scholarly journals Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 129 ◽  
Author(s):  
Richard D. Beger ◽  
Michael A Schmidt ◽  
Rima Kaddurah-Daouk
Keyword(s):  
Clinical Trials ◽  
Drug Treatment ◽  
Precision Medicine ◽  
Metabolic Profile ◽  
Biomarker Discovery ◽  
Response To Treatment ◽  
Individual Response ◽  
Patient Response ◽  
Drug Mechanism ◽  
The Individual

Pharmacometabolomics (PMx) studies use information contained in metabolic profiles (or metabolome) to inform about how a subject will respond to drug treatment. Genome, gut microbiome, sex, nutrition, age, stress, health status, and other factors can impact the metabolic profile of an individual. Some of these factors are known to influence the individual response to pharmaceutical compounds. An individual’s metabolic profile has been referred to as his or her “metabotype.” As such, metabolomic profiles obtained prior to, during, or after drug treatment could provide insights about drug mechanism of action and variation of response to treatment. Furthermore, there are several types of PMx studies that are used to discover and inform patterns associated with varied drug responses (i.e., responders vs. non-responders; slow or fast metabolizers). The PMx efforts could simultaneously provide information related to an individual’s pharmacokinetic response during clinical trials and be used to predict patient response to drugs making pharmacometabolomic clinical research valuable for precision medicine. PMx biomarkers can also be discovered and validated during FDA clinical trials. Using biomarkers during medical development is described in US Law under the 21st Century Cures Act. Information on how to submit biomarkers to the FDA and their context of use is defined herein.

scholarly journals Ten Years of Experience Support Pharmacogenetic Testing to Guide Individualized Drug Therapy

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 160
Author(s):  
María Celsa Peña-Martín ◽  
Belén García-Berrocal ◽  
Almudena Sánchez-Martín ◽  
Elena Marcos-Vadillo ◽  
María Jesús García-Salgado ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Adverse Events ◽  
Precision Medicine ◽  
Drug Efficacy ◽  
Response To Treatment ◽  
Individual Response ◽  
Test Results ◽  
Individualized Drug Therapy ◽  
The Individual ◽  
Multimorbid Patients

Precision medicine utilizing the genetic information of genes involved in the metabolism and disposition of drugs can not only improve drug efficacy but also prevent or minimize adverse events. Polypharmacy is common among multimorbid patients and is associated with increased adverse events. One of the main objectives in health care is safe and efficacious drug therapy, which is directly correlated to the individual response to treatment. Precision medicine can increase drug safety in many scenarios, including polypharmacy. In this report, we share our experience utilizing precision medicine over the past ten years. Based on our experience using pharmacogenetic (PGx)-informed prescribing, we implemented a five-step precision medicine protocol (5SPM) that includes the assessment of the biological–clinical characteristics of the patient, current and past prescription history, and the patient’s PGx test results. To illustrate our approach, we present cases highlighting the clinical relevance of precision medicine with a focus on patients with a complex history and polypharmacy.

Investigating variability in patient response to treatment – a case study from a replicate cross-over study

2010 ◽  
Vol 20 (6) ◽  
pp. 657-666 ◽  
Author(s):  
Stephen Senn ◽  
Katie Rolfe ◽  
Steven A Julious
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Individual Variation ◽  
Response To Treatment ◽  
Individual Response ◽  
Common Belief ◽  
Patient Response ◽  
Treatment Interaction ◽  
Lost Opportunity

It is a common belief that individual variation in response to treatment is an important explanation for the variation in observed outcomes in clinical trials. If such variation is large, it seems reasonable to suppose that progress in treating disease will be advanced by classifying patients according to their abilities or not to ‘respond’ to particular treatments. We consider that there is currently a lost opportunity in drug development. There is a great deal of talk about individual response to treatment and tailor-made drugs. However, relatively little work is being done to formally investigate, using suitable designs, where individual response to treatment may be important. Through a case study from a replicate cross-over study we show how, given suitable replication, it is possible to isolate the component of variation corresponding to patient-by-treatment interaction and hence investigate the possibility of individual response to treatment.

scholarly journals Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials

Blood ◽  
2019 ◽  
Vol 133 (10) ◽  
pp. 1020-1030 ◽  
Author(s):  
U. Platzbecker ◽  
P. Fenaux ◽  
L. Adès ◽  
A. Giagounidis ◽  
V. Santini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Myelodysplastic Syndromes ◽  
Working Group ◽  
Lower Risk ◽  
Response Assessment ◽  
Response To Treatment ◽  
Response Criteria ◽  
Patient Response ◽  
Erythroid Response ◽  
Clinical Responses

Abstract The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups.

scholarly journals Prediction of individual response to antidepressants and antipsychotics: an integrated concept

2014 ◽  
Vol 16 (4) ◽  
pp. 545-554 ◽  
Keyword(s):  
Clinical Trials ◽  
Conceptual Framework ◽  
Daily Practice ◽  
Intraindividual Variability ◽  
Individual Response ◽  
Antipsychotic Therapy ◽  
Patient Response ◽  
Antipsychotic Medications ◽  
New Information ◽  
Integrated Concept

In both clinical trials and daily practice, there can be substantial inter- and even intraindividual variability in response--whether beneficial or adverse--to antidepressants and antipsychotic medications. So far, no tools have become available to predict the outcome of these treatments in specific patients. This is because the causes of such variability are often not known, and when they are, there is no way of predicting the effects of their various potential combinations in an individual. Given this background, this paper presents a conceptual framework for understanding known factors and their combinations so that eventually clinicians can better predict what medication(s) to select and at what dose they can optimize the outcome for a given individual. This framework is flexible enough to be readily adaptable as new information becomes available. The causes of variation in patient response are grouped into four categories: (i) genetics; (ii) age; (iii) disease; and (iv) environment (internal). Four cases of increasing complexity are used to illustrate the applicability of this framework in a clinically relevant way In addition, this paper reviews tools that the clinician can use to assess for and quantify such inter- and intraindividual variability. With the information gained, treatment can be adjusted to compensate for such variability, in order to optimize outcome. Finally, the limitations of existing antidepressant and antipsychotic therapy and the way they reduce current ability to predict response is discussed.

scholarly journals A Precision Medicine Approach to Biomarker Utilization in Pediatric Sepsis-Associated Acute Kidney Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
James D. Odum ◽  
Hector R. Wong ◽  
Natalja L. Stanski
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Precision Medicine ◽  
Biomarker Discovery ◽  
Kidney Injury ◽  
Critically Ill Children ◽  
Diagnostic Strategies ◽  
Increased Risk ◽  
Pediatric Sepsis ◽  
The Individual

Sepsis is a leading cause of morbidity and mortality in critically ill children, and acute kidney injury (AKI) is a frequent complication that confers an increased risk for poor outcomes. Despite the documented consequences of sepsis-associated AKI (SA-AKI), no effective disease-modifying therapies have been identified to date. As such, the only treatment options for these patients remain prevention and supportive care, both of which rely on the ability to promptly and accurately identify at risk and affected individuals. To achieve these goals, a variety of biomarkers have been investigated to help augment our currently limited predictive and diagnostic strategies for SA-AKI, however, these have had variable success in pediatric sepsis. In this mini-review, we will briefly outline the current use of biomarkers for SA-AKI, and propose a new framework for biomarker discovery and utilization that considers the individual patient's sepsis inflammatory response. Now recognized to be a key driver in the complex pathophysiology of SA-AKI, understanding the dysregulated host immune response to sepsis is a growing area of research that can and should be leveraged to improve the prediction and diagnosis of SA-AKI, while also potentially identifying novel therapeutic targets. Reframing SA-AKI in this manner – as a direct consequence of the individual patient's sepsis inflammatory response – will facilitate a precision medicine approach to its management, something that is required to move the care of this consequential disorder forward.

scholarly journals Nanomedicine and Immunotherapy: A Step Further towards Precision Medicine for Glioblastoma

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 490 ◽  
Author(s):  
Neja Šamec ◽  
Alja Zottel ◽  
Alja Videtič Paska ◽  
Ivana Jovčevska
Keyword(s):  
Precision Medicine ◽  
Targeted Delivery ◽  
Biological Fluids ◽  
Circulating Tumor Dna ◽  
Fluorescent Nanoparticles ◽  
Patient Response ◽  
Individual Level ◽  
Magnetic Resonance Imaging Mri ◽  
The Individual ◽  
Genetic Profiles

Owing to the advancement of technology combined with our deeper knowledge of human nature and diseases, we are able to move towards precision medicine, where patients are treated at the individual level in concordance with their genetic profiles. Lately, the integration of nanoparticles in biotechnology and their applications in medicine has allowed us to diagnose and treat disease better and more precisely. As a model disease, we used a grade IV malignant brain tumor (glioblastoma). Significant improvements in diagnosis were achieved with the application of fluorescent nanoparticles for intraoperative magnetic resonance imaging (MRI), allowing for improved tumor cell visibility and increasing the extent of the surgical resection, leading to better patient response. Fluorescent probes can be engineered to be activated through different molecular pathways, which will open the path to individualized glioblastoma diagnosis, monitoring, and treatment. Nanoparticles are also extensively studied as nanovehicles for targeted delivery and more controlled medication release, and some nanomedicines are already in early phases of clinical trials. Moreover, sampling biological fluids will give new insights into glioblastoma pathogenesis due to the presence of extracellular vesicles, circulating tumor cells, and circulating tumor DNA. As current glioblastoma therapy does not provide good quality of life for patients, other approaches such as immunotherapy are explored. To conclude, we reason that development of personalized therapies based on a patient’s genetic signature combined with pharmacogenomics and immunogenomic information will significantly change the outcome of glioblastoma patients.

scholarly journals Personalised approaches to pharmacotherapy for schizophrenia

2016 ◽  
Vol 22 (2) ◽  
pp. 78-86 ◽  
Author(s):  
John Lally ◽  
James H. MacCabe
Keyword(s):  
Medical Treatment ◽  
Antipsychotic Medication ◽  
Traditional Approach ◽  
Personalised Medicine ◽  
Individual Characteristics ◽  
Response To Treatment ◽  
Individual Response ◽  
Trial And Error ◽  
Recent Advances ◽  
The Individual

SummaryThe traditional approach to selecting antipsychotic medication involves little more than trial and error. Recent advances in genetics and molecular science offer the hope of a ‘personalised medicine’ approach to antipsychotic development and prescribing in schizophrenia. Personalised medicine is the practice of tailoring medical treatment to the individual characteristics of each patient. In schizophrenia, this will involve the identification of more homogeneous subsets of patients through the application of genetics, epigenetics, proteomics and metabolomics, neuroimaging and other biomarkers, and the use of these findings to stratify patients according to their response to treatment. In this article, we focus on the emerging evidence in pharmacogenetics and biomarkers for assessing individual response and tolerability of antipsychotic medication in schizophrenia.

scholarly journals Esophageal Cancer: Should Gender Be Considered as an Influential Factor for Patient Safety in Drug Treatment?

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Fengxia Liu ◽  
Helin Feng ◽  
Sumin Guo ◽  
Yuhan Chen ◽  
Qingyi Liu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Esophageal Cancer ◽  
Gender Difference ◽  
Drug Treatment ◽  
Cancer Patients ◽  
Influential Factor ◽  
Response To Treatment ◽  
Significant Difference ◽  
Student’S T ◽  
Drug Influence

Aim. Analyze the gender difference of esophageal cancer patients in response to drug treatment. Methods. All publications on clinical trials were collected from PubMed, Scopus, and PMC. Each publication was examined to determine whether the publication is a clinical trial and whether data on gender difference were reported. Results. Selected from a total of 191 publications, data from 7 trials with a total of 2041 patients were evaluated for gender differences. These clinical trials involve different drugs and disease phenotype. A significant difference was obtained between male and female groups from Student’s t-test. There is no conclusive result on age, ethnicity, tumor size, and drug influence. Conclusions. Gender difference in response to treatment potentially most likely exists in esophageal cancer patients, regardless of age, race, and drugs.

scholarly journals The Host Genetic Diversity in Malaria Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Vitor R. R. de Mendonça ◽  
Marilda Souza Goncalves ◽  
Manoel Barral-Netto
Keyword(s):  
Genetic Factors ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Genetic Alterations ◽  
Response To Treatment ◽  
Individual Response ◽  
Genetic Mechanisms ◽  
Host Genetic ◽  
Different Populations ◽  
The Individual

Populations exposed toPlasmodiuminfection develop genetic mechanisms of protection against severe disease. The clinical manifestation of malaria results primarily from the lysis of infected erythrocytes and subsequent immune and inflammatory responses. Herein, we review the genetic alterations associated with erythrocytes or mediators of the immune system, which might influence malaria outcome. Moreover, polymorphisms in genes related to molecules involved in mechanisms of cytoadherence and their influence on malaria pathology are also discussed. The results of some studies have suggested that the combinatorial effects of a set of genetic factors in the erythrocyte-immunology pathway might be relevant to host resistance or susceptibility againstPlasmodiuminfection. However, these results must be interpreted with caution because of the differences observed in the functionality and frequency of polymorphisms within different populations. With the recent advances in molecular biology techniques, more robust studies with reliable data have been reported, and the results of these studies have identified individual genetic factors for consideration in preventing severe disease and the individual response to treatment.

Complexity of Delivering Precision Medicine: Opportunities and Challenges

2018 ◽  
pp. 998-1007 ◽  
Author(s):  
Andrew A. Davis ◽  
Amy E. McKee ◽  
Warren A. Kibbe ◽  
Victoria M. Villaflor
Keyword(s):  
Clinical Trials ◽  
Precision Medicine ◽  
Data Sharing ◽  
Response To Treatment ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Data Repositories ◽  
Molecular Features ◽  
Effective Manner ◽  
Tumor Boards

Precision medicine has emerged as a tool to match patients with the appropriate treatment based on the precise molecular features of an individual patient’s tumor. Although examples of targeted therapies exist resulting in dramatic improvements in patient outcomes, comprehensive genomic profiling of tumors has also demonstrated the incredible complexity of molecular alterations in tissue and blood. These sequencing methods provide opportunities to study the landscape of tumors at baseline and serially in response to treatment. These tools also serve as important biomarkers to detect resistance to treatment and determine higher likelihood of responding to particular treatments, such as immune checkpoint blockade. Federally funded and publicly available data repositories have emerged as mechanisms for data sharing. In addition, novel clinical trials are emerging to develop new ways of incorporating molecular matched therapy into clinical trials. Various challenges to delivery of precision oncology include understanding the complexity of advanced tumors based on evolving “omics” and treatment resistance. For physicians, determining when and how to incorporate genetic and molecular tools into clinic in a cost-effective manner is critical. Finally, we discuss the importance of well-designed prospective clinical trials, biomarkers such as liquid biopsies, the use of multidisciplinary tumor boards, and data sharing as evidence-based medicine tools to optimally study and deliver precision oncology to our patients.

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