Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease
Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitat...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Tractenberg, R. E. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2009 |
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| Schlagwörter: |
Standardize Root Mean Square Residual |
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| Anmerkung: |
© Serdi and Springer Verlag France 2009 |
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| Übergeordnetes Werk: |
Enthalten in: The journal of nutrition, health & aging - Paris : Springer, 2004, 13(2009), 3 vom: März, Seite 249-255 |
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| Übergeordnetes Werk: |
volume:13 ; year:2009 ; number:3 ; month:03 ; pages:249-255 |
| Links: |
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| DOI / URN: |
10.1007/s12603-009-0067-0 |
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| Katalog-ID: |
SPR02629057X |
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| 520 | |a Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. | ||
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| 650 | 4 | |a Principal Component Extraction |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Exploratory Factor Analysis Result |7 (dpeaa)DE-He213 | |
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10.1007/s12603-009-0067-0 doi (DE-627)SPR02629057X (SPR)s12603-009-0067-0-e DE-627 ger DE-627 rakwb eng Tractenberg, R. E. verfasserin aut Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Serdi and Springer Verlag France 2009 Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. Mild Cognitive Impairment (dpeaa)DE-He213 Exploratory Factor Analysis (dpeaa)DE-He213 Standardize Root Mean Square Residual (dpeaa)DE-He213 Principal Component Extraction (dpeaa)DE-He213 Exploratory Factor Analysis Result (dpeaa)DE-He213 Enthalten in The journal of nutrition, health & aging Paris : Springer, 2004 13(2009), 3 vom: März, Seite 249-255 (DE-627)350261369 (DE-600)2082520-1 1760-4788 nnns volume:13 year:2009 number:3 month:03 pages:249-255 https://dx.doi.org/10.1007/s12603-009-0067-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2009 3 03 249-255 |
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10.1007/s12603-009-0067-0 doi (DE-627)SPR02629057X (SPR)s12603-009-0067-0-e DE-627 ger DE-627 rakwb eng Tractenberg, R. E. verfasserin aut Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Serdi and Springer Verlag France 2009 Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. Mild Cognitive Impairment (dpeaa)DE-He213 Exploratory Factor Analysis (dpeaa)DE-He213 Standardize Root Mean Square Residual (dpeaa)DE-He213 Principal Component Extraction (dpeaa)DE-He213 Exploratory Factor Analysis Result (dpeaa)DE-He213 Enthalten in The journal of nutrition, health & aging Paris : Springer, 2004 13(2009), 3 vom: März, Seite 249-255 (DE-627)350261369 (DE-600)2082520-1 1760-4788 nnns volume:13 year:2009 number:3 month:03 pages:249-255 https://dx.doi.org/10.1007/s12603-009-0067-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2009 3 03 249-255 |
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10.1007/s12603-009-0067-0 doi (DE-627)SPR02629057X (SPR)s12603-009-0067-0-e DE-627 ger DE-627 rakwb eng Tractenberg, R. E. verfasserin aut Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Serdi and Springer Verlag France 2009 Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. Mild Cognitive Impairment (dpeaa)DE-He213 Exploratory Factor Analysis (dpeaa)DE-He213 Standardize Root Mean Square Residual (dpeaa)DE-He213 Principal Component Extraction (dpeaa)DE-He213 Exploratory Factor Analysis Result (dpeaa)DE-He213 Enthalten in The journal of nutrition, health & aging Paris : Springer, 2004 13(2009), 3 vom: März, Seite 249-255 (DE-627)350261369 (DE-600)2082520-1 1760-4788 nnns volume:13 year:2009 number:3 month:03 pages:249-255 https://dx.doi.org/10.1007/s12603-009-0067-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2009 3 03 249-255 |
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10.1007/s12603-009-0067-0 doi (DE-627)SPR02629057X (SPR)s12603-009-0067-0-e DE-627 ger DE-627 rakwb eng Tractenberg, R. E. verfasserin aut Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Serdi and Springer Verlag France 2009 Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. Mild Cognitive Impairment (dpeaa)DE-He213 Exploratory Factor Analysis (dpeaa)DE-He213 Standardize Root Mean Square Residual (dpeaa)DE-He213 Principal Component Extraction (dpeaa)DE-He213 Exploratory Factor Analysis Result (dpeaa)DE-He213 Enthalten in The journal of nutrition, health & aging Paris : Springer, 2004 13(2009), 3 vom: März, Seite 249-255 (DE-627)350261369 (DE-600)2082520-1 1760-4788 nnns volume:13 year:2009 number:3 month:03 pages:249-255 https://dx.doi.org/10.1007/s12603-009-0067-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2009 3 03 249-255 |
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10.1007/s12603-009-0067-0 doi (DE-627)SPR02629057X (SPR)s12603-009-0067-0-e DE-627 ger DE-627 rakwb eng Tractenberg, R. E. verfasserin aut Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Serdi and Springer Verlag France 2009 Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. Mild Cognitive Impairment (dpeaa)DE-He213 Exploratory Factor Analysis (dpeaa)DE-He213 Standardize Root Mean Square Residual (dpeaa)DE-He213 Principal Component Extraction (dpeaa)DE-He213 Exploratory Factor Analysis Result (dpeaa)DE-He213 Enthalten in The journal of nutrition, health & aging Paris : Springer, 2004 13(2009), 3 vom: März, Seite 249-255 (DE-627)350261369 (DE-600)2082520-1 1760-4788 nnns volume:13 year:2009 number:3 month:03 pages:249-255 https://dx.doi.org/10.1007/s12603-009-0067-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 13 2009 3 03 249-255 |
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This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. 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Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease Mild Cognitive Impairment (dpeaa)DE-He213 Exploratory Factor Analysis (dpeaa)DE-He213 Standardize Root Mean Square Residual (dpeaa)DE-He213 Principal Component Extraction (dpeaa)DE-He213 Exploratory Factor Analysis Result (dpeaa)DE-He213 |
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analytic methods for factors, dimensions and endpoints in clinical trials for alzheimer’s disease |
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Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease |
| abstract |
Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. © Serdi and Springer Verlag France 2009 |
| abstractGer |
Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. © Serdi and Springer Verlag France 2009 |
| abstract_unstemmed |
Abstract Alzheimer’s disease (AD) is a complex disease process, so finding a single biomarker to track in clinical trials has proven difficult. This paper describes and contrasts statistical methods that might be used with biomarkers in clinical trials for AD, highlighting their differences, limitations and interpretations. The first method is traditional regression, within which one dependent variable, the Best Empirically Supported Indicator (BESI), must be identified. In this approach one biomarker (e.g., the ratio of tau to Aβ42 from CSF) is the indicator for an individual’s disease status, and change in that status. The second approach is an exploratory factor analysis (EFA) to consolidate a multitude of candidate dependent variables into a sample-dependent, mathematically-optimized smaller set of ‘factors’. The third method is latent variable (LV) modeling of multiple indicators of an entity (e.g., “disease burden”). The LV approach can yield a complex ‘dependent variable’, the Best Measurement Model Indicator (BMMI). A measurement model represents an entity that several dependent variables reflect or measure, and so can include many ‘dependent variables’, and estimate their relative contributions to the underlying entity. The selection of a single BESI is an artifact of regression that limits the investigator’s ability to utilize all relevant variables representing the entity of interest. EFA results in sample-specific combination of biomarkers that might not generalize to a new sample — and fit of the EFA results cannot be tested. Latent variable methods can be useful to construct powerful, efficient statistical models that optimally combine diverse biomarkers into a single, multidimensional dependent variable that can generalize across samples when they are theory-driven and not sample-dependent. This paper shows that EFA can work to uncover underlying structure, but that it does not always yield solutions that ‘fit’ the data. It is not recommended as a method to build BMMIs, which will be useful in establishing diagnostic criteria, creating and evaluating benchmarks, and monitoring progression in clinical trials. © Serdi and Springer Verlag France 2009 |
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Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer’s disease |
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https://dx.doi.org/10.1007/s12603-009-0067-0 |
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| score |
7.3996735 |