PERSPECTIVE Tambuyzer as'a drug with more than(E or $)I billion in Role value of diagnostic testing les. If the definition of a blockbuster is taken Diagnostics and how to combine them with rather as 'a drug for a large patient population, therapeutics in terms of regulatory approval, then this premise may be more correct, but that clinical use and reimbursement now are looked definition is not the commonly used one for a at in terms of healthcare systems that are setup blockbuster. We do, however, expect the nature to look at standard solutions, for large patient of future blockbusters so-called 'nichebusters', groups, and not for small patient groups. This is to be different. Indeed, the value created by pro- what th e rare orld has bec viding targeted therapies that address the real with, and is only slowly changing unmet medical need is enormous, so some of According to the WHO, much greater use these products will still reach blockbuster sta- of evidence-based diagnostic and treatment tus, while bringing great value to a relatively guidelines by health professionals is needed (102) small patient group. Examples may be a disease- The use of diagnostics to predict individ- odifying treatment in a subset of Alzheimer's ual response to treatment will also offer more patients or in life-threatening cancer indications. safety and effectiveness [14]. The imperative use Regarding the development of diagnostics, the of diagnostic testing in personalized healthcare most optimistic scenario is for those diagnostics applications will require that the physicians are that enhance drug use and appropriate delivery. educated about rigorously using those diagnostic In this case, the company that has developed and testing capabilities and about interpreting their is selling the drug has an incentive to so pro- results to explain them to the patients. If not, vide the diagnostic test(e.g, the case of Roche's this would make personalized medicine fail. Herceptin ). If a therapeutic product requires the The introduction of the diagnostic test may be testing of a candidate population, a pharmaceuti- another layer of complexity but will improve al company will seek (a) partner(s)to develop patient outcomes, make them largely predict- biomarkers, which can hopefully be used as a able and reduc ty for the phy diagnostic test for global use Current healthcare may also be one of the reasons that personalized systems leave diagnostic companies financially medicine will be put into practice in a hospital vulnerable, especially in a case where the com- and specialized medicine setting and, only much pany selling the therapy is not also providing the later to primary care, if ever. This is another diagnostic test. Healthcare systems often reim- commonality with the field of rare diseases that burse testing activity and not the value brought by is also hospital controlled and highly specialized the test [1]. In the end, most probably, the major- Molecular genetic testing - looking for muta ity of pharmaceutical companies will not develop tions in human genes-is used to identify sin- and market tests with in-house resources, but will gle gene(Mendelian) disorders characterized by look for diagnostic companies to do so [13. 1241, this the absence of a critical protein or the presence is an important consideration that needs to be of an abnormal protein. Examples include cystic solved. In fact, that is a very recognizable situation fibrosis, muscular dystrophy, Gaucher's disease for the field of rare diseases nd Huntington disease, although also subsets of Surely not all diseases and approaches will common diseases may fall in this category in the benefit from personalized healthcare? Some future. Many common disorders have a genetic cientists, including Dr Malcolm Law of the component, which may involve several genes, as Wolfson Institute of Preventive Medicine, UK well as interactions of these genes with the envi- dvocate that polypills, a combination of several ronment, diet and lifestyle. The quality of, espe- medicines into one pill, may actually be a better cially genetic, testing has not always been guar- solution, for example, in the cardiovascular field. anteed, but the extensive use of diagnostic tests in This approach is going the other way compared the process will start to put much more emphasis with personalized healthcare [106] Also vaccines on the aspects of quality and quality control of will continue to be important preventative and such tests. Because treating physicians will heavily therapeutic tools in the future. The current rely on reliable diagnostic results, more rules for article is therefore not intended to criticize the quality control and quality assurance as well, and research to discover and develop medicines to diagnostic testing laboratory accreditation, includ- treat broad patient populations. Whatever works ing for genetic testing, are being put in place. In best in practice to treat a disease or a patient Europe, the project Euro Gentest was setup for population should be pursued, and personalized this reason [125]. Patients should be confident that healthcare adds another pathway to achieve that, diagnostic tests reliably give correct results when but will not be the only one used in making major medical decisions [3] 8 Personalized Medicine(2010)7(5)Perrsppective Tambuyzer Tambuyzer as ‘a drug with more than (€ or $) 1 billion in sales’. If the definition of a blockbuster is taken rather as ‘a drug for a large patient population’, then this premise may be more correct, but that definition is not the commonly used one for a blockbuster. We do, however, expect the nature of future blockbusters so-called ‘nichebusters’, to be different. Indeed, the value created by pro￾viding targeted therapies that address the real unmet medical need is enormous, so some of these products will still reach blockbuster sta￾tus, while bringing great value to a relatively small patient group. Examples may be a disease￾modifying treatment in a subset of Alzheimer’s patients or in life-threatening cancer indications. Regarding the development of diagnostics, the most optimistic scenario is for those diagnostics that enhance drug use and appropriate delivery. In this case, the company that has developed and is selling the drug has an incentive to also pro￾vide the diagnostic test (e.g., the case of Roche’s Herceptin®). If a therapeutic product requires the testing of a candidate population, a pharmaceuti￾cal company will seek (a) partner(s) to develop biomarkers, which can hopefully be used as a diagnostic test for global use. Current healthcare systems leave diagnostic companies financially vulnerable, especially in a case where the com￾pany selling the therapy is not also providing the diagnostic test. Healthcare systems often reim￾burse testing activity and not the value brought by the test [11]. In the end, most probably, the major￾ity of pharmaceutical companies will not develop and market tests with in-house resources, but will look for diagnostic companies to do so [13,124], this is an important consideration that needs to be solved. In fact, that is a very recognizable situation for the field of rare diseases. Surely not all diseases and approaches will benefit from personalized healthcare? Some scientists, including Dr Malcolm Law of the Wolfson Institute of Preventive Medicine, UK ,advocate that polypills, a combination of several medicines into one pill, may actually be a better solution, for example, in the cardiovascular field. This approach is going the other way compared with personalized healthcare [106]. Also vaccines will continue to be important preventative and therapeutic tools in the future. The current article is therefore not intended to criticize the research to discover and develop medicines to treat broad patient populations. Whatever works best in practice to treat a disease or a patient population should be pursued, and personalized healthcare adds another pathway to achieve that, but will not be the only one. Role & value of diagnostic testing Diagnostics and how to combine them with therapeutics in terms of regulatory approval, clinical use and reimbursement now are looked at in terms of healthcare systems that are setup to look at standard solutions, for large patient groups, and not for small patient groups. This is what the rare disease world has been confronted with, and is only slowly changing. According to the WHO, much greater use of evidence-based diagnostic and treatment guidelines by health professionals is needed [102]. The use of diagnostics to predict individ￾ual response to treatment will also offer more safety and effectiveness [14]. The imperative use of diagnostic testing in personalized healthcare applications will require that the physicians are educated about rigorously using those diagnostic testing capabilities and about interpreting their results to explain them to the patients. If not, this would make personalized medicine fail. The introduction of the diagnostic test may be another layer of complexity but will improve patient outcomes, make them largely predict￾able and reduce liability for the physician. This may also be one of the reasons that personalized medicine will be put into practice in a hospital and specialized medicine setting and, only much later to primary care, if ever. This is another commonality with the field of rare diseases that is also hospital controlled and highly specialized. Molecular genetic testing – looking for muta￾tions in human genes – is used to identify sin￾gle gene (Mendelian) disorders characterized by the absence of a critical protein or the presence of an abnormal protein. Examples include cystic fibrosis, muscular dystrophy, Gaucher’s disease and Huntington disease, although also subsets of common diseases may fall in this category in the future. Many common disorders have a genetic component, which may involve several genes, as well as interactions of these genes with the envi￾ronment, diet and lifestyle. The quality of, espe￾cially genetic, testing has not always been guar￾anteed, but the extensive use of diagnostic tests in the process will start to put much more emphasis on the aspects of quality and quality control of such tests. Because treating physicians will heavily rely on reliable diagnostic results, more rules for quality control and quality assurance as well, and diagnostic testing laboratory accreditation, includ￾ing for genetic testing, are being put in place. In Europe, the project EuroGentest was setup for this reason [125]. Patients should be confident that diagnostic tests reliably give correct results when used in making major medical decisions [3]. 578 Personalized Medicine (2010) 7(5) future science group Lessons learned from the field of rare diseases Perspective