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Journal of Laboratory Medicine

Official Journal of the German Society of Clinical Chemistry and Laboratory Medicine

Editor-in-Chief: Schuff-Werner, Peter

Ed. by Ahmad-Nejad, Parviz / Bidlingmaier, Martin / Bietenbeck, Andreas / Conrad, Karsten / Findeisen, Peter / Fraunberger, Peter / Ghebremedhin, Beniam / Holdenrieder, Stefan / Kiehntopf, Michael / Klein, Hanns-Georg / Kohse, Klaus P. / Kratzsch, Jürgen / Luppa, Peter B. / Meyer, Alexander von / Nebe, Carl Thomas / Orth, Matthias / Röhrig-Herzog, Gabriele / Sack, Ulrich / Steimer, Werner / Weber, Thomas / Wieland, Eberhard / Winter, Christoph / Zettl, Uwe K.


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2567-9449
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Volume 38, Issue 4

Issues

Ethical challenges of whole genome sequencing in translational research and answers by the EURAT-project

Eva C. Winkler / Christoph Schickhardt
Published Online: 2015-04-16 | DOI: https://doi.org/10.1515/labmed-2014-0048

Abstract:

The use of whole genome sequencing in translational research not only holds promise for finding new targeted therapies but also raises several ethical and legal questions. The four main ethical and legal challenges are as follows: (1) the handling of additional or incidental findings stemming from whole genome sequencing in research contexts; (2) the compatibility and balancing of data protection and research that is based on broad data sharing; (3) the responsibility of researchers, particularly of non-physician researchers, working in the field of genome sequencing; and (4) the process of informing and asking patients or research subjects for informed consent to the sequencing of their genome. In this paper, first, these four challenges are illustrated and, second, concrete solutions are proposed, as elaborated by the interdisciplinary Heidelberg EURAT project group, as guidelines for the use of genome sequencing in translation research and therapy in Heidelberg.

Reviewed publication

KleinH.-G.

Keywords: additional findings; data protection and privacy; genome sequencing; informed consent; research

The ethical and legal challenges of genome sequencing

Whole genome sequencing is increasingly being used in medical research, driven by the hope for new insights and rapid technical progress [1]. This is particularly true of cancer research, where genome-wide analyses are used to determine the genetic mutations in tumor tissue as opposed to germline tissue. The aim of such a comparison is to achieve a better understanding of the individual differences from one patient to the next with respect to the progression of illness and the response to treatment in what appears to be the same cancer condition, to identify the mutations that drive tumor growth and/or weaken or prevent the effectiveness of treatment, and last but not least to develop “targeted” therapies in terms of stratified and/or individualized medicine [2].

A key factor behind the enormous dynamic with which genome analyses are employed in medical research and care is the development of sequencing technology and bioinformatics. With almost breath-taking progress and increases in efficiency, the time needed for the complete sequencing of a human genome has been reduced to just a few days, and the costs for each whole genome sequencing have been brought closer to the “$1000 genome” [3].

However, the use of genome-wide analyses is not only interesting in terms of basic research, but is also growing considerably in clinically relevant research [4]. At this point, there is no way yet of knowing with certainty whether this will prevail to such an extent that it will become a routine part of medical care in national health care systems or certain disciplines, such as oncology.

In any case, as its use increases, so does the significance of ethical and legal challenges that are tightly linked to genome sequencing. The main questions being discussed in respect of ethics in Germany and around the world are the following:

  1. How should one handle the (additional) findings from genome sequencing?

  2. How can the protection of privacy rights and data-based research (“data sharing”) be reconciled?

  3. What are the non-physician researchers’ responsibilities in genome research?

  4. What form should the process of informing and obtaining consent from patients and/or research subjects take?

It is these normative questions that are being addressed in Heidelberg by the EURAT project on “Ethical and legal aspects of whole genome sequencing”. It brings together scientists from the University of Heidelberg, including the National Center for Tumor Diseases, the University Hospital, the German Cancer Research Center (DKFZ), the European Molecular Biology Laboratory (EMBL), the Max Planck Institute (MPI) for Comparative Public Law and International Law as well as the Center for Health Economics Research Hanover (CHERH) at the Leibniz University in Hanover. Through this collaborative effort, the project is to find answers to the ethical and legal questions. The solutions already developed were published as a statement in June 2013 and are currently being implemented as “good Heidelberg practices” in the existing local structures by way of a Best Practices guideline [5].

This paper will first introduce the four ethical-legal questions at the center of this issue, and explain them against the backdrop of the current debate in medical ethics. Secondly, potential solutions will then be shown, with the main focus being on the solution approaches from the overall concept of the interdisciplinary EURAT project group in Heidelberg.

A. How should one handle the (additional) findings from genome sequencing?

In genome sequencing, the whole genome of a person is sequenced. Thus, the sequencing data comprise, in theory, all the genetic information about any genetic conditions and dispositions that are relevant to health. However, the interpretation and use of sequencing data as health-relevant “information” is complex for several reasons. In fact, most cases are not about diagnosing an existing illness or condition, but about identifying dispositions for the potential, future occurrence of (mostly multifactorial) illnesses or conditions. Thus, at the center of it is the predictive potential of genome data sets, and this is essentially built on probabilities. In addition to the wide range of penetrance with which a disease occurs, dispositions also differ in terms of expressivity, the chances of therapeutic success prior to the outbreak of a disease (prevention) and after the outbreak (healing) as well as in terms of the severity and risk of a potential disease.

It is against this background that the sequencing of a genome is associated with several, challenging ethical-legal questions concerning the handling, benefit assessment and sharing of genetic “findings” and/or genetic research results. In some parts, this problem is similar to the already known issue of incidental findings [6]. Incidental findings are findings that are obtained by chance when running diagnostics. This happens, e.g., with modern imaging methods, and these incidental findings are increasingly being discussed in medical-ethical literature [7–10]. The new element in the complete sequencing of a human genome is that, even before sequencing the genome, one can and must expect that the sequencing data will reveal a large amount of potentially health-relevant data and information that are outside the primary intended purpose of the scientific or diagnostic study. It is, therefore, appropriate to call them “additional findings” rather than “incidental findings”.

What additional findings may or must be shared with the patient? Additional findings must be assessed in terms of their relevance to the patient, but who is to make this assessment and on the basis of what criteria? A doctor’s assessment as to whether specific information on a disposition helps the patient may deviate from the patient’s own personal benefit assessment. Being a non-expert, how can the patient be involved in decisions on sharing additional findings in advance? In human genetics, the principle of “Explain first, then test” applies [11], but what can and should be explained to the patient who is subject of a genome research project in view of the large number of potential additional findings and their enormous medical complexity? The patient ought to be informed, so that he/she can make informed decisions about his/her right to know or not to know- with respect to additional findings, but at the same time, this represents a considerable challenge.

Furthermore, the genetic properties of a person are not only potentially of interest to the sequenced person, but also his/her close relatives, such as in connection with the family planning prospects of that individual. This raises ethical-legal questions about whether a researcher or doctor is obligated to point out specific risks for relatives of the patient/research subject and for reproduction. What should a doctor do, and what is he/she allowed to do, if a patient refuses to inform a relative about the risk of a potential disposition, which could be treated preventively? What are the patient’s obligations towards his/her relatives, while potentially limiting his/her own health-related privacy, with respect to informing relatives about potential risks?

B. How can the protection of privacy rights and data-based research (“data sharing”) be reconciled?

Genome sequencing generates data. These data can be reproduced and shared. Genetic data and/or the sequenced genome are self-identifying and contain a large reservoir of information about a person the full extent of which is not yet fully known. In research, the data become all the more valuable, the more often they are combined with further data of the same person, such as clinical data on the progression of illness, as well as with genome and clinical data of other persons. For example, in cancer research it is important to create data cohorts of certain entities and subentities that must be as large as possible in order to analyze them for (statistical) correlations and anomalies. To form large and meaningful cohorts, researchers depend on collecting and sharing i data jointly (“data sharing”). Depending on the nature of the research project, this is done at the local, national or international level. To this end, international research consortia have formed, such as the International Cancer Genome Consortium (ICGC), which collect the genome data of tumor patients in many countries and evaluate them jointly from specific perspectives.

Thus, the data are also exchanged in very different legal and cultural environments with a variety of ethical and legal data protection standards. Research on genome data records, apart from an opportunity for new findings, also comes with a slew of ethical-legal issues and risks concerning data protection and privacy [12]. Even though genome data are pseudonymized or anonymized for research purposes, they still remain “self-identifying”. As few as 80 SNPs (single nucleotide polymorphisms – variations of single nucleotides) from a human genome are sufficient to identify the patient as an individual or to assign the entire genome data set to a single individual and determine his/her individual uniqueness. As a result, the study by Gymrek et al. on the re-identification of genome data and their carriers attracted a lot of attention. The authors managed to identify people who had supplied their genome data records anonymously to a public database for research [13]. They only used free information accessible on the Internet, particularly entries in publicly accessible databases used for genealogical research.

The re-identifiability of genomic data, i.e., the possibility of identifying a genome data set and linking it to the donor despite anonymization or pseudonymization, may have far-reaching consequences given the significance of a genome. As already emphasized under item A, the human genome contains a variety of information about the individual, from his/her parentage and family relationships to genetic dispositions and risks for illnesses. Thus, special efforts are necessary to safeguard the confidentiality and protection of the genetic privacy of a person whose genome has been sequenced and is used in research. This essentially requires a weighing of research benefits and the protection of the individual’s privacy (and his/her relatives). These two values are in considerable conflict with each other, because the research benefit of a genome data set is all the greater, the easier it is for researchers (from all over the world) to access and utilize the data. However, easy access increases the risks for the confidentiality of the identity of the genome carrier. The classic rules of data protection, such as data minimization, data separation and purpose limitation (see [14]) are mostly diametrically opposed to the interests of research. Ideally for research, data should be available without filters globally and without access limitations or time limits, while being as open and transparent as possible, nor should they ever be deleted.

C. What are the non-physician researchers’ responsibilities in genome research?

The complex and collaborative procedures of genome sequencing as well as analysis and interpretation of the genetic data obtained are mainly based on the work of non-medical specialists, such as bioinformaticians and molecular biologists. Given their role and specific skills and expertise, these researchers are assigned a new and special responsibility, particularly when it comes to the aforementioned handling of incidental findings and the protection of genetic data.

In the course of their scientific research on data from the sequencing of the human genome, non-medical researchers can learn about the genetic characteristics and dispositions of the patient. First, only they understand this information, and second, this information may be crucial to a patient, such as for his/her ongoing treatment. Is the researcher then obligated to share this information? If he/she does not share the information, does this constitute denial of assistance that is not only morally reprehensible, but also legally relevant? Does the research have a responsibility for communicating certain findings also to the relatives of a patient or test subject? Overall, non-physician researchers, in genome sequencing, move close to the patient and the clinical field, which forces them to confront sensitive questions. Yet, they are not adequately prepared for this, nor are they given institutional guidance. Besides this problem of handling findings, these questions concern, in particular, the aforementioned challenge of data protection.

D. What form should the process of informing and obtaining consent from patients and/or research subjects take?

In order to be allowed to sequence a human genome and use the subsequent genomic data for therapeutic or research purposes, the informed consent of the patient and/or test subject is indispensable both ethically and legally speaking. The concept that the consent of the person affected is an important element in the legal and ethical legitimacy of medical research on people and that, above all, human trials without the voluntary consent of the patient and/or test subject (or his/her representative) are ethically and legally reprehensible and prohibited, goes back to the so-called Nuremberg Code [15]. The statement of voluntary consent to a necessary normative requirement was a lesson drawn from the systematic forced trials on people, primarily prisoners, performed by doctors during the Nazi period. It is natural in this context to see an important function of informed consent in the fundamental protection from coercion and fraud [16]. The World Medical Association adopted the instrument of informed consent in the Declaration of Helsinki [17]. Important reasons in favor of obtaining the prior consent of the individual for genome sequencing also include the (potential) scope of genome sequencing as an intervention in the health-related self-awareness and informational privacy of an individual, as well as the potential implications of such an intervention.

For the correct use of additional findings, it is essential to know the preferences of the patient and to know if he/she wants to exercise his/her right to know or his/her right not to know. The patient should have the opportunity to decide whether, and if so, what additional evidence he/she wishes to learn about through feedback. In the ideal case, thus, a researcher or physician obtaining additional findings already has the patient’s prior consent that memorializes the patient’s preferences with respect to receiving feedback on findings. However an informed and solid consent by the patient requires that the patient have an adequate understanding of the matter. This is what must be conveyed to the patient during the education process. Given the complexity of possible additional findings, the process of informing and obtaining consent is a major challenge [18]. In addition, data protection, among other things, must be discussed. This raises the question of whether and how such issues can be communicated adequately as part of the education process. What consulting effort and what burden for the patient, as well as the educating team of doctors or the research project, are reasonable and necessary to ensure appropriate information?

Solutions proposed by EURAT

Generally, when looking at the four sets of questions mentioned, one must first note that the problems are not all new. Some of them are already familiar from other areas of medicine and medical research [19], and now appear in genome-based medicine under a different label or with new intensity. Second, one must generally observe that the four ethical-legal questions mentioned are closely linked to each other. For example, the question of how researchers are to handle additional findings can be assigned to the area of additional findings as well as to the issue of researchers’ responsibility; it also plays a role in designing the process of information.

The second part of this paper will now present the solutions worked out by EURAT with respect to the problem areas mentioned and published in the “statement” [5] (any mention of EURAT below refers to this statement). The objective of the interdisciplinary EURAT group has always been to work out specific proposals for solutions that could be applied in practice. The close intertwining of the four ethical-legal sets of questions mentioned means that the solutions presented cannot be separated from each other either. Some of them are mutually dependent on each other and must be understood within the framework of the overall concept.

Re A) How should one handle the (additional) findings from genome sequencing?

As for sharing findings obtained from research, there is a wide spectrum of views in the literature. This ranges from the position that all additional findings should be shared to the hypothesis that no additional findings should ever be shared with patients or test subjects [20]. Regarding cancer patients, the EURAT group calls for a differentiation between findings obtained within the context of the specific cancer condition of the patient and those that might be relevant to other conditions (additional findings). Research findings within the cancer context that may be potentially relevant to the treatment or prognosis of the individual cancer should be shared with patients. Whether or not information is medically relevant will be decided by the treating physician. This means that in the context of illness, the prerogative for assessing the situation rests with the physician. In the case of validated cancer-related findings that may be relevant to prevention or treatment, the patient will be contacted. A systematic screening of all data sets for tumor mutations, for which targeted therapies have been developed around the world, is to be developed over the long term and benefits the treatment of the patient.

As for additional findings, i.e., about other (potential) conditions, the EURAT group wants to find a middle ground where the patient’s will takes center stage. EURAT rejects the obligatory sharing of additional findings, as has at times been suggested by the American College of Medical Genetics [21]. Giving feedback without first exploring the patient’s wishes violates his/her right to know and/or not to know. These rights, derived from the fundamental right of the patient to autonomy and informational self-determination, must be respected also in connection with the difficult issue of additional findings. To respect the patient’s right to know or not to know, he/she must be given a chance to decide whether and, if so, which additional findings are to be shared with him/her and which ones are not to be shared. In this way, the patient is treated as an individual with his/her own will and personal, individual preferences.

Finding out the patient’s preferences is an ethical necessity, because determining the benefit of sharing findings with an individual patient is often very difficult. Ongoing social-empirical studies done as part of EURAT at the National Center of Tumor Diseases indicate that benefit assessments of patients vary considerably with respect to dispositions for non-treatable illnesses. Some patients want to know this information in order to plan their lives, while others would rather not burden themselves with knowledge about risks that are completely beyond their control. Just as varied is the way in which they deal with probabilities. Paternalistic attitudes towards the patient and third-party determination of the benefit of any additional findings for individual patients are to be eliminated by allowing the patient to express his/her preferences with respect to the feedback on additional findings, and if these are then respected. However this requires that the patient can form his/her own opinion based on appropriate information and autonomously. Therefore, the process of information and consent must enable the patient in this way, which comes with enormous challenges (see below re D).

As long as genome sequencing is not yet a recognized medical diagnostic procedure, each finding obtained through research, before being shared with the patient, should be validated by means of a certified procedure. In addition, EURAT recommends that additional findings and the sharing thereof should be recorded systematically in order to serve as an empirical basis for evaluation and any improvements to the feedback practice.

Re B): How can the protection of privacy rights and data-based research (“data sharing”) be reconciled?

Regarding privacy, EURAT’s recommendations are geared to the objective of achieving an appropriate and practical balance between the conflicting values of free, transparent and unrestricted research on the one hand, and protection of privacy on the other. EURAT starts with the classification of genetic data as personal data and sees the sensitivity of genetic data in their significance for the carrier and their inherent potential for re-identifiability. EURAT has issued recommendations to non-medical researchers with respect to the protection of genetic data. Nonphysician researchers, due to their professional ethics, have a value-based approach to data that differs from that of physicians. For physicians, confidentiality and the doctor-patient privilege, as well as the handling of patient data as part of their professional secrecy are cornerstones of their normative understanding of their profession. Secrecy and the right to silence are not only self-imposed obligations on doctors, but are also part of the law in Germany and many other legal systems. Researchers, however, tend to be more committed to openness, transparency and lack of restrictions in dealing with data due to their profession and the objective of obtaining scientific knowledge that can be verified by anyone. Where research involves genetic data and other personal patient data, this fundamental attitude of researchers cannot be left untouched. EURAT, therefore, proposes a code for non-physician researchers that contains specific recommendations for protecting the confidentiality of genetic data:

  1. Risk assessment: Prior to any research project, researchers should assess the risk to the confidentiality of data and run a risk-benefit analysis.

  2. Consent and ethics vote: Researchers must ensure that the patient’s consent has been obtained prior to any genome sequencing, as well as the vote or approval of the competent ethics committee. (Researchers can do this also by requiring research partners to submit to them or guarantee the existence of valid patient consent forms.) The use of genome sequencing data is permitted only with the patient’s consent.

  3. Pseudonymization: Only pseudonymized or anonymized data may be used in research. The most effective measure to prevent genomic data being attributed to a person (re-identification) is the – irreversible and definitive – anonymization of data. However, this makes sharing of research findings that may be useful to the patient and any recontacting impossible. As a result, EURAT recommends that all data transferred from the clinical field to research be pseudonymized.

  4. Databases: Genomic and/or genetic data sets (pseudonymized or anonymized) with a potential for re-identification may be shared for research purposes only with databases with controlled and restricted access. These data must not be stored in public databases.

  5. Withdrawal: To allow patients to withdraw their consent to their genomic data being used in research, there must be documentation that tracks the data. If possible, all patient data must then be deleted.

  6. Obligation of active effort: The heads of research facilities must actively ensure that external cooperation partners to whom pseudonymized genomic data are transferred or made available (“data sharing”) comply with ethical-legal guidelines similar to those in the Code when using and handling the data.

  7. DTA and DaCo: Furthermore, the sharing of data with national and international external cooperation partners is to be subject to a Data Transfer Agreement (DTA). Another institutional measure involves an Data Access Committee (DaCo) that deals with issues of data sharing and relevant checks.

Re C) What are the non-physician researchers’ responsibilities in genome research?

The considerations of the EURAT group, which led primarily to a code for non-physician researchers, are based on a few basic observations: a) Non-physician researchers play an essential role in genome sequencing and operate, due to the implications of genome sequencing (additional findings, data protection) and their proximity to the clinical field, in an area that is very sensitive ethically and legally – more so than, e.g., in basic research on animal cells. b) So far, there have not been any specific statutory regulations for research in this field [10]. The German Genetic Diagnostics Act (Section 2 (2) No. 1), e.g., explicitly excludes research from its scope [22]. c) As for norms and standards other than statutory ones, non-medical researchers do not have a general code of professional ethics that is sufficiently relevant to the ethical-legal implications of genome sequencing – unlike physicians, who have a traditional, adaptable and highly codified system of professional ethics. This resulted in d) the conclusion that it would be in the interest of all those involved if the responsibility of researchers in genome sequencing were circumscribed more accurately and documented in specific recommendations for local Heidelberg practices.

A code of conduct seemed the ideal tool and medium for clarifying the responsibilities and obligations of non-medical researchers. One objective behind such a code of conduct was to take a proactive approach to the ethical and legal issues emerging from genome sequencing. It did not seem a desirable alternative to wait for lawmakers to create rules and regulations, nor simply to let things stay as they were (until such statutory rules were introduced), providing no answers to the critical implications requiring clarification.

The intention was to address the “many hands problem” in the complex and highly collaborative process of research in genome sequencing and to provide protection for all – researchers, patients and institutions. The “many hands problem” refers to an organization or structure where different people contribute to a decision or activity, which causes the responsibilities to become blurred [23]. Non-physcian researchers are afforded protection by creating an institutionalized framework with defined responsibilities. It is true that some obligations are imposed on researchers in the process, but at the same time there are explicit and implicit definitions as to what is beyond their duties and responsibilities. Researchers are thus given a framework that guarantees them ethical-legal security and certainty (if they abide by the code of conduct). However, this was and is contingent on the code being recognized and put into effect.

The code of conduct, beyond an ideal or “soft” effect, could unfold specific or “hard” effects if it were made compulsory. When speaking of compulsory, this is to be understood in the way that any violations of the code can have direct consequences in terms of employment, liability or other sanctions. The code of conduct elaborated by EURAT has cleared a successful path towards a specific binding force in only a short amount of time. Even though the EURAT group worked out the code without any official institutional mandate, the code, shortly after its publication, was recognized as generally binding by the medical faculty and, by an official decision of the senate, the University of Heidelberg. Similar trends are taking place at the German Cancer Research Center.

Apart from the specific recommendations on data protection mentioned above, the code also contains recommendations on dealing with additional findings: researchers have a duty of care towards all patients to report to the treating physician research findings that may be important to the health or treatment of the patient where the prevention of suffering or harm is concerned. However, researchers are not assigned a general duty to look actively for additional findings outside the research context.

Re D): What form should the process of information and obtaining consent take?

Just as the code regulates the responsibilities of researchers with respect to the normatively sensitive problem areas of genome sequencing (data protection and additional findings), so must the information and consent process deal with these issues from the perspective of the patient. Regarding the usual tool of “informed consent”, it could be said that it is a formal ritual to protect doctors and researchers in terms of liability and under the law [24] and that the patient is usually not enabled by the information process to form a well-informed and autonomous opinion and to express it. The latter is particularly difficult in genome sequencing due to the complex implications. The effort that goes into the information process, which can form the basis of a patient’s well-informed and solid consent, is considerable in view of the complexity of genome sequencing. It must be kept in mind that this does not only place a burden on (researching) physicians and/or the research project. Patients, too, can experience a long education and consent process about complicated facts and issues as a considerable mental and time burden. This is especially true of cancer patients who usually find themselves in a situation that threatens their very existence and who focus first and foremost on their illness and its treatment, not to mention the problems and emotions related to that, rather than on abstract questions of (distant) research on genome sequencing.

Despite these obvious difficulties and concerns, the EURAT group has decided for a number of reasons to maintain the principle of informed consent. At this time, there is no generally recognized or ethically, and above all legally, practical alternative to informed consent. EURAT emphasizes that an attempt must be made to educate the patient appropriately despite all these difficulties. Given the highly sensitive nature and massive intervention in the genetic privacy of the patient that genome sequencing represents [25], an above-average expenditure of resources and costs is considered reasonable. EURAT believes that the patient should be asked tiers of questions and given several tiers of consent options due to the significance of many of the issues involved (“tiered consent”) [26]. This gives the patient several options, enabling him/her to authorize different uses of his/her data with varying degrees of scope.

The information and consent process must strike the right balance between the maximum possible information about the key implications and issues and a maximum of understanding and accessibility on the part of the patient. To this end, EURAT has designed sample consent documents and also believes that explicit and substantial information should be provided on additional findings and data. The following, in particular, should be mentioned: measures related to pseudonymization and anonymization, data sharing with national and international research facilities and databases, possibilities and limits of data deletion in the event that consent is withdrawn, and forms of access to data for review purposes in connection with publications. It also bears mentioning that certain risks to the definitive and long-term confidentiality of data cannot be ruled out. As for the problem of possible additional findings, the education process is subject to a demanding conflict: on the one hand, the patient should be able to decide whether and, if so, what additional findings he or she wants to know. On the other hand, it is not possible to educate the patient about all potential additional findings and their relevance in great detail. It is, therefore, appropriate to employ a simplified and schematic approach, ordering additional findings by category and explaining them to the patient on the basis of examples. According to this, Huntington’s disease, for e.g., belongs in the category of incurable diseases that are certain to occur.

Education should not be limited to the written education and consent form. Other media and, above all, talks and opportunities for questions should also be provided. The process and content structure of the education need to be based on the patient’s information needs and ability to comprehend, as researched and documented, for e.g., by social-empirical studies [18, 27].

Project group and contributors to the EURAT statement

Prof. Dr. Claus R. Bartram (human genetics); Prof. Dr. Roland Eils (bioinformatics), Prof. Dr. Christof von Kalle (oncology), Prof. Dr.Dres.h.c. Paul Kirchhof (constitutional law); Dr. Jan Korbel (tumor genetics, genome sequencing), Prof. Dr. Andreas E. Kulozik (pediatric oncology), Prof. Dr. Peter Lichter (tumor genetics, genome sequencing), Prof. Dr. Peter Schirmacher (pathology); Prof. Dr. J.-Matthias Graf von der Schulenburg (health economics), Prof. Dr. Klaus Tanner (theology, ethics); Prof. Dr. Stefan Wiemann (genome sequencing), PD Dr. Dr. Eva Winkler (ethics, oncology); Prof. Dr. Dr. h.c. Rüdiger Wolfrum (international law, constitutional law); Dr. Grit M. Schwarzkopf (ethics), Dr. Christoph Schickhardt (philosophy), Martin Frank, Dipl.-Ök. (health economics); Gösta Gantner, M.A. (ethics); Fruzsina Molnár-Gábor (law); Dr. Anne Prenzler (health economics).

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Article note

Original German online version at: http://www.degruyter.com/view/j/labm.2014.38.issue-4/labmed-2014-0027/labmed-2014-0027.xml?format=INT. The German article was translated by Compuscript Ltd. and authorized by the authors.

About the article

Correspondence: PD Dr.med.Dr.phil. Eva C. Winkler, Medizinische Onkologie, Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Im Neuenheimer Feld 460 D-69120 Heidelberg, Germany, Tel.: +49 6221 5636049, Fax: +49 6221 567225, E-Mail:

aEqual authorship.


Received: 2014-12-02

Accepted: 2014-12-02

Published Online: 2015-04-16


Citation Information: LaboratoriumsMedizin, Volume 38, Issue 4, ISSN (Online) 1439-0477, ISSN (Print) 0342-3026, DOI: https://doi.org/10.1515/labmed-2014-0048.

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