When is it appropriate to return individual research results to participants? The immense interest in this question has been fostered by the growing movement toward greater transparency and participant engagement in the research enterprise. Yet, the risks of returning individual research results—such as results with unknown validity—and the associated burdens on the research enterprise are competing considerations.Returning Individual Research Results to Participants reviews the current evidence on the benefits, harms, and costs of returning individual research results, while also considering the ethical, social, operational, and regulatory aspects of the practice. This report includes 12 recommendations directed to various stakeholders—investigators, sponsors, research institutions, institutional review boards (IRBs), regulators, and participants—and are designed to help (1) support decision making regarding the return of results on a study-by-study basis, (2) promote high-quality individual research results, (3) foster participant understanding of individual research results, and (4) revise and harmonize current regulations.

Returning Individual Research Results to Participants: Guidance for a New Research Paradigm

The evidence base supporting genetic and genomic sequence-variant interpretations is continuously evolving. An inherent consequence is that a variant's clinical significance might be reinterpreted over time as new evidence emerges regarding its pathogenicity or lack thereof. This raises ethical, legal, and financial issues as to whether there is a responsibility to recontact research participants to provide updates on reinterpretations of variants after the initial analysis. There has been discussion concerning the extent of this obligation in the context of both research and clinical care. Although clinical recommendations have begun to emerge, guidance is lacking on the responsibilities of researchers to inform participants of reinterpreted results. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in November 2018. The workgroup included representatives from the National Society of Genetic Counselors, the Canadian College of Medical Genetics, and the Canadian Association of Genetic Counsellors. The final statement includes twelve position statements that were endorsed or supported by the following organizations: Genetic Alliance, European Society of Human Genetics, Canadian Association of Genetic Counsellors, American Association of Anthropological Genetics, Executive Committee of the American Association of Physical Anthropologists, Canadian College of Medical Genetics, Human Genetics Society of Australasia, and National Society of Genetic Counselors.

The Responsibility to Recontact Research Participants after Reinterpretation of Genetic and Genomic Research Results

Personalized medicine (PM) aims to harness a wave of 'omics' discoveries to facilitate research and discovery of targeted diagnostics and therapies and increase the efficiency of healthcare systems by predicting and treating individual predispositions to diseases or conditions. Despite significant investment, limited progress has been made bringing PM to market. We describe the major perceived regulatory, intellectual property, and reimbursement challenges to the development, translation, adoption, and implementation of PM products into clinical care. We conducted a scoping review to identify (i) primary challenges for the development and implementation of PM identified in the academic literature; (ii) solutions proposed in the academic literature to address these challenges; and (iii) gaps that exist in that literature. We identified regulatory barriers to PM development and recommendations in 344 academic papers. Regulatory uncertainty was a cross-cutting theme that appeared in conjunction with other themes including: reimbursement; clinical trial regulation; regulation of co-development; unclear evidentiary requirements; insufficient incentives for research and development; incompatible information systems; and different regulation of different diagnostics. To fully realize the benefits of PM for healthcare systems and patients, regulatory, intellectual property, and reimbursement challenges need to be addressed in lock step with scientific advances.

Paving the road to personalized medicine: recommendations on regulatory, intellectual property and reimbursement challenges.

While the development of next-generation sequencing technology has had a paradigm-changing impact on biomedical research, there is likely to be a gap between discovery of therapeutic benefits in research and actual adoption of the new technology into clinical practice. This gap can create pressure on the research enterprise to provide individualized care more typical of the clinic setting because it is uniquely accessible in research. This blurring of the line between research and clinical care is understandable, and perhaps even inevitable. But even if the gap is only transitory, such a blurring can have lasting implications, both by expanding obligations imposed on researchers, but also by challenging long-held ethical views. We explore this idea, focusing on how the dissolving distinction between research and clinical care has influenced the vigorous debate around how researchers should manage genetic findings (sometimes separated into primary and incidental or secondary findings) resulting from research.

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The unintended implications of blurring the line between research and clinical care in a genomic age

The expanding use of genomic technologies encompasses all phases of life, from the embryo to the elderly, and even the posthumous phase. In this paper, we present the spectrum of genomic healthcare applications, and describe their scope and challenges at different stages of the life cycle. The integration of genomic technology into healthcare presents unique ethical issues that challenge traditional aspects of healthcare delivery. These challenges include the different definitions of utility as applied to genomic information; the particular characteristics of genetic data that influence how it might be protected, used and shared; and the difficulties applying existing models of informed consent, and how new consent models might be needed.

Genomic Testing for Human Health and Disease Across the Life Cycle: Applications and Ethical, Legal, and Social Challenges.

National advisory committees have considered the obligations owed to research participants in the event of research-related injuries. These committees have repeatedly concluded that injured research participants are entitled to compensation for their injuries, that the tort system provides inadequate remedies, and that the United States should adopt no-fault compensation. But because the advisory committees have made no concrete proposals and have taken no steps toward implementing no-fault compensation, the United States continues to rely on the tort system to compensate injured research participants. This Article argues that recent legal developments and a transformation in the global research landscape make maintaining the status quo morally indefensible and practically unsustainable. Recent legal developments exacerbate the longstanding difficulties associated with the tort system as a method of compensation; nearly every injured research participant will have difficulty recovering damages, and certain classes of injured research participants — those in federal research and those abroad — are prevented from recovering altogether, resulting in substantial unfairness. In the past ten years, many of the countries substantially involved in research have mandated systematic compensation. By not mandating compensation, the United States has become a moral outlier and risks having its noncompliant research embargoed by foreign ethics committees, thereby delaying important biomedical advances. This Article examines alternative compensation mechanisms and offers a concrete no-fault compensation proposal built on systems already in place. The proposed system can be implemented in the United States and countries around the world to help harmonize various national compensation systems and to more equitably and effectively make those injured by research whole.

Recovering from Research: A No-Fault Proposal to Compensate Injured Research Participants

National advisory committees have considered the obligations owed to research participants in the event of research-related injuries. These committees have repeatedly concluded that injured research participants are entitled to compensation for their injuries, that the tort system provides inadequate remedies, and that the United States should adopt no-fault compensation. But because the advisory committees have made no concrete proposals and have taken no steps toward implementing no-fault compensation, the United States continues to rely on the tort system to compensate injured research participants. This Article argues that recent legal developments and a transformation in the global research landscape make maintaining the status quo morally indefensible and practically unsustainable. Recent legal developments exacerbate the longstanding difficulties associated with the tort system as a method of compensation; nearly every injured research participant will have difficulty recovering damages, and certain classes of injured research participants--those in federal research and those abroad--are prevented from recovering altogether, resulting in substantial unfairness. In the past ten years, many of the countries substantially involved in research have mandated systematic compensation. By not mandating compensation, the United States has become a moral outlier and risks having its noncompliant research embargoed by foreign ethics committees, thereby delaying important biomedical advances. This Article examines alternative compensation mechanisms and offers a concrete no-fault compensation proposal built on systems already in place. The proposed system can be implemented in the United States and countries around the world to help harmonize various national compensation systems and to more equitably and effectively make those injured by research whole.

/pdf/recovering-from-research-a-no-fault-proposal-to-compensate-3xibbjgns0.pdf

The use of whole genome sequencing in biomedical research is expected to produce dramatic advances in human health. The increasing use of this powerful, data-rich new technology in research, however, will inevitably give rise to incidental findings (IFs), findings with individual health or reproductive significance that are beyond the aims of the particular research, and the related questions of whether and to what extent researchers have an ethical obligation to return IFs. Many have concluded that researchers have an ethical obligation to return some findings in some circumstances, but have provided vague or context-dependent approaches to determining which IFs must be returned and when. As a result, researchers have started returning IFs inconsistently, giving rise to concerns about legal liability in circumstances in which notification could have potentially prevented injury. While it is clear that ethical guidance should not be automatically codified as the law, and that crafting ethical obligations around legal duties can be inappropriate, the ethical debate should not proceed unaware of the potential legal ramifications of advancing and implementing an ethical obligation to return IFs. This article is the first to assess the legal claims that could be brought for a researcher’s failure to return IFs. The potential for researchers to be held liable in tort is still uncertain and turns largely on a number of factors — including customary practice and guidance documents — that are still in flux. Unlike medical care, which has a well-defined duty into which evolving scientific knowledge about genetics and genomics can readily be incorporated, a researcher’s duty to return IFs is less well defined, making it difficult to determine at the outset whether and when legal liability will attach. This article advocates for a clearer, ethically sound standard of requiring that researchers disclose in the informed consent document which approach to offering IFs will be taken. This approach enables participants to know at the outset which findings will be returned, allows researchers to ascertain when their failure to appropriately return incidental findings will give rise to liability, and enables courts to make determinations that will produce consistent legal guidance.

Finding Fault?: Exploring Legal Duties to Return Incidental Findings in Genomic Research

The use of whole-genome sequencing in biomedical research is expected to produce dramatic advances in human health. The increasing use of this powerful, data-rich new technology in research, however, will inevitably give rise to incidental findings (IFs)-findings with individual health or reproductive significance that are beyond the aims of the particular research-and the related questions of whether and to what extent researchers have an ethical obligation to return IFs. Many have concluded that researchers have an ethical obligation to return some findings in some circumstances but have provided vague or context-dependent approaches to determining which IFs must be returned and when. As a result, researchers have started returning IFs inconsistently, giving rise to concerns about legal liability in circumstances in which notification could have potentially prevented injury. Although it is clear that ethical guidance should not be automatically codified as law and that crafting ethical obligations around legal duties can be inappropriate, the ethical debate should not proceed unaware of the potential legal ramifications of advancing and implementing an ethical obligation to return IFs. This Article assesses the legal claims that could be brought for a researcher's failure to return IFs. The potential for researchers to be held liable in tort is still uncertain and turns largely on a number of factors-including customary practice and guidance documents-that are still in flux. Unlike medical care, which has a well-defined duty into which evolving scientific knowledge about genetics and genomics can readily be incorporated, a researcher's duty to return IFs is less well defined, making it difficult to determine at the outset whether and when legal liability will attach. This Article advocates for a clearer, ethically sound standard of requiring that researchers disclose in the informed consent document which approach to offering IFs will be taken. This approach enables participants to know at the outset which findings, if any, will be returned, allows researchers to ascertain when their failure to appropriately return incidental findings will give rise to liability, and enables courts to make determinations that will produce more consistent legal guidance.

/pdf/finding-fault-exploring-legal-duties-to-return-incidental-1117mzv15g.pdf

Finding Fault? Exploring Legal Duties to Return Incidental Findings in Genomic Research.

There is an emerging ethical consensus that injured research participants should receive medical care and compensation for their research-related injuries. This consensus is premised on notions of beneficence, distributive justice, compensatory justice and reciprocity. In response, countries around the world have implemented no-fault compensation systems to ensure that research participants are adequately protected in the event of injury. The United States, the world9s leading sponsor of research, has chosen instead to rely on its legal system to provide injured research participants with medical care and compensation. This article argues that US reliance on its legal system leaves injured research participants unprotected in the event of injury. Nearly every injured research participant will have difficulty receiving compensation in court, and certain classes of research participants will be barred from receiving compensation altogether. The United States’ outlier status also threatens to impede US-sponsored multinational research, potentially delaying important biomedical advances. To rectify this injustice, researchers, Institutional Review Boards, sponsors and research institutions should advocate systematic no-fault compensation in the United States to bring US law into accord with global ethical norms and ensure that injured research participants are adequately protected.

https://jme.bmj.com/content/medethics/40/3/182.full.pdf

Elizabeth R. Pike

Papers

Recovering from Research: A No-Fault Proposal to Compensate Injured Research Participants

Recovering from Research: A No-Fault Proposal to Compensate Injured Research Participants

Finding Fault?: Exploring Legal Duties to Return Incidental Findings in Genomic Research

Finding Fault? Exploring Legal Duties to Return Incidental Findings in Genomic Research.

In need of remedy: US policy for compensating injured research participants