Prioritizing Research in an Era of Personalized Medicine: The Potential Value of Unexplained Heterogeneity

2022 ◽  
pp. 0272989X2110728
Author(s):  
Anna Heath ◽  
Petros Pechlivanoglou
Keyword(s):  
Personalized Medicine ◽  
Patient Outcomes ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Treatment Decisions ◽  
Personalized Treatment ◽  
Sensitivity Analyses ◽  
Individual Treatment ◽  
Potential Value ◽  
The Individual

Background Clinical care is moving from a “one size fits all” approach to a setting in which treatment decisions are based on individual treatment response, needs, preferences, and risk. Research into personalized treatment strategies aims to discover currently unknown markers that identify individuals who would benefit from treatments that are nonoptimal at the population level. Before investing in research to identify these markers, it is important to assess whether such research has the potential to generate value. Thus, this article aims to develop a framework to prioritize research into the development of new personalized treatment strategies by creating a set of measures that assess the value of personalizing care based on a set of unknown patient characteristics. Methods Generalizing ideas from the value of heterogeneity framework, we demonstrate 3 measures that assess the value of developing personalized treatment strategies. The first measure identifies the potential value of personalizing medicine within a given disease area. The next 2 measures highlight specific research priorities and subgroup structures that would lead to improved patient outcomes from the personalization of treatment decisions. Results We graphically present the 3 measures to perform sensitivity analyses around the key drivers of value, in particular, the correlation between the individual treatment benefits across the available treatment options. We illustrate these 3 measures using a previously published decision model and discuss how they can direct research in personalized medicine. Conclusion We discuss 3 measures that form the basis of a novel framework to prioritize research into novel personalized treatment strategies. Our novel framework ensures that research targets personalized treatment strategies that have high potential to improve patient outcomes and health system efficiency. Highlights It is important to undertake research prioritization before conducting any research that aims to discover novel methods (e.g., biomarkers) for personalizing treatment. The value of unexplained heterogeneity can highlight disease areas in which personalizing treatment can be valuable and determine key priorities within that area. These priorities can be determined under assumptions of the magnitude of the individual-level treatment effect, which we explore in sensitivity analyses.

scholarly journals Personalized mathematical oncology: Challenges and opportunities

2021 ◽  
Author(s):  
Michael C. Luo ◽  
Elpiniki Nikolopoulou ◽  
Jana Gevertz
Keyword(s):  
Treatment Response ◽  
Clinical Care ◽  
Population Level ◽  
Personalized Treatment ◽  
Patient Specific ◽  
Individual Treatment ◽  
Specific Data ◽  
Level Statistics ◽  
Challenges And Opportunities ◽  
The Individual

An outstanding challenge in the clinical care of cancer is moving from a one-size-fits-all approach that relies on population-level statistics towards personalized therapeutic design. Mathematical modeling is a powerful tool in treatment personalization, as it allows for the incorporation of patient-specific data so that treatment can be tailor-designed to the individual. In this work, we employ two fitting methodologies to personalize treatment in a mathematical model of murine cancer immunotherapy. Unexpectedly, we found that the predicted personalized treatment response is sensitive to the fitting methodology utilized. This raises concerns about the ability of mathematical models, even relatively simple ones, to make reliable predictions about individual treatment response. Our analyses shed light onto why it can be challenging to make personalized treatment recommendations from a model, but also suggest ways we can increase our confidence in personalized mathematical predictions.

scholarly journals Personalized medicine in thrombosis: back to the future

Blood ◽  
2016 ◽  
Vol 127 (22) ◽  
pp. 2665-2671 ◽  
Author(s):  
Srikanth Nagalla ◽  
Paul F. Bray
Keyword(s):  
Personalized Medicine ◽  
Disease Risk ◽  
Platelet Reactivity ◽  
Clinical Care ◽  
Genomic Medicine ◽  
Personal Data ◽  
Value Added ◽  
Antiplatelet Agents ◽  
Small Effect Size ◽  
The Individual

Abstract Most physicians believe they practiced personalized medicine prior to the genomics era that followed the sequencing of the human genome. The focus of personalized medicine has been primarily genomic medicine, wherein it is hoped that the nucleotide dissimilarities among different individuals would provide clinicians with more precise understanding of physiology, more refined diagnoses, better disease risk assessment, earlier detection and monitoring, and tailored treatments to the individual patient. However, to date, the “genomic bench” has not worked itself to the clinical thrombosis bedside. In fact, traditional plasma-based hemostasis-thrombosis laboratory testing, by assessing functional pathways of coagulation, may better help manage venous thrombotic disease than a single DNA variant with a small effect size. There are some new and exciting discoveries in the genetics of platelet reactivity pertaining to atherothrombotic disease. Despite a plethora of genetic/genomic data on platelet reactivity, there are relatively little actionable pharmacogenetic data with antiplatelet agents. Nevertheless, it is crucial for genome-wide DNA/RNA sequencing to continue in research settings for causal gene discovery, pharmacogenetic purposes, and gene-gene and gene-environment interactions. The potential of genomics to advance medicine will require integration of personal data that are obtained in the patient history: environmental exposures, diet, social data, etc. Furthermore, without the ritual of obtaining this information, we will have depersonalized medicine, which lacks the precision needed for the research required to eventually incorporate genomics into routine, optimal, and value-added clinical care.

scholarly journals Pyoderma Gangrenosum: A Review of Updates in Diagnosis, Pathophysiology and Management

J ◽  
2021 ◽  
Vol 4 (3) ◽  
pp. 367-375
Author(s):  
Maria Skopis ◽  
Ayse Bag-Ozbek
Keyword(s):  
Early Diagnosis ◽  
Patient Outcomes ◽  
Pyoderma Gangrenosum ◽  
Treatment Strategies ◽  
Disease Course ◽  
Rare Entity ◽  
Skin Ulcers ◽  
The Individual ◽  
Delays In Diagnosis ◽  
Multiple Variants

Pyoderma gangrenosum (PG) is a rare entity that is characterized by infiltration of neutrophils into the dermis, causing the formation of rapidly enlarging, painful and necrotic skin ulcers. The pathophysiology of PG is still poorly understood. However, genetic, autoimmune and autoinflammatory mechanisms have been proposed that could potentially explain the etiology of this ulcerating skin disorder. Early diagnosis and treatment are key, as the disease course is rapidly progressive and can leave disfiguring, cribriform scars. However, the diagnosis of PG proves difficult, firstly because there are multiple variants of the disease and secondly because it is a clinical diagnosis and can appear similar to that of other diseases such as vasculitis, skin/soft tissue infections and malignancy. Additionally, there are no official diagnostic criteria to aid in the recognition of PG, which often leads to significant delays in diagnosis. The treatment of PG consists in immunosuppression. However, due to a lack of standardized guidelines, therapeutic regimens are usually dependent upon the individual clinician’s experience and are based on little evidence. Knowledge of the clinical features and pathophysiology of PG can aid in early diagnosis and targeted treatment strategies, which in turn results in improved patient outcomes.

scholarly journals Personalized laboratory medicine: a patient-centered future approach

2018 ◽  
Vol 56 (12) ◽  
pp. 1981-1991 ◽  
Author(s):  
Irena Prodan Žitnik ◽  
Darko Černe ◽  
Irene Mancini ◽  
Lisa Simi ◽  
Mario Pazzagli ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Treatment Strategies ◽  
Population Based ◽  
Laboratory Medicine ◽  
Response To Treatment ◽  
Medical Decision ◽  
Patient Centered ◽  
Evidence Based Treatment ◽  
Palliative Patient ◽  
The Individual

Abstract In contrast to population-based medical decision making, which emphasizes the use of evidence-based treatment strategies for groups of patients, personalized medicine is based on optimizing treatment at the level of the individual patient. The creation of molecular profiles of individual patients was made possible by the advent of “omics” technologies, based on high throughput instrumental techniques in combination with biostatistics tools and artificial intelligence. The goal of personalized laboratory medicine is to use advanced technologies in the process of preventive, curative or palliative patient management. Personalized medicine does not rely on changes in concentration of a single molecular marker to make a therapeutic decision, but rather on changes of a profile of markers characterizing an individual patient’s status, taking into account not only the expected response to treatment of the disease but also the expected response of the patient. Such medical approach promises a more effective diagnostics with more effective and safer treatment, as well as faster recovery and restoration of health and improved cost effectiveness. The laboratory medicine profession is aware of its key role in personalized medicine, but to empower the laboratories, at least an enhancement in cooperation between disciplines within laboratory medicine will be necessary.

scholarly journals Statistical Methods for Establishing Personalized Treatment Rules in Oncology

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Junsheng Ma ◽  
Brian P. Hobbs ◽  
Francesco C. Stingo
Keyword(s):  
Data Analysis ◽  
Personalized Medicine ◽  
Statistical Inference ◽  
Statistical Methods ◽  
Treatment Strategies ◽  
Optimal Treatment ◽  
Personalized Treatment ◽  
Statistical Software ◽  
Genetic Features ◽  
Treatment Rules

The process for using statistical inference to establish personalized treatment strategies requires specific techniques for data-analysis that optimize the combination of competing therapies with candidate genetic features and characteristics of the patient and disease. A wide variety of methods have been developed. However, heretofore the usefulness of these recent advances has not been fully recognized by the oncology community, and the scope of their applications has not been summarized. In this paper, we provide an overview of statistical methods for establishing optimal treatment rules for personalized medicine and discuss specific examples in various medical contexts with oncology as an emphasis. We also point the reader to statistical software for implementation of the methods when available.

The Development of Language-Training Programs for Postrubella Hearing-Impaired Children

1973 ◽  
Vol 38 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Linda Lynch ◽  
Annette Tobin
Keyword(s):  
Hearing Impaired ◽  
Treatment Programs ◽  
Individual Treatment ◽  
Target Behaviors ◽  
Systematic Fashion ◽  
Development Of Language ◽  
The Individual ◽  
Impaired Children ◽  
Hearing Impaired Children

This paper presents the procedures developed and used in the individual treatment programs for a group of preschool, postrubella, hearing-impaired children. A case study illustrates the systematic fashion in which the clinician plans programs for each child on the basis of the child’s progress at any given time during the program. The clinician’s decisions are discussed relevant to (1) the choice of a mode(s) for the child and the teacher, (2) the basis for selecting specific target behaviors, (3) the progress of each program, and (4) the implications for future programming.

In silico modeling of cellular probabilistic nanoparticle radiosensitization in head and neck cancers

Nanomedicine ◽  
2020 ◽  
Vol 15 (29) ◽  
pp. 2837-2850
Author(s):  
Myxuan Huynh ◽  
Ivan Kempson ◽  
Eva Bezak ◽  
Wendy Phillips
Keyword(s):  
Head And Neck ◽  
Patient Outcomes ◽  
Head And Neck Cancers ◽  
New Approach ◽  
Treatment Regimens ◽  
Therapeutic Benefits ◽  
In Silico Modeling ◽  
The Individual ◽  
Dose Deposition ◽  
Therapy Treatment

Background: The use of gold nanoparticles (AuNPs) as radiosensitizers may offer a new approach in the treatment of head and neck cancers; minimizing treatment-associated toxicities and improving patient outcomes. AuNPs promote localized dose deposition; permitting improved local control and/or dose reduction. Aim: This work aimed to address the theoretical optimization of radiation doses, fractionation and nanoparticle injection schedules to maximize therapeutic benefits. Materials & methods: Probabilistic nanoparticle sensitization factors were incorporated into the individual cell-based HYP-RT computer model of tumor growth and radiotherapy. Results: Total dose outcomes across all radiation therapy treatment regimens were found to be significantly reduced with the presence of AuNPs, with bi-weekly injections showing the most decrease. Conclusion: Outcomes suggest the need for regular AuNP administration to permit effective radiosensitization.

Quality of Life for Children with Persistent Sinonasal Symptoms

2003 ◽  
Vol 128 (1) ◽  
pp. 17-26 ◽  
Author(s):  
David J. Kay ◽  
Richard M. Rosenfeld
Keyword(s):  
Quality Of Life ◽  
Clinical Care ◽  
Longitudinal Change ◽  
Good Test ◽  
Routine Clinical Care ◽  
Before And After ◽  
The Mean ◽  
The Individual ◽  
Sinonasal Symptoms

OBJECTIVE: The goal was to validate the SN-5 survey as a measure of longitudinal change in health-related quality of life (HRQoL) for children with persistent sinonasal symptoms. DESIGN AND SETTING: We conducted a before and after study of 85 children aged 2 to 12 years in a metropolitan pediatric otolaryngology practice. Caregivers completed the SN-5 survey at entry and at least 4 weeks later. The survey included 5 symptom-cluster items covering the domains of sinus infection, nasal obstruction, allergy symptoms, emotional distress, and activity limitations. RESULTS: Good test-retest reliability ( R = 0.70) was obtained for the overall SN-5 score and the individual survey items ( R ≥ 0.58). The mean baseline SN-5 score was 3.8 (SD, 1.0) of a maximum of 7.0, with higher scores indicating poorer HRQoL. All SN-5 items had adequate correlation ( R ≥ 0.36) with external constructs. The mean change in SN-5 score after routine clinical care was 0.88 (SD, 1.19) with an effect size of 0.74 indicating good responsiveness to longitudinal change. The change scores correlated appropriately with changes in related external constructs ( R ≥ 0.42). CONCLUSIONS: The SN-5 is a valid, reliable, and responsive measure of HRQoL for children with persistent sinonasal symptoms, suitable for use in outcomes studies and routine clinical care.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals Considerations for the Management of Women with Breast Cancer during the COVID-19 Pandemic

2020 ◽  
Vol 5 (03) ◽  
pp. 260-263
Author(s):  
Monica Irukulla ◽  
Palwai Vinitha Reddy
Keyword(s):  
Breast Cancer ◽  
Resource Allocation ◽  
Patient Care ◽  
Cancer Patients ◽  
Cancer Care ◽  
Clinical Care ◽  
Current Availability ◽  
The Individual

AbstractOutcomes in cancer patients are strongly influenced by timeliness and quality of multidisciplinary interventions. The COVID-19 pandemic has led to severe disruption in cancer care in many countries. This has necessitated several changes in clinical care and workflow, including resource allocation, team segregation and deferment of many elective procedures. Several international oncological societies have proposed guidelines for the care of patients afflicted with breast cancer during the pandemic with a view to optimize resource allocation and maximize risk versus benefit for the individual and society. Clinicians may utilize these recommendations to adapt patient care, based on the current availability of resources and severity of the COVID-19 pandemic in each region. This article discusses the guidelines for care of patients afflicted with breast cancer during the pandemic.

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