"Choice of law" in precision medicine research.

Large-scale precision medicine research requires massive amounts of data representing people from all walks of life; thus, in the US, it is often multistate research. Significant legal and ethical quandaries arise as a result of the patchwork of laws states have enacted that may apply to research, are not preempted by federal law, and may impose requirements or provide participant rights and protections that differ from other states. Determining which state's laws apply, and under what circumstances, is not solved by the transition to a single-IRB model and researchers cannot simply choose one state's laws to apply uniformly. At a minimum, the current process of meeting each state's requirements could be made more reliable and efficient. To fundamentally change this status quo, however, requires action at multiple levels. Federally, well-known gaps in the Genetic Information Nondiscrimination Act should be closed, and a coherent system of compensation for research injury-including non-physical injuries-should be developed. States should clarify which of their laws are intended to apply to research and work collaboratively to harmonize them. At the level of individual research projects, numerous policies and procedures could be standardized through authoritative guidelines. Examples include clarifying the scope of broad consent, understanding and upholding Certificates of Confidentiality, offering individual research results responsibly, and consistently disseminating aggregate results to participants and the public. Overall, development of a choice of law framework specific to the research context could significantly promote clarity and consistency.

The Web of Legal Protections for Participants in Genomic Research.

The identification and arrest of the Golden State Killer using DNA uploaded to an ancestry database occurred shortly before recruitment for the National Institutes of Health's (NIH) All of Us Study commenced, with a goal of enrolling and collecting DNA, health, and lifestyle information from one million Americans. It also highlighted the need to ensure prospective research participants that their confidentiality will be protected and their materials used appropriately. But there are questions about how well current law protects against these privacy risks. This article is the first to consider comprehensively and simultaneously all the federal and state laws offering protections to participants in genomic research. The literature typically focuses on the federal laws in isolation, questioning the strengths of federal legal protections for genomic research participants provided in the Common Rule, the HIPAA Privacy Rule, or the Genetic Information Nondiscrimination Act. Nevertheless, we found significant numbers and surprising variety among state laws that provide greater protections than federal laws, often filling in federal gaps by broadening the applicability of privacy or nondiscrimination standards or by providing important remedies for individuals harmed by breaches. Identifying and explaining the protections these laws provide is significant both to allow prospective participants to accurately weigh the risks of enrolling in these studies and as models for how federal legal protections could be expanded to fill known gaps.

New and Improved? 21st Century Cures Act Revisions to Certificates of Confidentiality.

Certificates of Confidentiality ("Certificates") are a federal legal tool designed to protect sensitive, identifiable research data from compelled disclosure. Congress first authorized their use in 1970 to facilitate research on illegal drug use. The scope of their use was later expanded to cover mental health research and then again to apply broadly to identifiable, sensitive research data, regardless of topic. Certificates can be critical to enabling conduct of essential research on sensitive topics, such as effective interventions to curb the opioid epidemic or reduce HIV transmission among minority youth. Nevertheless, there have been criticisms about Certificates and their use on several grounds. For example, researchers and institutional review boards ("IRBs") may lack sufficient knowledge about them and, therefore, may not consider using them in studies for which they would be appropriate. In contrast to other protections, such as Department of Justice Privacy Certificates, Certificate protections were not automatically extended to these studies, but instead required an application. In addition, the concept of identifiable data had not kept up with technological changes that may allow for reidentification of data previously considered unidentifiable. Although a researcher who obtained a Certificate could use it to resist a legal demand for identifiable data, little was known about the actual effectiveness of the protection provided. The 21st Century Cures Act substantially revises the Certificates authorizing statute, and many of the changes are directly responsive to the criticisms that have been raised. Significantly, the Secretary of the Department of Health and Human Services ("HHS") must issue Certificate protection to federally funded research involving identifiable, sensitive research data, and the National Institutes of Health ("NIH") will automatically include such protections to research it funds. Non-federally funded researchers can continue to apply for Certificate protection. The definition of identifiable has been expanded to include data "for which there is at least a very small risk" of identification. Certificates will now not only protect against compelled disclosure, but also render protected data inadmissible in legal proceedings without participant consent. In addition, voluntary disclosure is no longer authorized, but there is now a broad exception for disclosure as required by federal, state, and local laws. In this paper, based on our previous research on Certificates, we critically evaluate the 21st Century Cures Act's Certificates revisions and their positive and negative impact on the dual goals of facilitating important, sensitive research while maximally protecting individual research participants.

Development of Plain Language Supplemental Materials for the Biobank Informed Consent Process.

The US Department of Health and Human Services addresses clear communication in the informed consent process as part of the Notice of Proposed Rulemaking for revisions to the Common Rule. However, prior research has shown that participants may not fully comprehend research studies despite completion of an informed consent process. Our main goal was to provide plain language information about donation processes to a cancer biobank to supplement an informed consent form. We developed and conducted cognitive testing with supplemental brochures that clearly communicated information about three different models for consent (notice, broad and study-specific) to future use of biospecimens. During the brochure development process, we conducted qualitative, semi-structured, individual, in-person cognitive interviews among 14 women to examine participants' perceptions of the brochures. Each participant provided feedback regarding the understandability, graphics and layout, and cultural appropriateness of the brochures. Our findings demonstrate that these methods may be used to tailor consent form brochures, such as the ones developed here, to other populations. This study therefore adds to our understanding of how best to present content to help women from two different racial groups make informed decisions about participation in a cancer biobank.

A taxing problem: The impacts of research payment practices on participants and inclusive research.

Empirical data regarding payments to participants in research is limited. This lack of information constrains our understanding of the effectiveness of payments to achieve scientific goals with respect to recruitment, retention, and inclusion. We conducted a content analysis of consent forms and protocols available on clinicaltrials.gov to determine what information researchers provide regarding payment. We extracted data from HIV (n = 101) and NIMH-funded studies (n = 65) listed on clinicaltrials.gov that had publicly posted a consent form. Using a manifest content analysis approach, we then coded the language regarding payment from the consent document and, where available, protocol for purpose and method of the payment. Although not part of our original planned analysis, the tax-related information that emerged from our content analysis of the consent form language provided additional insights into researcher payment practices. Accordingly, we also recorded whether the payment section mentioned social security numbers (or other tax identification number) in connection with payments and whether it made any statements regarding the Internal Revenue Service or the tax status of payments. We found studies commonly offered payment, but did not distinguish between the purposes for which payment may be offered (i.e., compensation, reimbursement, incentive, or appreciation). We also found studies that excluded some participants from receiving payment or treated them differently from other participants in the study. Differential treatment was typically linked to US tax laws and other legal requirements. A number of US studies also discussed the need to collect Social Security numbers and income reporting based on US tax laws. Collectively, these practices disadvantage some participants and may interfere with efforts to conduct more inclusive research.

Certificates of confidentiality: privileging research data.

With the Supreme Court's decision in Dobbs, reproductive research now joins other sensitive research topics that present legal risks to research participants, underscoring the role of Certificates in protecting them. Yet, stakeholders question whether Certificates will hold up in court. In this article, we describe the essential arguments supporting Congress's regulation of biomedical research and, thus, Certificates, under its authority to regulate interstate commerce. Our analysis should reassure researchers and Institutional review boards who rely on Certificates to protect the confidentiality of research participants' data. We conclude with recommendations for stakeholders based on our analysis.

Redressing past wrongs: changing the common rule to increase minority voices in research.

Numerous diseases disproportionately affect African Americans across socioeconomic, age, gender, and geographic groups. Despite the need for research into these disparities, African Americans are often underrepresented in research. The Tuskegee Syphilis Study receives much of the blame for this problem, but other contributing factors have also been identified. To date, government policies seeking to increase African American participation have had limited success, and recently proposed changes to the Common Rule do not address this problem. Therefore, we have proposed 3 changes: treating racial minorities as vulnerable, requiring community consultation in minority research, and increasing minority representation on institutional review boards. Coupled with other efforts, these changes could help increase minority representation in researching health disparities.

Recent developments in health care law: culture and controversy.

This article reviews recent developments in health care law, focusing on controversy at the intersection of health care law and culture. The article addresses: emerging issues in federal regulatory oversight of the rapidly developing market in direct-to-consumer genetic testing, including questions about the role of government oversight and professional mediation of consumer choice; continuing controversies surrounding stem cell research and therapies and the implications of these controversies for healthcare institutions; a controversy in India arising at the intersection of abortion law and the rights of the disabled but implicating a broader set of cross-cultural issues; and the education of U.S. health care providers and lawyers in the theory and practice of cultural competency.

Perspectives on choice of law challenges in multistate precision medicine research.

Federal law establishes minimum standards for protecting human research participants, but many states have enacted laws that may apply to research. Precision medicine research in particular implicates state laws that govern an array of topics, including human subjects research, genetic testing, and both general and genetic privacy and discrimination. Thus, the determination of which state's laws apply, and under what circumstances, can substantially alter participant rights and protections. To shed light on this topic, we conducted interviews with experts in law, human research protections, and precision medicine research. Our goal was to better understand their experiences with choice of law issues, the effects of state law variation on research practices and stakeholder groups, and approaches to addressing such variation. Interviewees were aware of state-based variation in laws that could be applied to research. However, the extent to which they perceived such variability as problematic differed, as did their perceptions of stakeholder roles and responsibilities for addressing state law variation, and their estimations of requisite knowledge among IRBs and researchers. These divergent perspectives create an ethical and legal quandary, and further empirical and normative work is needed to fully characterize the implications of substantive differences in participant rights and protections.

Addressing choice of law challenges in multi-state precision medicine research: experts' assessment of key factors.

Precision medicine research implicates numerous state laws that may affect participants' rights and protections and are not preempted by federal law. The choice of which state's laws apply, and under what circumstances, can have significant impact on research design and oversight. But neither of the traditional approaches to choice of law issues-contractual agreement or determination by a court after a dispute arises-fit the research context well. We hosted a series of workshops with choice of law experts and research law and ethics experts to identify factors that are most crucial to account for in a future choice of law precision medicine research framework. Our workshops focused on precision medicine 'places' and choice of law factors; there was consensus that 'place where the harm occurred' was relevant and best represented by where the participant resides and/or where the research/institution is located. Our experts identified factors that need to be accounted for in a future choice of law framework. They also identified potential approaches, including a federal law or model state law as ways of achieving more uniformity of protections and a comprehensive database of laws, which merit further consideration to provide IRBs and researchers the guidance they require.

Recent developments in health care law: partners in innovation.

This article reviews recent developments in health care law, focusing on the engagement of law as a partner in health care innovation. The article addresses: the history and contents of recent United States federal law restricting the use of genetic information by insurers and employers; the recent federal policy recommending routine HIV testing; the recent revision of federal policy regarding the funding of human embryonic stem cell research; the history, current status, and need for future attention to advance directives; the recent emergence of medical-legal partnerships and their benefits for patients; the obesity epidemic and its implications for the child's right to health under international conventions.

Protecting Participants in Genomic Research: Understanding the "Web of Protections" Afforded by Federal and State Law.

Researchers now commonly collect biospecimens for genomic analysis together with information from mobile devices and electronic health records. This rich combination of data creates new opportunities for understanding and addressing important health issues, but also intensifies challenges to privacy and confidentiality. Here, we elucidate the "web" of legal protections for precision medicine research by integrating findings from qualitative interviews with structured legal research and applying them to realistic research scenarios involving various privacy threats.

Implementing Regulatory Broad Consent Under the Revised Common Rule: Clarifying Key Points and the Need for Evidence.

The revised Common Rule includes a new option for the conduct of secondary research with identifiable data and biospecimens: regulatory broad consent. Motivated by concerns regarding autonomy and trust in the research enterprise, regulators had initially proposed broad consent in a manner that would have rendered it the exclusive approach to secondary research with all biospecimens, regardless of identifiability. Based on public comments from both researchers and patients concerned that this approach would hinder important medical advances, however, regulators decided to largely preserve the status quo approach to secondary research with biospecimens and data. The Final Rule therefore allows such research to proceed without specific informed consent in a number of circumstances, but it also offers regulatory broad consent as a new, optional pathway for secondary research with identifiable data and biospecimens. In this article, we describe the parameters of regulatory broad consent under the new rule, explain why researchers and research institutions are unlikely to utilize it, outline recommendations for regulatory broad consent issued by the Secretary's Advisory Committee on Human Research Protections (SACHRP), and sketch an empirical research agenda for the sorts of questions about regulatory broad consent that remain to be answered as the research community embarks on Final Rule implementation.

Certificates of Confidentiality and Mandatory Reporting.

This Viewpoint discusses the importance of obtaining federal certificates of confidentiality to free researchers to perform important research into child sexual abuse.

Life support for patients without a surrogate decision maker: who decides?

BACKGROUND: Physicians in intensive care units have withdrawn life support in incapacitated patients who lack surrogate decision makers and advance directives, yet little is known about how often this occurs or under what circumstances. OBJECTIVE: To determine the proportion of deaths in intensive care units that occur in patients who lack decision-making capacity and a surrogate and the process that physicians use to make these decisions. DESIGN: Multicenter, prospective cohort study. SETTING: Intensive care units of 7 medical centers in 2004 to 2005. PATIENTS: 3011 consecutive critically ill adults. MEASUREMENTS: Attending physicians completed a questionnaire about the decision-making process for each incapacitated patient without a surrogate or advance directive for whom they considered limiting life support. RESULTS: Overall, 5.5% (25 of 451 patients) of deaths in intensive care units occurred in incapacitated patients who lacked a surrogate decision maker and an advance directive. This percentage ranged from 0% to 27% across the 7 centers. Physicians considered limiting life support in 37 such patients or would have considered it if a surrogate had been available. In 6 patients, there was prospective hospital review of the decision, and in 1 patient, there was court review. In the remaining 30 patients, the decision was made by the intensive care unit team alone or by the intensive care unit team plus another attending physician. The authors found wide variability in hospital policies, professional society guidelines, and state laws regarding who should make life-support decisions for this patient population. Thirty-six of 37 life-support decisions were made in a manner inconsistent with American College of Physicians guidelines for judicial review. LIMITATIONS: The results are based on physicians' self-reported practices and may not match actual practices. The number of incapacitated patients without surrogates in the study is small. CONCLUSIONS: Incapacitated patients without surrogates accounted for approximately 1 in 20 deaths in intensive care units. Most life-support decisions were made by physicians without institutional or judicial review.

Risks and Legal Protections in the World of Big-Data.

The development of large electronic data sets, whether from electronic health records, health registries, or large-scale gene-environment interaction studies, offer unparalleled, innovated opportunities to learn more about human health and disease. However, because these data may be used in unexpected ways without the knowledge or consent of individuals whose data are being used, they also raise critical concerns about protections of individuals against risks. Traditional approaches to protecting research participants and patients may not address new or heightened risks in the "bid data" area.