The Microbe Farms: Microbial Biorepositories in Clinical Microbiology

Biorepositories aim to acquire, authenticate, preserve, develop, and distribute biological specimens, along with information, technology, intellectual property, and standards for the advancement and application of scientific knowledge. Biorepositories are critical components of modern healthcare, as they provide resources to advance translational biomedical research, navigation through the FDA process for in vitro devices, verification and validation of diagnostic methods, and personalized medicine. In order to fully realize the opportunities that biorepositories offer to medicine, laboratories must be able to guarantee high-quality biospecimens, associated information, and a system able to respond to the needs of method verification, quality control, or the requests of scientific colleagues. A biorepository requires funding resources and space, which are often difficult to find within existing health care resources, yet health care may benefit most from the resources biorepositories provide. It is crucial that institutions be able to recognize these issues and start preparing and releasing adequate resources to support the development of biorepositories with a common goal to improve health care by increasing the quality of biomedical research and diagnostic test development. The future of biorepositories depends on the development of more evidence-based practices in both the research and clinical settings. As the field matures, educating a new generation of biospecimen/biobanking scientists will be an important need.     

Shifting sands: the complexities and uncertainties of the evolving US regulatory,policy, and scientific landscape for biospecimen research

Human tissue biorepositories and the biospecimens they provide play a critical role in advancing research and medical care, especially in supporting research to develop precision medicine. However, advancements in genomics, informatics, and other sophisticated technologies and extensive biospecimen and data sharing have raised questions about how best to protect research participants. Complex ethical issues remain unresolved, such as the identifiability of biospecimens and associated data, the best consent models for future research, ownership and commercial use of biospecimens, and return of individual research results.This review summarizes the relevant US regulations and recent changes to them, as well as current and future ethical and policy issues related to biospecimen research. Because many issues remain unresolved, additional policy development will be needed. We discuss approaches for how researchers and other stakeholders can provide input to ensure that these policies will protect research participants while facilitating research important for scientific and medical advancements.     

Precision medicine research with American Indian and Alaska Native communities: Results of a deliberative engagement with tribal leaders

PurposeAmid calls for greater diversity in precision medicine research, the perspectives of Indigenous people have been underexplored. Our goals were to understand tribal leaders’ views regarding the potential benefits and risks of such research, explore its priority for their communities, and identify the policies and safeguards they consider essential. This article reports on the participants’ perspectives regarding governance and policy, stewardship and sharing of information and biospecimens, and informed consent.MethodsAfter informal local dialogs with 21 tribal leaders, we convened a 2.5-day deliberation with tribal leaders (N = 10) in Anchorage, Alaska, in June 2019 using a combination of small group and plenary discussion, ranking, and voting exercises to explore the perspectives on precision medicine research.ResultsTribal sovereignty was central to participants’ ideas about precision medicine research. Although views were generally positive, provided that the appropriate controls were in place, some kinds of research were deemed unacceptable, and the collection of certain biospecimens was rejected by some participants. Differences were observed regarding the acceptability of broad consent.ConclusionTribal leaders in this study were generally supportive of precision medicine research, with the caveat that tribal oversight is essential for the establishment of research repositories and the conduct of research involving Indigenous participants.     

Deep Brain Stimulation, Brain Maps and Personalized Medicine: Lessons from the Human Genome Project

Although the appellation of personalized medicine is generally attributed to advanced therapeutics in molecular medicine, deep brain stimulation (DBS) can also be so categorized. Like its medical counterpart, DBS is a highly personalized intervention that needs to be tailored to a patient’s individual anatomy. And because of this, DBS like more conventional personalized medicine, can be highly specific where the object of care is an N = 1. But that is where the similarities end. Besides their differing medical and surgical provenances, these two varieties of personalized medicine have had strikingly different impacts. The molecular variant, though of a more recent vintage has thrived and is experiencing explosive growth, while DBS still struggles to find a sustainable therapeutic niche. Despite its promise, and success as a vetted treatment for drug resistant Parkinson’s Disease, DBS has lagged in broadening its development, often encountering regulatory hurdles and financial barriers necessary to mount an adequate number of quality trials. In this paper we will consider why DBS—or better yet neuromodulation—has encountered these challenges and contrast this experience with the more successful advance of personalized medicine. We will suggest that personalized medicine and DBS’s differential performance can be explained as a matter of timing and complexity. We believe that DBS has struggled because it has been a journey of scientific exploration conducted without a map. In contrast to molecular personalized medicine which followed the mapping of the human genome and the Human Genome Project, DBS preceded plans for the mapping of the human brain. We believe that this sequence has given personalized medicine a distinct advantage and that the fullest potential of DBS will be realized both as a cartographical or electrophysiological probe and as a modality of personalized medicine.     

The role of academic medicine in improving health care quality.

Academic medicine, often entrenched in biomedical and clinical research, has largely ignored the development and application of quality metrics to ensure the delivery of high-quality health care. Nevertheless, academic medicine has substantial opportunities to lead the charge in building a quality infrastructure with the goal of delivering high-quality and cost-efficient health care to all Americans. The American College of Cardiology (ACC) and American Heart Association (AHA) have worked jointly to measure and improve the quality of cardiovascular care. This effort has led to the development of clinical practice guidelines, performance measures, data standards, national registries, and appropriateness criteria for cardiovascular care. Academic medicine should actively embrace and promote the type of quality metrics and criteria developed by ACC and AHA and apply this model across the entire academic medicine community. Academic medicine, with its many resources, could lead the way in the expanding field of quality science by supporting fundamental research in quality improvement, supporting academicians to improve quality at their own institutions, developing educational models for quality assessment and improvement, creating and implementing data registries, and serving as a conduit for developing the emerging science of quality assessment. In this and many other ways, academic medicine must offer the health care community leadership for improving our nation's health care quality with the same fervor presently exhibited for the advancement of basic science, the development of specialized and experimental therapy, and as centers for tertiary and quaternary patient care.     

Biospecimens and biorepositories for the community pathologist

Pathologists have long served as custodians of human biospecimens collected for diagnostic purposes. Rapid advancements in diagnostic technologies require that pathologists change their practices to optimize patient care. The proper handling of biospecimens creates opportunities for pathologists to improve their diagnoses while assessing prognosis and treatment. In addition, the growing need for high-quality biorepositories represents an opportunity for community pathologists to strengthen their role within the health care team, ensuring that clinical care is not compromised while facilitating research. This article provides a resource to community pathologists learning how to create high-quality biorepositories and participating in emerging opportunities in the biorepository field. While a variety of topics are covered to provide breadth of information, the intent is to facilitate a level of understanding that permits community pathologists to make more informed choices in identifying how best their skills and practice may be augmented to address developments in this field.     

Barriers for integrating personalized medicine into clinical practice: A qualitative analysis

Personalized medicine—tailoring interventions based on individual's genetic information—will likely change routine clinical practice in the future. Yet, how practitioners plan to apply genetic information to inform medical decision making remains unclear. We aimed to investigate physician's perception about the future role of personalized medicine, and to identify the factors that influence their decision in using genetic testing in their practice. We conducted three semi‐structured focus groups in three health regions (Fraser, Vancouver coastal, and Interior) in British Columbia, Canada. In the focus groups, participants discussed four topics on personalized medicine: (i) physicians' general understanding, (ii) advantages and disadvantages, (iii) potential impact and role in future clinical practice, and (iv) perceived barriers to integrating personalized medicine into clinical practice. Approximately 36% (n = 9) of physicians self‐reported that they were not familiar with the concept of personalized medicine. After introducing the concept, the majority of physicians (68%, n = 19 of 28) were interested in incorporating personalized medicine in their practice, provided they have access to the necessary knowledge and tools. Participants mostly believed that genetic developments will directly affect their practice in the future. The key concerns highlighted were physician's access to clinical guidelines and training opportunities for the use of genetic testing and data interpretation. Despite the challenges that personalized medicine can create, in general, physicians in the focus groups expressed strong interest in using genetic information in their practice if they have access to the necessary knowledge and tools. © 2013 Wiley Periodicals, Inc.     

Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research

Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address.Genet Med advance online publication 13 April 2017     

The Precision Medicine Initiative’s All of Us Research Program: an agenda for research on its ethical,legal, and social issues

The Precision Medicine Initiative (PMI) is an innovative approach to developing a new model of health care that takes into account individual differences in people’s genes, environments, and lifestyles. A cornerstone of the initiative is the PMI All of Us Research Program (formerly known as PMI-Cohort Program) which will create a cohort of 1 million volunteers who will contribute their health data and biospecimens to a centralized national database to support precision medicine research. The PMI All of US Research Program is the largest longitudinal study in the history of the United States. The designers of the Program anticipated and addressed some of the ethical, legal, and social issues (ELSI) associated with the initiative. To date, however, there is no plan to call for research regarding ELSI associated with the Program-PMI All of Us program. Based on analysis of National Institutes of Health (NIH) funding announcements for the PMI All of Us program, we have identified three ELSI themes: cohort diversity and health disparities, participant engagement, and privacy and security. We review All of Us Research Program plans to address these issues and then identify additional ELSI within each domain that warrant ongoing investigation as the All of Us Research Program develops. We conclude that PMI's All of Us Research Program represents a significant opportunity and obligation to identify, analyze, and respond to ELSI, and we call on the PMI to initiate a research program capable of taking on these challenges.Genet Med advance online publication 01 December 2016     

Considerations for uniform and accurate biospecimen labelling in a biorepository and research environment

Correct labelling of specimens in a biorepository or research laboratory is vital, especially for translational or clinical studies linking clinical data with biospecimens. While patient privacy must be carefully protected, confusing or inadequate labelling can potentially result in the study of the wrong biospecimens with detrimental effects to the accuracy of published findings or a requirement for invaluable biospecimens to be discarded. Labelling guidelines are described in the biorepository of the University of California-Los Angeles Brain Tumour Translational Resource, and in recipient neuro-oncology laboratories to which biospecimens and derivatives are provided. This approach includes specifying identifier types, types of dates and institutions on the biospecimen labels; using multiple identifiers on each specimen when feasible; and developing a three to four-letter alphanumeric code to aid in label recognition. In addition, steps are being taken to educate recipient laboratories on best practices in labelling.     

“I don’t want to be Henrietta Lacks”: diverse patient perspectives on donating biospecimens for precision medicine research

PurposeTo determine whether patients distinguish between biospecimens and electronic health records (EHRs) when considering research participation to inform research protections.MethodsWe conducted 20 focus groups with individuals who identified as African American, Hispanic, Chinese, South Asian, and non-Hispanic white on the collection of biospecimens and EHR data for research.ResultsOur study found that many participants did not distinguish between biospecimens and EHR data. However, some participants identified specific concerns about biospecimens. These included the need for special care and respect for biospecimens due to enduring connections between the body and identity; the potential for unacceptable future research, specifically the prospect of human cloning; heightened privacy risks; and the potential for unjust corporate profiteering. Among those who distinguished biospecimens from EHR data, many supported separate consent processes and would limit their own participation to EHR data.ConclusionConsidering that the potential misuse of EHR data is as great as, if not greater than, for biospecimens, more research is needed to understand how attitudes differ between biospecimens and EHR data across diverse populations. Such research should explore mechanisms beyond consent that can address diverse values, perspectives, and misconceptions about sources of patient information to build trust in research relationships.     

Pharmacogenetics of asthma in children

Allergic diseases such as bronchial asthma and atopic dermatitis develop by a combination of genetic and environmental factors. Several candidate causative genes of asthma and atopy have been reported as the genetic factors. The clinical features of patients and causes of diseases vary. Therefore, personalized medicine (tailor-made medicine) is necessary for the improvement of quality of life (QOL) and for asthma cure. Pharmacogenetics is very important for personalized medicine. Here, we present the genetics and pharmacogenetics of asthma in children. Finally, we show the guideline for personalized medicine for asthma, particularly in childhood, including the pharmacogenetics of anti-asthmatic drugs, preliminarily produced by the authors.     

Transfusion medicine: Overtime paradigm changes and emerging paradoxes

This essay aims to discuss some aspects of blood transfusion in the perspective of the changes that occurred over time as well as modifications of the paradigms that transformed the activities and the organization of blood transfusion services. Without specific knowledge, pioneers envisioned precision and personalized medicine, rendering transfusion medicine operational. Transfusion medicine is like The Picture of Dorian Grey: always young despite being old and sometimes appearing old-fashioned. Over the years, the transfusion medicine discipline has evolved, and major progress has been achieved, despite some troublesome periods (for example, the tainted blood scandal, and—at the time being—the offending plasma market and the selling of human parts). Transfusion medicine has at all times implemented the rapidly developing biomedical technologies to secure blood components. The safety of blood components has now reached an exceptional level in economically wealthy countries, especially compared to other health care disciplines. Strengthening of the safety has mandated that blood donors and recipients are unrelated, an issue which has eased preservation and fractionation practices; blood is no longer arm-to-arm transfused and neither is whole blood, the commonest component. However, it is interesting to note that a revival is occurring as whole blood is back on stage for certain specific indications, which is one among the many paradoxes encountered while studying this discipline.     

Personalized cancer medicine and the future of pathology

In February 2011, a group of pathologists from different departments in Europe met in Zurich, Switzerland, to discuss opportunities and challenges for pathology in the era of personalized medicine. The major topics of the meeting were assessment of the role of pathology in personalized medicine, its future profile among other biomedical disciplines with an interest in personalized medicine as well as the evolution of companion diagnostics. The relevance of novel technologies for genome analysis in clinical practice was discussed. The participants recognize that there should be more initiatives taken by the pathology community in companion diagnostics and in the emerging field of next-generation sequencing and whole genome analysis. The common view of the participants was that the pathology community has to be mobilized for stronger engagement in the future of personalized medicine. Pathologists should be aware of the challenges and the analytical opportunities of the new technologies. Challenges of clinical trial design as well as insurance and reimbursement questions were addressed. The pathology community has the responsibility to lead medical colleagues into embracing this new area of genomic medicine. Without this effort, the discipline of pathology risks losing its key position in molecular tissue diagnostics.     

Clinical trial participant characteristics and saliva and DNA metrics

Background  

Clinical trial and epidemiological studies need high quality biospecimens from a representative sample of participants to investigate genetic influences on treatment response and disease. Obtaining blood biospecimens presents logistical and financial challenges. As a result, saliva biospecimen collection is becoming more frequent because of the ease of collection and lower cost. This article describes an assessment of saliva biospecimen samples collected through the mail, trial participant demographic and behavioral characteristics, and their association with saliva and DNA quantity and quality.     

Representing a “revolution”: how the popular press has portrayed personalized medicine

PurposeThis study investigated the portrayal of “personalized” and “precision” medicine (PM) in North American news over the past decade. Content analysis of print and online news was conducted to determine how PM has been defined and to identify the frames used to discuss PM, including associated topics, benefits, and concerns.MethodsA data set was built using the FACTIVA database, searching for popular North American publications with the terms “personalized (personalised) medicine” and/or “precision medicine” from 1 January 2005 to 15 March 2016. The final set of publications totaled 774.ResultsPM is almost exclusively defined as related to genetics and is often part of a story related to cancer. The PM story is overwhelmingly one of highlighting (potential) benefits and optimism, especially in shorter publications, and ones where PM is not the main focus. This promotional PM discourse has remained fairly consistent over the past decade.ConclusionThe numerous concerns associated with PM have received little attention over the past decade, especially in articles more likely to be encountered by a more general audience. This promotion of PM serves as an example of the science hyping that takes place in science reportage and may have implications for consumers, public expectations, and related health policy.     

精准疫苗学研究进展

疫苗在对抗传染性疾病中发挥着关键的作用,特别是在新型冠状病毒感染疫情防控期间,疫苗的广泛使用显著降低了感染率与死亡率。然而,由于个体之间的免疫应答差异,不能使所有人都能获得好的疫苗保护。精准疫苗学理念的引入,正引领疫苗应用与研发向个性化、精确化的方向转型。本文系统性地梳理和阐述了精准疫苗学研究的进展,介绍其在全球公共卫生及个体健康保护领域的重要意义。     

Stakeholder engagement: a key component of integrating genomic information into electronic health records

Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine.Genet Med15 10, 792–801.     

The economic value of personalized medicine tests: what we know and what we need to know

PurposeThere is uncertainty about when personalized medicine tests provide economic value. We assessed evidence on the economic value of personalized medicine tests and gaps in the evidence base.MethodsWe created a unique evidence base by linking data on published cost–utility analyses from the Tufts Cost-Effectiveness Analysis Registry with data measuring test characteristics and reflecting where value analyses may be most needed: (i) tests currently available or in advanced development, (ii) tests for drugs with Food and Drug Administration labels with genetic information, (iii) tests with demonstrated or likely clinical utility, (iv) tests for conditions with high mortality, and (v) tests for conditions with high expenditures.ResultsWe identified 59 cost–utility analyses studies that examined personalized medicine tests (1998–2011). A majority (72%) of the cost/quality-adjusted life year ratios indicate that testing provides better health although at higher cost, with almost half of the ratios falling below $50,000 per quality-adjusted life year gained. One-fifth of the results indicate that tests may save money.ConclusionMany personalized medicine tests have been found to be relatively cost-effective, although fewer have been found to be cost saving, and many available or emerging medicine tests have not been evaluated. More evidence on value will be needed to inform decision making and assessment of genomic priorities.Genet Med 2014:16(3):251–257