Benefit-Sharing by Design: A Call to Action for Human Genomics Research.

The ethical standards for the responsible conduct of human research have come a long way; however, concerns surrounding equity remain in human genetics and genomics research. Addressing these concerns will help society realize the full potential of human genomics research. One outstanding concern is the fair and equitable sharing of benefits from research on human participants. Several international bodies have recognized that benefit-sharing can be an effective tool for ethical research conduct, but international laws, including the Convention on Biological Diversity and its Nagoya Protocol on Access and Benefit-Sharing, explicitly exclude human genetic and genomic resources. These agreements face significant challenges that must be considered and anticipated if similar principles are applied in human genomics research. We propose that benefit-sharing from human genomics research can be a bottom-up effort and embedded into the existing research process. We propose the development of a "benefit-sharing by design" framework to address concerns of fairness and equity in the use of human genomic resources and samples and to learn from the aspirations and decade of implementation of the Nagoya Protocol.

Public Preferences for Digital Health Data Sharing: Discrete Choice Experiment Study in 12 European Countries.

BACKGROUND: With new technologies, health data can be collected in a variety of different clinical, research, and public health contexts, and then can be used for a range of new purposes. Establishing the public's views about digital health data sharing is essential for policy makers to develop effective harmonization initiatives for digital health data governance at the European level. OBJECTIVE: This study investigated public preferences for digital health data sharing. METHODS: A discrete choice experiment survey was administered to a sample of European residents in 12 European countries (Austria, Denmark, France, Germany, Iceland, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) from August 2020 to August 2021. Respondents answered whether hypothetical situations of data sharing were acceptable for them. Each hypothetical scenario was defined by 5 attributes ("data collector," "data user," "reason for data use," "information on data sharing and consent," and "availability of review process"), which had 3 to 4 attribute levels each. A latent class model was run across the whole data set and separately for different European regions (Northern, Central, and Southern Europe). Attribute relative importance was calculated for each latent class's pooled and regional data sets. RESULTS: A total of 5015 completed surveys were analyzed. In general, the most important attribute for respondents was the availability of information and consent during health data sharing. In the latent class model, 4 classes of preference patterns were identified. While respondents in 2 classes strongly expressed their preferences for data sharing with opposing positions, respondents in the other 2 classes preferred not to share their data, but attribute levels of the situation could have had an impact on their preferences. Respondents generally found the following to be the most acceptable: a national authority or academic research project as the data user; being informed and asked to consent; and a review process for data transfer and use, or transfer only. On the other hand, collection of their data by a technological company and data use for commercial communication were the least acceptable. There was preference heterogeneity across Europe and within European regions. CONCLUSIONS: This study showed the importance of transparency in data use and oversight of health-related data sharing for European respondents. Regional and intraregional preference heterogeneity for "data collector," "data user," "reason," "type of consent," and "review" calls for governance solutions that would grant data subjects the ability to control their digital health data being shared within different contexts. These results suggest that the use of data without consent will demand weighty and exceptional reasons. An interactive and dynamic informed consent model combined with oversight mechanisms may be a solution for policy initiatives aiming to harmonize health data use across Europe.

Open science, data sharing and solidarity: who benefits?

Research, innovation, and progress in the life sciences are increasingly contingent on access to large quantities of data. This is one of the key premises behind the "open science" movement and the global calls for fostering the sharing of personal data, datasets, and research results. This paper reports on the outcomes of discussions by the panel "Open science, data sharing and solidarity: who benefits?" held at the 2021 Biennial conference of the International Society for the History, Philosophy, and Social Studies of Biology (ISHPSSB), and hosted by Cold Spring Harbor Laboratory (CSHL).

Public involvement in the governance of population-level biomedical research: unresolved questions and future directions.

Population-level biomedical research offers new opportunities to improve population health, but also raises new challenges to traditional systems of research governance and ethical oversight. Partly in response to these challenges, various models of public involvement in research are being introduced. Yet, the ways in which public involvement should meet governance challenges are not well understood. We conducted a qualitative study with 36 experts and stakeholders using the World Café method to identify key governance challenges and explore how public involvement can meet these challenges. This brief report discusses four cross-cutting themes from the study: the need to move beyond individual consent; issues in benefit and data sharing; the challenge of delineating and understanding publics; and the goal of clarifying justifications for public involvement. The report aims to provide a starting point for making sense of the relationship between public involvement and the governance of population-level biomedical research, showing connections, potential solutions and issues arising at their intersection. We suggest that, in population-level biomedical research, there is a pressing need for a shift away from conventional governance frameworks focused on the individual and towards a focus on collectives, as well as to foreground ethical issues around social justice and develop ways to address cultural diversity, value pluralism and competing stakeholder interests. There are many unresolved questions around how this shift could be realised, but these unresolved questions should form the basis for developing justificatory accounts and frameworks for suitable collective models of public involvement in population-level biomedical research governance.

The psychology of "cure" - unique challenges to consent processes in HIV cure research in South Africa.

BACKGROUND: Consent processes for clinical trials involving HIV prevention research have generated considerable debate globally over the past three decades. HIV cure/eradication research is scientifically more complex and consequently, consent processes for clinical trials in this field are likely to pose a significant challenge. Given that research efforts are now moving toward HIV eradication, stakeholder engagement to inform appropriate ethics oversight of such research is timely. This study sought to establish the perspectives of a wide range of stakeholders in HIV treatment and research to inform consent processes for cure research. METHODS: In total, 68 South African stakeholders participated in two qualitative research modalities. In-depth interviews (IDIs) were conducted with a purposive sample of 42 individuals - audiotaped with consent. Twenty-six stakeholders participated in three focus group discussions (FGDs). Thematic analysis of transcribed IDIs and FGDs was conducted. RESULTS: The majority of respondents indicated that there could be unique challenges in HIV cure research requiring special attention. In particular, given the complexity of cure science, translation of concepts into lay language would be critical for potential participants to adequately appreciate risks and benefits in early phase research with experimental interventions. Furthermore, to aid understanding of risks and benefits against a background of desperation for a cure, specially trained facilitators would be required to assist with a psychological assessment prior to consent to avoid curative misconceptions. Long-term participant engagement to assess durability of a cure would mean that the consent process would be prolonged, necessitating annual re-consent. Building trust to maintain such long-term relationships would be critical to retain study participants. CONCLUSION: Unique consent requirements for cure research in South Africa would include significant efforts to maximise understanding of trial procedures, risks and the need for long-term follow-up. However, the psychological dimension of cure must not be underestimated. Beyond an understanding of cure science, the emotional impact of HIV cure advances the discourse from cure to healing. Consequently, the consent process for cure research would need to be enhanced to include psychological support and counselling. This has several important implications for research ethics review requirements for consent in HIV cure research.

Engaging research ethics committees to develop an ethics and governance framework for best practices in genomic research and biobanking in Africa: the H3Africa model.

In the past decade, there has been an increase in genomic research and biobanking activities in Africa. Research initiatives such as the Human Heredity and Health in Africa (H3Africa) Consortium are contributing to the development of scientific capacity and infrastructure to support these studies on the continent. Despite this growth, genomic research and biobanking have raised important ethical challenges for key research stakeholders, including members of research ethics committees. One of these is the limited ethical and regulatory frameworks to guide the review and conduct of genomic studies, particularly in Africa. This paper is a reflection on a series of consultative activities with research ethics committees in Africa which informed the development of an ethics and governance framework for best practices in genomic research and biobanking in Africa. The paper highlights the engagement process and the lessoned learned.

Rules of engagement: perspectives on stakeholder engagement for genomic biobanking research in South Africa.

BACKGROUND: Genomic biobanking research is undergoing exponential growth in Africa raising a host of legal, ethical and social issues. Given the scientific complexity associated with genomics, there is a growing recognition globally of the importance of science translation and community engagement (CE) for this type of research, as it creates the potential to build relationships, increase trust, improve consent processes and empower local communities. Despite this level of recognition, there is a lack of empirical evidence of the practise and processes for effective CE in genomic biobanking in Africa. METHODS: To begin to address this vacuum, 17 in-depth face to face interviews were conducted with South African experts in genomic biobanking research and CE to provide insight into the process, benefits and challenges of CE in South Africa. Emerging themes were analysed using a contextualised thematic approach. RESULTS: Several themes emerged concerning the conduct of CE in genomic biobanking research in Africa. Although the literature tends to focus on the local community in CE, respondents in this study described three different layers of stakeholder engagement: community level, peer level and high level. Community level engagement includes potential participants, community advisory boards (CAB) and field workers; peer level engagement includes researchers, biobankers and scientists, while high level engagement includes government officials, funders and policy makers. Although education of each stakeholder layer is important, education of the community layer can be most challenging, due to the complexity of the research and educational levels of stakeholders in this layer. CONCLUSION: CE is time-consuming and often requires an interdisciplinary research team approach. However careful planning of the engagement strategy, including an understanding of the differing layers of stakeholder engagement, and the specific educational needs at each layer, can help in the development of a relationship based on trust between the research team and various stakeholder groups. Since the community layer often comprises vulnerable populations in low and middle income countries (LMICs), co-development of innovative educational tools on genomic biobanking is essential. CE is clearly a component of a broader process best described as stakeholder engagement.

Regulation of genomic and biobanking research in Africa: a content analysis of ethics guidelines, policies and procedures from 22 African countries.

BACKGROUND: The introduction of genomics and biobanking methodologies to the African research context has also introduced novel ways of doing science, based on values of sharing and reuse of data and samples. This shift raises ethical challenges that need to be considered when research is reviewed by ethics committees, relating for instance to broad consent, the feedback of individual genetic findings, and regulation of secondary sample access and use. Yet existing ethics guidelines and regulations in Africa do not successfully regulate research based on sharing, causing confusion about what is allowed, where and when. METHODS: In order to understand better the ethics regulatory landscape around genomic research and biobanking, we conducted a comprehensive analysis of existing ethics guidelines, policies and other similar sources. We sourced 30 ethics regulatory documents from 22 African countries. We used software that assists with qualitative data analysis to conduct a thematic analysis of these documents. RESULTS: Surprisingly considering how contentious broad consent is in Africa, we found that most countries allow the use of this consent model, with its use banned in only three of the countries we investigated. In a likely response to fears about exploitation, the export of samples outside of the continent is strictly regulated, sometimes in conjunction with regulations around international collaboration. We also found that whilst an essential and critical component of ensuring ethical best practice in genomics research relates to the governance framework that accompanies sample and data sharing, this was most sparingly covered in the guidelines. CONCLUSIONS: There is a need for ethics guidelines in African countries to be adapted to the changing science policy landscape, which increasingly supports principles of openness, storage, sharing and secondary use. Current guidelines are not pertinent to the ethical challenges that such a new orientation raises, and therefore fail to provide accurate guidance to ethics committees and researchers.

HIV cure research in South Africa: a preliminary exploration of stakeholder perspectives.

Innovative strategies for HIV cure are in development and research studies are being designed and planned globally. South Africa is no exception. However, little is known about stakeholders' knowledge, understanding and expectations of future cure research. This study aimed to obtain in-depth qualitative insights into stakeholder perspectives at this formative stage of HIV cure research. Fifteen stakeholders were interviewed in an HIV research clinic in the Western Cape, South Africa with their consent. Interviews were transcribed verbatim and analysed using thematic content analysis. Broad themes that emerged included the meaning of cure, awareness of HIV cure research, risks and benefits of such research. General awareness and understanding of HIV cure research was lower than expected. Some participants expressed a fatalistic attitude to HIV and described it as an "end-time illness" with no prospect of cure. In general, HIV cure research was regarded as risky - biologically psychologically and socially. If study designs were to include treatment interruption, participants would comply only if success was guaranteed. Given these perceptions of HIV cure research, significant challenges to consent processes and participant recruitment can be anticipated. Authentic community engagement and intensive educational interventions will be necessary prior to future cure research in South Africa.

Healing Without Waging War: Beyond Military Metaphors in Medicine and HIV Cure Research.

Military metaphors are pervasive in biomedicine, including HIV research. Rooted in the mind set that regards pathogens as enemies to be defeated, terms such as "shock and kill" have become widely accepted idioms within HIV cure research. Such language and symbolism must be critically examined as they may be especially problematic when used to express scientific ideas within emerging health-related fields. In this article, philosophical analysis and an interdisciplinary literature review utilizing key texts from sociology, anthropology, history, and Chinese and African studies were conducted to investigate the current proliferation of military metaphors. We found the use of these metaphors to be ironic, unfortunate, and unnecessary. To overcome military metaphors we propose to (1) give them less aggressive meanings, and/or (2) replace them with more peaceful metaphors. Building on previous authors' work, we argue for the increased use of "journey" (and related) metaphors as meaningful, cross-culturally appropriate alternatives to military metaphors.

Synergies, tensions and challenges in HIV prevention, treatment and cure research: exploratory conversations with HIV experts in South Africa.

BACKGROUND: The ethical concerns associated with HIV prevention and treatment research have been widely explored in South Africa over the past 3 decades. However, HIV cure research is relatively new to the region and significant ethical and social challenges are anticipated. There has been no published empirical enquiry in Africa into key informant perspectives on HIV cure research. Consequently, this study was conducted to gain preliminary data from South African HIV clinicians, researchers and activists. METHODS: In-depth interviews were conducted on a purposive sample of fourteen key informants in South Africa. Audiotaped interviews were transcribed verbatim with concurrent thematic analysis. The perspectives of HIV clinicians, researchers and activists were captured. Analyst triangulation occurred as the data were analysed by three authors independently. RESULTS: The rapid evolution of HIV cure research agendas was prominent with participants expressing some concern that the global North was driving the cure agenda. Participants described a symbiotic relationship between cure, treatment and prevention research necessitating collaboration. Assessing and managing knowledge and expectations around HIV cure research emerged as a central theme related to challenges to constructing 'cure' - how patients understand the idea of cure is important in explaining the complexity of cure research especially in the South African context where understanding of science is often challenging. Managing expectations and avoiding curative misconception will have implications for consent processes. Unique strategies in cure research could include treatment interruption, which has the potential to create therapeutic and ethical conflict and will be perceived as a significant risk. Ethical challenges in cure research will impact on informed consent and community engagement. CONCLUSIONS: It was encouraging to note the desire for synergy amongst researchers and clinicians working in the fields of prevention, treatment and cure. Translation of complex HIV cure science into lay language is critical. Moving forward, RECs must be adequately constituted with scientific expertise and community representation when reviewing cure protocols. It is hoped that knowledge and resource sharing in the context of collaboration between research scientists working in cure and those working in treatment and prevention will accelerate progress towards cure.

Informed consent for HIV cure research in South Africa: issues to consider.

BACKGROUND: South Africa has made great progress in the development of HIV/AIDS testing, treatment and prevention campaigns. Yet, it is clear that prevention and treatment campaigns alone are not enough to bring this epidemic under control. DISCUSSION: News that the "Berlin patient" and the "Mississippi baby" have both been "cured" of HIV brought hope to people living with HIV/AIDS in South Africa that a cure for HIV/AIDS is within reach. Despite the recent setbacks announced in the "Mississippi Baby" case, protocols aimed at curing HIV/AIDS are being developed in South Africa. However with evidence to suggest that participants in clinical trials do not understand the basic concepts in the informed consent process, there is concern that future participants in HIV/AIDS cure research will lack comprehension of the basic elements of future clinical trials that aims to cure HIV/AIDS and confuse research with clinical care. SUMMARY: Research ethics committees have an important role to play in ensuring that participants understand the basic concepts discussed in the informed consent process, that they understand that research is not clinical care and they are unlikely to benefit from any early phase trials seeking to cure HIV/AIDS.

The implications of methylphenidate use by healthy medical students and doctors in South Africa.

BACKGROUND: The use of medical stimulants to sustain attention, augment memory and enhance intellectual capacity is increasing in society. The use of Methylphenidate for cognitive enhancement is a subject that has received much attention in the literature and academic circles in recent times globally. Medical doctors and medical students appear to be equally involved in the off-label use of Methylphenidate. This presents a potential harm to society and the individual as the long-term side effect profile of this medication is unknown. DISCUSSION: The implication of the use of Methylphenidate by medical students and doctors has not been fully explored. This article considers the impact of this use on the traditional role of medicine, society, the patient and suggests a way forward. We discuss the salient philosophy surrounding the use of cognitive enhancement. We query whether there are cognitive benefits to the use of Methylphenidate in healthy students and doctors and whether these benefits would outweigh the risks in taking the medication. Could these benefits lead to tangible outcomes for society and could the off label-use of Methylphenidate potentially undermine the medical profession and the treatment of patients? If cognitive benefits are proven then doctors may be coerced explicitly or implicitly to use the drug which may undermine their autonomy. The increased appeal of cognitive enhancement challenges the traditional role of medicine in society, and calls into question the role of a virtuous life as a contributing factor for achievement. In countries with vast economic disparity such as South Africa an enhancement of personal utility that can be bought may lead to greater inequities. SUMMARY: Under the status quo the distribution of methylphenidate is unjust. Regulatory governmental policy must seek to remedy this while minimising the potential for competitive advantage for the enhanced. Public debate on the use of cognitive enhancement is long overdue and must be stimulated. The use of Methylphenidate for cognitive enhancement is philosophically defendable if long-term research can prove that the risks are negligible and the outcomes tangible.

Cross-border data sharing for research in Africa: An analysis of the data protection and research ethics requirements in 12 jurisdictions.

Background: In recent years, there has been a notable uptake in genomic and health-related research activities across the African continent. Similarly, there has been increased introduction of data protection legislation that affects the sharing of personal data such as health data and genomic data, including for research. Many of these statutes have stricter requirements when sharing personal data across borders. Consequently, the cross-border sharing of health data that includes genetic data requires careful navigation of the pertinent data protection legislation, in particular concerning the sharing of such data for research purposes. To help researchers navigate these legal frameworks, 12 African countries were analysed to develop country guides on cross-border data sharing. Results: Of the 12 countries that were analysed, ten have data protection laws in place (Botswana, Ghana, Kenya, Malawi, Nigeria, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe), while two countries (Cameroon and The Gambia) do not. With the exception of Ghana, all countries with data protection statutes or bills had additional requirements to be met when sharing personal data across borders. Consent and adequacy are the most common grounds for justifying the sharing of personal data across borders. Conclusion: Given the limitations of the current models of consent, consent is not a suitable basis to transfer large quantities of data for research. Adequacy is a common ground, but there are national differences in the implementation of this ground. Researchers must therefore analyse each national legal framework and make decisions on a case-by-case and country-by-country basis.

Ethical and social reflections on the proposed European Health Data Space.

The COVID-19 pandemic demonstrated the benefits of international data sharing. Data sharing enabled the health care policy makers to make decisions based on real-time data, it enabled the tracking of the virus, and importantly it enabled the development of vaccines that were crucial to mitigating the impact of the virus. This data sharing is not the norm as data sharing needs to navigate complex ethical and legal rules, and in particular, the fragmented application of the General Data Protection Regulation (GDPR). The introduction of the draft regulation for a European Health Data Space (EHDS) in May 2022 seeks to address some of these legal issues. If passed, it will create an obligation to share electronic health data for certain secondary purposes. While there is a clear need to address the legal complexities involved with data sharing, it is critical that any proposed reforms are in line with ethical principles and the expectations of the data subjects. In this paper we offer a critique of the EHDS and offer some recommendations for this evolving regulatory space.

Challenges in biobank governance in Sub-Saharan Africa.

BACKGROUND: Biological sample and data transfer within and out of Africa is steeped in controversy With the H3Africa project now aiming to establish biobanks in Africa, it is essential that there are ethical and legal governance structures in place to oversee the operation of these biobanks. Such governance is essential to ensuring that donors are protected, that cultural perspectives are respected and that researchers have a ready availability of ethically sourced biological samples. METHODS: A literature review of all legislation, regulations, guidelines and standard operating procedures on informed consent, confidentiality and the transfer of biological samples amongst countries in Sub-Saharan Africa was conducted. In addition, an examination of the websites of departments of health and national ethics committees was performed. Researchers and research ethics scholars in the field in various African countries were contacted for assistance. A literature review of all studies examining participants views on issues related to biobanking in Africa was carried out and five separate studies were found. RESULTS: It was found that biobanking guidelines differ substantially across Sub-Saharan Africa regarding biobanking and often conflicted across borders. This has the potential to negatively impact collaboration. Furthermore, the guidelines in place often do not recognise the ethical difficulties arising from the transfer of biological samples and are unsuitable to regulate biobanks. Additionally, there is insufficient research into the views of research participants and stakeholders on the use of biological /samples. CONCLUSION: Collaboration is necessary to ensure the success of biobanking projects in Africa. To achieve this, there should be some harmonization of guidelines across Africa which would aid in transferring biological samples across borders. These guidelines should reflect the unique ethical issues arising out of the storage and secondary uses of biological samples. Finally, further research into the views of research participants is necessary. Such studies should aid in the drafting of any new harmonization guidelines.

Appropriate Safeguards and Article 89 of the GDPR: Considerations for Biobank, Databank and Genetic Research.

The collection and use of biological samples and data for genetic research, or for storage in a biobank or databank for future research, impacts upon many fundamental rights, including the right to dignity, the right to private and family life, the right to protection of personal data, the right to freedom of arts and sciences, and the right to non-discrimination. The use of genetic data and other health-related data in this context must be used in a manner that is rooted in human rights. Owing in part to the General Data Protection Regulation (GDPR) coming into force, the right to the protection of personal data in the context of scientific research has been afforded increasing attention. The GDPR gives effect to the right to data protection, but states that this right must be balanced against other rights and interests. The GDPR applies to all personal data, with specific attention to special categories of data, that includes health and genetic data. The collection, access to, and sharing of such data must comply with the GDPR, and therefore directly impacts the use of such data in research. The GDPR does provide for several derogations and exemptions for research from many of the strict processing requirements. Such derogations are permitted only if there are appropriate safeguards in place. Article 89 states that to be appropriate, safeguards must be "in accordance" with the GDPR "for the rights and freedoms of the data subject". In particular, those safeguards must ensure "respect for the principle of data minimisation". Despite the importance of safeguards, the GDPR is silent as to the specific measures that may be adopted to meet these requirements. This paper considers Article 89 and explores safeguards that may be deemed appropriate in the context of biobanks, databanks, and genetic research.

Data protection, data management, and data sharing: Stakeholder perspectives on the protection of personal health information in South Africa.

The Protection of Personal Information Act (POPIA) 2013 came into force in South Africa on 1 July 2020. It seeks to strengthen the processing of personal information, including health information. While POPIA is to be welcomed, there are concerns about the impact it will have on the processing of health information. To ensure that the National Health Laboratory Service [NHLS] is compliant with these new strict processing requirements and that compliance does not negatively impact upon its current screening, treatment, surveillance and research mandate, it was decided to consider the development of a NHLS POPIA Code of Conduct for Personal Health. As part of the process of developing such a Code and better understand the challenges faced in the processing of personal health information in South Africa, 19 semi-structured interviews with stakeholders were conducted between June and September 2020. Overall, respondents welcomed the introduction of POPIA. However, they felt that there are tensions between the strengthening of data protection and the use of personal information for individual patient care, treatment programmes, and research. Respondents reported a need to rethink the management of personal health information in South Africa and identified 5 issues needing to be addressed at a national and an institutional level: an understanding of the importance of personal information; an understanding of POPIA and data protection; improve data quality; improve transparency in data use; and improve accountability in data use. The application of POPIA to the processing of personal health information is challenging, complex, and likely costly. However, personal health information must be appropriately managed to ensure the privacy of the data subject is protected, but equally that it is used as a resource in the individual's and wider public interest.

Return of research results (RoRR) to the healthy CHRIS cohort: designing a policy with the participants.

Legal, financial and organizational challenges and the absence of coherent international guidelines and legal frameworks still discourage many genetic studies to share individual research results with their participants. Studies and institutions deciding to return genetic results will need to design their own study-specific return policy after due consideration of the ethical responsibilities. The Cooperative Health Research in South Tyrol (CHRIS) study, a healthy cohort study, did not foresee the return of individual genomic results during its baseline phase. However, as it was expected that the follow-up phase would generate an increasing amount of reliable genetic results, an update of the return of research results (RoRR) policy became necessary. To inform this revision, an empirical study using mixed methods was developed to investigate the views of CHRIS research participants (20), local general practitioners (3) and the local genetic counselling service (1). During the interviews, three different examples of potential genetic results with a very diverse potential impact on participants were presented: breast cancer, Parkinson disease and Huntington disease. The CHRIS participants also completed a short questionnaire, collecting personal information and asking for a self-evaluation of their knowledge about genetics. This study made it clear that research participants want to make autonomous decisions on the disclosure or non-disclosure of their results. While the motivations for participants' decisions were very diverse, we were able to identify several common criteria that had a strong influence on their choices. Providing information on these factors is crucial to enable participants to make truly informed decisions.

Balancing scientific interests and the rights of participants in designing a recall by genotype study.

Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South Tyrol (CHRIS) study is a longitudinal cohort study based in South Tyrol, Italy. Demand has grown for CHRIS study participants to be enrolled in RbG studies, thus making the design of a suitable ethical framework a pressing need. We here report upon the design of a pilot RbG study conducted with CHRIS study participants. By reviewing the literature and by consulting relevant stakeholders (CHRIS participants, clinical geneticists, ethics board, GPs), we identified key ethical issues in RbG approaches (e.g. complexity of the context, communication of genetic results, measures to further protect participants). The design of the pilot was based on a feasibility assessment, the selection of a suitable test case within the ProtectMove Research Unit on reduced penetrance of hereditary movement disorders, and the development of appropriate recruitment and communication strategies. An empirical study was embedded in the pilot study with the aim of understanding participants' views on RbG. Our experience with the pilot study in CHRIS allowed us to contribute to the development of best practices and policies for RbG studies by drawing recommendations: addressing the possibility of RbG in the original consent, implementing tailored communication strategies, engaging stakeholders, designing embedded empirical studies, and sharing research experiences and methodology.