Lessons learned from the field of rare diseases PERSPECTIVE nd not face another wave of increasing regulatory if this is not always culturally easy (9.11,1231 costs by nonharmonization, which would make Whether a company is owning or developing innovative products even more costly to develop. its own diagnostics business or not, is a com Furthermore, some of the questions of what is pany-specific choice. This may not dramatically ethically allowedin research and clinical trials, influence its ability to be successful in person- including about predictive genetic testing, are not alized healthcare, as long as the understand- yet fully answered in society: there is not yet ethi- ing of the link with diagnostic testing is there al agreement on all aspects of what should be More importantly, companies will need to adapt allowed and what would be socially unacceptable. from purely supplying a product to providing a Many issues that came up in genetics research full service to the patient, and to making sure or in the application of genetic testing in medi- that a full service is in place to guarantee the cal practice, such as the right of the individual best possible patient outcomes. By contrast patients-to know or not to know the result of a personalized healthcare may have far-reaching particular test for a severe disease-are amplified and significant structural implications on the if used more broadly. In addition, personalized healthcare industry and on its business models, healthcare may also bring up some ethical issues and have profound effects on healthcare systems lated to gender overall. Some traditional pharmaceutical com- Such barriers are amplified because of the panies may encounter a great deal of trouble volume of information gathered in the research evolving their business model away from a core and development phase, and by potential lack competency of selling drugs that only work for of a system to allow effective management and a portion of treated patients using broad-based new approach become ethical issues, for example, the lack of face difficulties in including existing drugs sufficient quality assurance in genetic testing a personalized healthcare approach to optimize would be an ethical issue. Key to this is the their value, rather than hoping that their sales standardization of collection processes, quality of will not falter and that regulatory bodies will samples, full annotation(clinical, demographic not require new data to allow their further use and so on)of those biological samples and ready For all of this to materialize, it is clear that a access by investigators in both the public and pri- company needs to be willing to plan for the vate sectors. The further development of person- long view, and not expect quick results but for alized healthcare will also require a societal out- a pharmaceutical company used to working on reach component, which will need a collaborative development timelines in the order of 12 years, effort with all involved stakeholders this should not be an impossible requ The growing interest of industry in the field of A company should be prepared for sustained are diseases is not only a consequence of the need engagement with the patient groups, treating for diversification after the research and devel- physicians as well as other stakeholders. The field opment machine stalled. It is also because only of rare diseases and orphan drugs is a valuable 10-20%of rare diseases have some kind of treat- and appropriate model for such engagement, and ment today (n1o), and those treatments can still be these elements are a prerequisite for sustained improved, thus the medical need remains high. activity in the field However, even more important is that rare dis- Some believe that those companies that are eases as researched as models for more common slower to develop personalized targeted thera diseases in a different field, such as oncology, neu- pies risk losing substantial market share[12]. It is, rology, autoimmune and infectious diseases, and however, in society's best interest that companies provide a pathway to explore personalized medi- that adapt can be sure of an appropriate return cine because of the many commonalities between on investment. By giving much more predictable the fields [1101, or help identify molecularly dis- treatment outcomes, it is also expected that per- tinct subtypes of some common diseases, which sonalized healthcare will have a beneficial effect may lead to new therapeutic possibilities [31 image, if the industry can stay away from hyping the concept and advo cate true a Changing business models patient value. in industry At the same time, the premise that, in a future Despite industry's changing role, companies will dominated by personalized healthcare, there will need to change their view of a market that is no longer be 'blockbusters, is wrong-if we moving towards personalized healthcare, even low the commonly used definition of blockbuster w. futuremedicine cor 577Perrsppective Tambuyzer Tambuyzer and not face another wave of increasing regulatory costs by nonharmonization, which would make innovative products even more costly to develop. Furthermore, some of the questions of what is ‘ethically allowed’ in research and clinical trials, including about predictive genetic testing, are not yet fully answered in society: there is not yet ethi￾cal agreement on all aspects of what should be allowed and what would be socially unacceptable. Many issues that came up in genetics research or in the application of genetic testing in medi￾cal practice, such as the right of the individual patients – to know or not to know the result of a particular test for a severe disease – are amplified if used more broadly. In addition, personalized healthcare may also bring up some ethical issues related to gender or race. Such barriers are amplified because of the volume of information gathered in the research and development phase, and by potential lack of a system to allow effective management and interrogation of all that information internally. Without rigorous processes, process issues may become ethical issues, for example, the lack of sufficient quality assurance in genetic testing would be an ethical issue. Key to this is the standardization of collection processes, quality of samples, full annotation (clinical, demographic and so on) of those biological samples and ready access by investigators in both the public and pri￾vate sectors. The further development of person￾alized healthcare will also require a societal out￾reach component, which will need a collaborative effort with all involved stakeholders. The growing interest of industry in the field of rare diseases is not only a consequence of the need for diversification after the research and devel￾opment machine stalled. It is also because only 10–20% of rare diseases have some kind of treat￾ment today [110], and those treatments can still be improved, thus the medical need remains high. However, even more important is that rare dis￾eases as researched as models for more common diseases in a different field, such as oncology, neu￾rology, autoimmune and infectious diseases, and provide a pathway to explore personalized medi￾cine because of the many commonalities between the fields [110], or help identify molecularly dis￾tinct subtypes of some common diseases, which may lead to new therapeutic possibilities [3]. „ Changing business models in industry Despite industry’s changing role, companies will need to change their view of a market that is moving towards personalized healthcare, even if this is not always culturally easy [9,11,123]. Whether a company is owning or developing its own diagnostics business or not, is a com￾pany-specific choice. This may not dramatically influence its ability to be successful in person￾alized healthcare, as long as the understand￾ing of the link with diagnostic testing is there. More importantly, companies will need to adapt from purely supplying a product to providing a full service to the patient, and to making sure that a full service is in place to guarantee the best possible patient outcomes. By contrast, personalized healthcare may have far-reaching and significant structural implications on the healthcare industry and on its business models, and have profound effects on healthcare systems overall. Some traditional pharmaceutical com￾panies may encounter a great deal of trouble evolving their business model away from a core competency of selling drugs that only work for a portion of treated patients using broad-based sales and marketing teams, to a new approach targeting smaller populations. They may also face difficulties in including existing drugs in a personalized healthcare approach to optimize their value, rather than hoping that their sales will not falter and that regulatory bodies will not require new data to allow their further use. For all of this to materialize, it is clear that a company needs to be willing to plan for ‘the long view’, and not expect quick results but for a pharmaceutical company used to working on development timelines in the order of 12 years, this should not be an impossible requirement. A company should be prepared for sustained engagement with the patient groups, treating physicians as well as other stakeholders. The field of rare diseases and orphan drugs is a valuable and appropriate model for such engagement, and these elements are a prerequisite for sustained activity in the field. Some believe that those companies that are slower to develop personalized targeted thera￾pies risk losing substantial market share [12]. It is, however, in society’s best interest that companies that adapt can be sure of an appropriate return on investment. By giving much more predictable treatment outcomes, it is also expected that per￾sonalized healthcare will have a beneficial effect on the industry’s image, if the industry can stay away from hyping the concept and advocate true patient value. At the same time, the premise that, in a future dominated by personalized healthcare, there will no longer be ‘blockbusters’, is wrong – if we fol￾low the commonly used definition of blockbuster future science group www.futuremedicine.com 577 Lessons learned from the field of rare diseases Perspective