Personalizing Medicine: Disease Prevention in silico and in socio

Proponents of the emerging field of P4 medicine (defined as personalized, predictive, preventive and participatory) argue that computational integration and analysis of patient-specific “big data” will revolutionize our health care systems, in particular primary care-based disease prevention. While many ambitions remain visionary, steps to personalize medicine are already taken via personalized genomics, mobile health technologies and pilot projects. An important aim of P4 medicine is to enable disease prevention among healthy persons through detection of risk factors. In this paper, we examine the current status of P4 medicine in light of historical and current challenges to predictive and preventive medicine, including overdiagnosis and overtreatment. Moreover, we ask whether it is likely that in silico integration of patient-specific data will be able to better deal such challenges and to turn risk predictions into disease-preventive actions in a wider social context. Given the lack of evidence that P4 medicine can tip the balance between benefits and harms in preventive medicine, we raise concerns about the current promotion of P4 medicine as a solution to the current challenges in public health.

[1]  P. Gøtzsche,et al.  General health checks in adults for reducing morbidity and mortality from disease: Cochrane systematic review and meta-analysis , 2012, BMJ : British Medical Journal.

[2]  Brenda Wilson,et al.  A systematic review of perceived risks, psychological and behavioral impacts of genetic testing , 2008, Genetics in Medicine.

[3]  C. Silagy,et al.  A systematic review of the effectiveness of promoting lifestyle change in general practice. , 1997, Family practice.

[4]  Michelle L. McGowan,et al.  Personal genomics and individual identities: motivations and moral imperatives of early users , 2010, New genetics and society.

[5]  Anders Nordgren Neither as harmful as feared by critics nor as empowering as promised by providers: risk information offered direct to consumer by personal genomics companies , 2012, Journal of Community Genetics.

[6]  Russell E Glasgow,et al.  National Institutes of Health science agenda: a public health perspective. , 2007, American journal of public health.

[7]  J. Borén,et al.  Personalized Cardiovascular Disease Prediction and Treatment—A Review of Existing Strategies and Novel Systems Medicine Tools , 2016, Front. Physiol..

[8]  David Meyre,et al.  From big data analysis to personalized medicine for all: challenges and opportunities , 2015, BMC Medical Genomics.

[9]  A. Andermann,et al.  Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years. , 2008, Bulletin of the World Health Organization.

[10]  Nathan D. Price,et al.  Promoting Wellness & Demystifying Disease: The 100K Project , 2014 .

[11]  B. McEwen,et al.  Neuroscience, molecular biology, and the childhood roots of health disparities: building a new framework for health promotion and disease prevention. , 2009, JAMA.

[12]  L. Hood,et al.  P4 medicine: how systems medicine will transform the healthcare sector and society. , 2013, Personalized medicine.

[13]  Roger Strand,et al.  Complex Systems and Human Complexity in Medicine , 2005, Complexus.

[14]  A. Helvik,et al.  General practitioners' experiences with multiple clinical guidelines: A qualitative study from Norway , 2015 .

[15]  Nikolaus Forgó,et al.  Ethical and Legal Requirements for Transnational Genetic Research , 2010 .

[16]  T. Marteau,et al.  Effects of communicating DNA-based disease risk estimates on risk-reducing behaviours. , 2010, The Cochrane database of systematic reviews.

[17]  N. Sattar,et al.  Vitamin D and chronic disease prevention , 2014, BMJ : British Medical Journal.

[18]  S. Krokstad,et al.  Diagnostic labelling influences self-rated health. A prospective cohort study: the HUNT Study, Norway , 2015, Family practice.

[19]  K. Stange The Problem of Fragmentation and the Need for Integrative Solutions , 2009, The Annals of Family Medicine.

[20]  Len Lichtenfeld,et al.  Overdiagnosed: Making People Sick in Pursuit of Health , 2011 .

[21]  Thomas A. C. Reydon,et al.  Genetics, genomics and society: the responsibilities of scientists for science communication and education. , 2012, Personalized medicine.

[22]  Michael Marmot,et al.  Social determinants of health inequalities , 2005, The Lancet.

[23]  E. Diamandis,et al.  The hundred person wellness project and Google’s baseline study: medical revolution or unnecessary and potentially harmful over-testing? , 2015, BMC Medicine.

[24]  J. Vik,et al.  Bridging the genotype–phenotype gap: what does it take? , 2013, The Journal of physiology.

[25]  W. Hall,et al.  Being More Realistic about the Public Health Impact of Genomic Medicine , 2010, PLoS medicine.

[26]  B. Hofmann Too much technology , 2015, BMJ : British Medical Journal.

[27]  Manfred Gilli,et al.  Understanding complex systems , 1981, Autom..

[28]  G. Bray,et al.  Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. , 2013, The New England journal of medicine.

[29]  L. Getz,et al.  Current European guidelines for management of arterial hypertension: Are they adequate for use in primary care? Modelling study based on the Norwegian HUNT 2 population , 2009, BMC family practice.

[30]  Gregory M. Cooper Parlez-vous VUS? , 2015, Genome research.

[31]  Jung A Kim The Creative Destruction of Medicine: How the Digital Revolution Will Create Better Health Care , 2011 .

[32]  Primary care physicians' knowledge of and experience with pharmacogenetic testing , 2013 .

[33]  H. Willard,et al.  Considerations for the Impact of Personal Genome Information: A Study of Genomic Profiling among Genetics and Genomics Professionals , 2010, Journal of Genetic Counseling.

[34]  Kamil Dybczak,et al.  The role of technology in health care expenditure in the EU , 2010 .

[35]  B. Maher Personal genomes: The case of the missing heritability , 2008, Nature.

[36]  I. Heath Overdiagnosis: when good intentions meet vested interests—an essay by Iona Heath , 2013, BMJ.

[37]  J. Slattery,et al.  Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). 1994. , 1994, Atherosclerosis. Supplements.

[38]  Ruth McPherson,et al.  Genetics of Coronary Artery Disease. , 2016, Circulation research.

[39]  D. Lupton M-health and health promotion: The digital cyborg and surveillance society , 2012, Social Theory & Health.

[40]  Viktor Mayer-Schnberger,et al.  Big Data: A Revolution That Will Transform How We Live, Work, and Think , 2013 .

[41]  L. Hood,et al.  Bridging Systems Medicine and Patient Needs , 2015, CPT: pharmacometrics & systems pharmacology.

[42]  Ben Goldacre,et al.  Prediction of Cardiovascular Risk Using Framingham, ASSIGN and QRISK2: How Well Do They Predict Individual Rather than Population Risk? , 2014, PloS one.

[43]  B. Kholodenko,et al.  Systems medicine: helping us understand the complexity of disease. , 2013, QJM : monthly journal of the Association of Physicians.

[44]  D. Yach,et al.  New opportunities in the changing landscape of prevention. , 2014, JAMA.

[45]  Pauline C Ng,et al.  An agenda for personalized medicine. , 2009, Nature.

[46]  Wylie Burke,et al.  Systems medicine and the public's health , 2011, Genome Medicine.

[47]  E. Lander,et al.  The mystery of missing heritability: Genetic interactions create phantom heritability , 2012, Proceedings of the National Academy of Sciences.

[48]  M Benson,et al.  Clinical implications of omics and systems medicine: focus on predictive and individualized treatment , 2016, Journal of internal medicine.

[49]  D. Armstrong,et al.  The rise of surveillance medicine , 1995 .

[50]  Wylie Burke,et al.  Genetic Tests: Clinical Validity and Clinical Utility , 2014, Current protocols in human genetics.

[51]  Sabina Leonelli,et al.  What difference does quantity make? On the epistemology of Big Data in biology , 2014, Big Data Soc..

[52]  B Starfield,et al.  The concept of prevention: a good idea gone astray? , 2008, Journal of Epidemiology & Community Health.

[53]  N. Eriksson,et al.  Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing , 2013, PeerJ.

[54]  Bruce S. McEwen,et al.  Adverse childhood experiences, allostasis, allostatic load, and age-related disease , 2012, Physiology & Behavior.

[55]  Paul B Ginsburg,et al.  High and rising health care costs. , 2008, The Synthesis project. Research synthesis report.

[56]  Eugenio Paci,et al.  Overdiagnosis in Mammographic Screening for Breast Cancer in Europe: A Literature Review , 2012, Journal of medical screening.

[57]  L. Hood,et al.  Systems medicine and integrated care to combat chronic noncommunicable diseases , 2011, Genome Medicine.

[58]  J. Skolbekken The risk epidemic in medical journals. , 1995, Social science & medicine.

[59]  Jakob E. Bardram,et al.  Impact factor analysis: combining prediction with parameter ranking to reveal the impact of behavior on health outcome , 2015, Personal and Ubiquitous Computing.

[60]  R. Green,et al.  Personalized Genetic Risk Counseling to Motivate Diabetes Prevention , 2012, Diabetes Care.

[61]  Thomas Bodenheimer,et al.  High and Rising Health Care Costs. Part 2: Technologic Innovation , 2005, Annals of Internal Medicine.

[62]  Lisa M. Schwartz,et al.  Overdiagnosis: How cancer screening can turn indolent pathology into illness , 2014, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[63]  V. Pavlov,et al.  Neural circuitry and immunity , 2015, Immunologic Research.

[64]  David J. Duffy Problems, challenges and promises: perspectives on precision medicine , 2016, Briefings Bioinform..

[65]  Barbara Prainsack,et al.  The Powers of Participatory Medicine , 2014, PLoS biology.

[66]  Jordan Bartol Re-examining the Gene in Personalized Genomics , 2013 .

[67]  Timothy B. Smith,et al.  Social Relationships and Mortality Risk: A Meta-analytic Review , 2010, PLoS medicine.

[68]  Kenneth S Kendler,et al.  Toward a philosophical structure for psychiatry. , 2005, The American journal of psychiatry.

[69]  R. Verbrugge,et al.  Adoption of Pharmacogenomic Testing by US Physicians: Results of a Nationwide Survey , 2012, Clinical pharmacology and therapeutics.

[70]  D. Callahan Mirage of health: Utopias, progress, and biological change , 2007 .

[71]  W. Wayt Gibbs Medicine gets up close and personal , 2014, Nature.

[72]  Leroy Hood,et al.  Systems Biology and P4 Medicine: Past, Present, and Future , 2013, Rambam Maimonides medical journal.

[73]  S. Vasudevan,et al.  Systems Medicine: A New Model for Health Care , 2013 .

[74]  R B Haynes,et al.  Increased absenteeism from work after detection and labeling of hypertensive patients. , 1978, The New England journal of medicine.

[75]  P. Gøtzsche,et al.  Screening for breast cancer with mammography. , 2013, The Cochrane database of systematic reviews.

[76]  H L Greene,et al.  Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. , 1991, The New England journal of medicine.

[77]  Peter Jüni,et al.  Abolishing mammography screening programs? A view from the Swiss Medical Board. , 2014, The New England journal of medicine.

[78]  Victor M Montori,et al.  The epidemic of pre-diabetes: the medicine and the politics , 2014, BMJ : British Medical Journal.

[79]  Olle Melander,et al.  Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials , 2015, The Lancet.

[80]  N. Eisenberger,et al.  Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health , 2012, Nature Neuroscience.

[81]  G. L. Engel From biomedical to biopsychosocial. 1. Being scientific in the human domain. , 1997, Psychotherapy and psychosomatics.

[82]  F. Collins,et al.  A new initiative on precision medicine. , 2015, The New England journal of medicine.

[83]  A. Parekh,et al.  The challenge of multiple comorbidity for the US health care system. , 2010, JAMA.

[84]  N. Paneth,et al.  Seven Questions for Personalized Medicine. , 2015, JAMA.

[85]  richard tutton,et al.  Genomics and the Reimagining of Personalized Medicine. , 2014, Australian and New Zealand journal of public health.

[86]  Leroy Hood,et al.  Integrating big data and actionable health coaching to optimize wellness , 2015, BMC Medicine.

[87]  Jennette P. Moreno,et al.  Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes , 2014, Current Atherosclerosis Reports.

[88]  C. Rehmann-Sutter,et al.  Disclosure Dilemmas: Ethics of Genetic Prognosis after the 'Right to Know/Not to Know' Debate , 2009 .

[89]  T. Jørgensen,et al.  Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial , 2014, BMJ : British Medical Journal.

[90]  B. Farham Quantification of harms in cancer screening trials: Literature review , 2013 .

[91]  D. Longo,et al.  Precision medicine--personalized, problematic, and promising. , 2015, The New England journal of medicine.

[92]  J. Brodersen,et al.  Informed choice in screening needs more than information , 2015, The Lancet.

[93]  Eric J. Topol,et al.  A prospective randomized trial examining health care utilization in individuals using multiple smartphone-enabled biosensors , 2015, bioRxiv.

[94]  C. Wild,et al.  The exposome: from concept to utility. , 2012, International journal of epidemiology.

[95]  David L Sackett,et al.  The arrogance of preventive medicine. , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[96]  Paul Cilliers,et al.  Understanding Complex Systems , 2013 .

[97]  B. Hofmann,et al.  The new holism: P4 systems medicine and the medicalization of health and life itself , 2016, Medicine, Health Care and Philosophy.

[98]  M. Khoury,et al.  Personal genomics: information can be harmful , 2010, European journal of clinical investigation.

[99]  Muin J Khoury,et al.  A population approach to precision medicine. , 2012, American journal of preventive medicine.

[100]  Denis Noble,et al.  A theory of biological relativity: no privileged level of causation , 2012, Interface Focus.

[101]  Rudi Balling,et al.  Revolutionizing medicine in the 21st century through systems approaches. , 2012, Biotechnology journal.

[102]  Mario Beauregard,et al.  Mind does really matter: Evidence from neuroimaging studies of emotional self-regulation, psychotherapy, and placebo effect , 2007, Progress in Neurobiology.

[103]  Michael Bretthauer,et al.  Benefits and harms of mammography screening , 2015, Breast Cancer Research.

[104]  G. L. Engel From Biomedical to Biopsychosocial , 1997 .

[105]  Katharine Armstrong,et al.  Big data: a revolution that will transform how we live, work, and think , 2014 .

[106]  Elling Ulvestad,et al.  Getting personal: can systems medicine integrate scientific and humanistic conceptions of the patient? , 2014, Journal of evaluation in clinical practice.

[107]  B. Hofmann Diagnosing overdiagnosis: conceptual challenges and suggested solutions , 2014, European Journal of Epidemiology.

[108]  Olaf Wolkenhauer,et al.  The search for organizing principles as a cure against reductionism in systems medicine , 2013, The FEBS journal.

[109]  T. Wisniewski,et al.  THE ROLE OF BLOOD-PRESSURE CONTROL IN PREVENTING COMPLICATIONS OF HYPERTENSION. , 1964, Lancet.

[110]  P. Gøtzsche Mammography screening is harmful and should be abandoned , 2015, Journal of the Royal Society of Medicine.

[111]  Vivien Marx,et al.  The DNA of a nation , 2015, Nature.

[112]  J. Roberts,et al.  Direct-to-Consumer Genetic Testing and Personal Genomics Services: A Review of Recent Empirical Studies , 2013, Current Genetic Medicine Reports.

[113]  E. Juengst,et al.  Personalized genomic medicine and the rhetoric of empowerment. , 2012, The Hastings Center report.

[114]  L. Getz,et al.  Estimating the high risk group for cardiovascular disease in the Norwegian HUNT 2 population according to the 2003 European guidelines: modelling study , 2005, BMJ : British Medical Journal.

[115]  P. Sandøe,et al.  The structure of medical decisions: uncertainty, probability and risk in five common choice situations , 2013 .

[116]  Sharon L. R. Kardia,et al.  Current Applications of Genetic Risk Scores to Cardiovascular Outcomes and Subclinical Phenotypes , 2015, Current Epidemiology Reports.

[117]  L. Getz Sustainable and responsible preventive medicine: Conceptualising ethical dilemmas arising from clinical implementation of advancing medical technology , 2009 .

[118]  E. Cassell The person in medicine , 2010, International journal of integrated care.

[119]  A. Wu,et al.  Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. , 2005, JAMA.

[120]  Gerd Gigerenzer,et al.  Public Knowledge of Benefits of Breast and Prostate Cancer Screening in Europe , 2009, Journal of the National Cancer Institute.

[121]  A. Maturo Medicalization: Current Concept and Future Directions in a Bionic Society , 2012, Mens sana monographs.

[122]  L. Getz,et al.  [General practitioners who do not follow practice guidelines--may they have reasons not to?]. , 2008, Tidsskrift for Den Norske Laegeforening.

[123]  R. Ader,et al.  Psychosomatic Medicine: The Scientific Foundation of the Biopsychosocial Model , 2007, Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry.

[124]  L. Getz Sustainable and Responsible Preventive Medicine , 2009 .

[125]  Denis Noble,et al.  Biophysics and systems biology , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[126]  N. Schwennesen,et al.  Beyond informed choice: Prenatal risk assessment, decision-making and trust , 2008 .

[127]  L. Getz,et al.  Can individuals with a significant risk for cardiovascular disease be adequately identified by combination of several risk factors? Modelling study based on the Norwegian HUNT 2 population , 2009, Journal of evaluation in clinical practice.

[128]  D. Thelle,et al.  Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study. , 2012, Journal of evaluation in clinical practice.

[129]  A. Wu,et al.  Clinical Practice Guidelines and Quality of Care for Older Patients With Multiple Comorbid Diseases , 2005 .

[130]  John Brodersen,et al.  Long-Term Psychosocial Consequences of False-Positive Screening Mammography , 2013, The Annals of Family Medicine.

[131]  N. Hastie,et al.  Complex genetic diseases: controversy over the Croesus code , 2001, Genome Biology.

[132]  E. Fisher,et al.  Avoiding the unintended consequences of growth in medical care: how might more be worse? , 1999, JAMA.

[133]  C. Schmidt Leroy Hood looks forward to P4 medicine: predictive, personalized, preventive, and participatory. , 2014, Journal of the National Cancer Institute.