PERSPECTIVE Tambuyzer the disease treated, between 20 and 75% of As society looks to evolve its public policies the medicines in use today do not seem to work around the emergence of personalized health properly for a broad set of patients [1.2]. The care, it may be useful to examine the approaches WHO estimates that, worldwide, half of all used in the field of rare diseases. Learning from medicines are inappropriately prescribed, dis- this field may provide answers to some of the p pensed or sold, and that half of all patients fail icy questions as the field also features small(er) to take their medicine properly [102]. Therefore, patient populations and rare diseases are fre is in society's best interest to dramatically quently of genetic origin [105]. For that reason, change these numbers for the better. we will discuss herein, from a policy perspective, There are already several examples of this some of these commonalities although not all pproach to personalized medicine [103], but answers will obviously come from this field. the concept is still in its early days, albeit with This article is expanded from a presentation approximately 10% of US FDA-approved On'Commonalities between Personalized med- the potential to grow much larger. Today and Orphan Drugs by Erik Tambuyzer drugs contain pharmacogenomic informa- that was presented at the annual European tion [3]. The potential is also expressed by Forum for Good Clinical Practice(EFGCP) the Pharmacogenomics Working Party of the Conference, January 2010 [1061, and a subse- Committee for Human Medicinal Products at quent presentation by Wills Hughes-Wilson at the European Medicines Agency (EMA)indi- a Europa Bio Workshop on 19 March 2010 [1071 ating in their draft guideline that the high- Apart from a paper in social sciences [5l,we est level of pharmacokinetic polymorphism could not find another paper in the literature lism 1o4).Pharmacokinetics will indicate how medicine, which is quise hat e able In" is found in genes involved in drug metabo- regarding orphan drugs and personalized tration. This process can be affected by genetic similarities in terms of registration and in social factors causing differences in how the drug will and economic impacts, and are regarded both perform, which are called polymorphisms. positively and negatively at the same time Much time is still needed to turn all that new Much lies between the emergey are ce and the knowledge into practical progress. Incentives frequent application of personalized and disincentives for reimbursement and data In many ways, the current healthcare systems exclusivity also need to be addressed. Ethically, are indeed not designed to reward personalized it is also important to ensure that the emer- approaches but to rather favor standardization gence of a more stratified approach to groups of of approaches to patient groups, and there patients does not prematurely deny beneficial fore, a shift towards personalized healthcare treatment to an individual, because knowledge will require a major shift in healthcare systems, is still being added. A good but not yet per- as well as in the business models of research fect combination of a test with a therapy can based pharmaceutical companies. This will indeed inspire health technology assessment also affect the other stakeholders agencies to advice to delay reimbursement While rare diseases and orphan drugs share while the proposed treatment solution could some features with personalized medicine, they already benefit patients immediately. Such an are also different in other aspects. Rare diseases attitude was initially seen from the National may still not be economically interesting, are nstitute for Clinical Excellence(NICE)in the confronted with low awareness and expertise, UK, in the case of Herceptin, but has since and are very heterogeneous. By contrast, per- sonalized healthcare is aimed at subgroups of Of course, the practice of medicine will mostly well-known large patient populations remain part science and part art. Hippocrates often already addressed by the healthcare sys- already recognized that it's far more important tems and with well established infrastructures to know what person the disease has, than what We will mainly discuss the commonalities of disease the person has. Personalized healthcare both in this article. must continue to take some uncertainty of sci- entific results and the realities of human behav- What is personalized healthcare? ior into account, but the margins for uncer- One of the issues with the concept of personalized tainty will be made smaller. Even if sequencing healthcare is that it does not have a universally is 99.9999% accurate, a full genome sequence accepted working definition, which would be the will contain 6000 errors [4] first element to clarify the concept for broader use Personalized Medicine(2010)7(5) future science groupPerrsppective Tambuyzer Tambuyzer the disease treated, between 20 and 75% of the medicines in use today do not seem to work properly for a broad set of patients [1,2]. The WHO estimates that, worldwide, half of all medicines are inappropriately prescribed, dis￾pensed or sold, and that half of all patients fail to take their medicine properly [102]. Therefore, it is in society’s best interest to dramatically change these numbers for the better. There are already several examples of this approach to personalized medicine [103], but the concept is still in its early days, albeit with the potential to grow much larger. Today, approximately 10% of US FDA-approved drugs contain pharmacogenomic informa￾tion [3]. The potential is also expressed by the Pharmacogenomics Working Party of the Committee for Human Medicinal Products at the European Medicines Agency (EMA) indi￾cating in their draft guideline that the high￾est level of pharmacokinetic polymorphism is found in genes involved in drug metabo￾lism [104]. Pharmacokinetics will indicate how the body ‘digests’ a specific drug after adminis￾tration. This process can be affected by genetic factors causing differences in how the drug will perform, which are called polymorphisms. Much time is still needed to turn all that new knowledge into practical progress. Incentives and disincentives for reimbursement and data exclusivity also need to be addressed. Ethically, it is also important to ensure that the emer￾gence of a more stratified approach to groups of patients does not prematurely deny beneficial treatment to an individual, because knowledge is still being added. A good but not yet per￾fect combination of a test with a therapy can indeed inspire health technology assessment agencies to advice to delay reimbursement while the proposed treatment solution could already benefit patients immediately. Such an attitude was initially seen from the National Institute for Clinical Excellence (NICE) in the UK, in the case of Herceptin®, but has since been changed. Of course, the practice of medicine will remain part science and part art. Hippocrates already recognized that ‘it’s far more important to know what person the disease has, than what disease the person has’. Personalized healthcare must continue to take some uncertainty of sci￾entific results and the realities of human behav￾ior into account, but the margins for uncer￾tainty will be made smaller. Even if sequencing is 99.9999% accurate, a full genome sequence will contain 6000 errors [4]. As society looks to evolve its public policies around the emergence of personalized health￾care, it may be useful to examine the approaches used in the field of rare diseases. Learning from this field may provide answers to some of the pol￾icy questions as the field also features small(er) patient populations and rare diseases are fre￾quently of genetic origin [105]. For that reason, we will discuss herein, from a policy perspective, some of these commonalities although not all answers will obviously come from this field. This article is expanded from a presentation on ‘Commonalities between Personalized med￾icine and Orphan Drugs’ by Erik Tambuyzer that was presented at the annual European Forum for Good Clinical Practice (EFGCP) Conference, January 2010 [106], and a subse￾quent presentation by Wills Hughes-Wilson at a EuropaBio Workshop on 19 March 2010 [107]. Apart from a paper in social sciences [5], we could not find another paper in the literature regarding orphan drugs and personalized medicine, which is quite remarkable. In that paper, the conclusion is that there are many similarities in terms of registration and in social and economic impacts, and are regarded both positively and negatively at the same time. Much lies between the emergence and the frequent application of personalized healthcare. In many ways, the current healthcare systems are indeed not designed to reward personalized approaches but to rather favor standardization of approaches to patient groups, and there￾fore, a shift towards personalized healthcare will require a major shift in healthcare systems, as well as in the business models of research￾based pharmaceutical companies. This will also affect the other stakeholders. While rare diseases and orphan drugs share some features with personalized medicine, they are also different in other aspects. Rare diseases may still not be economically interesting, are confronted with low awareness and expertise, and are very heterogeneous. By contrast, per￾sonalized healthcare is aimed at subgroups of mostly well-known large patient populations often already addressed by the healthcare sys￾tems and with well established infrastructures. We will mainly discuss the commonalities of both in this article. What is personalized healthcare? One of the issues with the concept of personalized healthcare is that it does not have a universally accepted working definition, which would be the first element to clarify the concept for broader use 570 Personalized Medicine (2010) 7(5) future science group Lessons learned from the field of rare diseases Perspective