ArticlePDF Available

New Era of Personalized Medicine: A 10-Year Anniversary

Authors:

Abstract

Ten years ago, on April 16, 1999 appeared an article in Wall Street Journal by Robert Langreth and Michael Waldholz entitled “New Era of Personalized Medicine - Targeting Drugs for Each Unique Genetic Profile”. This article describe the formation of the SNP Consortium, an initiative that in 1999 was set up by ten major pharmaceutical companies, the Wellcome Trust and five academic research centers with the aim of drawing up a comprehensive SNP map of the humane genome. The hope with respect to the development of drugs specifically designed to target the individual patients genetic profile was also praised in the article. Some few months after the article was printed in Wall Street Journal it reappeared in The Oncologist.
A preview of the PDF is not available
... While it is the mainstay of treatment of breast cancer, it is yet to become a part of the management of other chronic diseases. [4] This review aims to critically evaluate the relative merits of PM and EBM in current glaucoma management. ...
... The targeted therapy as per the genetic markers has been used for a long time for the treatment of breast cancer. [4] As of now, there is no gene therapy for glaucoma treatment and many studies are still underway and there is a long way to go. The glaucoma types with a single gene defect as in myocilin in juvenile open-angle glaucoma have more potential for treatment by gene therapy. ...
Article
Full-text available
In the new era with ever-growing research and development of new concepts for patient care, it is important to interpret the information from the trials judiciously with the incorporation of patient targeted approach (precision medicine [PM]) along with evidence-based medicine to provide holistic care to the patient. As randomized controlled trials are usually conducted with strict criteria and a homogenous group of patients, the real-world situations are different, thus the individual-based approach has to be considered while managing patients, especially with chronic diseases which have a great impact on the patient's quality of life. This write-up highlights the importance of PM for glaucoma care and the factors which can help with decision making. A holistic and empathetic approach, with emphasis on lifestyle modifications including stress management, yoga therapy, and ocular motility exercises, can go a long way in improving both, the patient's coping skills, and the disease course. Newer empirical therapies, especially those without a demonstrable evidence base, may sometimes be considered for cases where all else fails, customized to the individual patient's requirements.
... Терминът "персонализирана медицина" се из-ползва за първи път през 1997 година от Ке-лал Джайн в нейна монография (Jain, 2015& Vogenberg, Barash, Pursel, 2010. Една година по-късно понятието «персона-лизирана медицина» е употребено за пър-ви път с актуалното си и до днес значение -предоставянето на индивидуално лечение на точния пациент спрямо неговия генетичен профил (Jørgensen, 2009, Langreth, Waldholz, 1999& Miner, Bolding, Hilbe, Goldstein, Hill, Nisbet,Walton,Miner, 2014), от Робърт Лангрит и Майкъл Валдхолц в статия, озаглавена "Нова ера на персонализираната медицина -таргетни лекарства за всеки отделен генетичен профил ("New Era of Personalized Medicine -Targeting Drugs for Each Unique Genetic Profile"), публи-кувана в The Wall Street Journal. ...
... Hippocrate a également évalué plusieurs facteurs, tels que : la stature, l'âge et la constitution d'un patient, ainsi que la période de l'année pour aider à prendre ses décisions lorsqu'il prescrivait des traitements.Le principe de la médecine personnalisée moderne a débuté avec les découvertes réalisées dans les domaines de la génétique, de la pharmacogénétique et génomique.Ce principe de personnalisation pourrait permettre la réduction des effets secondaires sévères de plus en plus nombreux et coûteux. En effet, les articles publiés sur ce sujet ont fortement augmenté ces dernières années grâce notamment à la médecine moléculaire, au diagnostic moléculaire et aux besoins médicaux réels.105 Un rapport de la Fondation européenne de la science a d'ailleurs souligné que la médecine dite « personnalisée » sera amenée à jouer un rôle de plus en plus important dans le système de santé futur car elle représente « une nouvelle approche pour classifier, comprendre, traiter et prévenir les maladies sur la base de données et d'information prenant en compte les différences biologiques et environnementales entre les individus ».106 Face à cette promesse de faire de chaque traitement un traitement unique à chaque patient, certains rappellent que la médecine personnalisée serait également « une capacité accrue de classer les individus en sous-groupes qui différent dans leur susceptibilité de contracter une maladie donnée ou de répondre à une thérapie spécifique ».107 Certains spécialistes préfèrent d'ailleurs parler de « médecine stratifiée » du fait que l'approche moléculaire n'apporte qu'un complément d'information aux autres facteurs de risque utilisés permettant de dire que la génomique n'est pas suffisante.[108][109][110] ...
Thesis
Introduction. Devant les nombreux facteurs pouvant influencer le risque hémorragique despatients sous anticoagulant, le concept de médecine personnalisée pourrait avoir unimpact favorable dans la prise en charge globale de ces patients.Hypothèse et objectif. L’hypothèse de ce travail de thèse est que l’utilisation et l’analysede registre de « vraie vie » pourrait permettre de définir des « profils » hémorragique depatient permettant une prise en charge personnalisée des patients.Matériel et Méthode. Ce travail de thèse a utilisé deux registres de vraie vie, le registreRIETE (registre international multicentrique prospectif) et le registre RATED (registremonocentrique).Résultats. Nous avons montré l’importance du recueil biologique dans l’analyse desaccidents hémorragiques sous anticogulants avec une perte plus élevée de facteurs decoagulation, lors d’hémorragie gastro-intestinales par rapport aux intracraniennes sousAVK. A l’inverse, ce risque est diminué de moitié en cas de mutation du facteur V Leiden.Grâce au registre RIETE, nous nous sommes ensuite intéressés aux métrorragies sousanticoagulant (peu décrites dans la littérature) où seulement 0,17% des femmesprésentaient des saignements utérins majeurs. Nous avons par la suite montré que lespatients fragiles (CrCl ≤50 mL / min, un âge ≥75 ans ou un poids corporel ≤50 kg) ont unrisque deux fois plus élevé de saignement grave. Enfin, afin de montrer lacomplémentarité des registres de vraie vie et des données d’essais randomisés, nousnous sommes intéressés aux patients exclus de ces essais randomisés et avons montréégalement un risque hémorragique 4 fois plus élevé.Conclusion. Ce travail de thèse a permis de démontrer l’intérêt de travailler non pastoutes hémorragies confondues mais hémorragies par hémorragies, avec un intérêt deréalisation de registres prospectifs de vraie vie avec la mise en oeuvre de bio-banquepermettant une analyse plus personnalisée de la prise en charge des patients.
... Терминът "персонализирана медицина" се из-ползва за първи път през 1997 година от Ке-лал Джайн в нейна монография (Jain, 2015& Vogenberg, Barash, Pursel, 2010. Една година по-късно понятието «персона-лизирана медицина» е употребено за пър-ви път с актуалното си и до днес значение -предоставянето на индивидуално лечение на точния пациент спрямо неговия генетичен профил (Jørgensen, 2009, Langreth, Waldholz, 1999& Miner, Bolding, Hilbe, Goldstein, Hill, Nisbet,Walton,Miner, 2014), от Робърт Лангрит и Майкъл Валдхолц в статия, озаглавена "Нова ера на персонализираната медицина -таргетни лекарства за всеки отделен генетичен профил ("New Era of Personalized Medicine -Targeting Drugs for Each Unique Genetic Profile"), публи-кувана в The Wall Street Journal. ...
Article
Full-text available
Развитието на персонализираната медицина се свързва не толкова със самата идея за персонализация, представена още от Хипократ преди повече от 2400 години, колкото с развитието и нарастването на прециз- ността в диагностицирането и лечението (Gordon & Koslow, 2011; Sykiotis, Kalliolias, Papavassiliou, 2005). Още тогава „бащата на медицината“ – Хипократ, отбелязва колко по-важно е да знаем какъв човек има дадена болест, а не каква болест има даден човек, както и че различните лекарства трябва да бъдат давани на раз- лични пациенти (Pray, 2008). В настоящето терминът „персонализирана медицина“ се определя като „осигуряване на правилния пациент с правилното лекарство в точната доза и в точното време“ (FDA). Според National Institutes of Health (NIH) прецизирана медицина е „нов подход в превенцията и лечението на болестта, на базата на индивидуалната изменчивост на гените, околната среда и начина на живот на всеки човек.“ Този подход дава възможност на лекарите и учените по-точно да предвиждат кои терапевтични и превантивни стратегии за определено заболяване биха имали ефект и при кои групи хора. Това е в противовес с универсалния подход, при който терапевтичните и превантивните стратегии са разработвани за „средно-ста- тистическия“ човек, без да се отчитат различията между отделните индивиди. Персонализираната медицина се определя още като „медицински модел, основан на определяне на фенотипа и генотипа на индивида (напр. молекулярно профилиране, образна диагностика, данни за начина на живот и пр.) за създаване на подходяща терапевтична стратегия за точния човек в точния момент и/или за определяне на предразположение към забо- ляване с цел навременна и фокусирана превенция“ (The European Alliance for Personalised Medicine (EAPM). Целта на статията е да се направи исторически преглед на персонализираната медицина, като се проследят и определят основните етапи на развитие – от нейното възникване до сега. Проучването се базира на литературен обзор на научни печатни и електронни източници, свързани пряко с темата на изследване. В резултат на изследването са определени следните 5 етапа на развитие на персонализираната медицина: • Подготвителен етап (1931 – 1984 г.) – от идеята за индивидуализиране на лечението до картографирането на човешкия геном. Поставя се въпросът за индивидуализираното лечение и се полагат основите за създа- ване на персонализираната медицина, водеща по-късно до революция в медицината; • Първи етап (1984 – 2002 г.) – картографира се човешкият геном, одобрени са първата таргетна терапия и първата съпътстваща диагностика, разработена успоредно с медикамента. Възниква понятието „персона- лизирана медицина . • Втори етап (2003 – 2012 г.) – създава се съпътстващата диагностика, с която медицинските специалисти определят коя таргетна терапия е подходяща за пациентите и в каква доза. • Трети етап (2012 – 2016 г.) – популяризират се резултатите от завършването на проекта „Човешки геном“. Осъзната е същността и важността на персоналзираната медицина и на съпътстващата диагностика. Създадени са Европейският алианс за персонализирана медицина (EAPM, 2012), Българската асоциация за персонализирана медицина (БАПЕМЕД, 2014) и Българският алианс за прецизирана и персонализирана меди- цина (БАППМ, 2016). Здравна икономика и мениджмънт, година 19, 2019 г., брой 1 (71) Copyright © ИК „Стено“ − Варна, 2001−2019 11 • Четвърти етап (от 2017 г.) – персонализираните лекарства и терапии стават обичайна и необходима прак- тика. Отбелязва се огромен ръст в развитието на персонализираната медицина. До 2018 година Агенцията за контрол на храните и лекарствата (FDA) е одобрила 115 персонализирани онкологични лекарства (тар- гетни терапии) (National Cancer Institute, 2018), а 41 лекарствени продукти за прицелна/таргетна терапия са регистрирани от Изпълнителната агенция по лекарствата ИАЛ в България до 2018 година. В заключение, днес персонализираната медицина променя медицината и грижата към пациента чрез предоста- вянето на персонализирано лечение, базирано на индивидуалните генетични характеристики на всеки пациент, или на неговото заболяване.
... Subsequently, medical societies started speaking for many decades that it is documented the prevalence of similar diseases within close relatives and ethnic groups, a range of different drug responses with adverse effects, and various signs and symptoms often observed with the same pathological condition [8][9][10][11] . Although some notion of personalized medicine exists nearing 60 years, it first appeared in 1999 in a published manuscript [12][13][14] . Personalized care ideas and thoughts now are almost in reality because of the development of very highly sensitive newer diagnostic tools 15,16 . ...
Article
Full-text available
The trend of NCDs in most LMIC countries is slowly but gradually follows that of in the developed countries. There are four significant diseases reported by WHO, which are equally common, such as CVDs, diabetes, cancer, and chronic respiratory disease that causes widespread early death & morbidity. Indeed, it incurs an overwhelming financial burden to most countries in the world. The rise of drug-resistant microbes is another major problem. To overcome this issue, precision medicine (PM) comes into play whereby individual variability in genes, environment, lifestyle, and nutrition of each person is considered for disease treatment & prevention. PM provides a personalized approach, the right treatment to the right people at the right time. Many wealthy countries in the West have started adopting PM though the initial cost is high, ultimately, in the long run, will reduce the healthcare cost by getting rid of the ineffective treatment strategies. However, the PM in LMICs is still at an early stage due to issues such as lack of population-specific data, competency, expertise, and poor financial support.
... Self-experiments are n-of-1 experiments in which an individual is their own control, highlighting that individual's response to an intervention rather than an average of many responses. Understanding individual variation and treating individual needs (i.e., personalized medicine [34]) is important in medicine and clinical science. Although personalized medicine historically emphasized genetics and pharmacology, the term is increasingly applied to other areas of health and disease [35], emphasizing the importance of personalized health. ...
Article
Full-text available
The rise of affordable sensors and apps has enabled people to monitor various health indicators via self-tracking. This trend encourages self-experimentation, a subset of self-tracking in which a person systematically explores potential causal relationships to try to answer questions about their health. Although recent research has investigated how to support the data collection necessary for self-experiments, less research has considered the best way to analyze data resulting from these self-experiments. Most tools default to using traditional frequentist methods. However, the US Agency for Healthcare Research and Quality recommends using Bayesian analysis for n-of-1 studies, arguing from a statistical perspective. To develop a complementary patient-centered perspective on the potential benefits of Bayesian analysis, this paper describes types of questions people want to answer via self-experimentation, as informed by (1) our experiences engaging with irritable bowel syndrome patients and their healthcare providers and (2) a survey investigating what questions individuals want to answer about their health and wellness. We provide examples of how those questions might be answered using (1) frequentist null hypothesis significance testing, (2) frequentist estimation, and (3) Bayesian estimation and prediction. We then provide design recommendations for analyses and visualizations that could help people answer and interpret such questions. We find the majority of the questions people want to answer with self-experimentation data are better answered with Bayesian methods than with frequentist methods. Our results therefore provide patient-centered support for the use of Bayesian analysis for n-of-1 studies.
... Genomic tests may identify individuals at risk of having a toxic response to a drug, thereby minimizing drug-related adverse events and associated costly consequences such as hospital admissions [4]. For example, pharmacogenomic tests for HLA-B*1502 can prevent potentially fatal carbamazepine-induced Stevens-Johnson syndrome. ...
Article
Full-text available
Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 private payers for 23 biomarkers (e.g., HER2 and EGFR) and multi-gene tests. We extracted policy coverage and criteria, prior authorization requirements, and an evidence basis for coverage. We reviewed professional society guidelines and their recommendations for use of pharmacogenomic tests. Coverage for KRAS, EGFR, and BRAF tests were common across Medicare contractors and private payers, but few policies covered PML/RARA, CD25, or G6PD. Thirteen payers cover multi-gene tests for nonsmall lung cancer, citing emerging clinical recommendations. Coverage policies for single and multi-gene tests for cancer treatments are consistent among Medicare contractors despite the lack of national coverage determinations. In contrast, coverage for these tests varied across private payers. Patient access to tests is governed by prior authorization among eight private payers. Substantial variations in how payers address guideline-recommended pharmacogenomic tests and the common use of prior authorization underscore the need for additional studies of the effects of coverage variation on cancer care and patient outcomes.
... Precision medicine and genomics-based technologies promise safer and more effective use of pharmacotherapy. Pharmacogenomic tests can predict which individuals are at risk of toxic response to a drug, thereby minimizing drug-related adverse events and the associated costly consequences, such as hospital admissions [1,2]. Such tests can also identify individuals likely to respond to an intervention based on molecular markers. ...
Article
Full-text available
Genomic tests are the fastest growing sector in medicine and medical science, yet there remains a dearth of research on access to pharmacogenomic tests and medications. The objective of this study is to explore providers' and patients' experiences and views on test access as well as strategies used for gaining access. We interviewed clinicians who prescribed medications that should be guided by pharmacogenomic testing and patients who received those prescriptions. We organized the themes into the four dimensions suggested by the World Health Organization framework on access to medications and health technologies. Guideline-recommended pharmacogenomic tests for cancer care are generally available, although the timeliness of return of test results is sometimes suboptimal. Accessibility of pharmacogenomic tests is made challenging by the process of ordering pharmacogenomic tests, which is time-consuming. Affordability is a barrier to some patients as expressed by both providers and patients, who noted that the cost of pharmacogenomic tests and medications is high. Acceptability of the tests is high as both providers and patients view the tests positively. Understanding challenges to accessing pharmacogenomic tests will allow policymakers to develop policies that streamline access to genomics-based technologies to improve population health.
Book
Cambridge Core - Neurology and Clinical Neuroscience - Assembly of the Executive Mind - by Michael W. Hoffmann
Conference Paper
Building of an accurate predictive model of clinical time series for a patient is critical for understanding of the patient condition, its dynamics, and optimal patient management. Unfortunately, this process is not straightforward. First, patient-specific variations are typically large and population-based models derived or learned from many different patients are often unable to support accurate predictions for each individual patient. Moreover, time series observed for one patient at any point in time may be too short and insufficient to learn a high-quality patient-specific model just from the patient's own data. To address these problems we propose, develop and experiment with a new adaptive forecasting framework for building multivariate clinical time series models for a patient and for supporting patient-specific predictions. The framework relies on the adaptive model switching approach that at any point in time selects the most promising time series model out of the pool of many possible models, and consequently, combines advantages of the population, patient-specific and short-term individualized predictive models. We demonstrate that the adaptive model switching framework is very promising approach to support personalized time series prediction, and that it is able to outperform predictions based on pure population and patient-specific models, as well as, other patient-specific model adaptation strategies.
Article
Full-text available
The selection of therapy for a particular breast cancer patient is traditionally based on average results from randomized clinical trials. Rational pharmacotherapy is in essence about selecting the right drug(s) for the right patient, and in order to guide this selection process pharmacodiagnostic tests are indispensable. A number of tests have been developed or are under development for targeted therapies, such as antiestrogens, human epidermal growth factor receptor 2 inhibitors, and topoisomerase inhibitors. Based on a biopsy from the tumor, the tests are able to identify patients with a high probability to benefit from these therapies. The detection of the predictive biomarkers is based on different technologies, such as immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ hybridization. Pharmacodiagnostic tests will play an important role in the further development of targeted therapies and may be seen as a prerequisite for the introduction of individualized medicine in oncology.
Article
One of the biggest challenges for the biotechnology and pharmaceutical companies in the 21st century will be to develop and deliver drugs that fit the individual patient’s biology and pathophysiology. This change from blockbuster medicine to personalized medicine will, to a large extent, influence the way that drugs are going to be developed, marketed and prescribed in the future. These changes could mean an end to the blockbuster philosophy in ‘big pharma’ and thereby impose major changes in company structures. The implementation of personalized medicine will be a stepwise process, where the division of patients into biological subgroups will be the first important step. Today, this is already the situation for several cancer diseases, for example, breast cancer. In the years to come, we will see more and more drugs being prescribed based on the results from pharmacodiagnostic testing. Within cancer medicine, which has been at the forefront of this field, it is expected that in 10–15 years time very few drugs will be prescribed without such a test.