Melody J. Slashinski

Are physicians prepared for whole genome sequencing? a qualitative analysis.

Although the integration of whole genome sequencing (WGS) into standard medical practice is rapidly becoming feasible, physicians may be unprepared to use it. Primary care physicians (PCPs) and cardiologists enrolled in a randomized clinical trial of WGS received genomics education before completing semi‐structured interviews. Themes about preparedness were identified in transcripts through team‐based consensus‐coding. Data from 11 PCPs and 9 cardiologists suggested that physicians enrolled in the trial primarily to prepare themselves for widespread use of WGS in the future. PCPs were concerned about their general genomic knowledge, while cardiologists were concerned about how to interpret specific types of results and secondary findings. Both cohorts anticipated preparing extensively before disclosing results to patients by using educational resources with which they were already familiar, and both cohorts anticipated making referrals to genetics specialists as needed. A lack of laboratory guidance, time pressures, and a lack of standards contributed to feeling unprepared. Physicians had specialty‐specific concerns about their preparedness to use WGS. Findings identify specific policy changes that could help physicians feel more prepared, and highlight how providers of all types will need to become familiar with interpreting WGS results.

“Snake-oil,” “quack medicine,” and “industrially cultured organisms:” biovalue and the commercialization of human microbiome research

BackgroundContinued advances in human microbiome research and technologies raise a number of ethical, legal, and social challenges. These challenges are associated not only with the conduct of the research, but also with broader implications, such as the production and distribution of commercial products promising maintenance or restoration of good physical health and disease prevention. In this article, we document several ethical, legal, and social challenges associated with the commercialization of human microbiome research, focusing particularly on how this research is mobilized within economic markets for new public health uses.MethodsWe conducted in-depth, semi-structured interviews (2009–2010) with 63 scientists, researchers, and National Institutes of Health project leaders (“investigators”) involved with human microbiome research. Interviews explored a range of ethical, legal, and social dimensions of human microbiome research, including investigators’ perspectives on commercialization. Using thematic content analysis, we identified and analyzed emergent themes and patterns.ResultsInvestigators discussed the commercialization of human microbiome research in terms of (1) commercialization, probiotics, and issues of safety, (2) public awareness of the benefits and risks of dietary supplements, and (3) regulation.ConclusionThe prevailing theme of ethical, legal, social concern focused on the need to find a balance between the marketplace, scientific research, and the public’s health. The themes we identified are intended to serve as points for discussions about the relationship between scientific research and the manufacture and distribution of over-the-counter dietary supplements in the United States.

Perspectives on Human Microbiome Research Ethics

Study of ethical, legal, and social implications (ELSI) of human microbiome research has been integral to the Human Microbiome Project (HMP). This study explores core ELSI issues that arose during the first phase of the HMP from the perspective of individuals involved in the research. We conducted semi-structured in-depth interviews with investigators and NIH employees (“investigators”) involved in the HMP, and with individuals recruited to participate in the HMP Healthy Cohort Study at Baylor College of Medicine (“recruits”). We report findings related to three major ELSI issues: Informed consent, data sharing, and return of results. Our findings demonstrate that investigators and recruits were similarly sensitive to these issues yet generally comfortable with study design in light of current knowledge about the microbiome.

Is Whole‐Exome Sequencing an Ethically Disruptive Technology? Perspectives of Pediatric Oncologists and Parents of Pediatric Patients With Solid Tumors

It has been anticipated that physician and parents will be ill prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive.

Parental Perspectives on Whole-Exome Sequencing in Pediatric Cancer: A Typology of Perceived Utility

Purpose To explore how parents of pediatric cancer patients perceived the utility of clinical tumor and germline whole-exome sequencing (WES) results. Patients and Methods We conducted longitudinal interviews with parents of a diverse pediatric cancer population before disclosure of WES results (n=64), then one to eight months (n=33) after disclosure. Interview transcripts were analyzed using a thematic qualitative approach. Results Parents identified a broad range of types of utility for their childs WES results. Even when results did not affect their childs current treatment, they expressed optimism about future clinical utility for their child, themselves, and other family members. Parents also reported experiencing psychological utility including peace of mind, relief of guilt, and satisfaction of curiosity. Pragmatic utility, such as the ability to plan for the future and make better reproductive decisions, was also described. Conclusion Parents of pediatric cancer patients perceive WES to have broad utility, including psychological and pragmatic utility, even if there is no direct impact on clinical care. Further work will need to consider how the value of genomic information should be characterized, how risks and benefits should be described, and how these results should inform recommendations and decisions about using WES.

It depends whose data are being shared: considerations for genomic data sharing policies

There is an urgent need for consistent data sharing policies that promote the advancement of science while respecting the values and interests of those providing their genetic data for research. Responding to the article of Jalayne J. Arias, Genevieve Pham-Kanter, and Eric G. Campbell, ‘The Growth and Gaps of Genetic Data Sharing Policies in the United States’, this commentary further explores the challenges of human subjects’ protection in existing data sharing policies. We will elaborate on the need for data sharing policies to accommodate variation in individual and group preferences around data sharing and privacy concerns by comparing our previously published data on patients’ and parents’ consent to data sharing and attitudes about privacy to data from focus groups with HIV-positive, underserved individuals who were asked about their willingness to participate in genetic research and share their data broadly. These studies support the observation of Arias, Pham-Kanter, and Campbell that researchers, and funding agencies will need to balance the privacy interests of groups as well as individuals in future genomic data sharing policies.

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study

BACKGROUND There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens. METHODS This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons. FINDINGS We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage). INTERPRETATION By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. FUNDING National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.

Portero versus portador: Spanish interpretation of genomic terminology during whole exome sequencing results disclosure

AIM Describe modifications to technical genomic terminology made by interpreters during disclosure of whole exome sequencing (WES) results. PATIENTS & METHODS Using discourse analysis, we identified and categorized interpretations of genomic terminology in 42 disclosure sessions where Spanish-speaking parents received their childs WES results either from a clinician using a medical interpreter, or directly from a bilingual physician. RESULTS Overall, 76% of genomic terms were interpreted accordantly, 11% were misinterpreted and 13% were omitted. Misinterpretations made by interpreters and bilingual physicians included using literal and nonmedical terminology to interpret genomic concepts. CONCLUSION Modifications to genomic terminology made during interpretation highlight the need to standardize bilingual genomic lexicons. We recommend Spanish terms that can be used to refer to genomic concepts.