Article

Return of Research Results: General Principles and International Perspectives

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Abstract

Five years ago, an article co-written by two of us (Joly and Simard) presented an emerging trend to disclose certain individual genetic results to research participants. Since then, both technologies and research practices have evolved significantly. Given this rapid evolution, our goal is to provide updated and thorough guidance on this issue. Our paper begins by identifying the ethical principles that support the return of results: justice, beneficence, and respect for persons. Then, it presents the results of an analysis of international norms on the return of results, covering both general and individual research results. It reveals existing divergence and consensus on these topics within the international community. With the goal of promoting greater harmonization, we conclude by proposing a flexible framework for the return of individual research results.

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... A review of international research ethics policies on the return of individual research results demonstrates a wide variability of recommendations. [16] A common anchor of existing policies is the potential health benefits that may be accrued by the return of clinically significant research findings. Several international policies, but not all, recommend that individual results (or incidental findings) be obligatorily disclosed when relevant to health or quality of life. ...
... Guidance issued by the World Health organization on the specific disclosure of individual genetic results further defines that disclosure should be made on the basis of a clear demonstration of clinical benefit and communicated in a way that averts or minimizes harm so long as there is no evidence that the individual would prefer not to know. [16] Levesque and colleagues' (2011) describe how some international guidance leaves room for return of results as an option rather than an obligation. ...
... Generally, recommendations for the return of results imply that the actual return of general (e.g., summaries) or individual research results is supported by three ethical principles. [16] 1. Principle of justice: reciprocity (fairness) is owed to the participant for the knowledge gained during research 2. Principle of beneficence: the benefits of research should be returned more globally to society and to participants through the communication of research results ...
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This report originated from discussions at the Annual Brain Development Conference in late 2013 between researchers in the Neuroethics Core and Autism Spectrum Disorders Project of NeuroDevNet. Discussants felt that return of research results is a pertinent issue but that researchers are missing a comprehensive picture of the recommendations, approaches and empirical data related to the return of research results in genetics studies in children, in neurodevelopmental disorders, and specifically in autism. This report provides an overview of recent genetic studies of autism spectrum disorder (ASD), and reviews the ethical guidance (policies and peer-reviewed literature) and best practices on the return of individual research results in adult and pediatric genetic research. We focus on this case because of the wealth of genetic research being carried out in families and cohorts to explain the etiology of ASD and because there is a burgeoning literature on parental perspectives on the return of results in this case. The empirical perspectives are collected and summarized and provide context with regard to researcher and parent perspectives on the return of genetic results in ASD studies. We conclude by making recommendations about the return of both incidental and ASD-related findings and highlight issues that merit further discussion, including the role of the child or adolescent with developmental disability in decision-making, and the importance of risk communication. We believe that the report will be of use not only for those working in the area of ASD but more broadly in the field of pediatric genetic research and neurodevelopmental disorder research. For example, the publication of new evidence showing that genetic alterations play an important role in the etiology of cerebral palsy in some children means that genetic research may becoming increasingly common in other areas of the study of neurodevelopmental disorders.
... Dissemination to participants has attracted debate and many agree it is an ethical imperative and essential marker of respect to people who participate in research studies, which often place a high burden on their time and energy. [5][6][7][8] Furthermore, the Declaration of Helsinki, the set of ethical principles regarding human experimentation developed by the World Medical Association states that "all medical research subjects should be given the option of being informed about the general outcome and results of the study". 9 Regulatory authorities have recently stipulated that results of clinical trials must be published in Open access open-access databases 10 and recommendations for sharing individual research data have also been made 11 although these have different ethical and practical implications to the dissemination of a study's aggregated results. ...
... With the sometimes-lengthy delay between study recruitment and study publication, researchers need a clear steer from the outset about when and how to contact participants and linked organisations. 8 They also need guidance on how to disseminate results that have the potential to cause harm to patients and unnecessary burden on health professionals if misunderstood. 4. Encourage early planning of dissemination. ...
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Objective Dissemination of research findings is central to research integrity and promoting discussion of new knowledge and its potential for translation into practice and policy. We investigated the frequency and format of dissemination to trial participants and patient groups. Design Survey of authors of clinical trials indexed in PubMed in 2014–2015. Results Questionnaire emailed to 19 321 authors; 3127 responses received (16%). Of these 3127 trials, 2690 had human participants and 1818 enrolled individual patients. Among the 1818, 498 authors (27%) reported having disseminated results to participants, 238 (13%) planned to do so, 600 (33%) did not plan to, 176 (10%) were unsure and 306 (17%) indicated ‘other’ or did not answer. Of the 498 authors who had disseminated, 198 (40%) shared academic reports, 252 (51%) shared lay reports, 111 (22%) shared both and 164 (33%) provided individualised study results. Of the 1818 trials, 577 authors (32%) shared/planned to share results with patients outside their trial by direct contact with charities/patient groups, 401 (22%) via patient communities, 845 (46%) via presentations at conferences with patient representation, 494 (27%) via mainstream media and 708 (39%) by online lay summaries. Relatively few of the 1818 authors reported dissemination was suggested by institutional bodies: 314 (17%) of funders reportedly suggested dissemination to trial participants, 252 (14%) to patient groups; 333 (18%) of ethical review boards reportedly suggested dissemination to trial participants, 148 (8%) to patient groups. Authors described many barriers to dissemination. Conclusion Fewer than half the respondents had disseminated to participants (or planned to) and only half of those who had disseminated shared lay reports. Motivation to disseminate results to participants appears to arise within research teams rather than being incentivised by institutional bodies. Multiple factors need to be considered and various steps taken to facilitate wide dissemination of research to participants.
... Nevertheless, in research settings there are two reasons why it may be acceptable or appropriate to communicate biomarker information related to Alzheimer's dementia risk to people without symptoms [9]. Some participants will want to know their estimated risk status, and communicating these individual research results may be an expression of respect for their autonomy and a form of reciprocity in some circumstances [10,11], even if this information is not currently actionable and the exact meaning of risk prediction and specific biomarkers within risk prediction in an individual is unknown. It has been estimated that between 50% and 90% of people are interested in knowing the results of a 'predictive' or 'reliable' test of their risk of developing dementia, with numbers varying across countries [12][13][14][15][16][17]. ...
... While their views may not be representative of the population, they have immediate relevance to questions regarding the development of responsible disclosure processes in research. The participants (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) from the EWGPWD, as members of a pre-existing, established group, represent a convenience sample. The groups were conducted according to the same protocol at the sites in London and Barcelona (see Supplementary Table 1). ...
Article
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In clinical trials which target pathophysiological mechanisms associated with Alzheimer's disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer's dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants' experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer's disease biomarkers.
... The two extreme positions of 'no disclosure at all' and 'full disclosure' of all individual genetic results are rarely advocated [6]. There is growing consensus that there is an obligation to return individual genetic results that are analytically and clinically valid, of clinical utility, and actionable, provided that the participant has consented to disclosure [9][10][11][12][13][14][15][16][17]. This position is based on principles of beneficence, respect for autonomy, and reciprocity toward research participants, as reviewed previously [6]. ...
... Duties have become more specific and detailed and go beyond the relationship between the primary researcher and the individual research participant [26]. For example, disclosure duties have arisen that apply or relate to secondary researchers, the research enterprise in general, participants' relatives, and society at large [12,16,19,21,29,34,36,41,49,50,54,71,73,86,88]. By contrast, ideas concerning consent tend to become more generalized, with new concepts such as broad consent [10,17,20,26,63,67,72,73]. ...
Article
Advances in genome sequencing together with the introduction of personalized medicine offer promising new avenues for research and precision treatment, particularly in the field of oncology. At the same time, the convergence of genomics, bioinformatics, and the collection of human tissues and patient data creates novel moral duties for researchers. After all, unprecedented amounts of potentially sensitive information are being generated. Over time, traditional research ethics principles aimed at protecting individual participants have become supplemented with social obligations related to the interests of society and the research enterprise at large, illustrating that genomic medicine is also a social endeavor. In this review we provide a comprehensive assembly of moral duties that have been attributed to genomics researchers and offer suggestions for responsible advancement of personalized genomic cancer care.
... Attention should also be paid to such a debatable issue as the provision of the genetic or genomic results results to third parties, in particular to relatives Lévesque, Joly, Simard, 2011;Zawati, Van Ness, Knoppers, 2012;Knoppers, Dam, 2011, etc.). In the United States, the implementation of genomic research has a close relationship with the information legal regime: on the one hand, the genomic research requires the transfer of research data for the science development, and on the other hand, the transfer of research data should not jeopardize personal, family and other types of secrets. ...
Article
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This article is devoted to the analysis of the genomic research legal regulation in the Russian Federation and the USA. In the United States, in addition to the legislation great importance is attached to medical and scientific institutions self-regulation, and such information is usually open. It is concluded that in Russia, despite the presence of both state and non-state scientific institutions engaged in genomic research, the mechanism of self-regulation as a whole is fragmented. It is also noted that Russia and the United States have specific legal regulation of these relations, which is reflected in the text of the article. For example, in the United States, unlike Russia, most organizations conducting genomic research, including genomic testing, are non-governmental. Currently, the general trend in the legal regulation of genomic research in Russia and the USA is the active development of normative legal regulation. Moreover, a significant difference in the approaches of these countries is the active role of the US states in the development of regional legal regulation on these issues. Despite the fact that Russia is a federal state, the subjects of the Russian Federation are significantly limited in the genomic research legal regulation possibilities. This is largely due to both legal and political reasons that were given in this article. In the United States, a number of statutes have been adopted at the state level that regulate genomic research in such aspects as health insurance, confidential of personal information, the prohibition of discrimination, screening of newborns, and certain types of clinical and scientific research. It should be noted that the genomic research regulation in the United States is not integrated into a single national consolidated act, which is a feature of this legal system. A comparative legal study of the fundamentals of legal regulation and self-regulation of genomic research in Russia and the USA made it possible to understand the specifics of regulation of these issues in different legal systems. The positive regulatory experience in conducting genomic research in the United States can be used to improve the regulatory framework of the Russian Federation in this area.
... Questions about whether and how to return research results, including individual and aggregate findings, are ethically and practically complex [7]. Though a vast literature has developed on the legal and ethical grounds for the return of research results [8], there remains substantial regulatory disagreement across jurisdictions over how these results ought to be managed [9]. International DTP genomic research might give this regulatory disagreement an especially challenging patina. ...
Article
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This paper summarizes the results of a 31-country qualitative study of expert perspectives on the regulation of international “direct-to-participant” (DTP) genomic research. We outline how the practice of directly recruiting participants for genomic studies online complicates ethics and regulatory considerations for the return of individual research results. As part of a larger project supported by the National Human Genome Research Institute, National Institutes of Health, we prepared and distributed to 31 global legal experts a questionnaire intended to ascertain opinions and perspectives on the way international DTP genomic research is likely to be regulated. We found significant disagreement across jurisdictions on the most favorable approach to managing such results, with some countries favoring return by default and others preferring to return only with the express consent of research participants. We conclude by outlining policy considerations that should guide researcher practices in this context. As international DTP genomic research evolves, jurists and ethicists should be attentive to the ways novel approaches to subject recruitment align with existing ethical and regulatory norms in research with human participants. This paper is a preliminary step toward documenting such alignment in the context of the return of individual research results.
... The World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects states that research participants 'should be given the option of being informed about the general results and outcomes of the study' [35]. Reporting research findings to trial participants is an ethical imperative because participants have had to accept the burden and risks of participating in trials and have a right to know about the research outcomes [36][37][38]. Despite this, a survey completed by >3000 trialists found that less than half had disseminated the results to participants, and only half had provided these findings in plain language [39]. ...
Article
Background: Slow recruitment and poor retention jeopardize the reliability and statistical power of clinical trials, delaying access to effective interventions and increasing costs, as commonly observed in nephrology trials. Involving patients in trial design, recruitment and retention is infrequent but potentially transformational. Methods: We conducted three workshops involving 105 patients/caregivers and 43 health professionals discussing patient recruitment and retention in clinical trials in chronic kidney disease. Results: We identified four themes. 'Navigating the unknown'-patients described being unaware of the research question, confused by technical terms, sceptical about findings and feared the risk of harm. 'Wary of added burden'-patients voiced reluctance to attend additional appointments, were unsure of the commitment required or at times felt too unwell and without capacity to participate. 'Disillusioned and disconnected'-some patients felt they were taken for granted, particularly if they did not receive trial results. Participants believed there was no culture of trial participation in kidney disease and an overall lack of awareness about opportunities to participate. To improve recruitment and retention, participants addressed 'Building motivation and interest'. Conclusions: Investigators should establish research consciousness from the time of diagnosis, consider optimal timing for approaching patients, provide comprehensive information in an accessible manner, emphasize current and future relevance to them and their illness, involve trusted clinicians in recruitment and minimize the burden of trial participation. Participation in clinical trials was seen as an opportunity for people to give back to the health system and for future people in their predicament.
... Still, the return of IF might not constitute an improper inducement to participate in research. For example, Lévesque et al. argued that the principle of reciprocity (or reciprocal justice) under the context of research can benefit a "group", but it might not always be inferred to benefit an "individual" [26]. In contrast, some individuals have argued that when personally-provided biospecimens are used in research, a participant generally has a strong awareness of the right to know the result [27][28][29]. ...
Article
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Background: In this article, incidental findings (IF) refer to unforeseen findings made possible through biobanking research and advances in medical diagnostic technologies that raise issues regarding the obligation and/or responsibility of biobank-users and biobanks to return clinically significant information to participants. The World Medical Association (WMA) Declaration of Taipei (2016) highlights the possibility of encountering IF and requires that research on biospecimens address biobank feedback policies in their informed consent process, leaving open the possibility that the policy may be "no return". As clinicians and researchers begin to use these "resources", the possibility of finding clinically significant IF is becoming a reality. Discussion: In line with the WMA's Declaration of Taipei, a pragmatic approach is needed to deal with the issue of returning IF in biobank governance. Indeed, the impacts and concerns associated with the return of IF differ across different stakeholder groups and jurisdictions. Therefore, the framework governing IF return needs to be custom-built, taking into account the nature of each research project and the unique features of biobanks. To this end, in addition to facilitating biobank transparency, establishing an endurable and horizontal connection among biobanks and clinical institutions under a public health system will improve efficiency and effectiveness. Hence, subject to contemporary Taiwanese ethical and/or legal regulations, this article argues for the establishment of an updated framework for imaging-related and genetic-related IF return within the Taiwan Biobank (TWB), mainly based on a limited obligation to disclose life-threatening information revealed by imaging, but not genetic, information. Summary: After discussing some of the ethical, legal and social issues encountered by the TWB and accounting for the experiences of other international biobanks, we propose a systematic framework for returning IF, mainly on a "limited obligation" basis, which offers better and more comprehensive protection for biobank-participants' rights and health.
... Duties among individual disclosure were mostly directed to the duty to return the results of experiments to participants (or their relatives under certain conditions). [12][13] Due to the limitation of variant references, the genetic research results are probability based, sometimes uncertain and pleiotropic. Both extreme positions of "0% disclosure" and "100% disclosure" are rarely recommended. ...
Article
The rapid growing and improvement of information promoted the progress of health science directly and indirectly, while accessary problems and difficulties might compromise the technological progress, especially the medical information converted from traditional recording to electronic based recording. Potential information leakage among communication tools, diagnostic platforms, data storage or transfer medium, social media, or inappropriate human factors among medical or healthcare agencies. Newly emerged data leakage through genome sequencing platforms triggered more potential cyber security weakness other than traditional electronic healthcare record, which required professional personnel’s contribution from lawyers, physicians, biomedical scientists, engineers, and government to work together to setup and update the duties and regulatory frameworks in time, with sufficient and continuous monitoring.
... Participants surveyed by Beskow and Dean (2008) raise the idea of researchers offering information about the research as fair exchange for the participants providing their data in the first place, especially in the case of biobanks, where there is rarely a direct benefit to participation. The concept of reciprocity is also discussed by Lévesque (2011) as important for upholding the ethical principle of justice in relation to provision of feedback to participants. If participants are going to provide their time, biologic samples, test outcomes etc. for research purposes, the knowledge gained from the research should be translated back to them. ...
Article
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It is becoming widely recognized that dissemination of research results to participants is an important action for the conclusion of a research study. Most research institutions have standardized consent documents or templates that they require their researchers to use. Consent forms are an ideal place to indicate that results of research will be provided to participants, and the practice of inserting statements to this effect is becoming more conventional. In order to determine the acceptance of this practice across Canada we conducted an assessment of 121 institutional consent document templates from 65 institutions (hospitals and universities) looking for language that endorsed results dissemination to participants. About half (51%) of the documents we examined had language included which stated that results should be made available. In an era where research participation in hospital settings and universities is becoming ubiquitous there should be a reciprocal expectation that results should be provided. The success of research should be measured in part by its accessibility and dissemination to all stakeholders.
... Most participants supported the return of results of all tests conducted during clinical trials. Currently, there exist very heterogeneous research ethics guidelines on the return of results to research participants, which vary between countries and even between institutions [37,38]. To some extent, the issue of return of results is addressed by ethical guidelines that recommend reporting incidental findings that are clinically relevant [39]. ...
Article
The importance of patient engagement in research has been gaining recognition since the turn of the 21st century. However, little is known about the perspectives of people with dementia on the process of discovery. To fill this gap and to inform priorities in patient engagement in the context of dementia research, the Clinic for Alzheimer Disease and Related Disorders at the University of British Columbia hosted an interactive session for members of the patient community and of the general public to share their views on various ethical aspects of the research process. Results from the session indicate that several current research ethics policies and norms in dementia research are not in line with participants' preferences. Here we discuss the importance of bridging the gap between researchers and patients and call for reforms in current standards of dementia research.
... In particular, we found that specific reasons to return results to include: result indicates a change in treatment, result answers clinical question, or result is asked for by the patient. The literature suggests that whether a result is returned should be based on the ACCE model (CDC 2010), which states results should be evaluated on four criteria: 1) Analytic validity: how accurately and reliably it measures the results; 2) Clinical validity: how consistently and accurately the test can detect or predict outcomes; 3) Clinical utility: how likely the result may significantly improve health or health related decisions made by the participant; and 4) Ethical, legal, and social implications (ELSI) (Lévesque et al. 2011). However, this does not solve the problem of who decides whether the results meet this criteria or how to actually return the results. ...
Article
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Genome science is rapidly shifting from research labs and biobanks to the clinical setting. The resulting genomic big data, or large-scale networked genetic material, is a disruptive technology. On one hand, clinical genomics advances life-saving innovation through precision medicine. On the other, the digital databases they are built upon raise new concerns for informational risk to personal privacy. While a traditional biomedical approach focuses on risks and benefits to the human body, our socio-technical analysis sheds lights on the emerging terrain of the human body as digital code. In this paper, we analyze emerging issues related to clinical genomics based on a 3-year collaborative clinical research project to develop a genomic test for Acute Myeloid Leukemia (AML) cancer in British Columbia (BC), the first of its kind in Canada. We found the most pressing issues for genomic researchers and clinicians were challenges around informed consent, return of results and return of incidental findings. In light of technological advances and the emerging context of networked privacy, we outline several recommendations for best practices in diffusing clinical genomics to the healthcare system.
... in the particular setting of medical genomics [5]. The term has been adopted by other authors, including Solomon, who used it when proposing an analogy between IFs in genomics and in radiology [6] The earliest definitions of IFs made no clear distinction between the problems involved in the return of unexpected results and those involved in the return of research results in general [7]. One of the few exceptions was the Statement on the Principled Conduct of Genetics Research of the Human Genome Organisation [8]. ...
Article
Genetic tests frequently produce more information than is initially expected. Several documents have addressed this issue and offer suggestions regarding how this information should be managed and, in particular, concerning the expedience of revealing (or not revealing) it to the persons concerned. While the approaches to the management of these incidental findings (IFs) vary, it is usually recommended that the information be disclosed if there is confirmed clinical utility and the possibility of treatment or prevention. However, this leaves unsolved some fundamental issues such as the different ways of interpreting "clinical utility", countless sources of uncertainty and varying ways of defining the notion of "incidental". Guidelines and other reference documents can offer indications to those responsible for managing IFs but should not be allowed to relieve researchers and healthcare professionals of their responsibilities.
... Second, communicating findings to participants gives them something in return for their contribution. Reciprocity reflects the idea "that individuals who voluntarily agree to contribute to research be provided some kind of access to the knowledge gained from such research" [4]. Finally, acting in the individual participant's interest is a concrete expression of respect: acknowledgement that participants are more than simply a means to knowledge generation. ...
Article
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This article outlines procedures for the feedback of individual research data to participants. This feedback framework was developed in the context of a personalized medicine research project in Canada. Researchers in this domain have an ethical obligation to return individual research results and/or material incidental findings that are clinically significant, valid and actionable to participants. Communication of individual research data must proceed in an ethical and efficient manner. Feedback involves three procedural steps: assessing the health relevance of a finding, re-identifying the affected participant, and communicating the finding. Re-identification requires researchers to break the code in place to protect participant identities. Coding systems replace personal identifiers with a numerical code. Double coding systems provide added privacy protection by separating research data from personal identifying data with a third "linkage" database. A trusted and independent intermediary, the "keyholder", controls access to this linkage database. Procedural guidelines for the return of individual research results and incidental findings are lacking. This article outlines a procedural framework for the three steps of feedback: assessment, re-identification, and communication. This framework clarifies the roles of the researcher, Research Ethics Board, and keyholder in the process. The framework also addresses challenges posed by coding systems. Breaking the code involves privacy risks and should only be carried out in clearly defined circumstances. Where a double coding system is used, the keyholder plays an important role in balancing the benefits of individual feedback with the privacy risks of re-identification. Feedback policies should explicitly outline procedures for the assessment of findings, and the re-identification and contact of participants. The responsibilities of researchers, the Research Ethics Board, and the keyholder must be clearly defined. We provide general guidelines for keyholders involved in feedback. We also recommend that Research Ethics Boards should not be directly involved in the assessment of individual findings. Hospitals should instead establish formal, interdisciplinary clinical advisory committees to help researchers determine whether or not an uncertain finding should be returned.
... The calls to disclose IF, becoming more and more voluminous, appear to rest upon an assumption in both the literature and guidelines that researchers have the clinical know-how, logistical capabilities, and sufficient funding to carry out the disclosure. This assumption, though, remains under study (11,35) and careful consideration is needed to better understand the practical implications of the ethical responsibility to disclose IF (2,(36)(37)(38)(39)(40). Certainly, concerns about funding for IF disclosure will only increase as more and more genetic links are found to more and more diseases (2,39,41,42). ...
Article
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The use of biobanks in biomedical research has grown considerably in recent years. As a result of the increasing analysis of tissue samples stored in biobanks, there has also been an increase in the probability of discovering—in addition to the research target—incidental findings (IF). We identified 23 laws, policies and guidelines from international, regional and national organizations that provide guidance or identify the need for the disclosure of IF to research participants. We analyzed these instruments to determine their contemplation of the funding considerations for the disclosure of IF, examining their guidance for who discloses and the extent of researcher responsibilities. We found that the available normative documents provide little guidance to researchers and biobanks for how they should address cost and funding concerns associated with IF disclosure. It is therefore essential that the research and policy communities think through the financial implications of imposing an ethical responsibility to disclose IF. Concerted efforts should be made by policymakers, ethicists, researchers, clinicians and research institutions to develop detailed funding recommendations, potentially universal in application, to aid in the disclosure of IF, and we provide recommendations on steps that can be taken to ensure full consideration of these issues.
... The issue of whether and how to manage information generated by next-generation sequencing and genomic biobanking methods is being widely discussed, for example, and various opposing viewpoints and approaches have been presented. [9][10][11] Although disclosure of aggregate research results, the second topic on which debate has focused, has been described as being less risky, 8 it has given rise to a great deal of discussion in the field of clinical research. In the early 2000s, although it was generally recognized that investigators were under an ethical obligation to inform participants about the results of their clinical research, 2 this was only rarely done in actual practice. ...
Article
Background Although greater attention is currently being paid to participants in research, no studies have dealt so far with the issue of returning aggregate psychosocial results to cohort participants.Objective(i) To explore participants’ views about disclosure of the aggregate results of a French national psychosocial cohort survey on the epidemiology of preventive behaviour in women from families with a hereditary breast cancer risk. (ii) To assess whether it is worth consulting participants before designing the disclosure process.DesignA qualitative study using semi-structured face-to-face interviews and a thematic analysis based on Grounded Theory methods.ParticipantsNineteen interviews were conducted with cancer-free female BRCA mutation carriers/non-carriers aged 31-79 who had participated in a cohort survey by answering self-administered questionnaires.ResultsParticipants showed considerable interest in the issue of result disclosure. The preferences expressed about disclosure were rarely relevant to the topic investigated, however, as they often focused on medical knowledge about BRCA and not on the psychosocial findings obtained. This confusion may have been due to the participants’ experience of the survey procedures, including its longitudinal nature, the occurrence of very few interactions with the investigators and the wide range of topics addressed in the questionnaires.Conclusion Investigators should ascertain participants’ expectations and preferences by consulting them before disclosing the results obtained. Although the disclosure process may not meet participants’ expectations completely, consultation is the key to preventing them from having irrealistic expectations about the information they are going to receive.
... As noted above, we were unable to reach clear consensus about the returning of results. Indeed, the disclosure of individual research results to participants is one of the most controversial areas in the ELSI of personal genomics (Knoppers et al. 2006;Wolf et al. 2008Wolf et al. , 2012McGuire and Lupski 2010;Levesque et al. 2011). In Japan, while there are national guidelines for human genome research, as described above, these leave decisions to the broad discretion of researchers. ...
Article
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As evidenced by high-throughput sequencers, genomic technologies have recently undergone radical advances. These technologies enable comprehensive sequencing of personal genomes considerably more efficiently and less expensively than heretofore. These developments present a challenge to the conventional framework of biomedical ethics; under these changing circumstances, each research project has to develop a pragmatic research policy. Based on the experience with a new large-scale project—the Genome Science Project—this article presents a novel approach to conducting a specific policy for personal genome research in the Japanese context. In creating an original informed-consent form template for the project, we present a two-tiered process: making the draft of the template following an analysis of national and international policies; refining the draft template in conjunction with genome project researchers for practical application. Through practical use of the template, we have gained valuable experience in addressing challenges in the ethical review process, such as the importance of sharing details of the latest developments in genomics with members of research ethics committees. We discuss certain limitations of the conventional concept of informed consent and its governance system and suggest the potential of an alternative process using information technology.
... 76 In extreme cases, studies can have legislative implications in countries where individuals have been prosecuted under criminal law for exposing others to infections such as HIV, 71,77 hepatitis B virus, 78 and herpes simplex virus. 79 The decision as to whether or not to return results to participants should also be presented and justifi ed by authors, 80 taking into account the public health implications for people who have been in contact with those diagnosed with (possibly asymptomatic) infections. Authors should therefore report ethical approval. ...
Article
Molecular data are now widely used in epidemiological studies to investigate the transmission, distribution, biology, and diversity of pathogens. Our objective was to establish recommendations to support good scientific reporting of molecular epidemiological studies to encourage authors to consider specific threats to valid inference. The statement Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) builds upon the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. The STROME-ID statement was developed by a working group of epidemiologists, statisticians, bioinformaticians, virologists, and microbiologists with expertise in control of infection and communicable diseases. The statement focuses on issues relating to the reporting of epidemiological studies of infectious diseases using molecular data that were not addressed by STROBE. STROME-ID addresses terminology, measures of genetic diversity within pathogen populations, laboratory methods, sample collection, use of molecular markers, molecular clocks, timeframe, multiple-strain infections, non-independence of infectious-disease data, missing data, ascertainment bias, consistency between molecular and epidemiological data, and ethical considerations with respect to infectious-disease research. In total, 20 items were added to the 22 item STROBE checklist. When used, the STROME-ID recommendations should advance the quality and transparency of scientific reporting, with clear benefits for evidence reviews and health-policy decision making.
... Current guidelines for return of research results in genomic studies focus on protecting participants from harm using criteria including analytic validity, clinical validity, actionability, and the severity of outcome, 4,14 but these criteria are being extensively debated. 5,6,15 For example, commentators urge reconsideration of traditionally restrictive disclosure policies that focus exclusively on protecting participants from harm of disclosure and that fail to take into account these persons' own formulation of benefit, harm, and acceptable risk. 5,16 They encourage reliance on empiric evidence to help guide conclusions about disclosure policy, citing data that suggest the prevalence of negative consequences is low and that individuals tend to find disclosure of test results beneficial, regardless of the actual result or accompanying psychological distress. ...
Article
To inform whether the Alzheimer's Disease Neuroimaging Initiative (ADNI) should change its policy of not returning research results to ADNI participants, we surveyed investigators and research staff about disclosing ADNI biomarker information to research participants, with particular emphasis on amyloid imaging results. In April 2012, just before Food and Drug Administration approval of the amyloid-binding radiotracer, florbetapir, all ADNI investigators and personnel were recruited to complete an anonymous online survey that contained fixed choice and free-text questions. Although ADNI participants often requested amyloid imaging results (the proportions of investigators who reported requests from more than half of their participants with normal cognition or mild cognitive impairment were 20% and 22%, respectively), across all diagnostic groups, the majority of ADNI investigators (approximately 90%) did not return amyloid imaging results to ADNI participants. However, the majority of investigators reported that, if the Food and Drug Administration approved florbetapir, they would support the return of amyloid imaging results to participants with mild cognitive impairment and normal cognition, but they emphasized the need for guidance on how to provide these results to participants and for research to assess the value of returning results as well as how returning results will affect study validity and participant well-being. A majority of ADNI investigators support returning amyloid imaging results to ADNI participants. The findings that they want guidance on how to do this and research on the impact of disclosure suggest how to develop and monitor a disclosure process.
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Background: In prevalence studies of sexually transmitted infections (STIs), investigators often provide syndromic management for symptomatic participants, but may not provide specific treatment for asymptomatic individuals with positive laboratory test results due to the delays between sample collection and availability of results as well as logistical constraints in re-contacting study participants. Methods: To characterize the extent of this issue, 80 prevalence studies from the World Health Organization's Report on global sexually transmitted infection surveillance, 2018, were reviewed. Studies were classified as to whether clinically relevant positive results were returned or if this was not specified. Results: More than half (56%) of the cited studies did not specify if participants were notified of clinically relevant positive STI test results. The percentages were similar for low- and middle-income country populations (57%) and high-income country populations (53%). Conclusions: The absence of documentation of the provision of test results raises the possibility that in some instances, results may not have been communicated, with potential negative effects for participants, their sexual partners, and newborns. From an ethical perspective, clinically relevant results should be returned to study participants and treating clinicians in a timely fashion to ensure appropriate management of identified infections. Study authors should document if they returned test results to study participants and report on numbers lost to follow-up.
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There is growing evidence that human genetics plays a significant role in shaping human responses to infectious diseases. For instance, individuals' genetic susceptibility or resistance to infectious disease is likely to affect disease transmission. Yet little attention has been paid to the ethical, legal, and social implications of research in genomics and infectious disease, despite the unique ethical issues that arise in this arena. This article presents results from a pilot study exploring ethics in research on human genetics and response to HIV and other infectious diseases and is focused on perspectives from expert stakeholders. Whereas chairs of institutional review boards, biobank directors, and researchers in genomics and infectious disease expressed similar views about research privacy in the context of a public health emergency, they expressed different perspectives about the role that public health considerations ought to play in the return of individual results to research participants. These perspectives highlight the need to emphasize the importance of broad dialogue for helping various parties navigate the ethically complex current and future challenges of genomics and infectious disease research.
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While risk of harm is an important focus for whether clinical research on humans can and should proceed, there is uncertainty about what constitutes harm to a trial participant. In Phase I trials on healthy volunteers, the purpose of the research is to document and measure safety concerns associated with investigational drugs, and participants are financially compensated for their enrollment in these studies. In this article, we investigate how characterizations of harm are narrated by healthy volunteers in the context of the adverse events (AEs) they experience during clinical trials. Drawing upon qualitative research, we find that participants largely minimize, deny, or re-attribute the cause of these AEs. We illustrate how participants' interpretations of AEs may be shaped both by the clinical trial environment and their economic motivation to participate. While these narratives are emblematic of the larger ambiguity surrounding harm in the context of clinical trial participation, we argue that these interpretations also problematically maintain the narrative of the safety of clinical trials, the ethics of testing investigational drugs on healthy people, and the rigor of data collected in the specter of such ambiguity.
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As evidenced by high-throughput sequencers, genomic technologies have recently undergone radical advances. These technologies enable comprehensive sequencing of personal genomes considerably more efficiently and less expensively than heretofore. These developments present a challenge to the conventional framework of biomedical ethics; under these changing circumstances, each research project has to develop a pragmatic research policy. Based on the experience with a new large-scale project—the Genome Science Project—this article presents a novel approach to conducting a specific policy for personal genome research in the Japanese context. In creating an original informed-consent form template for the project, we present a two-tiered process: making the draft of the template following an analysis of national and international policies; refining the draft template in conjunction with genome project researchers for practical application. Through practical use of the template, we have gained valuable experience in addressing challenges in the ethical review process, such as the importance of sharing details of the latest developments in genomics with members of research ethics committees. We discuss certain limitations of the conventional concept of informed consent and its governance system and suggest the potential of an alternative process using information technology.
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Australia is a multi-cultural society with a population of nearly 24 million. The Aboriginal heritage traces back some 40,000 years and continues to influence Australian culture as a whole. A large proportion of Australian citizens were of British descent or birth at the outset of the last century, but post-World War II there was significant immigration from other European nations, particularly from Greece and Italy. In the last decades, there has been a significant intake of migrants from Asia.
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Returning genetic research results to relatives raises complex issues. In order to inform the U.S. debate, this paper analyzes international law and policies governing the sharing of genetic research results with relatives and identifies key themes and lessons. The laws and policies from other countries demonstrate a range of approaches to balancing individual privacy and autonomy with family access for health benefit, offering important lessons for further development of approaches in the United States.
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In the growing field of genomics, the utility of returning certain research results to participants has become a highly debated issue. Existing guidelines are not explicit as to the kind of genomic information that should be returned to research participants. Moreover, very few current recommendations and articles in the literature address the return of pharmacogenomic results. Although genetics and pharmacogenomics have many similarities, the circumstances in which disclosure could have a benefit for the participants are different. This review aims to describe the conditions in which disclosure of pharmacogenomic results is appropriate.
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This paper provides an overview of measures regarding the ethical and social aspects of biobanks from the perspective of governance. A Biobanks is a system that manages samples taken from humans along with data of the sample donor(genetic information, information on medical records, information on lifestyle habits, etc.)in a centralized manner according to a set quality standard. In recent years, biobanks have become an essential research infrastructure, especiallyin the field of genome medical research and research concerning common diseases such as cancer and diabetes. Simultaneously, this indicates that biobanks are strongly linked to the realization of benefits that are highly public. For this reason, biobanks need to consider not only the promotion of medical research, but must also practice consideration for the ethical, social, and public aspects. In other words, biobanks need to be subject to governance. In this paper, three specific issues concerning the ethical and social aspects of biobank have been discussed: (i)issues regarding boroad or future consent, (ii)risks related to the handling of samples and data, and (iii) feedback on incidental findings. These are issues that accompany rapid advances in genome medicine and involve complex elements that cannot be completely resolved by the existing principles of life ethics and rules. For this reason, the parties managing biobanks are required to make an effort toward realizing an ethically and socially feasible operation of the biobank, with consideration paid not only to compliance but also to the reaction of research participants and society. Furthermore, there is an urgent need to establish a system of governance that enables organizational management with the wide perspective discussed here.
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Until the mid-20th century, biomedical research centered on the study of specific diseases, concerned with short periods of time and small groups of living research participants. However, the growth of longitudinal population studies and long-term biobanking now forces the research community to examine the possibility of the death of their research participants. The death of a research participant raises numerous ethical and legal issues, including the return of deceased individuals’ research results to related family members. As with the return of individual research results for living research participants, the question of the obligation to return a deceased person’s research results to family members has yet to be settled. This question is particularly acute in the context of genetic research since the research results from one individual may have health implications for all biological relatives.
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Currently, the return of results in the domain of biobanking constitutes an ethical and legal quagmire, whether it involves population or specific clinical research studies. In light of the fact that population biobanks are often not seen as distinct from those biobanks created for disease research, as well as the uncertainty as to what "return of results" means concretely, this lexicon attempts to demystify the terminology. The terms - results, return, clinical significance, and utility - are discussed. Through an analysis of international and national normative guidance on this issue, the authors propose a concordance of meaning and a simplified lexicon.
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The obligations of researchers to disclose clinically and/or personally significant individual research results are highly debated, but few empirical studies have addressed this topic. We describe the development of a protocol for returning research results to participants at one site of a multicenter study of the genetic epidemiology of melanoma. Protocol development involved numerous challenges: (1) deciding whether genotype results merited disclosure; (2) achieving an appropriate format for communicating results; (3) developing education materials; (4) deciding whether to retest samples for additional laboratory validation; (5) identifying and notifying selected participants; and (6) assessing the impact of disclosure. Our experience suggests potential obstacles depending on researcher resources and the design of the parent study, but offers a process by which researchers can responsibly return individual study results and evaluate the impact of disclosure.
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During the past decade, various guidelines that imply a duty for researchers to disclose information obtained through research to participants have emerged. The character and extent of this obligation have been debated extensively, with much attention devoted to the decisiveness of the validity and utility of the results in question. The aim of this paper is to argue that individual results from research on materials stored in large-scale biobanks, consisting of samples taken within the healthcare system or of altruistically donated materials, should not be returned. We will defend the thesis that medical research on these biobanks should be viewed as a collective project to improve public health, and that available resources should be utilized to pursue this goal. We argue that there is a need for a change of perspectives. Medical research should not primarily be viewed as a danger that individuals must be protected from, but rather be recognized as constituting a necessary defense against current and future diseases. Research that bears the prospect of advancing medicine and that can be carried out at no risk to individuals should be endorsed and facilitated. This calls for a shift of focus from autonomy and individual rights toward collective responsibility and solidarity.
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Bioethics increasingly relies on empirical research in order to resolve ethical issues. Bioethics has also, of late, begun reimagining the researcher-subject relationship to include new positive duties to subjects, such as providing ancillary care and offering to return research results. These trends have converged in the form of a growing stream of empirical studies of subjects’ preferences about being offered research results. The legal and ethical question at the intersection of these trends is how we should factor these preferences into research design.This short article in the leading bioethics journal takes a middle position on this question in the context of a proposed longitudinal study of genes, environment and health, in which the National Human Genome Research Institute hopes to enroll a cohort of 500,000, primarily through door-to-door recruitment. A survey found that most respondents would want to be offered the return of their individual genetic results. I reject both (1) the claim that evidence that subjects want to be offered results entails a duty by researchers to do so, but also (2) the paternalistic position that most individual results should not be returned.I reach the first conclusion by arguing that the subject-researcher relationship in this case should be viewed as a sort of arms-length donative contract: an agreement under which the donor-subject agrees to make a gift to the donee-researcher, who arguably holds the gift in trust for society (especially given that the research is government-funded) and does not promise anything directly in return. A contract’s terms need not, and rarely do, reflect the ideal preferences of either party, and researchers may make offers to potential research volunteers that reflect their own preferences, resource limitations, and conscientious beliefs about the wisdom of returning certain results. The acceptance of what often must be, for pragmatic reasons, a take-it-or-leave-it offer to volunteer is not invalidated, nor the ensuing research rendered unethical, because the volunteer’s gift is not “repaid” in the form of research results or, indeed, in any form (though subjects must be told results will not be disclosed). Moreover, returning individual results in an ethical manner can be costly, and it would be odd (and perhaps not in keeping with subjects’ overall preferences, which most surveys are not designed to elicit or construct) if researchers had a duty to subjects that undercut their ability to devote the maximum available resources to the research itself — the very end that should motivate the subjects to volunteer in the first place. Finally, even if we assume that subjects own or are otherwise entitled to their genetic information, surely such property can be alienated, or such entitlements waived, through the donative contract. A contract’s terms, however, must not sink to the level of unconscionability.Empirical data can, however, inform researchers who admirably want, and are able, to honor subjects’ preferences. Subjects have interests in receiving a much wider range of results than is often acknowledged, and most of the psychosocial risks they are said to face from disclosure remain speculative. Returning results may also help researchers recruit and retain subjects.
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The Pharmacogenomics Journal is dedicated to the rapid publication of original research on basic pharmacogenomics research and its clinical applications.
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Controversy exists about the responsibility of investigators to communicate the results of research to study participants. These research results may be categorized as either general study results, which represent aggregate data usually published by the research team, or individual results, which are research findings relevant to particular participants. Disclosure of individual research results has become particularly contentious in the context of genetics research, for which genotypes of individual participants often become known to investigators.1 However, disclosure of individual results should be addressed in all research involving human participants.
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The last decade has witnessed the emergence of international ethics guidelines discussing the importance of disclosing global and also, in certain circumstances, individual genetic research results to participants. This discussion is all the more important considering the advent of pharmacogenomics and the increasing incidence of 'translational' genetic research in the post-genomic era. We surveyed both the literature and the ethical guidelines using selective keywords. We then analyzed our data using a qualitative method approach and singled out countries or policies that were representative of certain positions. From our findings, we conclude that at the international level, there now exists an ethical duty to return individual genetic research results subject to the existence of proof of validity, significance and benefit. Even where these criteria are met, the right of the research participant not to know also has to be taken into consideration. The existence of an ethical duty to return individual genetic research results begs several other questions: Who should have the responsibility of disclosing such results and when? To whom should the results be disclosed? How? Finally, will this ethical 'imperative' become a legally recognized duty as well?
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The recent completion of the first two individual whole-genome sequences is a research milestone. As personal genome research advances, investigators and international research bodies must ensure ethical research conduct. We identify three major ethical considerations that have been implicated in whole-genome research: the return of research results to participants; the obligations, if any, that are owed to participants' relatives; and the future use of samples and data taken for whole-genome sequencing. Although the issues are not new, we discuss their implications for personal genomics and provide recommendations for appropriate management in the context of research involving individual whole-genome sequencing.
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Many research ethics guidelines now oblige researchers to offer research participants the results of research in which they participated. This practice is intended to uphold respect for persons and ensure that participants are not treated as mere means to an end. Yet some scholars have begun to question a generalised duty to disclose research results, highlighting the potential harms arising from disclosure and questioning the ethical justification for a duty to disclose, especially with respect to individual results. In support of this view, we argue that current rationales for a duty of disclosure do not form an adequate basis for an ethical imperative. We review policy guidance and scholarly commentary regarding the duty to communicate the results of biomedical, epidemiological and genetic research to research participants and show that there is wide variation in opinion regarding what should be disclosed and under what circumstance. Moreover, we argue that there is fundamental confusion about the notion of "research results," specifically regarding three core concepts: the distinction between aggregate and individual results, amongst different types of research, and across different degrees of result veracity. Even where policy guidance and scholarly commentary have been most forceful in support of an ethical imperative to disclose research results, ambiguity regarding what is to be disclosed confounds ethical action.
Article
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made it possible to sequence a whole human genome [1,2]. National and international funding initiatives have stimulated wholegenome research activities [3,4], and media coverage of both the science [5,6] and the emerging commercial offerings [7,8] related to genome research has heightened public awareness and interest in personal genomics. As technology continues to advance, whole-genome research activities seem likely to intensify and expand, necessitating carefully considered consensus guidelines for
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No consensus yet exists on how to handle incidental findings (IFs) in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are findings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed.
Chapter
The role of biobanks is changing to accommodate the expanding needs of the research enterprise. In addition to collecting human specimens, many biobanks also collect research results derived from those specimens. With the advent of technologies to screen the whole genome and the inter-relatedness of multiple genes with multiple diseases, research results will increasingly reveal information with health implications for the contributor of the specimen. What is the responsibility of the biobank to communicate these research findings? What are the benchmarks to guide decision-making on a daily basis? Although there is an emerging ethical imperative from international guidelines to communicate research results to the individual, how should these be implemented in practice? The answers to these questions are highly contextual and currently lack standards of reference. This creates tensions between the traditional boundaries of a biobank, as a resource to store specimens, and the moral intuition of the biobank personnel, as gatekeepers to potentially beneficial health information. This chapter explores these tensions and issues of disclosure of research results in the context of biobanking and provides practice recommendations and next steps for policy development.
Article
Despite extensive debate, there is no consensus on whether individual genetic data should be disclosed to research participants. The emergence of whole-genome sequencing methods is increasingly generating unequalled amounts of genetic data, making the need for a clear feedback policy even more urgent. In this debate two positions can be broadly discerned: a restrictive disclosure policy (‘no feedback except life-saving data’) and an intermediate policy of qualified disclosure (‘feedback if the results meet certain conditions’). We explain both positions and present the principal underlying arguments. We suggest that the debate should no longer address whether genetic research results should be returned, but instead how best to make an appropriate selection and how to strike a balance between the possible benefits of disclosure and the harms of unduly hindering biomedical research.
Article
Returning individual results to participants in research studies is gaining acceptance and policy guidance is now available for investigators to develop a plan for returning results at the local level. However, returning results discovered through the work of an international scientific research consortium presents additional ethical and procedural difficulties. No general guidance is available for international consortia that wish to consider this issue, but there are examples of internal policies that are being used by consortia such as the International Cancer Genome Consortium (ICGC) and the Type 1 Diabetes Genetics Consortium (T1DGC). This paper presents the policy stance these studies have adopted regarding returning individual research results and their reasons behind it, and gives specific examples from their policy documents and project consent materials. Finally, it suggests an oversight mechanism these and other international consortia can use to ensure that this important issue is addressed appropriately.
Article
Currently, the return of results in the domain of biobanking constitutes an ethical and legal quagmire, whether it involves population or specific clinical research studies. In light of the fact that population biobanks are often not seen as distinct from those biobanks created for disease research, as well as the uncertainty as to what "return of results" means concretely, this lexicon attempts to demystify the terminology. The terms - results, return, clinical significance, and utility - are discussed. Through an analysis of international and national normative guidance on this issue, the authors propose a concordance of meaning and a simplified lexicon.
Article
In this brief investigation, the informational needs of research participants [n = 62; mothers who had breastfed, taken codeine, and participated in a pharmacogenetic study] were probed during a counselling session in which they received their CYP2D6 pharmacogenetic research results and overall study results. In addition to the standard information, developed by a multidisciplinary team and provided to the participants, 38% of individuals had further questions related to potential adverse effects in babies, future codeine or medication use, heredity, and consequences for policies and programmes. The diversity and complexity of the questions raised support the need to communicate the results in the context of personalized genetic counselling information sessions.
Article
Sixty-two codeine-prescribed breastfeeding mothers from a pharmacogenetic study were interviewed regarding the communication of individual CYP2D6 genotype results and overall research findings. All participants wanted to receive the results of their individual genetic tests; however, individuals placed different values on the usefulness of this information toward future medical decisions. Receiving one's pharmacogenetic test results was not associated with a negative psychosocial impact. Thirty-three percent of the participants wished to withhold these results from their physicians. Participants' expectations seem to dictate the extent of transparency of pharmacogenetic research results.
Article
The disclosure of individual genetic research results to study participants continues to be the subject of vigorous debate, centered primarily on the nature of the results. We suggest that research context, which is foreseeable when a study is designed, is a vital consideration that has not been sufficiently incorporated into the discussion. Adapting an ancillary care framework to explore what different contexts might call for with regard to offering individual genetic research results, our analysis suggests that, beyond exceptionally rare circumstances that give rise to a duty to rescue, a one-size-fits-all threshold cannot be developed for decisions about returning individual results. Instead, researchers and institutional review boards must consider the scope of entrustment involved in the research, as well as the intensity and duration of interactions with participants and the vulnerability and dependence of the study population.
Article
Recent surveys about participation in cohort studies reconfirm that participants value and desire the return of research results to a degree that is out of step with the restrictive recommendations of various ethics advisory groups, which have historically limited disclosure based on clinician value judgments and the severity and treatability of the disease in question, among other factors. Rather than framing the current inconclusive ethics discussion as a standstill among competing ethical principles and their potential applicability, we introduce a new element, communicability (that is, those properties of a message that will determine how likely it is that its informational intent will be grasped by the study participant), as the subject of empirical research to align participants' goals with beneficent and responsible results reporting. Structural changes in research design, combined with governance changes in assessing impact, allow us to move beyond a binary construction of report/do not report and to create a structure in which the communicability of the message and the participants' preferences are variables in a function that affects results reporting. Here we illustrate this structure and its principles.
Article
Should the results of whole genome sequencing research be disclosed to participants, in particular when the results have uncertain or indeterminate phenotypic consequences? This controversial question is considered in light of one author's (J.L.) experience as a geneticist who recently had his own genome sequenced.
Article
DISCLOSURE OF INDIVIDUAL RESEARCH results to research participants has been the subject of professional guidelines as well as scholarly commentary, yet controversy remains. To gather data on participant perspectives, we interviewed 40 individuals from the Durham, North Carolina area about a biorepository consent form and conducted an in-depth analysis of responses to a series of questions concerning access to research results. Cross-cutting themes emerged about (1) the nature of research; (2) the nature of research results; (3) expectations concerning access to research results; and (4) practical issues in providing access to research results. Our findings highlight the importance for sound policy development of soliciting stakeholder input, and exploring the complexities behind their evaluations.
Article
Researchers do not owe their subjects the same level of care that physicians owe patients, but they owe more than merely what the research protocol stipulates. In keeping with the dynamics of the relationship between researcher and subject, they have limited but substantive fiduciary obligations.
Article
This paper is intended to stimulate debate amongst stakeholders in the international research community on the topic of returning individual genetic research results to study participants. Pharmacogenetics and disease genetics studies are becoming increasingly prevalent, leading to a growing body of information on genetic associations for drug responsiveness and disease susceptibility with the potential to improve health care. Much of these data are presently characterized as exploratory (non-validated or hypothesis-generating). There is, however, a trend for research participants to be permitted access to their personal data if they so choose. Researchers, sponsors, patient advocacy groups, ethics committees and regulatory authorities are consequently confronting the issue of whether, and how, study participants might receive their individual results. Noted international ethico-legal guidelines and public policy positions in Europe and the United States are reviewed for background. The authors offer 'Points-to-Consider' regarding returning results in the context of drug development trials based on their knowledge and experience. Theses considerations include: the clinical relevance of data, laboratory qualifications, informed consent procedures, confidentiality of medical information and the competency of persons providing results to participants. The discussion is framed as a benefit-to-risk assessment to balance the potential positive versus negative consequences to participants, while maintaining the integrity and feasibility of conducting genetic research studies.
Article
Investigators and institutional review boards should integrate plans about the appropriate disclosure of individual genetic results when designing research studies. The ethical principles of beneficence, respect, reciprocity, and justice provide justification for routinely offering certain results to research participants. We propose a result-evaluation approach that assesses the expected information and the context of the study in order to decide whether results should be offered. According to this approach, the analytic validity and the clinical utility of a specific result determine whether it should be offered routinely. Different results may therefore require different decisions even within the same study. We argue that the threshold of clinical utility for disclosing a result in a research study should be lower than the threshold used for clinical use of the same result. The personal meaning of a result provides additional criteria for evaluation. Finally, the context of the study allows for a more nuanced analysis by addressing the investigators' capabilities for appropriate disclosure, participants' alternative access to the result, and their relationship with the investigators. This analysis shows that the same result may require different decisions in different contexts.
Article
The completion of the Human Genome Project has resulted in increased epidemiological research to identify genes and their products as risk factors for adverse health events. A parallel increase in ethical issues associated with genetic research is noted. One such issue is whether or not epidemiologists should disclose individual genetic results to research participants. Existing ethical guidelines and frameworks are not helpful for determining whether disclosure is the moral choice. The purpose of this paper was to develop a framework for use by epidemiologists, research ethics boards, and institutional review boards during the protocol development stage to ethically address the dilemma regarding disclosure of individual genetic information. The core principles of research ethics were introduced and applied to the issues surrounding disclosure of genetic information. A principle-based framework was developed through analysis of the current ethical arguments for and against disclosure. Finally, examples demonstrating the use of the framework were provided. The proposed framework will not solve all ethical dilemmas related to individual disclosure of genetic information. It is, however, a useful starting point to facilitate the consideration process.
Declaration of Helsinki -Ethical Principles for Medical Research Involving Human Subjects
World Medical Association, Declaration of Helsinki -Ethical Principles for Medical Research Involving Human Subjects, 2008, at Articles 18, 20-21, available at <http://www.wma. net/en/30publications/10policies/b3/> (last visited August 17, 2011).
Good Epidemiological Practice -IEA Guidelines for Proper Conduct in Epidemiologic Research
International Epidemiological Association, Good Epidemiological Practice -IEA Guidelines for Proper Conduct in Epidemiologic Research, 2007, available at <http://www.ieaweb. org/index.php?option=com_content&view=article&id=15&Ite mid=43> (last visited August 17, 2011).
Norms from international consortia will be analyzed in an article from this symposium issue. See S. Wallace
Norms from international consortia will be analyzed in an article from this symposium issue. See S. Wallace, "The Needle in the Haystack-International Consortia and the Return of Individual Research Results," Journal of Law, Medicine & Ethics 39, no. 4 (2011): 631-639.
A clinician's duty to act in the beneficiary's (patient) interests is not the same in research contexts because research does not seek to serve individual interests (see
  • M N Meyer
A clinician's duty to act in the beneficiary's (patient) interests is not the same in research contexts because research does not seek to serve individual interests (see M. N. Meyer, "The Kindness of Strangers: The Donative Contract between Subjects and Researchers and the Non-Obligation to Return Individual Results of Genetic Research," American Journal of Bioethics 8, no. 11 (2008): 44-50, at 44).
“Research Participants' Rights to Access Information about Themselves Held by Public Research Institutions,”
  • Ries
N. M. Ries, "Research Participants' Rights to Access Information about Themselves Held by Public Research Institutions," Health Law Review 18, no. 3 (2010): 5-14.
Organisation for Economic Co-operation and Development
See World Medical Association, supra note 11, at Article 20. 27. Organisation for Economic Co-operation and Development, Guidelines on Human Biobanks and Genetic Research Databases, 2009, at Article 1.H, available at <http://www.oecd.org/ dataoecd/41/47/44054609.pdf> (last visited August 17, 2011).
at Guideline 5; see CIOMS, supra note 10
  • See
  • Research
See CIOMS Biomedical Research, supra note 13, at Guideline 5; see CIOMS, supra note 10, at Guideline 5.
Additional Protocol to the Convention on Human Rights and Biomedicine
Council of Europe, Additional Protocol to the Convention on Human Rights and Biomedicine, Concerning Biomedical Research, 2005, at Article 28, available at <http://conventions.coe.int/treaty/en/treaties/html/195.htm> (last visited August 17, 2011).
International Declaration on Human Genetic Data
UNESCO, International Declaration on Human Genetic Data, 2003, at Article 10, available at <http://portal.unesco.org/en/ ev.php-URL_ID=17720&URL_DO=DO_TOPIC&URL_SEC-TION=201.html> (last visited August 17, 2011).
Ethical and Practical Guidelines for Reporting Genetic Research Results to Study Participants
  • R Fabsitz
R. Fabsitz et al., "Ethical and Practical Guidelines for Reporting Genetic Research Results to Study Participants," Circulation Cardiovascular Genetics 3, no. 6 (2011): 574-580; see Bredenoord et al., supra note 6.
supra note 4; Beskow and Burke, supra note 60; Wolf et al., supra note 6; Fabsitz et al., supra note 60
  • See Ravitsky
  • Wilfond
See Ravitsky and Wilfond, supra note 4; Beskow and Burke, supra note 60; Wolf et al., supra note 6; Fabsitz et al., supra note 60, at 576.
at 44; Richardson and Belsky, supra note 67, at 26; Bredenoord et al., supra note 6
  • See Meyer
See Meyer, supra note 22, at 44; Richardson and Belsky, supra note 67, at 26; Bredenoord et al., supra note 6, at 45.
Offering Individual Genetic Research Results: Context Matters
  • See Ravitsky
  • Wilfond
  • Shalowitz
See Ravitsky and Wilfond, supra note 4; Shalowitz et al., supra note 16; L. M. Beskow and W. Burke, "Offering Individual Genetic Research Results: Context Matters," Science Translational Medicine 2, no. 38 (2010): 38cm20-31; see Fernandez et al., supra note 15;
“Offering Individual Genetic Research Results: Context Matters,”
  • Ravitsky