Defining the Critical Components of Informed Consent for Genetic Testing

Defining the Critical Components of Informed Consent for Genetic Testing
Kelly E. Ormond, Maia J. Borensztein, Miranda L. G. Hallquist, Adam H. Buchanan, William Andrew Faucett, Holly L. Peay, Maureen E. Smith, Eric P. Tricou, Wendy R. Uhlmann, Karen E. Wain, Curtis R. Coughlin, Clinical Genome CADRe Workgroup
Journal of Personalised Medicine, 5 December 2021
Open Access
Abstract
Purpose
Informed consent for genetic testing has historically been acquired during pretest genetic counseling, without specific guidance defining which core concepts are required.
Methods
The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendations Workgroup (CADRe) used an expert consensus process to identify the core concepts essential to consent for clinical genetic testing. A literature review identified 77 concepts that are included in informed consent for genetic tests. Twenty-five experts (9 medical geneticists, 8 genetic counselors, and 9 bioethicists) completed two rounds of surveys ranking concepts’ importance to informed consent.
Results
The most highly ranked concepts included: (1) genetic testing is voluntary; (2) why is the test recommended and what does it test for?; (3) what results will be returned and to whom?; (4) are there other types of potential results, and what choices exist?; (5) how will the prognosis and management be impacted by results?; (6) what is the potential family impact?; (7) what are the test limitations and next steps?; and (8) potential risk of genetic discrimination and legal protections.
Conclusion
Defining the core concepts necessary for informed consent for genetic testing provides a foundation for quality patient care across a variety of healthcare providers and clinical indications.

Responding from the Place of Suffering: Informed Consent and Non-invasive Prenatal Genetic Screening [BOOK CHAPTER]

Responding from the Place of Suffering: Informed Consent and Non-invasive Prenatal Genetic Screening [BOOK CHAPTER]
Michael McCarthy
Suffering in Theology and Medical Ethics, 3 December 2021; pp 179–187 [Brill]
Introduction
…Informed consent after a positive screen for Trisomy 21, Down syndrome, should move from an individualist model of autonomy to a principled autonomy that allows the patient to explore the decision from her reality. This shift would need to incorporate the medical facts, understanding the risks and benefits, and learning from those faced previously with similar decisions. This chapter begins, first, by describing non-invasive prenatal genetic screening. Secondly, it explores what constitutes informed consent through an individual/utilitarian model of autonomy and juxtaposes that with principled autonomy grounded in Ada María Isasi-Díaz’s mujerista hermeneutic, lo cotidiano. The chapter concludes by drawing on both insights from minority participants in clinical research and parents of a child with Trisomy 21 in order to enhance the process for informed consent. Better understanding the reality of the patient and explaining the potential options in a way that prioritizes the patient’s reality allows her to make a responsible and informed decision…

A Blockchain-Based Dynamic Consent Architecture to Support Clinical Genomic Data Sharing (ConsentChain): Proof-of-Concept Study

A Blockchain-Based Dynamic Consent Architecture to Support Clinical Genomic Data Sharing (ConsentChain): Proof-of-Concept Study
Faisal Albalwy, Andrew Brass, Angela Davies
JMIR Medical Informatics, 3 November 2021; 9(11)
Abstract
Background
In clinical genomics, sharing of rare genetic disease information between genetic databases and laboratories is essential to determine the pathogenic significance of variants to enable the diagnosis of rare genetic diseases. Significant concerns regarding data governance and security have reduced this sharing in practice. Blockchain could provide a secure method for sharing genomic data between involved parties and thus help overcome some of these issues.
Objective
This study aims to contribute to the growing knowledge of the potential role of blockchain technology in supporting the sharing of clinical genomic data by describing blockchain-based dynamic consent architecture to support clinical genomic data sharing and provide a proof-of-concept implementation, called ConsentChain, for the architecture to explore its performance.
Methods
The ConsentChain requirements were captured from a patient forum to identify security and consent concerns. The ConsentChain was developed on the Ethereum platform, in which smart contracts were used to model the actions of patients, who may provide or withdraw consent to share their data; the data creator, who collects and stores patient data; and the data requester, who needs to query and access the patient data. A detailed analysis was undertaken of the ConsentChain performance as a function of the number of transactions processed by the system.
Results
We describe ConsentChain, a blockchain-based system that provides a web portal interface to support clinical genomic sharing. ConsentChain allows patients to grant or withdraw data requester access and allows data requesters to query and submit access to data stored in a secure off-chain database. We also developed an ontology model to represent patient consent elements into machine-readable codes to automate the consent and data access processes.
Conclusions
Blockchains and smart contracts can provide an efficient and scalable mechanism to support dynamic consent functionality and address some of the barriers that inhibit genomic data sharing. However, they are not a complete answer, and a number of issues still need to be addressed before such systems can be deployed in practice, particularly in relation to verifying user credentials.

Improving patient informed consent for haemophilia gene therapy: the case for change

Improving patient informed consent for haemophilia gene therapy: the case for change
Review Article
Laurence Woollard, Richard Gorman, Dakota J. Rosenfelt
Therapeutic Advances in Rare Disease, 26 September 2021
Abstract
Adeno-associated virus-based gene therapy points to a coming transformation in the treatment of people living with haemophilia, promising sustained bleed control and potential improvement in quality of life. Nevertheless, the consequences of introducing new genetic material are not trivial. The perceived benefits should not minimise the challenges facing patients in understanding the long-term risks and providing a valid and meaningful informed consent, whether in a research or clinical setting. Informed consent is a fundamentally important doctrine in both medical ethics and health law, upholding an individual’s right to define their personal goals and make their own autonomous choices. Patients should be enabled to recognise their clinical situation, understand the implications of treatment and integrate every facet of their life into their decision. This review describes informed consent processes for haemophilia gene therapy clinical trials, factors affecting patients’ decision making and the availability of patient-centred decision support interventions, to ensure that patients’ interests are being protected. Regulatory guidance has been published for physicians and manufacturers in haemophilia on informed consent, including for gene therapy, while best-practice recommendations for patient–physician discussions are available. In all settings, however, communicating and presenting highly technical and complex therapeutic information is challenging, especially where multiple barriers to scientific knowledge and health literacy exist. We propose several evidence-informed strategies to enhance the consent procedure, such as utilising validated literacy and knowledge assessment tools as well as participatory learning environments over an extended period, to ensure that patients are fully cognisant of the consent they give or deny. Further research is needed to define new, creative approaches for patient education and the upholding of ethical values in the informed consent process for gene therapy. The lessons learnt and approaches developed within haemophilia could set the gold standard for good practice in ensuring ethical preparedness amidst advances in genetic therapies.

Improving patient informed consent for haemophilia gene therapy: the case for change

Improving patient informed consent for haemophilia gene therapy: the case for change
Laurence Woollard, Richard Gorman, Dakota J. Rosenfelt
Therapeutic Advances in Rare Disease, 31 August 2021; 2 pp 1-16
Open Access
Abstract
Adeno-associated virus-based gene therapy points to a coming transformation in the treatment of people living with haemophilia, promising sustained bleed control and potential improvement in quality of life. Nevertheless, the consequences of introducing new genetic material are not trivial. The perceived benefits should not minimise the challenges facing patients in understanding the long-term risks and providing a valid and meaningful informed consent, whether in a research or clinical setting. Informed consent is a fundamentally important doctrine in both medical ethics and health law, upholding an individual’s right to define their personal goals and make their own autonomous choices. Patients should be enabled to recognise their clinical situation, understand the implications of treatment and integrate every facet of their life into their decision. This review describes informed consent processes for haemophilia gene therapy clinical trials, factors affecting patients’ decision making and the availability of patient-centred decision support interventions, to ensure that patients’ interests are being protected. Regulatory guidance has been published for physicians and manufacturers in haemophilia on informed consent, including for gene therapy, while best practice recommendations for patient–physician discussions are available. In all settings, however, communicating and presenting highly technical and complex therapeutic information is challenging, especially where multiple barriers to scientific knowledge and health literacy exist. We propose several evidence-informed strategies to enhance the consent procedure, such as utilising validated literacy and knowledge assessment tools as well as participatory learning environments over an extended period, to ensure that patients are fully cognisant of the consent they give or deny. Further research is needed to define new, creative approaches for patient education and the upholding of ethical values in the informed consent process for gene therapy. The lessons learnt and approaches developed within haemophilia could set the gold standard for good practice in ensuring ethical preparedness amidst advances in genetic therapies.

Parents’ experiences of decision making for rapid genomic sequencing in intensive care

Parents’ experiences of decision making for rapid genomic sequencing in intensive care
Fiona Lynch, Amy Nisselle, Zornitza Stark, Clara L. Gaff, Belinda McClaren
European Journal of Human Genetics, 23 August 2021
Abstract
The clinical utility of rapid genomic sequencing (rGS) for critically unwell infants and children has been well demonstrated. Parental capacity for informed consent has been questioned, yet limited empirical data exists to guide clinical service delivery. In an Australian nationwide clinical implementation project offering rGS for critically unwell infants and children, parents made a decision about testing in under a day on average. This study reports parents’ experiences of decision making for rGS within this rapid timeframe to inform pre-test counselling procedures for future practice. A nationwide sample of 30 parents, whose children were amongst the first to receive rGS, were interviewed. We found that framing and delivery of rGS require careful consideration to support autonomous decision making and avoid implicit coercion in a stressful intensive care setting. Many parents described feeling ‘special’ and ‘lucky’ that they were receiving access to expensive and typically time-consuming genomic sequencing. Thematic analysis revealed a spectrum of complexity for decision making about rGS. Some parents consented quickly and were resistant to pre-test counselling. Others had a range of concerns and described deliberating about their decision, which they felt rushed to make. This research identifies tensions between the medical imperative of rGS and parents’ decision making, which need to be addressed as rGS becomes routine clinical care.

Should Feedback of Individual Results be Integrated into the Consent Process in African Genomics? Participants’ Views from an HIV-TB Genomics Research Project in Botswana

Should Feedback of Individual Results be Integrated into the Consent Process in African Genomics? Participants’ Views from an HIV-TB Genomics Research Project in Botswana
Dimpho Ralefala, Mary Kasule, Ambroise Wonkam, Mogomotsi Matshaba, Jantina de Vries
AJOB Empirical Bioethics, 1 July 2021
Open Access
Abstract
Background
Whilst informed consent is a key component of considering whether individual genomic research results could or should be fed back to research participants, little is known about the views of African research participants on its role.
Methods
We carried out a qualitative study to explore views of adolescents and parents or caregivers regarding informed consent for feedback of individual results from a genomics research project in Botswana. We conducted 24 deliberative focus group discussions with 93 participants (44 adolescents and 49 parents or caregivers) and 12 in-depth interviews (6 adolescents and 6 parents).
Results
Our findings revealed that most participants would like to be informed about the possibility of discovering individual genetic results during the consent process and that consent be obtained for feedback during the enrollment process. They further expressed that in cases where prior consent to feedback was not obtained, then participants should be re-contacted where life-saving genetic information is discovered. Participants emphasized the need for researchers to ensure that participants’ decisions regarding feedback of results are well-informed. Autonomy, transparency, and communication were identified as key values to uphold during the consent process.
Conclusion
In conclusion, obtaining participants’ consent for feedback of results is important to ensure that their rights and wellbeing are protected in research. This is critical in building trust relationships between participants and researchers.

The Ethics of Consent in a Shifting Genomic Ecosystem

The Ethics of Consent in a Shifting Genomic Ecosystem
Sandra Soo-Jin Lee
Annual Review of Biomedical Data Science, July 2021; 4 pp 145-164
Abstract
The collection and use of human genetic data raise important ethical questions about how to balance individual autonomy and privacy with the potential for public good. The proliferation of local, national, and international efforts to collect genetic data and create linkages to support large-scale initiatives in precision medicine and the learning health system creates new demands for broad data sharing that involve managing competing interests and careful consideration of what constitutes appropriate ethical trade-offs. This review describes these emerging ethical issues with a focus on approaches to consent and issues related to justice in the shifting genomic research ecosystem.

Views on genomic research result delivery methods and informed consent: a review

Views on genomic research result delivery methods and informed consent: a review
Danya F Vears , Joel T Minion, Stephanie J Roberts, James Cummings, Mavis Machirori & Madeleine J Murtagh
Personalized Medicine, 6 April 2021; 18(3)
Abstract
There has been little discussion of the way genomic research results should be returned and how to obtain informed consent for this. We systematically searched the empirical literature, identifying 63 articles exploring stakeholder perspectives on processes for obtaining informed consent about return of results and/or result delivery. Participants, patients and members of the public generally felt they should choose which results are returned to them and how, ranging from direct (face-to-face, telephone) to indirect (letters, emails, web-based delivery) communication. Professionals identified inadequacies in result delivery processes in the research context. Our findings have important implications for ensuring participants are supported in deciding which results they wish to receive or, if no choice is offered, preparing them for potential research outcomes.

Mainstreaming informed consent for genomic sequencing: A call for action

Mainstreaming informed consent for genomic sequencing: A call for action
Current Perspective
Eline M. Bunnik, Wybo J. Dondorp, Annelien L. Bredenoord, Guido de Wert, Martina C. Corneld
European Journal of Cancer, May 2021; 148 pp 405-410
Abstract
The wider availability of genomic sequencing, notably gene panels, in cancer care allows for personalised medicine or the tailoring of clinical management to the genetic characteristics of tumours. While the primary aim of mainstream genomic sequencing of cancer patients is therapy-focussed, genomic testing may yield three types of results beyond the answer to the clinical question: suspected germline mutations, variants of uncertain significance (VUS), and unsolicited findings pertaining to other conditions. Ideally, patients should be prepared beforehand for the clinical and psychosocial consequences of such findings, for themselves and for their family members, and be given the opportunity to autonomously decide whether or not to receive such unsolicited genomic information. When genomic tests are mainstreamed into cancer care, so should accompanying informed consent practices. This paper outlines what mainstream oncologists may learn from the ethical tradition of informed consent for genomic sequencing, as developed within clinical genetics. It argues that mainstream informed consent practices should focus on preparing patients for three types of unsolicited outcomes, briefly and effectively. Also, it argues that when the chance of unsolicited findings is very low, opt-out options need not be actively offered. The use of a layered approach – integrated in information systems – should render informed consent feasible for non-geneticist clinicians in mainstream settings. (Inter) national guidelines for mainstreaming informed consent for genomic sequencing must be developed.