Re-focusing the ethical discourse on personalized medicine: a qualitative interview study with stakeholders in the German healthcare system
© Schleidgen and Marckmann; licensee BioMed Central Ltd. 2013
Received: 1 February 2013
Accepted: 21 May 2013
Published: 24 May 2013
In recent years, personalized medicine (PM) has become a highly regarded line of development in medicine. Yet, it is still a relatively new field. As a consequence, the discussion of its future developments, in particular of its ethical implications, in most cases can only be anticipative. Such anticipative discussions, however, pose several challenges. Nevertheless, they play a crucial role for shaping PM’s further developments. Therefore, it is vital to understand how the ethical discourse on PM is conducted, i.e. on what – empirical and normative – assumptions ethical arguments are based regarding PM’s current and future developments.
To gather this information, we conducted a qualitative interview study with stakeholders in the German health care system. Our purposive sample included 17 representatives of basic research, clinical research, health economics, regulatory authorities, reimbursement institutions, pharmaceutical industry, patient organizations, as well as clinicians and legal experts involved in PM developments or policy making. We used an interview guide with open-ended questions and analyzed transcriptions of the interviews by means of qualitative content analysis.
The respondents addressed a multitude of concerns in the context of research on as well as application of personalized preventive and therapeutic measures both on the individual and on the societal level. Interestingly, regarding future developments of PM the ethical evaluation seemed to follow the rule: the less likely its application, the more problematic a PM measure is assessed. The more likely its application, on the other hand, the less problematic it is evaluated.
The results of our study suggest re-focusing the ethical discourse on PM in Germany towards a constructive ethical monitoring which ensures to include only, nevertheless all of the actual and/or potential concerns that are ethically relevant in order to allow balancing them against the actual and potential ethically relevant benefits of PM measures. To render this possible, we propose a strategy for evaluating ethical concerns in the context of PM.
In recent years, so-called personalized medicine (PM) has become a highly regarded line of development in modern medicine. Basically, this trend results from the overarching goal of PM to develop tailored approaches of prevention and treatment for certain patient subpopulations. The basic concept thereby consists of identifying genetic, phenotypic, or environmental factors, which affect the subpopulation’s health risks and help to find the most appropriate type and dose of medication and/or intervention. In detail, PM promises the following benefits: [1–4] first, it is expected to permit an early identification of persons who carry a genetic or phenotypic variation that increases their risk for developing a certain disease. This would allow preventive measures before disease outbreak. Second, possibilities of better diagnostic and prognostic assessment of diseases are expected resulting in earlier and improved therapeutic interventions. Third, PM is anticipated to develop more effective and safer treatment strategies based on increased knowledge about individual determinants of diseases. Finally, an identification of patient subgroups, which will benefit from a certain therapy, is awaited. This could result in reduced trial and error prescribing with improved effectiveness and efficiency of care.
However, approaches of PM raise several ethical concerns: [1–3, 5–10] first, with regard to research on PM, measures of adequately implementing informed consent for biomarker studies is discussed as well as issues of confidentiality, data protection and the individuals’ right to know/not to know. Furthermore, it is debated how to allocate resources into as well as within different fields of research on PM in ethically justified ways. Second, when looking at the clinical usage of PM measures, concerns are expressed that predictive test results may influence individual well-being negatively, increase individual responsibility for one’s health or lead to (genetic) discrimination of persons with predispositions for certain diseases. As regards personalized diagnostic test results, worries are articulated that individuals with a certain response rate to a drug could be (genetically) discriminated. Moreover, in reference to personalized therapeutic measures, it is suspected that establishing small patient subgroups may lead to insufficient drug testing before their application and thus result in higher risks for patients. Both with regard to personalized prevention and personalized treatment, issues of confidentiality and data protection as well as the individual’s right to know/not to know are discussed. Finally, it is argued that PM measures may lead to significant cost increases and thus result in an additional financial burden for the health care systems. This, it is suspected, could further exacerbate problems of equal access to health care services.
However, PM, understood as biomarker-based targeted treatment or prevention, is still a relatively new field: in Germany, for instance, only 27 drugs are currently authorized for personalized treatment, i.e. their application is based on preceding diagnostic tests on efficacy or (potential) side effects . Meaningful numbers for predictive tests or preventive measures do not exist. Therefore, analysis of PM’s future development, in particular of its opportunities and risks as well as its ethical implications, in most cases can only be anticipatory. Such anticipative discussions, however, pose several challenges, primarily the risks of debating irrelevant ethical concerns or – more importantly – neglecting relevant ones, if debates are not based on a realistic assessment of current and future developments. Nevertheless, such debates play a crucial role for shaping PM’s further developments. Therefore, it is vital to understand how the ethical discourse on PM is conducted, i.e. on what – empirical and normative – assumptions ethical arguments are based regarding PM’s current and future developments. Additionally, it is highly relevant for an adequate ethical monitoring of PM which ethical implications are considered relevant – and which are neglected. Researchers and clinicians who are involved in the development of PM can provide valuable insights both into the current state of development of PM and into the ethical discourse on PM. Furthermore, an examination of ethical concerns requires input from stakeholders of the health care system in which a PM measure is developed and/or used. To gather this important information, we conducted a qualitative interview study with stakeholders in the German health care system.
In detail, the study aimed at answering the following questions: What is the current state of developments of PM? What prospects does PM offer according to the stakeholders’ opinions, i.e. what are the medical areas in which they expect the most significant progress? Which areas are considered less important? What ethical implications of PM are expected, in general and more specifically for the German health care system? The results of this study provide a clearer picture of the perspectives of the rapidly growing field of PM. Moreover, they suggest re-focusing the ethical discourse on PM in Germany, especially regarding a realistic assessment of PM’s current state of development and clinical usage as well as expected future developments.
Participants: professional roles
Basic Research (BR)
Clinical Research (CR)
Health Economics (HE)
Regulatory Authorities (RA)
Reimbursement Institutions (RI)
Pharmaceutical Industry (PI)
Patient Organizations (PO)
Legal Experts (LE)
Data collection and analysis
We conducted semi-structured interviews based on an interview guide with open-ended questions on the stakeholders’ assessments of current trends and developments as well as their expectations and concerns regarding PM. Except for two interviews, which took place at the interviewers’ office, all conversations were carried out at the respective participants’ office. The interviews took about one hour each. All conversations were held between May and July 2011 and conducted in German, consistently by the same interviewer (SS; trained in qualitative methods). They were audio recorded; the interview guide was adapted to the current state of findings at several stages of the study.
In order to render this adaptation possible as well as to determine the point of saturation, data collection and data analysis were carried out simultaneously. The interviews were transcribed and analyzed following the qualitative content analysis according to Mayring  with the software MAXqda. For this purpose, the interview passages relevant to our research questions were identified and coded in order to develop generalizations of the individual statements and conclude overarching categories (Additional file 1). Codes and categories were validated internally (by intercoder consensus) as well as externally (by discussion with experts in the field of qualitative research). As all interviews were conducted in German, the interview passages quoted below are direct translations of the originals. To ensure the least possible bias the passages were translated by an English native speaker.
The results are divided into three sections: first, the stakeholders’ assessments of the current state of research as well as the clinical use of PM measures are presented. The second section depicts the respondents’ expectations regarding future developments of PM. Finally, their ethical concerns are presented.
Current state of PM
Personalized therapeutic interventions
(RI) Momentarily, there is actually nothing that speaks in favor of this being more than just humoralism or something like that. It goes a little further, in that it differs in its biotechnological foundations […], but I initially doubt the whole thing […] for the same reason that basically all other assumptions, which have constituted the basis of a theoretical body with this absoluteness in medicine, turned out to be false.
(RI) This is primarily a propagandistic idea by the pharmaceutical industry, which recognized that one could achieve increasingly higher prices for niche products.
(C) The [classical chemotherapy] is not that much worse in many cases. There is not a large discrepancy and many patients often are too optimistic on what antibodies and modern cancer therapies can achieve. The two only differ by a few months [of survival].
(PO) We also noticed that, conspicuously, the pharmaceutical industry, and this is just a feeling, I do not have any evidence that this is true, is slowing the whole process down. […] One could assume that the pharmaceutical industry thinks along the lines of: well, if we support research efforts then we are risking that the sales volume for substance X will not remain as large because it will be implemented selectively.
Personalized preventive interventions
(PI1) An interesting approach is Alzheimer’s, which when combining all of the available parameters allows one to determine to 95 percent who will suffer from Alzheimer’s at a later point. However, to this day, we do not have the possibility of fighting it in any way. So, we do know a lot about this disease […], but even with all of our molecular understanding, we have no chance of interfering properly or halting this process in any way.
Future perspectives of PM
Personalized therapeutic interventions
(RI) I believe that the whole discussion concerning personalized medicine is experiencing a phase of disillusionment, which is part of the typical cycle that such hypes undergo. I also indeed believe that if it is possible to successfully establish an objective, rational point of view of the actual possibilities, then this disillusionment will increase.
(RA) This medicine, I would say, has a future, a very significant future, however, not within the next two years. In fact, if I take the scientists that are working on this seriously, then this is a process that, according to them, will take about another ten years until one can truly say that this is a secure application of medical findings that are evidence-based and confirmed through research.
(PI2) [W]e will move forward step by step. I believe that we will have more and more therapeutic stratification based on the molecular structure of the body.
(BR) The least we can say is that this process will be a long and enduring one. Nevertheless, I still consider it to be possible and achievable. It has a lot to do with the fact, I think, that we can accumulate and merge knowledge better and thus, bring about new findings […]. I think […] momentarily, we are limited by the fact that each individual scientist who works in their respective field does not possess all of the information needed to create an overall concept.
Personalized preventive interventions
(PI1) However, it would be ideal if we could finally move in the direction of prevention by using biomarkers through certain diagnoses. Not just offering treatment for a disease, but rather avoiding the disease. This would be a vision that one should pursue.
Ethical implications of PM
Personalized therapeutic interventions
(BR) I just heard that if a breast cancer patient is between the age of 35 and 45 then she will, more or less, have no problems receiving a prescription for [Herceptin]. If she is between the age of 55 and 65, then she will have a major problem getting the prescription and, if she is insured with the AOK [major public health insurance provider in Germany], she will most likely not get the prescription at all. So, it is thus calculated what the life of a 65-year old is worth. Is it worth it to possibly have to spend 50,000 Euros annually for the treatment of this patient? […] What does personalized medicine mean for the equal treatment of patients?
In contrast, some stakeholders expressed the opinion that personalized therapies based on stratification may contribute to the solution of existing distributional issues by reducing inefficiencies. Finally, several respondents expressed the fear that stratification may result in additional risks for patients: as clinical studies on personalized therapeutic measures can be carried out with small patient groups only, drugs might be authorized without being sufficiently tested, especially with respect to possible side effects.
Personalized preventive interventions
(HE) A label is established and this label does something to human beings. Basically, the passing on of information is a type of intervention. In the worst case, this leads to fear and low-spirits, depression, and so on.
According to some respondents, this problem is apparent especially in view of possible false-positive prognostic test results.
Research on PM
(BR) One question that continuously consumes us and that, I personally believe, has not been answered satisfactorily, and where parameters have to be set up, is: is it recommendable, from a health economics perspective, to go this way? If we go ahead with stratification and then […] we end up having to wait for the final answer: did he survive or not? Instead, I would prefer to have parameters beforehand so that I can intervene.
(RI) We go so far as to say that progression-free survival is not enough, instead, one needs to be able to have a longer life in good quality.
(RA) Especially with regard to cancer therapies, there is hardly any research that is conducted along the lines of these [patient-relevant] outcomes, but instead they are conducted according to surrogate parameters. […] However, this has nothing to do with the patients’ quality of life.
On the other hand, one respondent expressed the opinion that standards for clinical trials are too demanding. As a consequence, clinical trials would require too much time and effort before therapeutic measures can be launched which, in turn, would lead to an unjustified negative impact on patients that could have benefitted from an earlier introduction. Therefore, standards for clinical trials should be scaled down, even if this results in higher risks for patients.
To summarize, all statements concerning the state of PM can be assigned to either of two categories: (I) “development of PM is in its fledgling stages” (optimistic) or (II) “the approach of PM is unsound” (pessimistic), where there is a clear predominance on part of category (I) (15 of 17 respondents). However, even the optimistic respondents assessed the research state of therapeutic measures much more positively than the state of measures of primary prevention.
A similar picture was drawn regarding future perspectives of PM: On the one hand, some stakeholders were generally pessimistic regarding future developments. On the other hand, however, optimistic assessments, which ascribe great potential to personalized treatment approaches based on stratification, clearly dominate. Nevertheless, most of the optimistic stakeholders assessed future developments of personalized prevention rather pessimistically. A third group of stakeholders felt unable to predict future developments: according to them, the plausibility of PM’s basic idea as well as its additional benefits for patients needs to be proven first in order to render informed predictions possible. In their opinion, PM’s cost impact on the health care system should also be clarified before making forecasts regarding its development.
It has to be noticed, however, that at least some of the assessments of PM’s current and future perspectives seem to follow the respective stakeholder’s interests: one representative of the reimbursement institutions, for instance, assesses PM pessimistically as “a propagandistic idea by the pharmaceutical industry” (interview passage (2)). A representative of patient organizations, on the other hand, grounds his pessimistic evaluation on the suspicion that “the pharmaceutical industry […] is slowing the whole process [of developing PM] down” due to economic considerations (4). Representatives of the pharmaceutical industry, in turn, assess PM, especially its future perspectives, much more optimistic (8), even with regard to personalized prevention (10). These exemplary statements seem to represent the actual competitive situation in the German healthcare system: whereas pharmaceutical companies in recent years increasingly changed their strategy towards development and marketing of PM , patient organizations as well as reimbursement institutions are taking a critical look at exactly these changes.
In contrast to such competitively motivated assessments, it is striking that almost all respondents agreed in exclusively alluding to the field of oncology as regarding future perspectives of therapeutic PM measures. Only one expert additionally referred to personalized approaches of pain management, another explicitly demanded research in medical areas outside oncology. This is remarkable as approaches of PM increasingly are discussed outside oncology . Besides, in Germany several interventions outside oncology are already established, e.g. agents for treating epilepsy, HIV/AIDS or multiple sclerosis . In contrast to such developments, the respondents’ focus suggests that the most significant progress of PM can probably be expected in oncology – and that the development of PM in other medical field might be neglected. A possible reason for this is the fact that PM is a rather heterogeneous field of development and application. As a consequence, the respondents’ focus on oncology is probably due to the specific composition of our sample, i.e. the respondents’ specific working fields and personal interests.
Stakeholders’ ethical concerns by fields of PM
Fields of PM
Clinical Use( Health Care)
Informed Consent for Biomarker Studies
Impact on Individual Well-Being
Higher Risks for Patients
Confidentiality & Data Protection
Confidentiality & Data Protection
Right to Know/Right not to Know
Right to Know/Right not to Know
Study Designs (Patient Relevant Outcomes)
Increased Individual Responsibility for Health
Allocation of Resources
It is of interest that no concerns were mentioned that exclusively arise in the field of PM, but rather issues that are well-known from other contexts, such as biobanking, (conventional) genetic diagnostics, and other fields of biomedical research. Besides, the respondents did neither mention (potential) distributional issues regarding personalized preventive measures nor did they allude to concerns of data protection, right to know/not to know or potential (genetic) discrimination regarding personalized therapeutic measures. Concerning the issues of data protection as well as the right to know/not to know, it is intriguing that another German interview study found that experts in the field of PM pointed exactly to these issues . It is, however, important to realize that the study’s sample (n=19) consisted exclusively of researchers and clinicians involved in the same research group working on PM in the field of colorectal cancer. In contrast, the ratio of researchers (including basic researchers) and clinicians was 5 out of 17 in our sample. This difference in sample composition might explain the different focus of the involved experts regarding ethical concerns in the field of PM. It has to be noticed, however, that the results of the two studies generally are difficult to compare as we used a different methodological approach with open questions and no concrete PM-example as stimulus (the experts in  were asked explicitly about the implications of their own development, the Rectumchip).
Apart from these methodological considerations, it is particularly the neglect of potential discrimination resulting from personalized therapeutic measures that is striking: after all, disadvantages for certain patient subgroups are to be feared as a consequence of secondary information regarding the prognosis and efficacy of treatments gained by diagnostic tests. This becomes clear by analyzing the praxis of applying the agent Trastuzumab (Herceptin®) for treatment of breast cancer. The drug, especially when applied in combination with chemotherapy or as an adjuvant (postoperative) treatment, significantly improves the response rate and the progression-free as well as overall survival rate in patients with an overexpression of the HER2/neu receptor (HER2/neu positive) as compared to HER2/neu negative patients [15–19]. For this reason, in Germany in the year 2000, treatment with Trastuzumab has been tied down to an HER2/neu positive test result . This practice, however, means to categorize breast cancer patients as either “good responders”, “non-responders” or “difficult to treat“, which is at least a potential cause of discrimination: such categorizations eventually result in restricting access for the subpopulations labeled as “non-responder” or “difficult to treat” to health care interventions and health insurances or disadvantaging them in other areas, for instance on the job market [20–23]. As was the case for the respondents’ focus on oncology, a possible reason for their neglect of these issues probably lies in the specific composition of our sample: respondents may had only such agents in mind that are positively connoted (e.g. Imatinib) , while not bearing in mind negatively connoted ones (e.g. Cetuximab) .
In summary, the results of our study show at least two biases in the discourse about PM: first, the respondents’ almost exclusively focus on the field of oncology and second, their neglect of certain ethical concerns. Needless to say, these biases indicate a fundamental problem of the ethical discourse on PM: ethical concerns in many cases apparently do not adequately reflect PM’s current state of research and clinical usage as well as the prognosis of its future developments. This impression also is supported by the fact that, although most respondents assessed future developments of personalized prevention rather pessimistically, they nevertheless located a multitude of potential ethical issues in this context. On the other hand, relatively few concerns were mentioned regarding personalized therapeutic approaches even though their future developments were assessed much more optimistically. As regards future developments of PM the ethical evaluation seems to follow the rule: the less likely its application (i.e. a pessimistic assessment), the more problematic a PM measure is assessed. The more likely its application (i.e. an optimistic assessment), on the other hand, the less problematic it is evaluated. As a consequence, ethical discourse on PM runs the risk of debating (currently) less relevant ethical concerns while neglecting more relevant ones.
Against this background, our findings strongly suggest a re-adjustment of the ethical debate on PM. A constructive ethical monitoring must ensure to include only, nevertheless all of the actual and/or potential concerns that are ethically relevant in order to allow balancing them against the actual and potential ethically relevant benefits of PM measures. This is the only way to ensure an ethical monitoring of PM’s developments and clinical usage, which carves out ethical issues while not, on the other hand, retarding reasonable developments and applications.
Yet, as has been noted above, PM is a rather heterogeneous field of development and application. Therefore, ethically relevant concerns differ decisively with regard to different PM measures. On this account, an overall assessment of PM’s (potential) ethical issues is impossible. Rather, an adequate evaluation strategy requires assessing each personalized approach separately with regard to its actual or potential concerns. Furthermore, it is necessary to re-focus towards more likely fields of application. Consequently, in order to determine ethically relevant concerns of a certain PM intervention, its respective current state of research and clinical usage as well as its expected future developments has to be analyzed and evaluated. It generally holds: the less likely that a PM measure be applied, the less relevant are the concerns associated with it. The more likely that a PM measure be applied, the more relevant are the concerns associated with it. However, the (potential) impact of an ethical concern on individual patients as well as the healthcare system and the society is also important for evaluating its relevance. With respect to this aspect it holds: the less critical a concern associated with a PM measure, the less relevant it is for evaluating the measure. The more critical a concern, the more relevant it is. Needless to say, evaluating a (potential) impact as highly critical may makes is necessary to regard concerns as relevant that are associated with PM measures whose application is unlikely. After all, the quality of an ethical concern may overrule the results of evaluating the current state of research and clinical usage as well as the expected future developments of an PM measure. Thus, the more critical an ethical concern associated with an PM measure is, the less important is the likelihood of the measures’ application for evaluating the concerns’ relevance and vice versa. It is obvious, however, that this criterion again increases the risk of debating irrelevant ethical concerns, either if concerns are evaluated as highly critical which are very unlikely to occur, or if critical concerns are associated with PM measures whose application is very unlikely. In order to avoid such debates, both (potential) ethical concerns and the application of a PM measure have to be plausible to a certain degree in order to qualify a concern as relevant . If this is guaranteed, we claim that ethical concerns should have priority in the ethical discourse according to our criteria of relevance. As none of the potential concerns seems to arise exclusively in the context of PM, they can be approached by referring to standard bioethics debates and applying accordant approaches.
Like in all qualitative research, the empirical results of this study are not representative, but rather dependent on the particular sample underlying the analysis. Consequently, in that the need for a re-accentuation of the ethical discourse on PM is inferred from the empirical results of a qualitative study, it is to be understood as a hypothesis, which has to be supported by further quantitative studies, e.g. on the ethical concerns mentioned by a representative sample of stakeholders in the German healthcare system.
This study was carried out as part of the research project “Personalized Health Care: Ethical, Economic and Legal Implications for the German Health Care System,” funded by the German Federal Ministry of Education and Research (reference number 01GP1006). We would like to thank our fellow colleagues at the Institute of Ethics, History and Theory of Medicine (Ludwig-Maximilians-University Munich), especially Katja Kühlmeyer and Ralf Jox as well as the participants of the research colloquium at the Institute of Ethics, History and Theory of Medicine, Orsolya Friedrich, Julia Lotz, and Tobias Budick for their support with regard to content and methodological matters. Furthermore, we are grateful to Janina Bojahr for transcribing the interview records as well as to Dorothee Wagner von Hoff for translating the interview passages quoted above and proofreading the manuscript.
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