Lawyers, judges, and courts monitoring and enforcing obedience to laws and rules How is this group defined? This group involves all legal professional as far as they are concerned with any aspects of personalised medicine. This includes lawyers supporting law makers in parliament to encode political decisions into the “legalise” of laws and executive orders. Also the many lawyers involved in writing and interpreting regulatory rules for hospitals, health care providers and insurers are part of that group. And last, not least, the attorneys and judges dealing with health care claims in courts, when rules seem to have been broken or parties cannot agree on terms of settlement for whatever disagreements they might have.  What are the major roles of this group in personalised medicine? Especially the lawyers actually writing the laws and providing the guidelines for interpretation and application are at the forefront of determining the impact on personalised medicine. After all this is the codex everything else is held to defining the space and boundaries of potential actions. About equally important is how the courts and judges interpret these rules in their decisions and rulings of individual cases.  What is the major impact of this group on the development of personalised medicine? There are two almost equally important fields directly influenced and controlled by laws and lawyers. The first is of course, which methods can be used for personalised medicine. Hot topics here would be gene editing (somatic and/or germline) and any therapeutic approach based on stem cells, again somatic and or embryonic. Currently, there is a general tendency to avoid germline or embryonic stem cells. Any changes made at these critical tissues would not only affect the treated individual but all children and further generations. It is hardly possible to even estimate the long-term effects of such interventions. The second part concerns data protection and is of vital interest to all developments in medicine and especially personalised medicine. Of course, nobody really wants to make all medical data publicly available (except for special interest groups, who still would object on a personal basis). On the other hand without access (controlled and anonymised) we will never find out whether a new treatment worked or did not help or even harmed the patient. Of course, a general argument is that everybody can decide on this on their own. However, in reality most people just follow the defaults set by the laws. If these are biased towards NOT-sharing then getting the required data for the development of personalised medicine becomes an uphill battle. Opt-in or opt-out make a huge difference! Fig. 33 Legal professionsWith whom has this group the most important interactions? Funny enough NOT with the people most affected by their work, except when representing plaintiffs suing some doctors, hospitals, or insurances. Most of the ground work is being done in direct contact with politicians or large organisations of health care providers or insurers.  What is required of this group to further the development and application of personalised medicine? Well, first of all a profound level of information about personalised medicine at least on a layman’s level would be a great complement to all their legal expertise. This would help them to understand early on where laws and rules contain impractical or outright impairing sections that should be revised immediately. In my opinion lawyers involved in any part of legal conduct (law making, law enforcing, legal challenges) pertinent to personalised medicine should give and seek feedback from scientific and medical experts in the field. This might help to mitigate a lot of tensions before they end up in court.   What’s coming up next? Next week it’s time to have a look at politicians, the guys officially responsible to turn their voters wishes into politics. ​

Members of ethical committees I will restrict this entry to the German National Ethics committee which includes 26 members. These members are selected to represent life sciences, medicine, theology, philosophy, ethics, social and economic affairs as well as the legal part. Members are appointed for four year terms and can be once reappointed.  How is this group defined? These are experts, usually at the professor level at universities, who meet once per month and hold a yearly meeting. The German Ethics Committee is dealing with all aspects of ethical concerns not just personalised medicine. Topics include anonymous baby deposits at institutions, human bio-banking, genetic diagnostics, cost-return considerations in heath care, preimplantation diagnostics, as well as dementia and self-determination. Many of these topics are relevant for personalised medicine. What are the major roles of this group in personalized medicine? The German Ethics Committee advises politics and defines measures of value for personalised medicine treatments. Finally, such measures are also yardsticks for the amount of reimbursement by health care providers / insurers. Distinguishing the technical possible from the ethical desirable is also a task of the German Ethics Committee. The committee serves a dual role: it is a discussion forum to shape opinions but also serves as an advisory board for ethical and legal considerations. What is the major impact of this group on the development of personalized medicine? The cost-return question becomes quickly relevant when treatments of life-threatening (and usually deadly) tumours are considered. Implicit is the thorny question how much monetary value is assigned to a day/month/year of prolonged life for a patient. When does the interest of the community / society prevail who simply cannot pay the most costly treatments for everybody. And when does the personal interest of the patient prevail? These are only a few of the questions pondered in the German Ethics Committee.   Fig 32 German Ethics Committee With whom has this group the most important interactions? The recommendations of the German Ethics Committee influence politics and thus subsequently also the reimbursement policies of the health insurers. However, there is a multitude of local ethics committees at hospitals, churches or social institutions that all rely on the guidelines of the German Ethics Committee. In turn they also influence these guidelines by sending members to the Ethics Committee. What is required of this group to further the development and application of personalized medicine? Ethical and economic considerations are rarely in agreement. This creates a permanent zone of conflict for the German Ethics Committee which requires the constant negotiation of compromises of all sorts. Biomedical technology continues to open new doors and opportunities for personalised medicine. In response the Ethics Committee needs to incorporate such progress into its guidelines and recommendations. If this can be done in a timely manner, progress of personalised medicine can continue at the pace of discoveries. The Ethics committee is one of the pacemakers for the legal framework within which personalised medicine is working.   What’s coming up next? Next week I will briefly highlight the involvement of lawyers and other legal professionals, who get always involved as soon as there is a dispute to settle.​

Data protection officers in Hospitals and at companies Molecular medical data are really valuable as they allow far-reaching conclusion about a patient. This is important and necessary for MDs and hospitals to determine the best treatment regimes for patients. However, it can clash with our basic ethical common sense when used by employers or insurance companies. In a positive sense to select the best fit for jobs and insurance policies. In a negative view, to discriminate against the less fortunate people. Data protection laws and officers are there to prevent this kind of data abuse and control the compliance with the laws.  How is this group defined? Data protection officers (in Germany) need to be independent and free of conflicts of interest. There is no special education for the job, but data protection officers are required to know about the basics of pertinent laws. This can be some ordeal given the complicated data protection laws on national and international level. On top of that a variety of institutions and committees is also involved in ensuring that data protection laws are applied properly. Data protection officers can be part of a company or institution or being hired as externals.  What are the major roles of this group in personalized medicine? The main job of a data protection officer is to monitor procedures and data protection measures for compliance with the pertinent laws. In personalized medicine this can lead to some conflicts as to stringent data protection might actually impair use of the data even if it would be beneficial for the patients. However, the laws restrict the options of data protection officers and they have to stay within these limits regardless of the consequences.  What is the major impact of this group on the development of personalized medicine? Data protection officers represent the first line of defence against data abuse and thus are directly aware of application and consequences of data protection laws. They could take an active role to initiate amendments of pertinent laws taking the special requirements of personalized medicine into account. This could facilitate the advance of research and treatment schemes significantly.  Fig 31 Data protection officersWith whom has this group the most important interactions? By definition this includes everybody involved in processing of personal data in industry, agencies, or surgeries of MDs. This also includes the executives responsible for setting up and directing all pertinent procedures. Direct contact to politics is usually restricted to federal or state data protection officers, who are not in direct contact with the field application due to their jobs priorities. What is required of this group to further the development and application of personalized medicine? Preventing unauthorised access to personal data is the main job of data protection officers. However, they also should ensure that principally authorised people can access the data. This usually requires an explicit written consent from patients. This scheme becomes ridiculous in cases where not giving the consent results in no treatment at all. Somebody contacting an MD to be cured basically has already given consent to use their medical data to help them. Data protection officers could aim at defining an internal circle automatically authorised and seal off only outsiders not involved in the treatment.  What’s coming up next? Next week I will briefly describe the role of ethical committees. Their job is to ensure that treatments but especially research stays within the ethical limits our society has defined. ​

Scientists in academia (universities and public research institutes) and industry Scientists are seen quite differently depending on the views and beliefs of the groups a person belongs to. This ranges from evil heretics (in the mind of religious fundamentalists) to wasters of public money (by the ultraconservative right-wings) to problem-solvers for pragmatic people all the way to being seen as ivory-tower thinkers entirely detached from the world down below. None of these views is entirely correct but except for the far extremes on both sides individual scientists fitting the bill can be found for everything. How is this group defined? Scientists are very inhomogeneous and I will focus mainly on these that have the greatest connection with personalised medicine, i.e. life sciences in bio-medical research. This includes both MDs in research as well as biologists, biochemists, chemists, bioinformaticians, and computer scientists.  What are the major roles of this group in personalized medicine? There are three major columns of research important for medicine in general and personalised medicine in particular: Discovery of health and disease mechanisms, discovery and testing of new compounds and drug candidates, devising and scaling up of production methods for promising new drugs. All three are the realm of the scientists mentioned above.  What is the major impact of this group on the development of personalized medicine? Scientists are the driving force behind the acquisition of new, especially molecular, knowledge about how our organism works. They also represent the spearhead of cutting-edge developments in the pharma-industry and the rather recent biotech-industry. Scientific discoveries almost invariable come at a significant cost for research. They may later on actually help to save not only lives but also money. The big problem for investors is the imbalance between the rocksolid reality of the upfront costs involved and the “maybe” for the return off investment later on. However, discoveries cannot be guaranteed to yield financial gains. There is always the risk to fail, which on the other hand is the only way to learn. Nobody learns from success but keeps repeating the same scheme over and over again - till it fails.  Fig. 30 Life science scientists With whom has this group the most important interactions? Scientists heavily interact with other scientists in a mixture between competition and cooperation driving scientific developments. The home of the “pure” researchers is usually a university or a research institute (governmental or private) not aiming for profit. The more applied researchers can be found in the biotech and pharma-industry. Their work is always under financial scrutiny by the managements of these companies looking for short-term return of investment. Scientists are also called on by other stake-holders such as politicians and governments to testify as experts in political discussions, usually with rather limited impact. Especially bio-medical research is often brushing with ethical considerations. This is why scientists (at least in Germany) always need ethics committees to approve of their planned research upfront.  What is required of this group to further the development and application of personalized medicine? Scientists are pivotal to develop and shape the basic paradigms used to further medicine and biomedical research and application. For decades the prevalent paradigm was one gene - one function, and one compound - one drug - one disease. Based on recent discoveries (recent going back two decades in this case) the paradigm came under fire. Today we know that this is basically the opposite of what biology really is about. Everything is linked, nothing works in isolation. However, a large fraction of biotech and pharma-industry is still reluctant to abandon that old paradigm mainly for monetary reasons. If multiple components with a variety of effects enter the picture patent issue become much more complicated. This hits the lifeblood of pharma-industry generating high resistance. It is the responsibility of the scientists to convince the industry that biology cannot be adapted to their business models but they will have to adapt those to biological facts. Ignoring this fact will stall biomedical progress and cost lives.   What’s coming up next? Next week we will come to thorny issue - data protection. Seemingly there to protect people from big brother, too rigid data protection may actually harm the very same people it is meant to protect. ​

Economists, trying to calculate a benefit/cost analysis  Any kind  of medicine has to find a balance between cost and benefit for the patient as well as for the society. Personalized medicine is no exception and also has to operate under the same limitations. There is inevitably a clash between ethics and economics as putting a monetary value oil human life or health is clearly difficult decision. Here, I will focus as far as possible on the economics side of the equation, which is difficult enough.  The promise of P4-medicine is to increase health and wellness first hand causing a reduction in treatment costs as a result of avoiding or delaying the onset of diseases. Which illustrates one of the biggest problems in the economics of personalised medicine: Pay now (more) to save later. This concept does not rest well with CEOs of companies, governments, politicians, or health care payers bound to realise any benefits during their current term.  How is this group defined? Basically, there are two subgroups here, the professional economists. Those working at heath care insurers, the government, or large hospital groups, trying to manage health care like an industry. And there are the myriads of involuntary economists such as the practising MDs. They need to make ends meet in their daily practice of financial balancing between effort, expenses, and income.  Many decisions small and far-reaching about the development and deployment of personalised medicine are actually influenced or even dictated by economic considerations.  What are the major roles of this group in personalized medicine? It is difficult to accept seemingly unnecessary expenses for prophylactic measures and test which might pay back decades later. Whoever makes such decision will have to defend the increase in cost now. On the other hand there is little to no chance of reaping in the benefits during their term of professional life. Medicine and personalised medicine are a bit better off in that respect than environmental protection programs. These get very little help from ethical considerations as their effects do not directly influence the health and well-being of the currently living generation. In contrast, personalised medicine’s promises are meant for the currently living generations to be realised in part today (better treatment) or within one generation (decades). In both cases ethics play are much more prominent role. Denying generations to come a heathy environment is much easier to accommodate than denying treatment to a patient TODAY. Economists can only help the development of personalised medicine when they carry out really forward looking modelling. Just looking at the effects on the budgets of the next and the 4 years after that is not enough. We must at least take one generation (about 20-30 years) into account. Only then will savings from preventive programs become tangible. The very best they can do is Pointing out that just accepting the inevitable increase in cost for conventional disease-oriented treatments is short-sighted. Showing the potential of a P4-approach in various scenarios illustrates a viable alternative.  Fig 29 P4-Economics What is the major impact of this group on the development of personalized medicine? The same as the major roles. Development of economic models that show the influence and consequences of various scenarios is necessary. They should emphasise no-change scenarios as well as a number of potential P4-scenarios with different focus. This will provide the numerical basis for politicians and health care insurers upon which to base future-oriented decisions. Any treatment of terminal caner patients prolonging their lives (and thus treatment periods)  by personalised medicine will inevitably increase costs. Under that focus personalised medicine becomes an unbearable cost-driver making its large-scale implementation look like an utopia. That is quite different If the focus is on the balance between preventive measures and money saved later on. Saving come from NOT having to treat the current amount of chronic diseases.  In such cases personalised medicine looks more like the shiny white knight saving not only our heath but our wallets too. Of course, as with any kind of assumption-based modelling the final proof is in the pudding. However, it is easier to convince decision makers if they are at least given some ballpark-numbers considered halfway reliable.  With whom has this group the most important interactions? Money goes around also in health care and wherever money is involved, economists are too. Whether pharmacies fill prescriptions, a MD performs a medical procedure, you enter a hospital or receive a flu-shot. There is always a price tag attached to everything. Hoewever, not getting a flu-shot may also have a steep price attached:  being incapacitated for two or three weeks including the much increased risk in the elderly population for succumbing to the disease. Economists have a major influence on every stakeholder in personalised medicine responsible for shouldering medical costs. Politics (e.g. think of the raging battle about Obamacare), health care insurers as well as their immediate customers. These are not the patients but the hospitals, pharmacies (as selling outlets of the pharma industry) and MDs as these groups are mainly payed. However, economics also plays a role in winning the support of patients or all of us to directly should part of the cost by patient contributions.   What is required of this group to further the development and application of personalized medicine? Trying to get realistic data and prognostic trends regarding the major cost-driving and cost-saving factors in personalised medicine. Then building models that explain the current situation as closely as possible and extrapolate various scenarios. If such models show cost-saving only after several decades, so be it. The main point is to make clear that personalised medicine is not just a costly adventure never paying off financially. I do not believe this pessimistic view to be true and we all will have to rely on economists to illustrate the financial effects of potential scenarios for the future.   What’s coming up next? Next week we will come to one the pillars of innovation in personalised medicine: scientists.​