Christoph Schickhardt

Stakeholders’ perspectives on biobank-based genomic research: systematic review of the literature

The success of biobank-based genomic research is widely dependent on people’s willingness to donate their tissue. Thus, stakeholders’ opinions should be considered in the development of best practice guidelines for research and recruiting participants. We systematically analyzed the empirical literature describing different stakeholders’ views towards ethical questions with regard to type of consent, data sharing and return of incidental findings. Patients are more open to one-time general consent than the public. Only a small proportion desires recontact if the research aim changed. A broad consent model would prevent only a small proportion of patients from participating in research. Although professionals are concerned about a risk of reidentification, patients and the public support data sharing and find that the benefit of research outweighs the potential risk of reidentification. However, they desire detailed information about the privacy protection measures. Regarding the return of incidental findings, the public and professionals focus on clinically actionable results, whereas patients are interested in receiving as much information as possible. For professionals, concrete guidelines that help managing the return of incidental findings should be warranted. For this it would be helpful addressing the different categories – actionable, untreatable and inheritable diseases – upfront with patients and public.

So rare we need to hunt for them: reframing the ethical debate on incidental findings

Incidental findings are the subject of intense ethical debate in medical genomic research. Every human genome contains a number of potentially disease-causing alterations that may be detected during comprehensive genetic analyses to investigate a specific condition. Yet available evidence shows that the frequency of incidental findings in research is much lower than expected. In this Opinion, we argue that the reason for the low level of incidental findings is that the filtering techniques and methods that are applied during the routine handling of genomic data remove these alterations. As incidental findings are systematically filtered out, it is now time to evaluate whether the ethical debate is focused on the right issues. We conclude that the key question is whether to deliberately target and search for disease-causing variations outside the indication that has originally led to the genetic analysis, for instance by using positive lists and algorithms.

Key Implications of Data Sharing in Pediatric Genomics

Accurate clinical interpretation of children’s whole-genome and whole-exome sequences relies on comparing the patient’s linked genomic and phenotypic data with variant reference databases of both healthy and affected patients. The robustness of such comparisons, in turn, is made possible by sharing pediatric genomic and associated clinical data. Despite this, sparse ethical-legal policy attention has been paid to making such sharing routine in practice. The interdisciplinary Paediatric Task Team of the Global Alliance for Genomics and Health considered in detail the current ethical, legal, and social implications of sharing genomic and associated clinical data involving children. An initial set of points to consider was presented at a meeting of the Paediatric Task Team at the 4th Plenary of the Global Alliance for Genomics and Health. The Key Implications for Data Sharing (KIDS) framework for pediatric genomics was developed based on feedback from this group and was supplemented by findings from a critical appraisal of the data-sharing literature. The final points to consider that comprise the KIDS framework are categorized into the following 4 primary themes: children’s involvement, parental consent, balancing benefits and risks, and data protection and release requirements.

Applying systems biology to biomedical research and health care: a précising definition of systems medicine

BackgroundSystems medicine has become a key word in biomedical research. Although it is often referred to as P4-(predictive, preventive, personalized and participatory)-medicine, it still lacks a clear definition and is open to interpretation. This conceptual lack of clarity complicates the scientific and public discourse on chances, risks and limits of Systems Medicine and may lead to unfounded hopes. Against this background, our goal was to develop a sufficiently precise and widely acceptable definition of Systems Medicine.MethodsIn a first step, PubMed was searched using the keyword “systems medicine”. A data extraction tabloid was developed putting forward a means/ends-division. Full-texts of articles containing Systems Medicine in title or abstract were screened for definitions. Definitions were extracted; their semantic elements were assigned as either means or ends. To reduce complexity of the resulting list, summary categories were developed inductively. In a second step, we applied six criteria for adequate definitions (necessity, non-circularity, non-redundancy, consistency, non-vagueness, and coherence) to these categories to derive a so-called précising definition of Systems Medicine.ResultsWe identified 185 articles containing the term Systems Medicine in title or abstract. 67 contained at least one definition of Systems Medicine. In 98 definitions, we found 114 means and 132 ends. From these we derived the précising definition: Systems Medicine is an approach seeking to improve medical research (i.e. the understanding of complex processes occurring in diseases, pathologies and health states as well as innovative approaches to drug discovery) and health care (i.e. prevention, prediction, diagnosis and treatment) through stratification by means of Systems Biology (i.e. data integration, modeling, experimentation and bioinformatics). Our study also revealed the visionary character of Systems Medicine.ConclusionsOur insights, on the one hand, allow for a realistic identification of actual ethical as well as legal issues arising in the context of Systems Medicine and, in consequence, for a realistic debate of questions concerning its matter and (future) handling. On the other hand, they help avoiding unfounded hopes and unrealistic expectations. This especially holds for goals like improving patient participation which are intensely debated in the context of Systems Medicine, however not implied in the concept.

Researchers’ Duty to Share Pre-publication Data: From the Prima Facie Duty to Practice

The purpose of this chapter is to offer an ethical investigation into whether researchers have a duty to share pre-published bio-medical data with the scientific community. The central questions of the chapter are the following: do researchers have a prima facie duty to share pre-published data? And if so, what stakes and aspects of a concrete situation need to be taken into consideration in order to assess whether and to what extent researchers’ prima facie duty to share data applies? We will argue that based upon their basic duties to benefit society and to promote scientific knowledge, researchers have a prima facie duty to share data. We will also argue that in order to determine whether the prima facie duty applies in practice it is indispensable to take into account the stakes of the persons concerned as well as context dependent aspects. The chapter’s overall goal is to build an analytical and ethical framework that helps to assess with regard to concrete situations whether researchers’ duty to share data applies. To this end we analyse the concept of data sharing and clarify what data sharing might imply in practice. To offer an overview of the different stakeholders’ concerns we will analyse the normative-informational environment in which data producing researchers (to whom the prima facie duty to share data applies) are usually situated. In the last step we focus on the ethically relevant context dependent aspects and illustrate how they affect researchers’ prima facie duty to share data and stakeholders’ potentially conflicting stakes.

Eating Disorders in Minors and the Role of the Media. An Ethical Investigation

In his paper, Christoph Schickhardt proposes an ethical analysis of the role of the media for the development of eating disorders such as Anorexia Nervosa and Bulimia Nervosa and related issues such as unhealthy weight control behavior in children and adolescents. Eating disorders are highly severe mental diseases and relatively common among minors. Although their pathogenesis is complex, there is considerable evidence suggesting that the idealizing presentation of very slim bodies in the media, to which many children are exposed intensively for years since early childhood, might contribute to minors’ risk of developing eating disorders. This raises ethical questions concerning the well-being and rights of children and adolescents as well as the rights and responsibility of the media. Applying a liberal-egalitarian point of view, Schickhardt argues that while using seductive presentations of thin bodies is no core element of the freedom of the media, it jeopardizes central elements of children’s well-being. Putting susceptible and vulnerable young people at risk for eating disorders is ethically inacceptable. Measures to protect minors and foster their media literacy and resilience are due. In his conclusion, the author mentions some concrete measures which might be suitable.

Trust and responsibility in molecular tumour boards

Molecular tumour boards (MTBs) offer recommendations for potentially effective, but potentially burdensome, molecularly targeted treatments to a patients treating physician. In this paper, we discuss the question of who is responsible for ensuring that there is an adequate evidence base for any treatments recommended to a patient. We argue that, given that treating oncologists cannot usually offer a robust evaluation of the evidence underlying an MTBs recommendation, members of the MTB are responsible for ensuring that the evidence level is adequate. We explore two models for how to share responsibility between MTB members. According to the first model, each MTB member, as well as the treating physician, should be held maximally and equally responsible for the recommendations. We argue that this insufficiently accounts for differences in roles and expertise of MTB members. We propose instead that responsibility is delegated via relationships of trust. We argue if these relationships of trust are to be instances of reasonable trust, (a) MTBs should offer a clinical representative to whom a treating physician may delegate the responsibility of ensuring there is sufficient evidence for treatment recommendations, (b) the relationships of trust between the representative and the other MTB members should be clearly defined, and (c) MTB members should be carefully selected. Treating oncologists retain a responsibility to consider general limitations of the evidence for targeted treatments in assessing whether the treatment recommendation offered by an MTBs representative is adequate for a given clinical situation.

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

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.

Ethische Herausforderungen der Genomsequenzierung in der translationalen Forschung und Antworten aus dem EURAT-Projekt

Zusammenfassung Die Genomsequenzierung in der translationalen Forschung bringt neben vielen medizinischen Chancen auch erhebliche ethisch-rechtliche Herausforderungen mit sich. Die vier wichtigsten betreffen die folgenden Aspekte: (1) den Umgang mit Befunden und Zufallsbefunden der Genomsequenzierung aus dem Forschungskontext; (2) die Vereinbarkeit von Datenschutz und einer Forschung, die wesentlich auf die gemeinsame Nutzung von Genomdaten angewiesen ist (data sharing); (3) die Verantwortung der Forscher, vor allem der nicht-ärztlichen Wissenschaftler, die bei der Genomsequenzierung mitwirken; (4) die Gestaltung des Aufklärungs- und Einwilligungsprozesses für Patienten und Probanden bezüglich der Sequenzierung ihres Genoms. Diese vier Problemfelder werden zunächst dargelegt. In einem zweiten Schritt werden konkrete Lösungsvorschläge aufgezeigt, wie sie von der interdisziplinären Heidelberger EURAT-Projektgruppe als Empfehlungen für die Verwendung von Genomsequenzierung in der translationalen Forschung und Versorgung in Heidelberg ausgearbeitet wurden.