Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation
<i>Background and Objectives</i>: The US Food and Drug Administration (FDA) defines a biomarker as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention. Biomarkers may be used in clinical care...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/58/7/952 |
| _version_ | 1827605104058957824 |
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| author | Jeffrey Cummings Jefferson Kinney |
| author_facet | Jeffrey Cummings Jefferson Kinney |
| author_sort | Jeffrey Cummings |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: The US Food and Drug Administration (FDA) defines a biomarker as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention. Biomarkers may be used in clinical care or as drug development tools (DDTs) in clinical trials. The goal of this review and perspective is to provide insight into the regulatory guidance for the use of biomarkers in clinical trials and clinical care. <i>Materials and Methods</i>: We reviewed FDA guidances relevant to biomarker use in clinical trials and their transition to use in clinical care. We identified instructive examples of these biomarkers in Alzheimer’s disease (AD) drug development and their application in clinical practice. <i>Results</i>: For use in clinical trials, biomarkers must have a defined context of use (COU) as a risk/susceptibility, diagnostic, monitoring, predictive, prognostic, pharmacodynamic, or safety biomarker. A four-stage process defines the pathway to establish the regulatory acceptance of the COU for a biomarker including submission of a letter of intent, description of the qualification plan, submission of a full qualification package, and acceptance through a qualification recommendation. Biomarkers used in clinical care may be companion biomarkers, in vitro diagnostic devices (IVDs), or laboratory developed tests (LDTs). A five-phase biomarker development process has been proposed to structure the biomarker development process. <i>Conclusions</i>: Biomarkers are increasingly important in drug development and clinical care. Adherence to regulatory guidance for biomarkers used in clinical trials and patient care is required to advance these important drug development and clinical tools. |
| first_indexed | 2024-03-09T06:15:02Z |
| format | Article |
| id | doaj.art-b408b4ac66ae418985405e460ff76085 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-09T06:15:02Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-b408b4ac66ae418985405e460ff760852023-12-03T11:55:00ZengMDPI AGMedicina1010-660X1648-91442022-07-0158795210.3390/medicina58070952Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical ImplementationJeffrey Cummings0Jefferson Kinney1Pam Quirk Brain Health and Biomarker Laboratory, Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV 89154, USAPam Quirk Brain Health and Biomarker Laboratory, Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV 89154, USA<i>Background and Objectives</i>: The US Food and Drug Administration (FDA) defines a biomarker as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention. Biomarkers may be used in clinical care or as drug development tools (DDTs) in clinical trials. The goal of this review and perspective is to provide insight into the regulatory guidance for the use of biomarkers in clinical trials and clinical care. <i>Materials and Methods</i>: We reviewed FDA guidances relevant to biomarker use in clinical trials and their transition to use in clinical care. We identified instructive examples of these biomarkers in Alzheimer’s disease (AD) drug development and their application in clinical practice. <i>Results</i>: For use in clinical trials, biomarkers must have a defined context of use (COU) as a risk/susceptibility, diagnostic, monitoring, predictive, prognostic, pharmacodynamic, or safety biomarker. A four-stage process defines the pathway to establish the regulatory acceptance of the COU for a biomarker including submission of a letter of intent, description of the qualification plan, submission of a full qualification package, and acceptance through a qualification recommendation. Biomarkers used in clinical care may be companion biomarkers, in vitro diagnostic devices (IVDs), or laboratory developed tests (LDTs). A five-phase biomarker development process has been proposed to structure the biomarker development process. <i>Conclusions</i>: Biomarkers are increasingly important in drug development and clinical care. Adherence to regulatory guidance for biomarkers used in clinical trials and patient care is required to advance these important drug development and clinical tools.https://www.mdpi.com/1648-9144/58/7/952Alzheimer’s diseasebiomarkersplasmaphospho-tauamyloidblood |
| spellingShingle | Jeffrey Cummings Jefferson Kinney Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation Medicina Alzheimer’s disease biomarkers plasma phospho-tau amyloid blood |
| title | Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation |
| title_full | Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation |
| title_fullStr | Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation |
| title_full_unstemmed | Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation |
| title_short | Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation |
| title_sort | biomarkers for alzheimer s disease context of use qualification and roadmap for clinical implementation |
| topic | Alzheimer’s disease biomarkers plasma phospho-tau amyloid blood |
| url | https://www.mdpi.com/1648-9144/58/7/952 |
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