Personalized Medicine Technologies Research Articles

Digitalization of Genetic Information: Prospects and Challenges

—The process of the digitalization of biological information is currently in its early stages of development and is characterized by the accelerated exponential growth of databases, which offers great opportunities for the development of personalized medicine, biodiversity conservation, the development of biotechnology and agriculture, but, at the same time, provides additional opportunities for the development of dual-use technologies and biological terrorism. The purpose of this work is to analyze the current situation in the field of digital sequence information and the global challenges facing humanity as the volume of genetic information continues to increase. It is urgent to develop mechanisms of national and international control in this area, as well as to find the optimal balance between the requirements of confidentiality of personal data of the population, compliance with legal and ethical standards, the need for scientific research, the development of personalized medicine technologies, and the development of business models and organizational and legal forms able to accompany further growth of digital sequence information.

Medicina personalizada: panorama e comparação de desafios e oportunidades para sua implantação no SUS

The objective of this work is, through a literature review, to promote the debate on personalized medicine and acquire a broad view of the subject and its tools from the perspective of oncology, disseminate the topic, support, and encourage initiatives to implement its technologies in the Brazilian public healthcare system, collaborating for a sustainable ecosystem in the incorporation of technologies, and above all, with the health and quality of life of patients. The implementation of personalized medicine technologies in SUS is feasible and effective. The scenario is optimistic considering the latest updates from the Ministry of Health with the establishment of the Brazilian Genomes Program. With wise management of resources and actions focused on creating an infrastructure that supports it, the entire public healthcare system will be benefited and can take advantage of the improvements. Personalized medicine is the future of healthcare.

Scientific Basics of Personalized Medicine: Realities and Opportunities.

Modern trends in the development of health care suggest its focus on the interests of the patient and its holistic nature, as well as deep penetration into all parts of health care information technology. Thedriving force behind the ongoing changes, of course, are scientific achievements, the importance of which in the development of new medical technologies and the creation of innovative diagnostic devices, aswell as medicines, has grown significantly in recent years. These processes provide conditions for the introduction into clinical practice of a new model of medical care-personalized medicine, based on the choice of methods of diagnosis and treatment with account for the individual characteristics of the course of the disease, as well as the patient's lifestyle. Personalized medicine technologies, which involve the creation of an appropriate, often expensive, infrastructure of omics technologies, should ultimately lead to an increase inthe efficiency, quality, and, most importantly, safety of medical care. In the Russian Federation, this area is actively developing in four world-class research centers, including the Almazov National Medical Research Center. The current state and prospects of research in the field of personalized medicine are discussed in this article, prepared by the author on the basis of his scientific report at a meeting of the Presidium of the Russian Academy of Sciences.

Additive Manufacturing and Printing Approaches for the Development of Pharmaceutical Dosage Forms with Improved Biopharmaceutical Attributes.

The pharmaceutical industry is moving towards the future and is witnessing innovation in drug development through the introduction of personalized medicine technologies. Instead of adapting the dose thata patient needs, they were adapted to the manufacturer's dose. Nowpatient-specific or customized dosing methods and dosing combinations have superior persistence to the standard mass-produced drugs. Printing technology has gained interest during the last few years to manufacture personalized dosage forms. For manufacturing personalized drug products, three-dimensional printing (3DP) has expanded to the pharmaceutical industry. With the approval of the first 3DP product, an unprecedented opportunity for discovering new compounds and technologies has arisen. This article has re-evaluated various printing technology and theirutilization in personalized medicines. Further, we also discussed its history, advantages, challenges and differenttypes of printing technologies with advantages and limitations, particularly in the area of pharmaceutical research.

Personalized Medicine for the Critically Ill Patient: A Narrative Review

Personalized Medicine (PM) is rapidly advancing in everyday medical practice. Technological advances allow researchers to reach patients more than ever with their discoveries. The critically ill patient is probably the most complex of all, and personalized medicine must make serious efforts to fulfill the desire to “treat the individual, not the disease”. The complexity of critically ill pathologies arises from the severe state these patients and from the deranged pathways of their diseases. PM constitutes the integration of basic research into clinical practice; however, to make this possible complex and voluminous data require processing through even more complex mathematical models. The result of processing biodata is a digitized individual, from which fragments of information can be extracted for specific purposes. With this review, we aim to describe the current state of PM technologies and methods and explore its application in critically ill patients, as well as some of the challenges associated with PM in intensive care from the perspective of economic, approval, and ethical issues. This review can help in understanding the complexity of, P.M.; the complex processes needed for its application in critically ill patients, the benefits that make the effort of implementation worthwhile, and the current challenges of PM.

Custom total knee arthroplasty facilitates restoration of constitutional coronal alignment

PurposeTo describe a strategy for coronal alignment using a computed tomography (CT) based custom total knee arthroplasty (TKA) system, and to evaluate the agreement between the planned and postoperative Hip–Knee–Ankle (HKA) angle, Femoral Mechanical Angle (FMA) and Tibial Mechanical Angle (TMA).MethodsFrom a consecutive series of 918 primary TKAs, 266 (29%) knees received CT-based posterior-stabilized cemented custom TKA. In addition to a preoperative CT-scan, pre- and post-operative radiographs of weight-bearing long leg, anterior–posterior and lateral views of the knee were obtained, on which the FMA, TMA and HKA angles were measured. CT-based three-dimensional (3D) models enabled to correct for cases with bony wear by referring to the non-worn areas and to estimate the native pre-arthritic angles. The alignment technique aimed to preserve or restore constitutional alignment (CA) within predetermined limits, by defining a ‘target zone’ based on three criteria: 1) a ± 3° (range 87°–93°) primary tolerance for the femoral and tibial resections; 2) a ± 2° secondary tolerance for component obliquity, extending the bounds for FMA and TMA (range 85°–95°); 3) a planned HKA angle range of 175°–183°. Agreement between preoperative, planned and postoperative measurements of FMA, TMA and HKA angle were calculated using intra-class correlation coefficients (ICC).ResultsPreoperative radiograph and CT-scan measurements revealed that, respectively, 73 (28%) and 103 (40%) knees were in the ‘target zone’, whereas postoperative radiographs revealed that 217 (84%) TKAs were in the ‘target zone’. Deviation from the planned angles were − 0.5° ± 1.8° for FMA, − 0.5° ± 1.8° for TMA, and − 1.1° ± 2.1° for HKA angle. Finally, the agreement between the planned and achieved targets, indicated by ICC, were good for FMA (0.701), fair for TMA (0.462) and fair for HKA angle (0.472).ConclusionUsing this strategy for coronal alignment, 84% of custom TKAs were within the ‘target zone’ for FMA, TMA and HKA angles. These findings support the concepts of emerging personalized medicine technologies, and emphasise the importance of accurate strategies for preoperative planning, which are key to achieving satisfactory ‘personalised alignment’ that can further be improved by customisation of implant components.Level of evidenceIV.

Guest Editorial for the Special Issue on Wireless Real-time Health Monitoring Technology for Personalized Medicine

Recent global focus on healthcare has stimulated research and development of innovative technologies which address many sustainability issues of the current healthcare provision models. Rapid advances in mobile, wireless, and sensing technologies have enabled new opportunities in healthcare, enabling cost-effective and efficient healthcare delivery in home, hospital, assisted living, and nursing home settings [1] . Remote diagnosis, patient and elderly monitoring, sensing of vital parameters of people suffering from chronic diseases such as asthma, diabetes, neurodegenerative and cardiovascular diseases, are just a few examples.

PNS167 A REVIEW OF EVALUATION CRITERIA AND STRATEGIES FOR INSURANCE COVERAGE OF PERSONALIZED MEDICINE: U.S. PAYER PERSPECTIVES

Personalized medicine (PM) such as pharmacogenomics tests and whole genome sequencing can be used to support treatment decision and improve health outcomes via more accurate risk-stratification and better prevention. The objectives of the study were: 1) Understand payer strategies and evaluation criteria for PM; 2) Identify opportunities and barriers to their coverage. A targeted review of the literature was conducted in EMBASE and PubMed. Selection criteria were used to identify payer perspectives and strategies for coverage of PM. Reviews from both public and private payers were included, and name of payer was captured if reported. 1078 studies were captured by our search strategy and 27 were included for extraction. Overall, 21 studies reported key evaluation criteria for reimbursement from both private and public payers. Payers perceived PM as useful if it allowed targeting responders specifically and reducing costs downstream. They are, however, cautious that this would expand populations for drugs and increase budgets. The top four attributes reportedly used by payers in their decision-making were clinical utility, analytic validity and efficacy, role in medical decision-making as well as cost offsets. One study reported that formulary management varied more among private payers. From the reviews, six studies included payer strategies: two payers offered coverage with evidence development, four offered coverage with conditions, and one payer used external services to price diagnostic tests based on value. For PM technologies to be adopted by all types of payers, manufacturers need to demonstrate that it accurately informs treatment decisions while showing both clinical and cost benefits. Assessment of the added value of PM remains complex and uncertain. Overall, generating evidence for PM meeting payers’ expectations is challenging. Payers, PM manufacturers and other stakeholders ought to collaborate to come up with innovative approaches for coverage, leading to better access for patients.

Early cost-effectiveness modeling for better decisions in public research investment of personalized medicine technologies.

Millions of dollars are spent on the development of new personalized medicine technologies. While these research costs are often supported by public research funds, many diagnostic tests and biomarkers are not adopted by the healthcare system due to lack of evidence on their cost-effectiveness. We describe a stepwise approach to conducting cost-effectiveness analyses that are performed early in the technology's development process and can help mitigate the potential risks of investment. Decision analytic modeling can identify the key drivers of cost effectiveness and provide minimum criteria that the technology needs to meet for adoption by public and private healthcare systems. A value of information analysis can quantify the added value of conducting more research to provide further evidence for policy decisions. These steps will allow public research funders to make better decisions on their investments to maximize the health benefits and to minimize the number of suboptimal technologies.

Innovation and shortage: The Yin and Yang of the health sector

The economic challenges countries face when adopting personalized medicine technologies provide an important illustration of many of the concepts articulated by János Kornai in his pioneering research on innovation in market-driven, capitalist surplus economies. In Chinese philosophy, Yin and Yang often represent contradictory yet inseparable opposites – two forces that not merely coexist, but are synergistic and mutually dependent. This concept is an apt analogy for the relationship between innovation and shortage in the health sector. Dangers arise from over-emphasizing the Yin of innovation over the Yang of access, and vice versa. If we over-constrain innovation, we die needlessly early and forfeit quality of life that innovations might have enabled. If we do not distribute access to innovations equitably, we diminish our humanity, suffer backlashes from populism and distrust of science and expertise, and risk social instability, even violent conflict.

Stages of development and implementation of personalized medicine technologies in clinical practice

In the article, the authors proposed the concept of developing and introducing into the clinical practice the technologies of personalized medicine, and first of all, genomic as well as other «omics» technologies. These are the stages from the choice of the problem, which is solved by personalizing the management of patients on the basis of genomic studies to the formation of a model for the introduction of personalized medicine technologies into clinical practice. The role of medical organizations of the Ministry of Health and scientific institutions of the Russian Academy of Sciences in all the proposed stages is presented.

Finnish Innovations in Medicine and Social Sphere

The article presents data collected during the tour dedicated to the medical and social institutions of Finland about new solutions and Finnish innovations in medicine and the social sphere. The article describes the principles of the Finnish health care system, including the work of maternal and child welfare clinics, as well as common European approaches in geriatrics. Thе article describes the features of geriatric services in Finland. It reflects the role of the municipal social services to provide residents of barrier-free environment in their regions. The article presents the facts from the personal experience exploring the Finnish system of medical and social support to older generation focused on the application of the latest scientific developments. The article presents innovative products for comfortable living of older people, including a traveling exhibition of technologies for older people, specialized furniture and household items available in the functional building DoMedi and others. This article describes the function of public and private Finnish services and the Finnish Centre for Elderly, including a Finnish non-profit organization Valli. The article presents the features of a private home for the elderly “Wilhelmiina” in Helsinki and scientific developments behalf Miyna Sillanpää Foundation. The article describes the innovative products, created in the Health Innovation Village at the Finnish office of GE: vacuum therapy device for the treatment of edema, a portable device for the treatment of depression, a sensor for measuring the electrical activity of muscles. The paper presents the solutions offered by the Finnish university hospitals, including personalized medicine technology for patients with cancer, developed at the Institute of Molecular Medicine, University of Helsinki. The article describes the work of one of the divisions of the institute - Biobank. The article describes the general approach to reform the health care system in Finland.

CARDIOCYTOPROTECTION PERSPECTIVES WITH ISCHEMIC PRECONDITIONING: HYPOXIA-INDUCED FACTOR 1 — POSSIBLE MOLECULAR MECHANISM AND TARGET FOR PHARMACOTHERAPY

The article is focused on the analysis of modern fundamental studies of the preconditioning/preintervention phenomenon in coronary heart disease and heart failure. Brief prerequisites are given for the phenomenon assessment. Molecular and genetic base of the phenomenon presented, as the results of modern experimental works in the area of fundamental medicine and clinical observations of the patients with various cardiovascular diseases. Hypoxia-induced factor 1 — main pathogenetic adaptation factor for hypoxia — plays critical protection role in pathophysiology of coronary heart disease and heart failure, controlling and determining the supply and utilization of oxygen, regulating angiogenesis and vascular remodelling, glucose metabolism and redox exchange. Personalized medicine technology, based on the pharmacogenomics, pharmacoproteomics, makes it to implement fundamental discoveries in medicine to clinical practice.

FACTORS LEADING TO ACCEPTANCE OF, AND WILLINGNESS TO PAY FOR PREDICTIVE TESTING AMONG CHRONICALLY ILL PATIENTS

ABSTRACT Background: Personalized medicine can lower healthcare system costs and help ensure that chronic patients get the most appropriate treatment for their individual illness. However, individual factors leading to acceptance of personalized medicine technologies such as predictive testing by chronic patients remain largely unknown. Objectives: This study was aimed at identifying individual sociodemographic factors leading to the acceptance of predictive testing in chronic patients and their willingness to pay for these tests. Design and methods: A web survey was conducted with 210 Canadian patients affected by Inflammatory Bowel Disease (IBD). The data was processed using the SPSS software. Inferential statistical analyses were conducted using the chi square test. Results: Chronic patients were massively in favour of undergoing a genetic test that could predict response to treatment options, and the majority were in favour of paying for the test. While the population in general has concerns regarding genetic testing, the present study indicates that the seriousness of chronic illness along with side effects of treatments leads to a higher acceptance among patients. Only the yearly number of consultations was positively related to acceptance and willingness to pay. Conclusions: While previous studies have reported resistance to genomic technologies amongst the general population, the present study demonstrates that chronic patients are largely open to genetic predictive testing. Furthermore, a vast majority was even prepared to pay for such tests. Clinicians, healthcare organizations and pharmaceutical companies should take this result into consideration when building and promoting predictive testing options. Based on these findings, future studies are warranted for further investigating and characterizing patients’ perception towards genetic predictive testing across other chronic illnesses. Keywords personalized medicine, predictive testing, chronic illness, treatment satisfaction, patient anxiety

Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin's lymphomas: a preliminary study.

Biodynamic imaging (BDI) is a novel phenotypic cancer profiling technology which optically characterizes changes in subcellular motion within living tumor tissue samples in response to ex vivo treatment with cancer chemotherapy drugs. The purpose of this preliminary study was to assess the ability of ex vivo BDI to predict in vivo clinical response to chemotherapy in ten dogs with naturally-occurring non-Hodgkin's lymphomas. Pre-treatment tumor biopsy samples were obtained from all dogs and treated ex vivo with doxorubicin (10 μM). BDI measured six dynamic biomarkers of subcellular motion from all biopsy samples at baseline and at regular intervals for 9 h following drug application. All dogs subsequently received doxorubicin to treat their lymphomas. Best overall response to and progression-free survival time following chemotherapy were recorded for all dogs. Receiver operating characteristic (ROC) curves were used to determine accuracy and identify possible cut-off values for the BDI-measured biomarkers which could accurately predict those dogs' cancers that would and would not respond to doxorubicin chemotherapy. One biomarker (designated 'MEM') showed 100% discriminative capability for predicting clinical response to doxorubicin (area under the ROC curve = 1.00, 95% CI 0.692-1.000), while other biomarkers also showed promising predictive capability. These preliminary findings suggest that ex vivo BDI can accurately predict treatment outcome following doxorubicin chemotherapy in a spontaneous animal cancer model, and is worthy of further investigation as a technology for personalized cancer medicine.

The Patent Eligibility of Personalized Medicine Technologies

First Prize Orr Postdoctoral Student Writing Competition 2014Personalized medicine holds great promise for improving the diagnosis, treatment, and management of cancer. Personalized cancer therapie...

Citizens' perspectives on personalized medicine: a qualitative public deliberation study

Our objective was to explore citizens' informed and reasoned values and expectations of personalized medicine, a timely yet novel genomics policy issue. A qualitative, public deliberation study was undertaken using a citizens' reference panel on health technologies, established to provide input to the health technology assessment process in Ontario, Canada. The citizens' panel consisted of five women and nine men, aged 18-71 years, with one member selected from each health authority region. There were shared expectations among the citizens' panel members for the potential of personalized medicine technologies to improve care, provided they are deemed clinically valid and effective. These expectations were tempered by concerns about value for money and the possibility that access to treatment may be limited by personalized medicine tests used to stratify patients. Although they questioned the presumed technological imperative presented by personalized medicine technologies, they called for increased efforts to prepare the health-care system to effectively integrate these technologies. This study represents an early but important effort to explore public values toward personalized medicine. This study also provides evidence of the public's ability to form coherent judgments about a new policy issue. Concerned that personalized tests might be used to ration care, they suggested that treatment should be made available if patients wanted it, irrespective of tests that indicate little benefit. This issue raises clinical and policy challenges that may undermine the value of personalized medicine. Further efforts to deliberate with the public are warranted to inform effective, efficient and equitable translation of personalized medicine.

Challenges in the Development and Reimbursement of Personalized Medicine—Payer and Manufacturer Perspectives and Implications for Health Economics and Outcomes Research: A Report of the ISPOR Personalized Medicine Special Interest Group

BackgroundPersonalized medicine technologies can improve individual health by delivering the right dose of the right drug to the right patient at the right time but create challenges in deciding which technologies offer sufficient value to justify widespread diffusion. Personalized medicine technologies, however, do not neatly fit into existing health technology assessment and reimbursement processes. ObjectivesIn this article, the Personalized Medicine Special Interest Group of the International Society for Pharmacoeconomics and Outcomes Research evaluated key development and reimbursement considerations from the payer and manufacturer perspectives. MethodsFive key areas in which health economics and outcomes research best practices could be developed to improve value assessment, reimbursement, and patient access decisions for personalized medicine have been identified. ResultsThese areas are as follows: 1 research prioritization and early value assessment, 2 best practices for clinical evidence development, 3 best practices for health economic assessment, 4 addressing health technology assessment challenges, and 5 new incentive and reimbursement approaches for personalized medicine. ConclusionsKey gaps in health economics and outcomes research best practices, decision standards, and value assessment processes are also discussed, along with next steps for evolving health economics and outcomes research practices in personalized medicine.

Tradeoffs of Using Administrative Claims and Medical Records to Identify the Use of Personalized Medicine for Patients With Breast Cancer

Administrative claims and medical records are important data sources to examine healthcare utilization and outcomes. Little is known about identifying personalized medicine technologies in these sources. To describe agreement, sensitivity, and specificity of administrative claims compared with medical records for 2 pairs of targeted tests and treatments for breast cancer. Retrospective analysis of medical records linked to administrative claims from a large health plan. We examined whether agreement varied by factors that facilitate tracking in claims (coding and cost) and that enhance medical record completeness (records from multiple providers). Women (35 to 65 y of age) with incident breast cancer diagnosed in 2006 to 2007 (n=775). Use of human epidermal growth factor receptor 2 (HER2) and gene expression profiling (GEP) testing, trastuzumab, and adjuvant chemotherapy in claims and medical records. Agreement between claims and records was substantial for GEP, trastuzumab, and chemotherapy, and lowest for HER2 tests. GEP, an expensive test with unique billing codes, had higher agreement (91.6% vs. 75.2%), sensitivity (94.9% vs. 76.7%), and specificity (90.1% vs. 29.2%) than HER2, a test without unique billing codes. Trastuzumab, a treatment with unique billing codes, had slightly higher agreement (95.1% vs. 90%) and sensitivity (98.1% vs. 87.9%) than adjuvant chemotherapy. Higher agreement and specificity were associated with services that had unique billing codes and high cost. Administrative claims may be sufficient for examining services with unique billing codes. Medical records provide better data for identifying tests lacking specific codes and for research requiring detailed clinical information.

Patient reactions to personalized medicine vignettes: An experimental design

PurposeTranslational investigation on personalized medicine is in its infancy. Exploratory studies reveal attitudinal barriers to “race-based medicine” and cautious optimism regarding genetically personalized medicine. This study describes patient responses to hypothetical conventional, race-based, or genetically personalized medicine prescriptions. MethodsThree hundred eighty-seven participants (mean age = 47 years; 46% white) recruited from a Baltimore outpatient center were randomized to this vignette-based experimental study. They were asked to imagine a doctor diagnosing a condition and prescribing them one of three medications. The outcomes are emotional response to vignette, belief in vignette medication efficacy, experience of respect, trust in the vignette physician, and adherence intention. ResultsRace-based medicine vignettes were appraised more negatively than conventional vignettes across the board (Cohen's d = −0.51−0.57−0.64, P < 0.001). Participants rated genetically personalized comparably with conventional medicine (−0.14−0.15−0.17, P = 0.47), with the exception of reduced adherence intention to genetically personalized medicine (Cohen's d = −0.38−0.41−0.44, P = 0.009). This relative reluctance to take genetically personalized medicine was pronounced for racial minorities (Cohen's d = −0.38−0.31−0.25, P = 0.02) and was related to trust in the vignette physician (change in R2 = 0.23, P < 0.001). ConclusionThis study demonstrates a relative reluctance to embrace personalized medicine technology, especially among racial minorities, and highlights enhancement of adherence through improved doctor- patient relationships.