PERSPECTIVE Forreprintorderspleasecontactreprints@futuremedicine.com Towards a framework for personalized healthcare lessons learned from the field of rare diseases A large percentage of medicines do not work for the patient populations they are intended to treat. Increased knowledge regarding genomics and the underlying biological mechanism of diseases should help us be able to stratify patients into groups of likely responders and nonresponders, and to identify those patients for whom a treatment might do more harm than good. This article sets out different policy perspectives for the healthcare systems, and draws in on 25 years of particular experience from the rare disease and orphan drug field, to illuminate the pathway forward in relation to key implementation aspects of personalized healthcare. In principle, we submit that targeting medicines to preidentified groups for whom we can predict a beneficial outcome is a good thing for everyone- first of all for the patients, but also for all the other stakeholders, including payers, treating physicians and industry- because it has the potential to create sustainable and functioning healthcare systems directed to better health and prevention of disease. Personalized healthcare over time could also lead to shorter drug-development times because of lower rates of failure in late-stage drug development. Using orphan medicines to treat well-diagnosed patients suffering from a life-threatening or seriously debilitating rare disease, is an attempt to work according to these principles. As there is much that needs to be done to turn the promise into reality, we need to identify the barriers and challenges to transform the potential opportunities into real-life benefits, and what needs to be done in order to overcome them. Learning from the field of rare diseases and orphan drugs may provide, perhaps unexpectedly, some of the answers to public policy questions related to future (personalized) healthcare, but of course not all aspects, are common between the two fields KEYWORDS: biomarkers business models diagnostic testing education ethics Erik Tambuyzer incentives multistakeholder collaboration orphan drugs patients outcomes personalized healthcare pharmacogenomics rare diseases registries atem, Belgium regulatory framework Some form of personalized healthcare has been personalized'therapies. Society in Europe practiced since the dawn of modern medicine. across stakeholders, seems to broadly embrace The concept of personalized healthcare today, personalized healthcare across different stake- however, is something very different, and its holders, as proven by a survey done in central emergence is based on the development of the Europe [1o1]. The new findings may be used, for fields of life sciences and genomics. It is tar- example, to facilitate clinical translation and geted at the genetic and biological make-up of subsequent availability of beneficial drugs by the individual, or groups of individuals. This stratifying patient populations during clinical paradigm shift in science has created a much trials, and by using input by the patients on logical mechanisms of discase nding of the bio- quality of life, to guide clinical development more comprehensive understan and the lucida- of a product. This would increase the likeli tion of the genome and of epigenome is still hood of showing benefit and, subsequently ongoing. In turn, this has led, and still leads, allows the physician to use patient-specific to a better understanding of a larger number diagnostic information to guide the choice of of life-threatening or seriously debilitating rare therapy most likely to benefit that patient, if diseases, for which treatments are being devel- the right biomarker can be identified early in oped. Such treatments are called "orphan drugs, the development phase. The benefits of such a as they had no 'sponsoring parents' in the past targeted approach are multiple but would have to develop them. an impact on the entire healthcare framework The new scientific findings provide an from patients to industry; and from academic opportunity for stakeholders across the health- researchers to payers. It has the potential to care spectrum to move towards the develop- move us away from the current trial-and re ment,use and reimbursement of targeted or error' paradigm of medicine -depending on edicine fsg 10.2217/PME 10.52@ 2010 Future Medicine Ltd Personalized Medicine(2010)7(5), 569-586 ssN1741-0541 569Towards a framework for personalized healthcare: lessons learned from the field of rare diseases Some form of personalized healthcare has been practiced since the dawn of modern medicine. The concept of personalized healthcare today, however, is something very different, and its emergence is based on the development of the fields of life sciences and genomics. It is tar￾geted at the genetic and biological make-up of the individual, or groups of individuals. This paradigm shift in science has created a much more comprehensive understanding of the bio￾logical mechanisms of disease, and the elucida￾tion of the genome and of epigenome is still ongoing. In turn, this has led, and still leads, to a better understanding of a larger number of life-threatening or seriously debilitating rare diseases, for which treatments are being devel￾oped. Such treatments are called ‘orphan drugs’, as they had no ‘sponsoring parents’ in the past to develop them. The new scientific findings provide an opportunity for stakeholders across the health￾care spectrum to move towards the develop￾ment, use and reimbursement of targeted or ‘personalized’ therapies. Society in Europe, across stakeholders, seems to broadly embrace personalized healthcare across different stake￾holders, as proven by a survey done in central Europe [101]. The new findings may be used, for example, to facilitate clinical translation and subsequent availability of beneficial drugs by stratifying patient populations during clinical trials, and by using input by the patients on quality of life, to guide clinical development of a product. This would increase the likeli￾hood of showing benefit and, subsequently allows the physician to use patient-specific diagnostic information to guide the choice of therapy most likely to benefit that patient, if the right biomarker can be identified early in the development phase. The benefits of such a targeted approach are multiple but would have an impact on the entire healthcare framework, from patients to industry; and from academic researchers to payers. It has the potential to move us away from the current ‘trial-and￾error’ paradigm of medicine – depending on A large percentage of medicines do not work for the patient populations they are intended to treat. Increased knowledge regarding genomics and the underlying biological mechanism of diseases should help us be able to stratify patients into groups of likely responders and nonresponders, and to identify those patients for whom a treatment might do more harm than good. This article sets out different policy perspectives for the healthcare systems, and draws in on 25 years of particular experience from the rare disease and orphan drug field, to illuminate the pathway forward in relation to key implementation aspects of personalized healthcare. In principle, we submit that targeting medicines to preidentified groups for whom we can predict a beneficial outcome is a good thing for everyone – first of all for the patients, but also for all the other stakeholders, including payers, treating physicians and industry – because it has the potential to create sustainable and functioning healthcare systems directed to better health and prevention of disease. Personalized healthcare over time could also lead to shorter drug-development times because of lower rates of failure in late-stage drug development. Using orphan medicines to treat well-diagnosed patients suffering from a life-threatening or seriously debilitating rare disease, is an attempt to work according to these principles. As there is much that needs to be done to turn the promise into reality, we need to identify the barriers and challenges to transform the potential opportunities into real-life benefits, and what needs to be done in order to overcome them. Learning from the field of rare diseases and orphan drugs may provide, perhaps unexpectedly, some of the answers to public policy questions related to future (personalized) healthcare, but of course not all aspects, are common between the two fields. KEYWORDS: biomarkers n business models n diagnostic testing n education n ethics n incentives n multistakeholder collaboration n orphan drugs n patients outcomes n personalized healthcare n pharmacogenomics n rare diseases n registries n regulatory framework Erik Tambuyzer Genzyme Belgium NV/SA, 53 Ikaroslaan, Zaventem, Belgium Tel.: +32 2714 1740 Fax: +32 2714 1747 erik.tambuyzer@genzyme.com 569 Review 10.2217/PME.10.52 © 2010 Future Medicine Ltd Personalized Medicine (2010) 7(5), 569–586 ISSN 1741-0541 Perspective For reprint orders, please contact: reprints@futuremedicine.com