceuticals. Funding Information: Max J. Hilz received grant support for research, lecture and consultancy fees from Genzyme Corporation, and for a fellowship program at New York University, New York, NY, USA. Funding Information: Michael Beck has received unrestricted grants, honoraria and travel support from Genzyme Corporation, Shire Human Genetic Therapies Inc., BioMarin Pharmaceutical Inc. and Actelion Pharmaceuticals. Funding Information: Daniel G. Bichet receives occasional honoraria for medical conferences from Genzyme Corporation and his research laboratory is receiving grants from Genzyme Corporation. Funding Information: Michael West received honoraria and/or research funding from Amicus Therapeutics Inc., Genzyme Corporation and Shire Human Genetic Therapies Inc. Funding Information: Dominique P. Germain has received speaker{\textquoteright}s honoraria and research grants from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Amicus Therapeutics Inc. Funding Information: Christoph Wanner has received grant support from Genzyme Corporation and lecture fees from Genzyme Corporation and Shire Human Genetic Therapies Inc., as well as honoraria for participation in the Fabry Registry board of advisors. Funding Information: Stephen Waldek has received honoraria for participation in the Fabry Registry board of advisors from Genzyme Corporation, and grant support from Genzyme Corporation and Amicus Therapeutics Inc. Funding Information: Joe T.R. Clarke has received honoraria and research funding from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Actelion Pharmaceuticals. Funding Information: J{\"o}rg M. Strotmann has received research grants, speaker{\textquoteright}s honoraria and consultant fees from Genzyme Corporation. Funding Information: Ales Linhart received speaker{\textquoteleft}s honoraria and research support from Shire Human Genetic Therapies Inc. and Genzyme Corporation. ",

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T1 - A validated disease severity scoring system for Fabry disease

AU - Giannini, Edward H.

AU - Mehta, Atul B.

AU - Hilz, Max J.

AU - Beck, Michael

AU - Bichet, Daniel G.

AU - Brady, Roscoe O.

AU - West, Michael

AU - Germain, Dominique P.

AU - Wanner, Christoph

AU - Waldek, Stephen

AU - Clarke, Joe T.R.

AU - Mengel, Eugen

AU - Strotmann, Jörg M.

AU - Warnock, David G.

AU - Linhart, Ales

N1 - Funding Information: The various Fabry DS3 instrument development initiatives, as well as the validation and optimization conferences, were supported by an unrestricted grant from Genzyme Corporation. Funding Information: Atul B. Mehta has received unrestricted grants, honoraria and travel support from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Actelion Pharmaceuticals. Funding Information: Max J. Hilz received grant support for research, lecture and consultancy fees from Genzyme Corporation, and for a fellowship program at New York University, New York, NY, USA. Funding Information: Michael Beck has received unrestricted grants, honoraria and travel support from Genzyme Corporation, Shire Human Genetic Therapies Inc., BioMarin Pharmaceutical Inc. and Actelion Pharmaceuticals. Funding Information: Daniel G. Bichet receives occasional honoraria for medical conferences from Genzyme Corporation and his research laboratory is receiving grants from Genzyme Corporation. Funding Information: Michael West received honoraria and/or research funding from Amicus Therapeutics Inc., Genzyme Corporation and Shire Human Genetic Therapies Inc. Funding Information: Dominique P. Germain has received speaker’s honoraria and research grants from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Amicus Therapeutics Inc. Funding Information: Christoph Wanner has received grant support from Genzyme Corporation and lecture fees from Genzyme Corporation and Shire Human Genetic Therapies Inc., as well as honoraria for participation in the Fabry Registry board of advisors. Funding Information: Stephen Waldek has received honoraria for participation in the Fabry Registry board of advisors from Genzyme Corporation, and grant support from Genzyme Corporation and Amicus Therapeutics Inc. Funding Information: Joe T.R. Clarke has received honoraria and research funding from Genzyme Corporation, Shire Human Genetic Therapies Inc. and Actelion Pharmaceuticals. Funding Information: Jörg M. Strotmann has received research grants, speaker’s honoraria and consultant fees from Genzyme Corporation. Funding Information: Ales Linhart received speaker‘s honoraria and research support from Shire Human Genetic Therapies Inc. and Genzyme Corporation.

PY - 2010/3

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N2 - Fabry disease is a lysosomal storage disorder with onset of adverse signs and symptoms usually during childhood and progressive life-threatening decline in organ functions. A validated and feasible Fabry disease severity scoring system (DS3) is needed to reliably quantify the disease burden, monitor disease progression and treatment response, and compare disease status among patient cohorts in clinical studies. We developed a new Fabry DS3 and tested its reliability and validity using a combination of expert consensus formation and statistical techniques. Relevant Fabry disease domains and items were identified, inclusion of items was refined and scaling of scores for individual assessments was optimized to maximize the correlation between the instrument's total score and the assigned clinical global impression of severity (CGI-S scores). Furthermore, the minimum clinically important difference in each of the instrument's domains was estimated and the DS3's quantitative content validity was judged. The current Fabry DS3 working model has 5 domains; 4 clinical domains (Peripheral Nervous System, Renal, and Cardiac, each with 3 items, Central Nervous System with 2 items) and a patient-reported domain (Patient-Reported domain with one item). The domain score is obtained by averaging the scores for all domain items. The Content Validity Index and Feasibility Index were shown to be good; 0.96 and 0.97, respectively. There was no significant inter-rater difference and the level of concordance was high. Correlation with the CGI-S was R2 = 0.89 indicating excellent criterion and construct (convergent) validity. In summary, initial estimations of validity, reliability and feasibility for the new Fabry DS3 instrument suggest that it is a feasible and reliable means of assessing disease severity and progression over time and comparing inter-patient severity of Fabry disease. Our results demonstrate that the Fabry DS3 correlates highly with the clinical assessment by Fabry disease experts.

AB - Fabry disease is a lysosomal storage disorder with onset of adverse signs and symptoms usually during childhood and progressive life-threatening decline in organ functions. A validated and feasible Fabry disease severity scoring system (DS3) is needed to reliably quantify the disease burden, monitor disease progression and treatment response, and compare disease status among patient cohorts in clinical studies. We developed a new Fabry DS3 and tested its reliability and validity using a combination of expert consensus formation and statistical techniques. Relevant Fabry disease domains and items were identified, inclusion of items was refined and scaling of scores for individual assessments was optimized to maximize the correlation between the instrument's total score and the assigned clinical global impression of severity (CGI-S scores). Furthermore, the minimum clinically important difference in each of the instrument's domains was estimated and the DS3's quantitative content validity was judged. The current Fabry DS3 working model has 5 domains; 4 clinical domains (Peripheral Nervous System, Renal, and Cardiac, each with 3 items, Central Nervous System with 2 items) and a patient-reported domain (Patient-Reported domain with one item). The domain score is obtained by averaging the scores for all domain items. The Content Validity Index and Feasibility Index were shown to be good; 0.96 and 0.97, respectively. There was no significant inter-rater difference and the level of concordance was high. Correlation with the CGI-S was R2 = 0.89 indicating excellent criterion and construct (convergent) validity. In summary, initial estimations of validity, reliability and feasibility for the new Fabry DS3 instrument suggest that it is a feasible and reliable means of assessing disease severity and progression over time and comparing inter-patient severity of Fabry disease. Our results demonstrate that the Fabry DS3 correlates highly with the clinical assessment by Fabry disease experts.

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A validated disease severity scoring system for Fabry disease

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ASJC Scopus Subject Areas

ODS de las Naciones Unidas

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