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
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
Dimpho Ralefala, Mary Kasule, Ambroise Wonkam, Mogomotsi Matshaba, Jantina de Vries
AJOB Empirical Bioethics, 1 July 2021
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.
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).
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.
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
Sandra Soo-Jin Lee
Annual Review of Biomedical Data Science, July 2021; 4 pp 145-164
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
Danya F Vears , Joel T Minion, Stephanie J Roberts, James Cummings, Mavis Machirori & Madeleine J Murtagh
Personalized Medicine, 6 April 2021; 18(3)
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
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
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.
Written Informed Consent-Translating into Plain Language. A Pilot Study
Agnieszka Zimmermann, Anna Pilarska, Aleksandra Gaworska-Krzemińska, Jerzy Jankau, Marsha N Cohen
Healthcare, 20 February 2021; 9(2)
Informed consent is important in clinical practice, as a person’s written consent is required prior to many medical interventions. Many informed consent forms fail to communicate simply and clearly. The aim of our study was to create an easy-to-understand form.
Our assessment of a Polish-language plastic surgery informed consent form used the Polish-language comprehension analysis program (jasnopis.pl, SWPS University) to assess the readability of texts written for people of various education levels; and this enabled us to modify the form by shortening sentences and simplifying words. The form was re-assessed with the same software and subsequently given to 160 adult volunteers to assess the revised form’s degree of difficulty or readability.
The first software analysis found the language was suitable for people with a university degree or higher education, and after revision and re-assessment became suitable for persons with 4-6 years of primary school education and above. Most study participants also assessed the form as completely comprehensible.
There are significant benefits possible for patients and practitioners by improving the comprehensibility of written informed consent forms.
Old Challenges or New Issues? Genetic Health Professionals’ Experiences Obtaining Informed Consent in Diagnostic Genomic Sequencing
Danya F. Vears, Pascal Borry, Julian Savulescu, Julian J. Koplin
American Journal of Bioethics, 5 October 2020; pp 12-23
While integrating genomic sequencing into clinical care carries clear medical benefits, it also raises difficult ethical questions. Compared to traditional sequencing technologies, genomic sequencing and analysis is more likely to identify unsolicited findings (UF) and variants that cannot be classified as benign or disease-causing (variants of uncertain significance; VUS). UF and VUS pose new challenges for genetic health professionals (GHPs) who are obtaining informed consent for genomic sequencing from patients.
We conducted semi-structured interviews with 31 GHPs across Europe, Australia and Canada to identify some of these challenges.
Our results show that GHPs find it difficult to prepare patients to receive results because a vast amount of information is required to fully inform patients about VUS and UF. GHPs also struggle to engage patients – many of whom may be focused on ending their ‘diagnostic odyssey’ – in the informed consent process in a meaningful way. Thus, some questioned how ‘informed’ patients actually are when they agree to undergo clinical genomic sequencing.
These findings suggest a tension remains between sufficient information provision at the risk of overwhelming the patient and imparting less information at the risk of uninformed decision-making. We suggest that a shift away from ‘fully informed consent’ toward an approach aimed at realizing, as far as possible, the underlying goals that informed consent is meant to promote.
Informed consent for genetic testing in hematology
Jonathan M. Marron
Hematology, 4 December 2020; 1 pp 213–218
Informed consent is a fundamental component of modern health care. All competent adult patients have the legal and ethical authority to accept (consent) or refuse (dissent) recommended health-related interventions. Various models of informed consent have been described, and herein I introduce a model that divides informed consent into 7 distinct elements: competence, voluntariness, disclosure, recommendation, understanding, decision, and authorization. Genetic testing, which is rapidly becoming a common feature of both clinical care and research in hematology, adds additional layers of complexity to each of these consent elements. Using the example case of Mr. Smith, a man with newly diagnosed acute myeloid leukemia whose clinicians offer him genetic testing of the leukemia through a clinical trial, I highlight the challenges and controversies of informed consent for genetic testing, focusing on each consent element as it pertains to genetic testing in such a setting. Ultimately, given the growing importance of genetic testing for hematologic disorders, clinicians, and researchers in hematology should be facile at participating in all aspects of informed consent for genetic testing.
Informed Consent for Genetic and Genomic Research
Jeffrey R. Botkin
Current Protocols in Human Genetics, 17 November 2020
Genetic research often utilizes or generates information that is potentially sensitive to individuals, families, or communities. For these reasons, genetic research may warrant additional scrutiny from investigators and governmental regulators, compared to other types of biomedical research. The informed consent process should address the range of social and psychological issues that may arise in genetic research. This article addresses a number of these issues, including recruitment of participants, disclosure of results, psychological impact of results, insurance and employment discrimination, community engagement, consent for tissue banking, and intellectual property issues. Points of consideration are offered to assist in the development of protocols and consent processes in light of contemporary debates on a number of these issues. © 2020 Wiley Periodicals LLC.
The Meaning of Informed Consent: Genome Editing Clinical Trials for Sickle Cell Disease
Stacy Desine, Brittany M. Hollister, Khadijah E. Abdallah, Anitra Persaud, Sara Chandros Hull, Vence L. Bonham
AJOB Empirical Bioethics, 12 October 2020; 11(4) pp 195-207
A first therapeutic target of somatic genome editing (SGE) is sickle cell disease (SCD), the most commonly inherited blood disorders, affecting more than 100,000 individuals in the United States. Advancement of SGE is contingent on patient participation in first in human clinical trials. However, seriously ill patients may be vulnerable to overestimating the benefits of early phase studies while underestimating the risks. Therefore, ensuring potential clinical trial participants are fully informed prior to participating in a SGE clinical trial is critical.
We conducted a mixed-methods study of adults with SCD as well as parents and physicians of individuals with SCD. Participants were asked to complete a genetic literacy survey, watch an educational video about genome editing, complete a twopart survey, and take part in focus group discussions. Focus groups addressed topics on clinical trials, ethics of gene editing, and what is not understood regarding gene editing. All focus groups were audio-recorded, transcribed, and analyzed using conventional content analysis techniques to identify major themes.
Our study examined the views of SCD stakeholders regarding what they want and need to know about genome editing to make an informed decision to participate in a SGE clinical trial. Prominent themes included stakeholders’ desire to understand treatment side effects, mechanism of action of SGE, trial qualification criteria, and the impact of SGE on quality of life. In addition, some physicians expressed concerns about the extent to which their patients would understand concepts related to SGE; however, individuals with SCD demonstrated higher levels of genetic literacy than estimated by physicians.
Designing ethically robust genome editing clinical trials for the SCD population will require, at a minimum, addressing the expressed information needs of the community through culturally sensitive engagement, so that they can make informed decisions to consider participation in clinical trials.