Clin Chem Lab Med 2015; 53(7): 959–960
Editorial Giuseppe Lippi* and Mario Plebani
Personalized medicine: moving from simple theory to daily practice DOI 10.1515/cclm-2015-0291
The paradigm of “personalized medicine” has gained broad popularity in the past decade due to the fact that convincing evidence was brought that the concept “one fits all” should be overwhelmed by the so-called patient-tailored approach in health care [1, 2]. Although the term personalized medicine is repeated like a mantra in scientific papers, meetings, media, and even the Internet, its exact definition is vague and remains almost unclear for many. A recurrent but rather incomplete definition is “prevention, diagnosis, and therapy of a certain disease according to an individual genetic profile” [3]. Indeed, the complete picture cannot be limited to genomic analysis, wherein mole cular methods that make personalized medicine possible include testing a wide spectrum of biological pathways, thus embracing gene polymorphisms and expression, epigenetics and metabolomics, along with identification of therapies aimed to target molecular mechanisms that are responsible of several human disorders, including cancer [4], cardiovascular disease [5], and systemic infections [6], among others. The current designation proposed by the EU Commission seems more appropriate, wherein personalized medicine is defined as a medical model using molecular profiling for tailoring the right therapeutic strategy for the right person at the right time, and/or to determine the predisposition to disease and/or to deliver timely and targeted prevention. Throughout this ample picture, laboratory diagnostics is seemingly playing a prominent – even predominant – role, which is probably much larger than that of any other branch of science and medicine. Despite the fact that transition from traditional medicine toward personalized health care seems now a virtually unavoidable journey, some important challenges emerge. The leading principle is indeed represented by the convincing awareness of the pivotal role that laboratory professionals should play in translating theory to practice. To assess whether laboratory medicine would be able to help develop innovative diagnostic tools, skill, and guidance about personalized medicine, the joint working
group “Personalized Laboratory Medicine” of the EFLM (European Federation of Clinical Chemistry and Laboratory Medicine) and ESPT (European Society of Pharmacogenomics and Personalised Therapy) has developed and disseminated to 48 laboratories from 18 European countries an interesting questionnaire entitled “Is Laboratory Medicine ready for the era of Personalized Medicine?”, the results of which are published in this issue of Clinical Chemistry and Laboratory Medicine [7]. Encouraging information emerged from the results of this survey, indicating that laboratory professionals not only do acknowledge that personalized medicine may be regarded as an innovative and promising health model, but also that laboratory diagnostics will play an essential role for supporting a widespread implementation of this new approach to health care in the clinical setting. Now, despite the fact that we can probably consider these aspects for granted, it seems necessary to move further and put forward another crucial question, that is, “how should we reach the goal”? There is no single right track, indeed, wherein moving from simple theory to daily practice entails a challenging and multifaceted enterprise, in which many aspects should be considered (Figure 1). First and foremost, the gap between basic research and clinical practice should be narrowed, with identification and validation of biomarkers (or panels of biomarkers) that may realistically generate medical knowledge and be effective to impact on the outcomes (i.e., disability, morbidity, or mortality) [8]. A number of well-designed and large international initiatives are under way, and results are expected to be delivered soon [9]. A second necessary step entails the development of robust and reliable assays that may be able to precisely identify biological patterns associated to (or responsible for) the most prevalent human disorders [10]. Once these basic requirements are fulfilled, we should then overcome the traditional theory of reference ranges, toward a new concept of individual reference values that would allow a more reliable risk prediction in the single patient [11]. Then, the awareness of the increasing importance of personalized medicine should not be regarded as an ending point but as just a beginning, wherein its use should be much broadened
960 Lippi and Plebani: Personalized medicine: moving from simple theory to daily practice Identify biomarkers (or panels of) that may be predictive of disability, morbidity and mortality
Appropriate use of diagnostic resources
Broaden the use of personalized medicine in clinical practice
Development of robust and reliable assays
Moving from longitudinal to individual reference values
Figure 1: Personalized medicine: from theory to practice.
in clinical practice, over the strict boundaries of basic research where it is currently confined [12]. A last but essential aspect in a world with limited resources is the appropriate use of innovative (and often expensive) tools such as genomic, transcriptomics, pharmacogenomics, proteomics, and metabolomics, in order to prevent that precious human and economic resources are dissipated for targeting theory rather than patient-centered practice [13]. As we are entering the era of the so-called direct-to-consumer marketing of personalized medicine [14], in particular the offer over the Internet of direct-to-consumer genetic testing services [15], further considerations should be made. Test relevance and accuracy are still fundamental issues, as emphasized by the decision of the US Food and Drug Administration to ask a direct-to-consumer genetic testing company to stop selling its personal genetic testing kits to consumers owing to significant concerns regarding clinical basis, relevance, and accuracy of results [16]. Therefore, the need for training of physicians and health-care professionals to correctly request and interpret genomic data and to integrate genomic information with the patient’s clinical condition and all other variables in an expert and systematic way should be regarded as additional barriers to broader adoption of personalized medicine [15]. Nevertheless, a simple approach can be applied, entailing the use of the right test, with the right method, at the right time, to the right patient, at the right cost, and for the right outcome [17].
References 1. Plebani M, Lippi G. Personalized (laboratory) medicine: a bridge to the future. Clin Chem Lab Med 2013;51:703–6.
2. Baggio G, Corsini A, Floreani A, Giannini S, Zagonel V. Gender medicine: a task for the third millennium. Clin Chem Lab Med 2013;51:713–27. 3. Carlson B. What the devil is personalized medicine? Biotechnol Healthc 2008;5:17–9. 4. Diamandis EP. Present and future of cancer biomarkers. Clin Chem Lab Med 2014;52:791–4. 5. Völzke H, Schmidt CO, Baumeister SE, Ittermann T, Fung G, Krafczyk-Korth J, et al. Personalized cardiovascular medicine: concepts and methodological considerations. Nat Rev Cardiol 2013;10:308–16. 6. Christaki E, Giamarellos-Bourboulis EJ. The beginning of personalized medicine in sepsis: small steps to a bright future. Clin Genet 2014;86:56–61. 7. Malentacchi F, Mancinia I, Brandslundb I, Vermeerschc P, Schwabd M, Marce J et al. Is laboratory medicine ready for the era of personalized medicine? A survey addressed to laboratory directors of hospitals/academic schools of medicine in Europe. Clin Chem Lab Med 2015;53:981–8. 8. Lippi G, Plebani M. Biomarker research and leading causes of death worldwide: a rather feeble relationship. Clin Chem Lab Med 2013;51:1691–3. 9. Lippi G, Jansen-Duerr P, Viña J, Durrance-Bagale A, Abugessaisa I, Gomez-Cabrero D, et al., on behalf of the FRAILOMIC consortium. Laboratory biomarkers and frailty: presentation of the FRAILOMIC Initiative. Clin Chem Lab Med 2015; doi: 10.1515/cclm-2015-0147. 10. Plebani M. From symptoms to biomarkers: a change of paradigm. Clin Chem Lab Med 2014;52:1513–5. 11. Siest G, Henny J, Gräsbeck R, Wilding P, Petitclerc C, Queraltó JM, et al. The theory of reference values: an unfinished symphony. Clin Chem Lab Med 2013; 51:47–64. 12. Godman B, Finlayson AE, Cheema PK, Zebedin-Brandl E, Gutiérrez-Ibarluzea I, Jones J, et al. Personalizing health care: feasibility and future implications. BMC Med 2013;11:179. 13. Plebani M. Harmonization in laboratory medicine: the complete picture. Clin Chem Lab Med 2013;51:741–51. 14. Plebani M, Laposata M, Lundberg GD. The brain-to-brain loop concept for laboratory testing 40 years after its introduction. Am J Clin Pathol 2011;136:829–33. 15. Morse BL, Kim RB. Is personalized medicine a dream or a reality? Crit Rev Clin Lab Sci 2015;52:1–11. 16. Annas GJ, Elias S. 23andMe and the FDA. N Engl J Med 2014;370:2248–9. 17. Lippi G, Mattiuzzi C. The biomarker paradigm: between diagnostic efficiency and clinical efficacy. Pol Arch Med Wewn. pii: AOP_15_026. [Epub ahead of print 2015 Feb 10]. *Corresponding author: Prof. Giuseppe Lippi, U.O. Diagnostica Ematochimica, Azienda Ospedaliero, Universitaria di Parma, Via Gramsci, 14, 43126 Parma, Italy, Phone: 0039-0521-703050 or 0039-0521-703791, E-mail: [email protected] or [email protected]. http://orcid.org/0000-0001-9523-9054 Mario Plebani: Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy
Copyright of Clinical Chemistry & Laboratory Medicine is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Editorial Giuseppe Lippi* and Mario Plebani
Personalized medicine: moving from simple theory to daily practice DOI 10.1515/cclm-2015-0291
The paradigm of “personalized medicine” has gained broad popularity in the past decade due to the fact that convincing evidence was brought that the concept “one fits all” should be overwhelmed by the so-called patient-tailored approach in health care [1, 2]. Although the term personalized medicine is repeated like a mantra in scientific papers, meetings, media, and even the Internet, its exact definition is vague and remains almost unclear for many. A recurrent but rather incomplete definition is “prevention, diagnosis, and therapy of a certain disease according to an individual genetic profile” [3]. Indeed, the complete picture cannot be limited to genomic analysis, wherein mole cular methods that make personalized medicine possible include testing a wide spectrum of biological pathways, thus embracing gene polymorphisms and expression, epigenetics and metabolomics, along with identification of therapies aimed to target molecular mechanisms that are responsible of several human disorders, including cancer [4], cardiovascular disease [5], and systemic infections [6], among others. The current designation proposed by the EU Commission seems more appropriate, wherein personalized medicine is defined as a medical model using molecular profiling for tailoring the right therapeutic strategy for the right person at the right time, and/or to determine the predisposition to disease and/or to deliver timely and targeted prevention. Throughout this ample picture, laboratory diagnostics is seemingly playing a prominent – even predominant – role, which is probably much larger than that of any other branch of science and medicine. Despite the fact that transition from traditional medicine toward personalized health care seems now a virtually unavoidable journey, some important challenges emerge. The leading principle is indeed represented by the convincing awareness of the pivotal role that laboratory professionals should play in translating theory to practice. To assess whether laboratory medicine would be able to help develop innovative diagnostic tools, skill, and guidance about personalized medicine, the joint working
group “Personalized Laboratory Medicine” of the EFLM (European Federation of Clinical Chemistry and Laboratory Medicine) and ESPT (European Society of Pharmacogenomics and Personalised Therapy) has developed and disseminated to 48 laboratories from 18 European countries an interesting questionnaire entitled “Is Laboratory Medicine ready for the era of Personalized Medicine?”, the results of which are published in this issue of Clinical Chemistry and Laboratory Medicine [7]. Encouraging information emerged from the results of this survey, indicating that laboratory professionals not only do acknowledge that personalized medicine may be regarded as an innovative and promising health model, but also that laboratory diagnostics will play an essential role for supporting a widespread implementation of this new approach to health care in the clinical setting. Now, despite the fact that we can probably consider these aspects for granted, it seems necessary to move further and put forward another crucial question, that is, “how should we reach the goal”? There is no single right track, indeed, wherein moving from simple theory to daily practice entails a challenging and multifaceted enterprise, in which many aspects should be considered (Figure 1). First and foremost, the gap between basic research and clinical practice should be narrowed, with identification and validation of biomarkers (or panels of biomarkers) that may realistically generate medical knowledge and be effective to impact on the outcomes (i.e., disability, morbidity, or mortality) [8]. A number of well-designed and large international initiatives are under way, and results are expected to be delivered soon [9]. A second necessary step entails the development of robust and reliable assays that may be able to precisely identify biological patterns associated to (or responsible for) the most prevalent human disorders [10]. Once these basic requirements are fulfilled, we should then overcome the traditional theory of reference ranges, toward a new concept of individual reference values that would allow a more reliable risk prediction in the single patient [11]. Then, the awareness of the increasing importance of personalized medicine should not be regarded as an ending point but as just a beginning, wherein its use should be much broadened
960 Lippi and Plebani: Personalized medicine: moving from simple theory to daily practice Identify biomarkers (or panels of) that may be predictive of disability, morbidity and mortality
Appropriate use of diagnostic resources
Broaden the use of personalized medicine in clinical practice
Development of robust and reliable assays
Moving from longitudinal to individual reference values
Figure 1: Personalized medicine: from theory to practice.
in clinical practice, over the strict boundaries of basic research where it is currently confined [12]. A last but essential aspect in a world with limited resources is the appropriate use of innovative (and often expensive) tools such as genomic, transcriptomics, pharmacogenomics, proteomics, and metabolomics, in order to prevent that precious human and economic resources are dissipated for targeting theory rather than patient-centered practice [13]. As we are entering the era of the so-called direct-to-consumer marketing of personalized medicine [14], in particular the offer over the Internet of direct-to-consumer genetic testing services [15], further considerations should be made. Test relevance and accuracy are still fundamental issues, as emphasized by the decision of the US Food and Drug Administration to ask a direct-to-consumer genetic testing company to stop selling its personal genetic testing kits to consumers owing to significant concerns regarding clinical basis, relevance, and accuracy of results [16]. Therefore, the need for training of physicians and health-care professionals to correctly request and interpret genomic data and to integrate genomic information with the patient’s clinical condition and all other variables in an expert and systematic way should be regarded as additional barriers to broader adoption of personalized medicine [15]. Nevertheless, a simple approach can be applied, entailing the use of the right test, with the right method, at the right time, to the right patient, at the right cost, and for the right outcome [17].
References 1. Plebani M, Lippi G. Personalized (laboratory) medicine: a bridge to the future. Clin Chem Lab Med 2013;51:703–6.
2. Baggio G, Corsini A, Floreani A, Giannini S, Zagonel V. Gender medicine: a task for the third millennium. Clin Chem Lab Med 2013;51:713–27. 3. Carlson B. What the devil is personalized medicine? Biotechnol Healthc 2008;5:17–9. 4. Diamandis EP. Present and future of cancer biomarkers. Clin Chem Lab Med 2014;52:791–4. 5. Völzke H, Schmidt CO, Baumeister SE, Ittermann T, Fung G, Krafczyk-Korth J, et al. Personalized cardiovascular medicine: concepts and methodological considerations. Nat Rev Cardiol 2013;10:308–16. 6. Christaki E, Giamarellos-Bourboulis EJ. The beginning of personalized medicine in sepsis: small steps to a bright future. Clin Genet 2014;86:56–61. 7. Malentacchi F, Mancinia I, Brandslundb I, Vermeerschc P, Schwabd M, Marce J et al. Is laboratory medicine ready for the era of personalized medicine? A survey addressed to laboratory directors of hospitals/academic schools of medicine in Europe. Clin Chem Lab Med 2015;53:981–8. 8. Lippi G, Plebani M. Biomarker research and leading causes of death worldwide: a rather feeble relationship. Clin Chem Lab Med 2013;51:1691–3. 9. Lippi G, Jansen-Duerr P, Viña J, Durrance-Bagale A, Abugessaisa I, Gomez-Cabrero D, et al., on behalf of the FRAILOMIC consortium. Laboratory biomarkers and frailty: presentation of the FRAILOMIC Initiative. Clin Chem Lab Med 2015; doi: 10.1515/cclm-2015-0147. 10. Plebani M. From symptoms to biomarkers: a change of paradigm. Clin Chem Lab Med 2014;52:1513–5. 11. Siest G, Henny J, Gräsbeck R, Wilding P, Petitclerc C, Queraltó JM, et al. The theory of reference values: an unfinished symphony. Clin Chem Lab Med 2013; 51:47–64. 12. Godman B, Finlayson AE, Cheema PK, Zebedin-Brandl E, Gutiérrez-Ibarluzea I, Jones J, et al. Personalizing health care: feasibility and future implications. BMC Med 2013;11:179. 13. Plebani M. Harmonization in laboratory medicine: the complete picture. Clin Chem Lab Med 2013;51:741–51. 14. Plebani M, Laposata M, Lundberg GD. The brain-to-brain loop concept for laboratory testing 40 years after its introduction. Am J Clin Pathol 2011;136:829–33. 15. Morse BL, Kim RB. Is personalized medicine a dream or a reality? Crit Rev Clin Lab Sci 2015;52:1–11. 16. Annas GJ, Elias S. 23andMe and the FDA. N Engl J Med 2014;370:2248–9. 17. Lippi G, Mattiuzzi C. The biomarker paradigm: between diagnostic efficiency and clinical efficacy. Pol Arch Med Wewn. pii: AOP_15_026. [Epub ahead of print 2015 Feb 10]. *Corresponding author: Prof. Giuseppe Lippi, U.O. Diagnostica Ematochimica, Azienda Ospedaliero, Universitaria di Parma, Via Gramsci, 14, 43126 Parma, Italy, Phone: 0039-0521-703050 or 0039-0521-703791, E-mail: [email protected] or [email protected]. http://orcid.org/0000-0001-9523-9054 Mario Plebani: Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy
Copyright of Clinical Chemistry & Laboratory Medicine is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
