Companion and complementary diagnostics: an important treatment decision tool in precision medicine

Jørgensen, Jan Trøst

doi:10.1080/14737159.2020.1762573

Cited by 12 publications

(7 citation statements)

References 22 publications

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“…These statements above apply specifically to CDx; there are no corresponding written rules for complementary diagnostics, the definition of which is currently by usage ( Milne et al, 2015 ; Scheerens et al, 2017 ; Jorgensen, 2020 ).…”

Section: Mif Companion Diagnostics Product Conceptmentioning

confidence: 99%

Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging

Locke

Hoyt

2023

Front. Mol. Biosci.

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Immunohistochemistry has long been held as the gold standard for understanding the expression patterns of therapeutically relevant proteins to identify prognostic and predictive biomarkers. Patient selection for targeted therapy in oncology has successfully relied upon standard microscopy-based methodologies, such as single-marker brightfield chromogenic immunohistochemistry. As promising as these results are, the analysis of one protein, with few exceptions, no longer provides enough information to draw effective conclusions about the probability of treatment response. More multifaceted scientific queries have driven the development of high-throughput and high-order technologies to interrogate biomarker expression patterns and spatial interactions between cell phenotypes in the tumor microenvironment. Such multi-parameter data analysis has been historically reserved for technologies that lack the spatial context that is provided by immunohistochemistry. Over the past decade, technical developments in multiplex fluorescence immunohistochemistry and discoveries made with improving image data analysis platforms have highlighted the importance of spatial relationships between certain biomarkers in understanding a patient’s likelihood to respond to, typically, immune checkpoint inhibitors. At the same time, personalized medicine has instigated changes in both clinical trial design and its conduct in a push to make drug development and cancer treatment more efficient, precise, and economical. Precision medicine in immuno-oncology is being steered by data-driven approaches to gain insight into the tumor and its dynamic interaction with the immune system. This is particularly necessary given the rapid growth in the number of trials involving more than one immune checkpoint drug, and/or using those in combination with conventional cancer treatments. As multiplex methods, like immunofluorescence, push the boundaries of immunohistochemistry, it becomes critical to understand the foundation of this technology and how it can be deployed for use as a regulated test to identify the prospect of response from mono- and combination therapies. To that end, this work will focus on: 1) the scientific, clinical, and economic requirements for developing clinical multiplex immunofluorescence assays; 2) the attributes of the Akoya Phenoptics workflow to support predictive tests, including design principles, verification, and validation needs; 3) regulatory, safety and quality considerations; 4) application of multiplex immunohistochemistry through lab-developed-tests and regulated in vitro diagnostic devices.

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Section: Mif Companion Diagnostics Product Conceptmentioning

confidence: 99%

Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging

Locke

Hoyt

2023

Front. Mol. Biosci.

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“…The terminology of “complementary diagnostic” may be used to describe a test that identifies a biomarker-defined subset of patients that respond particularly well to a drug and aid risk/benefit assessments for individual patients but are not prerequisites for receiving the drug. Complementary diagnostics are IVDs and are subject to the same regulatory requirements as other IVDs [ 94 , 95 ].…”

Section: Biomarkers For Use In Clinical Carementioning

confidence: 99%

Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation

Cummings

Kinney

2022

Medicina

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Background and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.

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“…The first predictive biomarker associated with drug development was the HER2 protein, which resulted in the approval of trastuzumab (Herceptin) and HER2 immunohistochemical (IHC) assay, HercepTest (Dako) (see Figure 1 ) for the detection and treatment of metastatic HER2-positive breast cancer in 1998 by the FDA. 2 , 11 , 28 , 29 Since then, the development and nomenclature of predictive biomarker assays linked to specific pharmaceutical agents has rapidly grown. 1 , 3 At the dawn of the millennium, the term “companion diagnostic” was introduced and adopted by FDA (see Table 2 for current definition).…”

Section: State Of the Art For CDXmentioning

confidence: 99%

“…Such in vitro diagnostics (IVD) can be used alone or in combination with other devices and/or therapies. [1][2][3][4] When used in combination with a therapeutic drug, they are referred to as Companion Diagnostics (CDx). 5 The development of CDx depends on companion biomarker(s), intending to stratify patients based on their predicted response to a drug and its potential toxicity levels.…”

Section: Introductionmentioning

confidence: 99%

Companion Diagnostics: State of the Art and New Regulations

et al. 2021

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Companion diagnostics (CDx) hail promise of improving the drug development process and precision medicine. However, there are various challenges involved in the clinical development and regulation of CDx, which are considered high-risk in vitro diagnostic medical devices given the role they play in therapeutic decision-making and the complications they may introduce with respect to their sensitivity and specificity. The European Union (E.U.) is currently in the process of bringing into effect in vitro Diagnostic Medical Devices Regulation (IVDR). The new Regulation is introducing a wide range of stringent requirements for scientific validity, analytical and clinical performance, as well as on post-market surveillance activities throughout the lifetime of in vitro diagnostics (IVD). Compliance with General Safety and Performance Requirements (GSPRs) adopts a risk-based approach, which is also the case for the new classification system. This changing regulatory framework has an impact on all stakeholders involved in the IVD Industry, including Authorized Representatives, Distributors, Importers, Notified Bodies, and Reference Laboratories and is expected to have a significant effect on the development of new CDx.

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Companion and complementary diagnostics: an important treatment decision tool in precision medicine

Cited by 12 publications

References 22 publications

Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging

Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging

Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation

Companion Diagnostics: State of the Art and New Regulations

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