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      Personalizing health care: feasibility and future implications

      review-article
      1 , 2 , 3 , , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 2 , 13 , 13 , 6 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 4 , 21 , 22 , 23 , 24 , 25 , 23 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 28 , 41 , 42 , 43 , 44 , 1
      BMC Medicine
      BioMed Central
      Biomarkers, Drug development, Genomics, Genotyping, Healthcare policy, Pharmacogenetics precision medicine, Personalized medicine, Health authorities, Rational use of medicines, Reimbursement, Targeted treatments

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          Abstract

          Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer’s perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.

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          Most cited references144

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          Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.

          The recommended treatment for patients with chronic hepatitis C, pegylated interferon-alpha (PEG-IFN-alpha) plus ribavirin (RBV), does not provide sustained virologic response (SVR) in all patients. We report a genome-wide association study (GWAS) to null virological response (NVR) in the treatment of patients with hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR (rs12980275, P = 1.93 x 10(-13), and rs8099917, 3.11 x 10(-15)). We replicated these associations in an independent cohort (combined P values, 2.84 x 10(-27) (OR = 17.7; 95% CI = 10.0-31.3) and 2.68 x 10(-32) (OR = 27.1; 95% CI = 14.6-50.3), respectively). Compared to NVR, these SNPs were also associated with SVR (rs12980275, P = 3.99 x 10(-24), and rs8099917, P = 1.11 x 10(-27)). In further fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142, rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region showed the most significant associations (P = 5.52 x 10(-28)-2.68 x 10(-32); OR = 22.3-27.1). Real-time quantitative PCR assays in peripheral blood mononuclear cells showed lower IL28B expression levels in individuals carrying the minor alleles (P = 0.015).
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            Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.

            To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients. Four electronic databases were searched from 1966 to 1996. Of 153, we selected 39 prospective studies from US hospitals. Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death. The overall incidence of serious ADRs was 6.7% (95% confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%-0.41%) of hospitalized patients. We estimated that in 1994 overall 2216000 (1721000-2711000) hospitalized patients had serious ADRs and 106000 (76000-137000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death. The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.
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              IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

              Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.
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                Author and article information

                Contributors
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central
                1741-7015
                2013
                13 August 2013
                : 11
                : 179
                Affiliations
                [1 ]Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86, Stockholm, Sweden
                [2 ]Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
                [3 ]National Institute for Science and Technology on Innovation on Neglected Diseases, Centre for Technological Development in Health, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
                [4 ]King’s Centre for Global Health, Global Health Offices, Weston Education Centre, Cutcombe Road, London SE5 9RJ, UK
                [5 ]Sunnybrook Odette Cancer Centre, 2075 Bayview Avenue, Toronto, ON, Canada
                [6 ]Hauptverband der Österreichischen Sozialversicherungsträger, 21 Kundmanngasse, AT-1031, Wien, Austria
                [7 ]Institute of Pharmacology and Toxicology, Department for Biomedical Sciences, University of Vienna, Vienna, Austria
                [8 ]Osteba Basque Office for HTA, Ministry of Health of the Basque Country, Donostia-San Sebastian 1, 01010, Vitoria-Gasteiz, Basque Country, Spain
                [9 ]NHS Tayside, Kings Cross, Dundee DD3 8EA, UK
                [10 ]Department of Medicine, Clinical Pharmacology Unit, Karolinska Institutet, Karolinska University Hospital Solna, SE-17176, Stockholm, Sweden
                [11 ]Pharmaceutical Pricing Board, Ministry of Social Affairs and Health, PO Box 33, FI-00023 Government, Helsinki, Finland
                [12 ]Austrian Medicines and Medical Devices Agency, Traisengasse 5, Wien, Austria
                [13 ]Public Health & Intelligence Strategic Business Unit, NHS National Services Scotland, Edinburgh EH12 9EB, UK
                [14 ]Centre for Primary Care, Institute of Population Health, University of Manchester, Manchester M13 9PL, UK
                [15 ]NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre, Manchester M13 9PL, UK
                [16 ]Unitat de Coordinació i Estratègia del Medicament, Direcció Adjunta d'Afers Assistencials, Catalan Institute of Health, Barcelona, Spain
                [17 ]London School of Economics and Political Science, LSE Health, Houghton Street, London WC2A 2AE, UK
                [18 ]Health Insurance Institute, Miklosiceva 24, SI-1507, Ljubljana, Slovenia
                [19 ]Medicines Reimbursement Department, National Health Insurance Fund, Europas a. 1, Vilnius, Lithuania
                [20 ]INFARMED, Parque da Saúde de Lisboa, Avenida do Brasil 53, 1749-004, Lisbon, Portugal
                [21 ]Liverpool Health Economics Centre, University of Liverpool, Chatham Street, Liverpool L69 7ZH, UK
                [22 ]Kassenärztliche Vereinigung Hessen, 15 Georg Voigt Strasse, DE-60325, Frankfurt am Main, Germany
                [23 ]Norwegian Medicines Agency, Sven Oftedals vei 8, 0950, Oslo, Norway
                [24 ]Clinical Programs, Pharmacy Management, Horizon Blue Cross Blue Shield of New Jersey, Newark, USA
                [25 ]Republic Institute for Health Insurance, Jovana Marinovica 2, 11000, Belgrade, Serbia
                [26 ]State Agency of Medicines, Nooruse 1, 50411, Tartu, Estonia
                [27 ]Department of Healthcare Development, Stockholm County Council, Stockholm, Sweden
                [28 ]HTA Consulting, Starowiślna Street, 17/3, 31-038, Cracow, Poland
                [29 ]Public Health School, The Medical Centre of Postgraduate Education, Kleczewska Street, 61/63, 01-813, Warsaw, Poland
                [30 ]NHS Greater Manchester Commissioning Support Unit, Salford, Manchester, UK
                [31 ]National Centre for Pharmacoeconomics, St James's Hospital, Dublin 8, Ireland
                [32 ]Dental and Pharmaceuticals Benefits Agency (TLV), PO Box 22520 Flemingatan 7, SE-104, Stockholm, Sweden
                [33 ]University of Glasgow, Glasgow, Scotland, UK
                [34 ]University of Heidelberg, Institute of Pharmacology, D-69120, Heidelberg, Germany
                [35 ]Wissenschaftliches Institut der AOK (WIDO), Rosenthaler Straße 31, 10178, Berlin, Germany
                [36 ]IRDES, 10 rue Vauvenargues, 75018, Paris, France
                [37 ]KU Leuven Department of Pharmaceutical and Pharmacological Sciences, 3000, Leuven, Belgium
                [38 ]Faculty of Pharmacy, Comenius University and Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia
                [39 ]Unit for Clinical Pharmacology, University Hospital Rijeka, Krešimirova 42, 51000, Rijeka, Croatia
                [40 ]Ministry of Health, Republic of Croatia, Ksaver 200a, Zagreb, Croatia
                [41 ]Dutch Institute for Rational Use of Medicines, 3527 GV, Utrecht, Netherlands
                [42 ]Institute for Optimizing Health Outcomes, 151 Bloor Street West, Suite 600, Toronto, ON M5S 1S4, Canada
                [43 ]Barcelona Health Region, Catalan Health Service, Esteve Terrades 30, 08023, Barcelona, Spain
                [44 ]INDOX Cancer Research Network, Cancer Epidemiology Unit, University of Oxford, Oxford, UK
                Article
                1741-7015-11-179
                10.1186/1741-7015-11-179
                3750765
                23941275
                ea5f6d1a-c0ea-4965-b9b4-685f4da932fe
                Copyright ©2013 Godman et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 January 2013
                : 9 July 2013
                Categories
                Review

                Medicine
                biomarkers,drug development,genomics,genotyping,healthcare policy,pharmacogenetics precision medicine,personalized medicine,health authorities,rational use of medicines,reimbursement,targeted treatments

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