title: Systems Medicine 2.0: potential benefits of combining electronic health care records with systems science models.
abstract: BACKGROUND
  The global burden of disease is increasingly dominated by non-communicable diseases.These diseases are less amenable to curative and preventative interventions than communicable disease. This presents a challenge to medical practice and medical research, both of which are experiencing diminishing returns from increasing investment.
  
  
  OBJECTIVE
  Our aim was to (1) review how medical knowledge is generated, and its limitations, (2) assess the potential for emerging technologies and ideas to improve medical research, and (3) suggest solutions and recommendations to increase medical research efficiency on non-communicable diseases.
  
  
  METHODS
  We undertook an unsystematic review of peer-reviewed literature and technology websites.
  
  
  RESULTS
  Our review generated the following conclusions and recommendations. (1) Medical knowledge continues to be generated in a reductionist paradigm. This oversimplifies our models of disease, rendering them ineffective to sufficiently understand the complex nature of non-communicable diseases. (2) Some of these failings may be overcome by adopting a "Systems Medicine" paradigm, where the human body is modeled as a complex adaptive system. That is, a system with multiple components and levels interacting in complex ways, wherein disease emerges from slow changes to the system set-up. Pursuing systems medicine research will require larger datasets. (3) Increased data sharing between researchers, patients, and clinicians could provide this unmet need for data. The recent emergence of electronic health care records (EHR) could potentially facilitate this in real-time and at a global level. (4) Efforts should continue to aggregate anonymous EHR data into large interoperable data silos and release this to researchers. However, international collaboration, data linkage, and obtaining additional information from patients will remain challenging. (5) Efforts should also continue towards "Medicine 2.0". Patients should be given access to their personal EHR data. Subsequently, online communities can give researchers the opportunity to ask patients for direct access to the patient's EHR data and request additional study-specific information. However, selection bias towards patients who use Web 2.0 technology may be difficult to overcome.
  
  
  CONCLUSIONS
  Systems medicine, when combined with large-scale data sharing, has the potential to raise our understanding of non-communicable diseases, foster personalized medicine, and make substantial progress towards halting, curing, and preventing non-communicable diseases. Large-scale data amalgamation remains a core challenge and needs to be supported. A synthesis of "Medicine 2.0" and "Systems Science" concepts into "Systems Medicine 2.0" could take decades to materialize but holds much promise.
authors.affiliation: Department of Epidemiology & Public Health, University College London, London, United Kingdom. taavi.tillmann@gmail.com.
authors.forename: Taavi
authors.identifier: http://orcid.org/0000-0002-8428-3719
authors.initials: T
authors.lastname: Tillmann
authors.forename: Alexander R
authors.identifier: http://orcid.org/0000-0002-7314-0325
authors.initials: AR
authors.lastname: Gibson
authors.forename: Gregory
authors.identifier: http://orcid.org/0000-0001-8063-5871
authors.initials: G
authors.lastname: Scott
authors.forename: Oliver
authors.identifier: http://orcid.org/0000-0003-1515-9586
authors.initials: O
authors.lastname: Harrison
authors.forename: Anna
authors.identifier: http://orcid.org/0000-0003-4913-3608
authors.initials: A
authors.lastname: Dominiczak
authors.forename: Phil
authors.identifier: http://orcid.org/0000-0002-4971-5221
authors.initials: P
authors.lastname: Hanlon
mesh_terms: D035843:Biomedical Research; D057286:Electronic Health Records; D006301:Health Services Needs and Demand; D006801:Humans; D020407:Internet; D019359:Knowledge; D011642:Publications
keywords: Web 2.0; crowd-sourcing; electronic health records; epidemiology; gene-environment interaction; online social networks; systems theory
references.citation: Nat Med. 2000 May;6(5):536-42
references.pmid: 10802709
references.citation: Nat Biotechnol. 2011 May;29(5):411-4
references.pmid: 21516084
references.citation: PLoS Genet. 2009 Feb;5(2):e1000369
references.pmid: 19197344
references.citation: Genome Med. 2009 Sep 29;1(9):88
references.pmid: 19754960
references.citation: PLoS Genet. 2010 Apr;6(4):e1000888
references.pmid: 20369019
references.citation: Science. 2003 Jul 18;301(5631):386-9
references.pmid: 12869766
references.citation: Circulation. 2000 Jan 4-11;101(1):8-10
references.pmid: 10618296
references.citation: AMIA Jt Summits Transl Sci Proc. 2013 Mar 18;2013:27
references.pmid: 24303291
references.citation: Int Immunol. 2003 Jan;15(1):59-69
references.pmid: 12502726
references.citation: Nat Biotechnol. 2007 Oct;25(10):1119-26
references.pmid: 17921997
references.citation: Front Physiol. 2014 Jan 28;5:21
references.pmid: 24478728
references.citation: Yale J Biol Med. 2002 Sep-Dec;75(5-6):247-60
references.pmid: 14580107
references.citation: Clin Neurophysiol. 2005 Oct;116(10):2266-301
references.pmid: 16115797
references.citation: J Med Internet Res. 2008;10(3):e24
references.pmid: 18701421
references.citation: J Clin Invest. 1997 Jan 15;99(2):305-14
references.pmid: 9005999
references.citation: Nat Genet. 2005 Mar;37(3):243-53
references.pmid: 15711544
references.citation: J Med Internet Res. 2014;16(2):e46
references.pmid: 24509520
references.citation: Nat Rev Genet. 2008 May;9(5):406-11
references.pmid: 18379574
references.citation: PLoS Comput Biol. 2013;9(5):e1003047
references.pmid: 23671412
references.citation: Mol Syst Biol. 2007;3:124
references.pmid: 17625512
references.citation: Int J Cancer. 2009 Dec 15;125(12):2844-53
references.pmid: 19569046
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2011 Nov-Dec;3(6):619-27
references.pmid: 21928407
references.citation: PLoS One. 2013;8(7):e69935
references.pmid: 23936122
references.citation: Immunity. 1999 Nov;11(5):507-13
references.pmid: 10591175
references.citation: J Med Internet Res. 2010;12(2):e19
references.pmid: 20542858
references.citation: BMJ. 2009;339:b2803
references.pmid: 19671932
references.citation: Prev Med. 2013 Nov;57(5):434-5
references.pmid: 23872173
references.citation: Trends Pharmacol Sci. 2005 Apr;26(4):178-82
references.pmid: 15808341
references.citation: PLoS Med. 2006 May;3(6):e208
references.pmid: 16681415
references.citation: Lancet. 1997 Jan 25;349(9047):241-4
references.pmid: 9014911
references.citation: Nat Rev Genet. 2011 Jan;12(1):56-68
references.pmid: 21164525
references.citation: Soc Sci Med. 2001 Jun;52(11):1629-41
references.pmid: 11327137
references.citation: N Engl J Med. 2008 Apr 17;358(16):1732-7
references.pmid: 18420506
references.citation: Crit Care Med. 2000 Jul;28(7):2193-200
references.pmid: 10921540
references.citation: Nat Rev Genet. 2009 Jun;10(6):392-404
references.pmid: 19434077
references.citation: Mol Syst Biol. 2007;3:140
references.pmid: 17940530
references.citation: Eur Heart J. 2015 Apr 21;36(16):984-92
references.pmid: 25005706
references.citation: Clin Sci (Lond). 1998 Apr;94(4):373-81
references.pmid: 9640343
references.citation: Nature. 2008 Mar 27;452(7186):429-35
references.pmid: 18344982
references.citation: Science. 2009 Jan 23;323(5913):498-501
references.pmid: 19164747
references.citation: Stud Health Technol Inform. 2010;156:171-7
references.pmid: 20543352
references.citation: PLoS Comput Biol. 2009 Apr;5(4):e1000353
references.pmid: 19360091
references.citation: J Med Internet Res. 2008;10(1):e5
references.pmid: 18343794
references.citation: PLoS Med. 2008 Jun 24;5(6):e131
references.pmid: 18578563
references.citation: BMJ. 2008 May 10;336(7652):1029-30
references.pmid: 18460554
references.citation: Mol Nutr Food Res. 2013 Apr;57(4):721-34
references.pmid: 22961839
references.citation: Arch Gen Psychiatry. 1995 Nov;52(11):947-59
references.pmid: 7487343
references.citation: Infect Immun. 2002 Nov;70(11):5931-7
references.pmid: 12379667
references.citation: J Med Internet Res. 2013;15(8):e166
references.pmid: 23968998
references.citation: BMJ. 2013;347:f6650
references.pmid: 24270505
references.citation: Am J Epidemiol. 2010 Jun 1;171(11):1225-32
references.pmid: 20406760
references.citation: Am J Respir Crit Care Med. 2005 Jul 15;172(2):173-82
references.pmid: 15879416
references.citation: J Med Internet Res. 2008;10(3):e22
references.pmid: 18725354
references.citation: Genome Med. 2011 Jul 06;3(7):43
references.pmid: 21745417
references.citation: Mol Syst Biol. 2012;8:594
references.pmid: 22806142
references.citation: Nat Genet. 2013 May;45(5):468-9
references.pmid: 23619782
references.citation: BMC Syst Biol. 2011;5:4
references.pmid: 21214945
references.citation: Phys Rev Lett. 2005 Apr 1;94(12):128701
references.pmid: 15903968
references.citation: Sci Transl Med. 2011 Aug 17;3(96):96ra77
references.pmid: 21849665
references.citation: Crit Care Med. 2002 May;30(5 Suppl):S180-5
references.pmid: 12004233
references.citation: Horm Behav. 2003 Jan;43(1):2-15
references.pmid: 12614627
references.citation: Mol Syst Biol. 2007;3:82
references.pmid: 17299418
references.citation: Nature. 2012 Nov 8;491(7423):183-5
references.pmid: 23135449
references.citation: J Med Internet Res. 2011;13(1):e24
references.pmid: 21447469
references.citation: BMJ. 2013;346:f2350
references.pmid: 23692896
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D216-21
references.pmid: 22080514
references.citation: Nature. 2002 Nov 14;420(6912):246-51
references.pmid: 12432410
references.citation: BMC Bioinformatics. 2009;10 Suppl 2:S14
references.pmid: 19208189
references.citation: Cell. 2013 Apr 25;153(3):707-20
references.pmid: 23622250
references.citation: Acta Cardiol. 2008 Dec;63(6):741-7
references.pmid: 19157170
references.citation: Nat Rev Genet. 2012 Jun;13(6):395-405
references.pmid: 22549152
references.citation: Hist Philos Life Sci. 2011;33(4):477-96
references.pmid: 22662506