The ethics of precision health.

In this paper, I defend an account of the ethics of precision medicine that can explain both its possibilities and limits. Creating a new conceptual and normative model of the ethics of precision health can ensure that good medicine is also excellent and that excellent medicine is also good by providing a resource to scientists and clinicians. First, I propose a new conceptual analysis of precision health. I argue that precision health is defined primarily by targeted medical interventions and not by stratification, as others have asserted. Next, I argue that failure to be adequately responsive to this conceptual analysis explains common ethical abuses in the field. Third, I argue that this conceptual analysis can also pave the way for future research heretofore overlooked. Thus, we can limit abuses in precision health research and care while at the same time opening new avenues to help historically oppressed communities.

Ethical considerations in elderly patients with acute coronary syndrome.

Acute coronary syndrome (ACS) is one of the main causes of mortality and morbidity in the elderly. The prevalence of ACS increases with age and patients with advanced age have some co-morbidities that require an individualized approach, which includes a comprehensive geriatric assessment. Ageism is a matter of great concern. In this scenario, some ethical conflicts may arise which should be anticipated, considered, and solved. Clinicians will need to prioritize and allocate resources, to avoid futility/proportionality, which is not always easy to assess in these patients. This review aims to summarize the evidence regarding ethical conflicts that may arise in the management of patients with ACS and advanced age. We will discuss how to choose the best option (which frequently is not the only one) with the lowest risk for harm, considering and respecting the patients' decision. The four basic principles of bioethics (beneficence, non-maleficence, autonomy, and justice) are thoroughly reviewed, and discussed, regarding their role in the decision making process.

Beyond inclusion: Enacting team equity in precision medicine research.

PURPOSE: To identify meanings of and challenges to enacting equitable diversification of genomics research, and specifically precision medicine research (PMR), teams. METHODS: We conducted in-depth interviews with 102 individuals involved in three U.S.-based precision medicine research consortia and conducted over 400 observation hours of their working group meetings, consortium-wide meetings, and conference presentations. We also reviewed published reports on genomic workforce diversity (WFD), particularly those relevant to the PMR community. RESULTS: Our study finds that many PMR teams encounter challenges as they strive to achieve equitable diversification on scientific teams. Interviewees articulated that underrepresented team members were often hired to increase the study's capacity to recruit diverse research participants, but are limited to on-the-ground staff positions with little influence over study design. We find existing hierarchies and power structures in the academic research ecosystem compound challenges for equitable diversification. CONCLUSION: Our results suggest that meaningful diversification of PMR teams will only be possible when team equity is prioritized as a core value in academic research communities.

Basic principles of biobanking: from biological samples to precision medicine for patients.

The term "biobanking" is often misapplied to any collection of human biological materials (biospecimens) regardless of requirements related to ethical and legal issues or the standardization of different processes involved in tissue collection. A proper definition of biobanks is large collections of biospecimens linked to relevant personal and health information (health records, family history, lifestyle, genetic information) that are held predominantly for use in health and medical research. In addition, the International Organization for Standardization, in illustrating the requirements for biobanking (ISO 20387:2018), stresses the concept of biobanks being legal entities driving the process of acquisition and storage together with some or all of the activities related to collection, preparation, preservation, testing, analysing and distributing defined biological material as well as related information and data. In this review article, we aim to discuss the basic principles of biobanking, spanning from definitions to classification systems, standardization processes and documents, sustainability and ethical and legal requirements. We also deal with emerging specimens that are currently being generated and shaping the so-called next-generation biobanking, and we provide pragmatic examples of cancer-associated biobanking by discussing the process behind the construction of a biobank and the infrastructures supporting the implementation of biobanking in scientific research.

Application of the community dialogues method to identify ethical values and priorities related to pharmacogenomics.

Given the expansion of genetics in medicine, there is a growing need to develop approaches to engage patients in understanding how genetics affects their health. Various qualitative methods have been applied to gain a deeper understanding of patient perspectives in topics related to genetics. Community dialogues (CD) are a bi-directional research method that invites community members to discuss a pertinent, challenging topic over the course of a multi-week period and the community members openly discuss their positions on the topic. Authors discuss the first application of the CD method to the topic of pharmacogenetics testing. Additional CD are needed to engage diverse participant populations on this topic to improve genetics literacy, enhance physician engagement and drive policy change.

Ancestry matters: Building inclusivity into preclinical study design.

Human cell lines (CLs) are key assets for biomedicine but lack ancestral diversity. Here, we explore why genetic diversity among cell-based models is essential for making preclinical research more equitable and widely translatable. We lay out practical actions that can be taken to improve inclusivity in study design.

My Data, My Choice? - German Patient Organizations' Attitudes towards Big Data-Driven Approaches in Personalized Medicine. An Empirical-Ethical Study.

Personalized medicine (PM) operates with biological data to optimize therapy or prevention and to achieve cost reduction. Associated data may consist of large variations of informational subtypes e.g. genetic characteristics and their epigenetic modifications, biomarkers or even individual lifestyle factors. Present innovations in the field of information technology have already enabled the procession of increasingly large amounts of such data ('volume') from various sources ('variety') and varying quality in terms of data accuracy ('veracity') to facilitate the generation and analyzation of messy data sets within a short and highly efficient time period ('velocity') to provide insights into previously unknown connections and correlations between different items ('value'). As such developments are characteristics of Big Data approaches, Big Data itself has become an important catchphrase that is closely linked to the emerging foundations and approaches of PM. However, as ethical concerns have been pointed out by experts in the debate already, moral concerns by stakeholders such as patient organizations (POs) need to be reflected in this context as well. We used an empirical-ethical approach including a website-analysis and 27 telephone-interviews for gaining in-depth insight into German POs' perspectives on PM and Big Data. Our results show that not all POs are stakeholders in the same way. Comparing the perspectives and political engagement of the minority of POs that is currently actively involved in research around PM and Big Data-driven research led to four stakeholder sub-classifications: 'mediators' support research projects through facilitating researcher's access to the patient community while simultaneously selecting projects they preferably support while 'cooperators' tend to contribute more directly to research projects by providing and implemeting patient perspectives. 'Financers' provide financial resources. 'Independents' keep control over their collected samples and associated patient-related information with a strong interest in making autonomous decisions about its scientific use. A more detailed terminology for the involvement of POs as stakeholders facilitates the adressing of their aims and goals. Based on our results, the 'independents' subgroup is a promising candidate for future collaborations in scientific research. Additionally, we identified gaps in PO's knowledge about PM and Big Data. Based on these findings, approaches can be developed to increase data and statistical literacy. This way, the full potential of stakeholder involvement of POs can be made accessible in discourses around PM and Big Data.

Ethics of Pharma Clinical Trials in the Era of Precision Oncology.

Pharmaceutical industry clinical trials are ethically problematic: human research subjects are being used as a means to the end of demonstrating statistically significant efficacy of novel anticancer agents to achieve regulatory registration and marketing approval. Randomized controlled trial design is inequitable since control arm patients are denied access to the postulated best treatment. Most pharma studies do not provide clinically meaningful benefit of increased overall survival and enhanced quality of life (QOL) to cohorts and are not reliably generalizable to real-world patients. Precision oncology now enables prospective identification of patients expressing a specific cancer biomarker to determine their particular eligibility for evaluation of efficiency of molecular-targeted treatments. A patient-centered approach, collecting prospective real-world data in large populations, could provide real-world evidence of cost-effective, sustained clinical benefits of survival and QOL, while preserving the ethical beneficent compact between patient and doctor.

Transparency, trust, and community welfare: towards a precision public health ethics framework for the genomics era.

Infectious disease control is experiencing a paradigm shift, as pathogen sequencing technologies and digital applications are increasingly implemented for control of diseases such as tuberculosis, Ebola, and COVID-19. A new ethical framework should be a critical part of this emerging paradigm to ensure that the benefit of precision public health interventions based on advances in genomics research is not outweighed by the risks they pose to individuals, families, and vulnerable segments of the population. We suggest that the ethical framework guiding practice in this domain combines standard precepts from public health ethics with emerging ethics principles from precision medicine.

Perspectives on Precision Medicine in a Tribally Managed Primary Care Setting.

BACKGROUND: Precision medicine (PM) research and clinical application is moving forward at a rapid pace. To ensure ethical inclusion of all populations in PM, in-depth understanding of diverse communities' views of PM research and PM implementation is necessary. METHODS: Semi-structured interviews were conducted to explore perspectives on PM in a tribally managed healthcare organization. Thematic analysis was used to analyze data from 46 interviews. RESULTS: Participants described gains in diagnostic efficiency, risk identification for preventable disease, and the advancement of population-specific biomedical research as key benefits of PM. Concerns expressed related to privacy risks associated with data-sharing, overpromising on PM, and managing patient expectations related to PM. Stakeholders encouraged PM implementation to be preceded by health education activities that leverage a range of communication strategies. CONCLUSION: Perspectives described in this study may aid in and should be considered prior to implementation of PM in this and other healthcare systems, especially those serving diverse populations.

Consent and Privacy in the Era of Precision Medicine and Biobanking Genomic Data.

"Big Data represents a challenge that points to the need for collective and political approaches to self-protection rather than solely individual, atomistic approaches."- Anita Allen, "Protecting One's Own Privacy in a Big Data Economy".

NIMHD Transdisciplinary Collaborative Centers for Health Disparities Research Focused on Precision Medicine.

The NIMHD Transdisciplinary Collaborative Centers for Health Disparities Research Focused on Precision Medicine (PM TCCs) comprise regional coalitions of research institutions and consortium partners focused on priority research topics in minority health and health disparities. In April 2016, NIMHD, in partnership with the National Human Genome Research Institute (NHGRI) and the National Cancer Institute (NCI), launched the PM TCC program to fund five centers across the United States to stimulate health disparities research with an emphasis on precision medicine to address one or more documented health disparities. The programs draw on expertise in genomics and other 'omics, physiology and medicine, population health disparities, behavioral and social sciences, and the science of translation, implementation and dissemination. The TCC program's overarching goal is to develop and disseminate effective interventions that can be implemented in real-world settings with the goal of promoting health equity and reducing health disparities. This special issue of Ethnicity & Disease is dedicated to cutting-edge research conducted by the five PM TCCs at the intersection between precision medicine and health disparities. Articles in this issue will enhance knowledge in a variety of research topics from perspectives on precision medicine among different health disparity populations to methods for reducing inequities in protocols, interventions, and health information and further efforts to promote inclusion of all populations, especially the most vulnerable.

Perspectives on Precision Health Among Racial/Ethnic Minority Communities and the Physicians That Serve Them.

Background: In order for precision health to address health disparities, engagement of diverse racial/ethnic minority communities and the physicians that serve them is critical. Methods: A community-based participatory research approach with mixed methods was employed to gain a deeper understanding of precision health research and practice among American Indian, African American, Latino, Chinese, and Vietnamese groups and physicians that serve these communities. A survey assessed demographics and opinions of precision health, genetic testing, and precision health research. Focus groups (n=12) with each racial/ethnic minority group and physicians further explored attitudes about these topics. Results: One hundred community members (American Indian [n=17], African American [n=13], Chinese [n=17], Latino [n=27], and Vietnamese [n=26]) and 14 physicians completed the survey and participated in the focus groups. Familiarity with precision health was low among community members and high among physicians. Most groups were enthusiastic about the approach, especially if it considered influences on health in addition to genes (eg, environmental, behavioral, social factors). Significant concerns were expressed by African American and American Indian participants about precision health practice and research based on past abuses in biomedical research. In addition, physician and community members shared concerns such as security and confidentiality of genetic information, cost and affordability of genetic tests and precision medicine, discrimination and disparities, distrust of medical and research and pharmaceutical institutions, language barriers, and physician's specialty. Conclusions: Engagement of racial/ethnic minority communities and the providers who serve them is important for advancing a precision health approach to addressing health disparities.

Responsible use of organoids in precision medicine: the need for active participant involvement.

Organoids are three-dimensional multicellular structures grown in vitro from stem cells and which recapitulate some organ function. They are derivatives of living tissue that can be stored in biobanks for a multitude of research purposes. Biobank research on organoids derived from patients is highly promising for precision medicine, which aims to target treatment to individual patients. The dominant approach for protecting the interests of biobank participants emphasizes broad consent in combination with privacy protection and ex ante (predictive) ethics review. In this paradigm, participants are positioned as passive donors; however, organoid biobanking for precision medicine purposes raises challenges that we believe cannot be adequately addressed without more ongoing involvement of patient-participants. In this Spotlight, we argue why a shift from passive donation towards more active involvement is particularly crucial for biobank research on organoids aimed at precision medicine, and suggest some approaches appropriate to this context.

Allele-specific genome targeting in the development of precision medicine.

The CRISPR-based genome editing holds immense potential to fix disease-causing mutations, however, must also handle substantial natural genetic variations between individuals. Previous studies have shown that mismatches between the single guide RNA (sgRNA) and genomic DNA may negatively impact sgRNA efficiencies and lead to imprecise specificity prediction. Hence, the genetic variations bring about a great challenge for designing platinum sgRNAs in large human populations. However, they also provide a promising entry for designing allele-specific sgRNAs for the treatment of each individual. The CRISPR system is rather specific, with the potential ability to discriminate between similar alleles, even based on a single nucleotide difference. Genetic variants contribute to the discrimination capabilities, once they generate a novel protospacer adjacent motif (PAM) site or locate in the seed region near an available PAM. Therefore, it can be leveraged to establish allele-specific targeting in numerous dominant human disorders, by selectively ablating the deleterious alleles. So far, allele-specific CRISPR has been increasingly implemented not only in treating dominantly inherited diseases, but also in research areas such as genome imprinting, haploinsufficiency, spatiotemporal loci imaging and immunocompatible manipulations. In this review, we will describe the working principles of allele-specific genome manipulations by virtue of expanding engineering tools of CRISPR. And then we will review new advances in the versatile applications of allele-specific CRISPR targeting in treating human genetic diseases, as well as in a series of other interesting research areas. Lastly, we will discuss their potential therapeutic utilities and considerations in the era of precision medicine.

Visualizing an Ethics Framework: A Method to Create Interactive Knowledge Visualizations From Health Policy Documents.

BACKGROUND: Data have become an essential factor in driving health research and are key to the development of personalized and precision medicine. Primary and secondary use of personal data holds significant potential for research; however, it also introduces a new set of challenges around consent processes, privacy, and data sharing. Research institutions have issued ethical guidelines to address challenges and ensure responsible data processing and data sharing. However, ethical guidelines directed at researchers and medical professionals are often complex; require readers who are familiar with specific terminology; and can be hard to understand for people without sufficient background knowledge in legislation, research, and data processing practices. OBJECTIVE: This study aimed to visually represent an ethics framework to make its content more accessible to its stakeholders. More generally, we wanted to explore the potential of visualizing policy documents to combat and prevent research misconduct by improving the capacity of actors in health research to handle data responsibly. METHODS: We used a mixed methods approach based on knowledge visualization with 3 sequential steps: qualitative content analysis (open and axial coding, among others); visualizing the knowledge structure, which resulted from the previous step; and adding interactive functionality to access information using rapid prototyping. RESULTS: Through our iterative methodology, we developed a tool that allows users to explore an ethics framework for data sharing through an interactive visualization. Our results represent an approach that can make policy documents easier to understand and, therefore, more applicable in practice. CONCLUSIONS: Meaningful communication and understanding each other remain a challenge in various areas of health care and medicine. We contribute to advancing communication practices through the introduction of knowledge visualization to bioethics to offer a novel way to tackle this relevant issue.