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Validation Strategy for Biomarker-Guided Precision/Personalized Medicine
Published in Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow, Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
Due to biological variability, only a subset of patients may benefit from therapeutic products. Indeed, a number of therapeutic products have been approved only for particular patient subpopulations (de Weers et al. 2011, Roth and Diller 2014, Grilo and Mantalaris 2019). Precision medicine stratifies patients by biological information (e.g., genes, RNA/DNA, proteins) and targets those patients most likely to respond to a specific treatment. While a number of names have evolved in this field, such as targeted treatment, individualized care and stratified treatments, the current preferred term is “precision medicine”. With the development of whole genomic data sequencing, new disease pathways relevant to this disease are being discovered and more and more new therapeutic targets, as well as adverse drug effects and effective subpopulations, are being identified. Precision medicine treatment targets only responders, which means there is an increase in tolerability and treatment adherence in the clinical trials (Hersom and Jorgensen 2018, Hwang et al. 2015, Lin et al. 2017). It in turn improves health outcomes and ultimately, makes more efficient use of limited health services. Despite these achievements, the promise of personalized medicine for the right treatment, for the right patient, at the right time will remain unfulfilled without strong support for a Companion Diagnostic (CDx) test. CDx tests detect specific genetic mutations and biomarkers in those patients who are most likely to respond to precision medicine treatment, thus reduce the number of patients treated.
Introduction
Published in Nusrat Rabbee, Biomarker Analysis in Clinical Trials with R, 2020
A companion diagnostic (CDx) test for a drug is a test for a predictive biomarker of the response of the drug in a patient. It is at the heart of personalized medicine. The Food and Drug Administration (FDA) is in the forefront of guiding the industry to co-develop the drug along with its companion diagnostic (CDx) where both products (not necessarily from the same company) follow a set regulatory pathway for approval.
Clinical Trial Designs for Testing Companion Diagnostics (CDx)
Published in Il-Jin Kim, Companion Diagnostics (CDx) in Precision Medicine, 2019
Rumiko Shimazawa, Masayuki Ikeda
Companion diagnostics (CDx) is defined as “[any] in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product” in the FDA guidance.1 The clinical performance of CDx in selecting patients to receive or avoid a particular therapy can only be provided by data from clinical trials. In this chapter, we provide an overview of trial designs for assessing the ability of a biomarker.
Predictive biomarkers and personalized pharmacotherapy
Published in Expert Review of Molecular Diagnostics, 2022
Jan Trøst Jørgensen, Niels Westergaard
Oncological and hematological diseases are areas with great unmet medical needs, and for the past 20 years, a number of new and more effective drugs have been developed, as listed in Table 1. These drugs have been developed for molecular subsets of patients using the drug-diagnostic co-development model [7]. In this model, the clinical documentation is generated based on data from different types of enrichment trials. If such a trial demonstrates a link between the CDx assay result and the outcome following treatment with the investigational drug, the likelihood of concomitant regulatory approval will be high. After approval, when these drugs are going to be used in the clinic for routine patient care, it is crucial to have access to a validated assay, which, unfortunately, is not always the situation [8]. It is important to note that a CDx assay acts as a gatekeeper for the prescribing process; hence, an analytical and clinically validated assay must be available for regulatory approval at the same time as the drug.
An update on companion and complementary diagnostic assays for PD-1/PD-L1 checkpoint inhibitors in NSCLC
Published in Expert Review of Molecular Diagnostics, 2021
The first assay to be approved as a CDx was the HercepTest (Dako/Agilent), which was linked to the monoclonal antibody trastuzumab (Herceptin, Roche/Genentech) for treatment of metastatic HER2 positive breast cancer. In September 1998, the FDA simultaneously granted approval to trastuzumab and the HER2 IHC assay HercepTest through a new coordinated procedure. The parallel approval makes sense, as the assay is an important treatment decision tool that must be available at the same time as the drug [13]. When the FDA in 2014 issued the first regulatory guidance document on CDx, this included a definition of this type of assay. According to this definition, a CDx assay is an in vitro diagnostic device (IVD) that provides information that is essential for the safe and effective use of a corresponding therapeutic product [14]. This means that testing with this type of assay is mandatory and is part of the labeling for the drug which it is meant to guide. At the end of 2020, the total number of CDx assays approved by the FDA was 44 [15]. With the adoption of the new EU regulations on IVD medical devices in 2017, Europe also got an official CDx definition, which is similar to the one that came from the FDA a few years earlier [16]. The new regulation that will come into force as of 2022 means more strict documentation requirements for CDx assays, and CE-marking by self-certification will no longer be a possible, which has been the practice so far in order to get market access.
Companion and complementary diagnostics: an important treatment decision tool in precision medicine
Published in Expert Review of Molecular Diagnostics, 2020
The term used to describe a predictive biomarker assay linked to a specific drug has varied over time. In the years following the US FDA approval of the HercepTest, this type of assay was referred to as pharmacodiagnostics, theranostics or pharmacogenetics [20]. Almost a decade later, the term companion diagnostic appeared in the literature and was subsequently adopted by the regulatory authorities as the preferred term [21]. The first regulatory guidance document on CDx was issued by the US FDA in 2014, and here, this type of assay was officially defined for the first time [22]. According to this definition, a CDx assay is an in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product. This means that testing with this type of assay is mandatory and must be stated in both the labeling for the drug and the CDx assay.