Informed consent in a tuberculosis genetic study in Cameroon: information overload, situational vulnerability and diagnostic misconception
Ali Ibrahim Mohammed-Ali, Eyoab Iyasu Gebremeskel, Emmanuel Yenshu, Theobald Nji, Apungwa Cornelius Ntabe, Samuel Wanji, Godfrey B Tangwa, Nchangwi Syntia Munung
Research Ethics, 14 June 2022
Concerns around comprehension and recall of consent information by research participants have typically been associated with low health and research literacy levels. In genomics research, this concern is heightened as the scientific and ethical complexities of genetics research, such as biobanking, genetic susceptibility, data sharing, and incidental findings may be more difficult for potential research participants to understand. However, challenges to research participants’ comprehension of consent information may be compounded by factors beyond health and research literacy levels. To identify factors that may impact research participants’ understanding and recall of consent information, we designed a qualitative study to explore whether participants enrolled in a tuberculosis genetics study (TBGEN-Africa) in Cameroon understood the objectives of the study, the risks and benefits and certain key aspects of the study such as biobanking and data sharing. The results showed that research participants had limited understanding and/or recall of the TBGEN-Africa study goals and methods. Some participants were of the opinion that TBGEN-Africa was not a genetics study because tuberculosis is not an inheritable condition. Factors that may have hindered understanding and/or recall of study information are diagnostic misconception (research participants consider research as part of medical diagnosis), and information overload and situational vulnerability (consent at a time of physical and emotional distress). There is a need for improved practices to support research participants’ understanding of consent information in genetics studies including designing the consent process in ways that minimize psychological distress and diagnostic/therapeutic misconception.
Information Assessment for the Implementation of Electronic Informed Consent for Genetic Studies in a High Complexity Hospital
Juan Descalzo, Eliana Frutos, Romina Rebrij, Daniel Luna, Sonia Benítez
Studies in Health Technology and Informatics, 6 June 2022; 290 pp 227-229
The objective of this study was to investigate and analyze the most relevant aspects that influence the development and implementation of electronic informed consent for genetic studies. Interviews were conducted with experts in the area within our institution, the different informed consents available and the number of genetic studies requested in the last 5 years were analyzed. Professionals acknowledged the ethical dilemmas related to the genetic studies and the importance of having an electronic informed consent that not only provides the patient with the information necessary to understand the implications of the study, but also be flexible enough to adapt to the various genetic studies today. The development of informed consent is a challenge for health IT professionals, due to the complexity of the information it contains and the ethical implications it represents.
Moving from ‘fully’ to ‘appropriately’ informed consent in genomics: The PROMICE framework
Julian J Koplin, Christopher Gyngell, Julian Savulescu, Danya F Vears
Bioethics, 7 April 2022
Genomic sequencing technologies (GS) pose novel challenges not seen in older genetic technologies, making traditional standards for fully informed consent difficult or impossible to meet. This is due to factors including the complexity of the test and the broad range of results it may identify. Meaningful informed consent is even more challenging to secure in contexts involving significant time constraints and emotional distress, such as when rapid genomic testing (RGS) is performed in neonatal intensive care units. In this article, we propose that informed consent matters not for its own sake, but because obtaining it furthers a range of morally important goals, such as promoting autonomy, well-being, and trust in medicine. These goals form the basis of a new framework [PROmoting Morally Important Consent Ends (PROMICE)] for assessing the ethical appropriateness of various informed consent models. We illustrate this framework with two examples: (a) a tiered and layered consent model for obtaining consent for GS, and (b) consent for RGS in critically ill newborns. We conclude that appropriately-rather than fully-informed consent provides the correct standard for genomic medicine and research.
Informed consent, genomic research and mental health: A integrative review
Nina Kilkku, Arja Halkoaho
Nursing ethics, 4 February 2022
Research on genomics has increased while the biobank activities are becoming more common in different countries. In the mental health field, the questions concerning the potential participants’ vulnerability as well as capacity to give the informed consent can cause reluctancy in recruiting persons with mental health problems, although the knowledge and understanding of mental health problems has remarkably changed, and practice is guided with inclusive approaches, such as recovery approach.
The aim of this study was to describe the current knowledge of informed consent practices in the context of genomic research on mental health from the nurses’ viewpoint.
An integrative review was conducted with search from seven international databases. Data consist 14 publications which were analyzed with thematic analysis.
Ethical requirements were respected in every phase of the research process.
Most of the papers were published in USA and between 2000-2010. Eight reports were categorized as discussion papers, four qualitative studies and one quantitative study. The thematic analysis provided information on five themes: complexity with the capacity to consent, mixed emotions towards participation, factors influencing the decision to participate, nurses’ informed consent process competence and variations between consent procedures.
In the informed consent practices, there are various aspects which may affect both the willingness to participate in the study and the informed consent process itself. Implications for practice, education, research, and policies are discussed.
There is a need for more updated international research on the topic in the context of different international and national guidelines, legislation, and directives. This study provided a viewpoint to the more collaborative research activities with people with lived experiences also in this field of research following the ideas of recovery approach.
Informed consent practices for exome sequencing: An interview study with clinical geneticists in the Netherlands
Wendy Bos, Eline M. Bunnik
Molecular Genetics & Genomic Medicine, 14 January 2022
Genomic sequencing is being used more frequently in the clinic, not only by clinical geneticists, but also by other specialists (“mainstreaming”). The use of genomic sequencing gives rise to challenges regarding informed consent, as it can yield more, and more complex results.
This study maps the informed consent process for exome sequencing in the Netherlands by means of semistructured interviews with 14 clinical geneticists. Interviewees were asked about their strategies for informing patients about exome sequencing and supporting patients in their decision making, about what they think of as essential information elements, about the challenges they experience, and about their preferences for future policy and practice.
Clinical geneticists typically discuss the following topics: the nature and aim of the test, the possible results (including unsolicited or incidental findings and Variants of Uncertain Significance) of the test and the consequences of those results for the patient and their family members. Some clinical geneticists use a layered approach to informed consent, meaning that they give short and concise information at first, and provide more detailed information depending on the situation or the needs of the patient.
During pre-test counseling for genomic sequencing, clinical geneticists use various strategies to enhance patient understanding and personalization of the informed consent process. Going forward, layering information may be part of a solution to ethical challenges of informed consent, also in mainstream settings.
Consent for rapid genomic sequencing for critically ill children: legal and ethical issues
Christopher Gyngell, Fiona Lynch, Zornitza Stark, Danya Vears
Monash Bioethics Review, 31 December 2021; 39 pp 117–129
Although rapid genomic sequencing (RGS) is improving care for critically ill children with rare disease, it also raises important ethical questions that need to be explored as its use becomes more widespread. Two such questions relate to the degree of consent that should be required for RGS to proceed and whether it might ever be appropriate to override parents’ decisions not to allow RGS to be performed in their critically ill child. To explore these questions, we first examine the legal frameworks on securing consent for genomic sequencing and how they apply to the specific context of RGS for critically ill children. We then use a tool from clinical ethics, the Zone of Parental Discretion, to explore two case studies and identify under which circumstances it might be appropriate for parental refusal of RGS to be overridden. We argue that RGS may be a context where, in addition to assessing the complexity of the test offered, it is ethically appropriate to consider an effect on patient outcomes when deciding the degree of consent required. We also suggest that there are some contexts where it may be ethically justified to perform RGS, even when it is actively against the wishes of the parents. More work is needed to examine exactly how ‘time-sensitive’ exceptions to current guidance on consent for genomic sequencing could be formulated and operationalised for RGS for critically ill-children.
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
Informed consent for genetic testing has historically been acquired during pretest genetic counseling, without specific guidance defining which core concepts are required.
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.
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.
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]
Suffering in Theology and Medical Ethics, 3 December 2021; pp 179–187 [Brill]
…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
Faisal Albalwy, Andrew Brass, Angela Davies
JMIR Medical Informatics, 3 November 2021; 9(11)
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.
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.
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.
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.
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
Laurence Woollard, Richard Gorman, Dakota J. Rosenfelt
Therapeutic Advances in Rare Disease, 26 September 2021
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.