Returning Individual Research Results from Digital Phenotyping in Psychiatry.

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants' locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant's real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas.

HIPAA's Individual Right of Access to Genomic Data: Reconciling Safety and Civil Rights.

In 2014, the United States granted individuals a right of access to their own laboratory test results, including genomic data. Many observers feel that this right is in tension with regulatory and bioethical standards designed to protect the safety of people who undergo genomic testing. This commentary attributes this tension to growing pains within an expanding federal regulatory program for genetic and genomic testing. The Genetic Information Nondiscrimination Act of 2008 expanded the regulatory agenda to encompass civil rights and consumer safety. The individual access right, as it applies to genomic data, is best understood as a civil-rights regulation. Competing regulatory objectives-safety and civil rights-were not successfully integrated during the initial rollout of genomic civil-rights regulations after 2008. Federal law clarifies how to prioritize safety and civil rights when the two come into conflict, although with careful policy design, the two need not collide. This commentary opens a dialog about possible solutions to advance safety and civil rights together.

Improving recommendations for genomic medicine: building an evolutionary process from clinical practice advisory documents to guidelines.

Genomic sequencing and multigene panel tests are moving rapidly into clinical practice for a range of indications, but the evidence to guide appropriate use is currently limited. Well-crafted advice is needed to reduce unjustified practice variation, minimize risk of error and harm to patients, and encourage best practices. In the absence of definitive evidence, provisional advice can be helpful if it clarifies the potential benefits and risks of different courses of action and identifies the knowledge gaps most important to address in future research. This paper proposes an evolutionary process starting with clinical practice advisory documents (CPADs) and culminating in clinical practice guidelines (CPGs), using two case examples to illustrate the need for this process. When evidence is limited, CPADs can clarify current practice options and identify key knowledge gaps. Added evidence can then support updates to the CPADs over time. Ultimately CPADs can provide the foundation for definitive CPGs as the evidence base matures. This approach addresses an important challenge in genomics and may be applicable to other fields in which technology and practice are outpacing evidence generation.

Impact of HIPAA's minimum necessary standard on genomic data sharing.

This article provides a brief introduction to the Health Insurance Portability and Accountability Act of 1996 (HIPAA) Privacy Rule's minimum necessary standard, which applies to sharing of genomic data, particularly clinical data, following 2013 Privacy Rule revisions. This research used the Thomson Reuters Westlaw database and law library resources in its legal analysis of the HIPAA privacy tiers and the impact of the minimum necessary standard on genomic data sharing. We considered relevant example cases of genomic data-sharing needs. In a climate of stepped-up HIPAA enforcement, this standard is of concern to laboratories that generate, use, and share genomic information. How data-sharing activities are characterized-whether for research, public health, or clinical interpretation and medical practice support-affects how the minimum necessary standard applies and its overall impact on data access and use. There is no clear regulatory guidance on how to apply HIPAA's minimum necessary standard when considering the sharing of information in the data-rich environment of genomic testing. Laboratories that perform genomic testing should engage with policy makers to foster sound, well-informed policies and appropriate characterization of data-sharing activities to minimize adverse impacts on day-to-day workflows.

Return of genomic results to research participants: the floor, the ceiling, and the choices in between.

As more research studies incorporate next-generation sequencing (including whole-genome or whole-exome sequencing), investigators and institutional review boards face difficult questions regarding which genomic results to return to research participants and how. An American College of Medical Genetics and Genomics 2013 policy paper suggesting that pathogenic mutations in 56 specified genes should be returned in the clinical setting has raised the question of whether comparable recommendations should be considered in research settings. The Clinical Sequencing Exploratory Research (CSER) Consortium and the Electronic Medical Records and Genomics (eMERGE) Network are multisite research programs that aim to develop practical strategies for addressing questions concerning the return of results in genomic research. CSER and eMERGE committees have identified areas of consensus regarding the return of genomic results to research participants. In most circumstances, if results meet an actionability threshold for return and the research participant has consented to return, genomic results, along with referral for appropriate clinical follow-up, should be offered to participants. However, participants have a right to decline the receipt of genomic results, even when doing so might be viewed as a threat to the participants' health. Research investigators should be prepared to return research results and incidental findings discovered in the course of their research and meeting an actionability threshold, but they have no ethical obligation to actively search for such results. These positions are consistent with the recognition that clinical research is distinct from medical care in both its aims and its guiding moral principles.

Barbarians at the Gate: Consumer-Driven Health Data Commons and the Transformation of Citizen Science.

"The expression 'barbarians at the gate' was … used by the Romans to describe foreign attacks against their empire." 1 "[It] is often used in contemporary English within a sarcastic, or ironic context, when speaking about a perceived threat from a rival group of people, often deemed to be less capable or somehow 'primitive.'" 2.

The Limits of FDA's Authority to Regulate Clinical Research Involving High-Throughput DNA Sequencing.

The United States Food and Drug Administration (FDA) recently signaled its interest in subjecting clinical investigations that employ high-throughput gene sequencing, also called next-generation sequencing, to the agency's Part 812 investigational device exemption (IDE) regulation. Genome sequencing--for reasons explained in this article--blurs the line between categories of in vitro diagnostic (IVD) research that FDA traditionally has regulated and categories of research that FDA traditionally has not regulated. This blurring creates a risk that FDA may overstep its proper authority to regulate fundamental genomic and medical research. This article surveys the legal limits of FDA's authority'to subject genomic research to its IDE requirements. Section 1 explains that FDA has authority to regulate clinical investigations of devices, but is not authorized to regulate investigations that merely use devices to expand medical knowledge or to conduct fundamental research, unless special circumstances apply. Section 2 discusses the special circumstances that can expand or limit FDA's authority to regulate a specific clinical investigation, and Section 3 demonstrates these using an example. Section 4 explores concerns that arose in recent years about risks to human subjects in a certain type of investigation known as sponsor-investigator studies. In response to these concerns, FDA has suggested that it can regulate such studies in ways that threaten to expand FDA's regulation of research at academic medical centers beyond its proper scope. These concerns, while valid in some academic research contexts, seem inapposite in the setting of genomic research programs funded by responsible.entities such as the National Institutes of Health (NIH). Moreover, FDA's regulations do not. appear to support the proposition that FDA can regulate sponsor-investigator studies more expansively than it regulates other studies. Section 5 explores specific ways that NIH, clinical investigators, and FDA might work together to rationalize FDA's regulation of NIH-funded-genomic research.

Return of results: ethical and legal distinctions between research and clinical care.

The return of individual results to research participants has been vigorously debated. Consensus statements indicate that researchers and bioethicists consider the return of research results most appropriate when the findings are clinically relevant. Even when clinical utility is the motivator, however, the return of individual research results is not equivalent to clinical care. There are important differences in the domains of research and medical care, both from a legal standpoint and in terms of the ethical responsibilities of clinicians and researchers. As a corollary, researchers risk promoting a therapeutic misconception if they create quasi-clinical settings for return of clinically relevant research results. Rather, efforts should be focused on clarity in the provision of research results, appropriate caveats and, most important, appropriate referrals when the results may be helpful to consider in medical care.

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

Regulatory changes raise troubling questions for genomic testing.

By 6 October 2014, many laboratories in the United States must begin honoring new individual data access rights created by recent changes to federal privacy and laboratory regulations. These access rights are more expansive than has been widely understood and pose complex challenges for genomic testing laboratories. This article analyzes regulatory texts and guidances to explore which laboratories are affected. It offers the first published analysis of which parts of the vast trove of data generated during next-generation sequencing will be accessible to patients and research subjects. Persons tested at affected laboratories seemingly will have access, upon request, to uninterpreted gene variant information contained in their stored variant call format, binary alignment/map, and FASTQ files. A defect in the regulations will subject some non-CLIA-regulated research laboratories to these new access requirements unless the Department of Health and Human Services takes swift action to avert this apparently unintended consequence. More broadly, all affected laboratories face a long list of daunting operational, business, compliance, and bioethical issues as they adapt to this change and to the Food and Drug Administration's recently announced plan to publish draft guidance outlining a new oversight framework for lab-developed tests.

Ethical, legal, and policy challenges in field-based neuroimaging research using emerging portable MRI technologies: guidance for investigators and for oversight.

Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG's consensus recommendations. These recommendations address technology quality control, design and oversight of research, including safety of research participants and others in the scanning environment, engagement of diverse participants, therapeutic misconception, use of artificial intelligence algorithms to acquire and analyze MRI data, data privacy and security, return of results and managing incidental findings, and research participant data access and control.

Minimizing liability risks under the ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing.

Recent recommendations by the American College of Medical Genetics and Genomics (ACMG) for reporting incidental findings present novel ethical and legal issues. This article expresses no views on the ethical aspects of these recommendations and focuses strictly on liability risks and how to minimize them. The recommendations place labs and clinicians in a new liability environment that exposes them to intentional tort lawsuits as well to traditional suits for negligence. Intentional tort suits are especially troubling because of their potential to inflict ruinous personal financial losses on individual clinicians and laboratory personnel. This article surveys this new liability landscape and describes analytical approaches for minimizing tort liabilities. To a considerable degree, liability risks can be controlled by structuring activities in ways that make future lawsuits nonviable before the suits ever arise. Proactive liability analysis is an effective tool for minimizing tort liabilities in connection with the testing and reporting activities that the ACMG recommends.

Rules for robots, and why medical AI breaks them.

This article critiques the quest to state general rules to protect human rights against AI/ML computational tools. The White House Blueprint for an AI Bill of Rights was a recent attempt that fails in ways this article explores. There are limits to how far ethicolegal analysis can go in abstracting AI/ML tools, as a category, from the specific contexts where AI tools are deployed. Health technology offers a good example of this principle. The salient dilemma with AI/ML medical software is that privacy policy has the potential to undermine distributional justice, forcing a choice between two competing visions of privacy protection. The first, stressing individual consent, won favor among bioethicists, information privacy theorists, and policymakers after 1970 but displays an ominous potential to bias AI training data in ways that promote health care inequities. The alternative, an older duty-based approach from medical privacy law aligns with a broader critique of how late-20th-century American law and ethics endorsed atomistic autonomy as the highest moral good, neglecting principles of caring, social interdependency, justice, and equity. Disregarding the context of such choices can produce suboptimal policies when - as in medicine and many other contexts - the use of personal data has high social value.

Digital health and acute kidney injury: consensus report of the 27th Acute Disease Quality Initiative workgroup.

Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelming. The rapid growth of digital technologies has provided a new platform to improve patient care, and reports show demonstrable benefits in care processes and, in some instances, in patient outcomes. However, despite great progress, the potential benefits of using digital technology to manage AKI has not yet been fully explored or implemented in clinical practice. Digital health studies in AKI have shown variable evidence of benefits, and the digital divide means that access to digital technologies is not equitable. Upstream research and development costs, limited stakeholder participation and acceptance, and poor scalability of digital health solutions have hindered their widespread implementation and use. Here, we provide recommendations from the Acute Disease Quality Initiative consensus meeting, which involved experts in adult and paediatric nephrology, critical care, pharmacy and data science, at which the use of digital health for risk prediction, prevention, identification and management of AKI and its consequences was discussed.