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.

Written Informed Consent-Translating into Plain Language. A Pilot Study

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)
Open Access
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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

Old Challenges or New Issues? Genetic Health Professionals’ Experiences Obtaining Informed Consent in Diagnostic Genomic Sequencing
Research Article
Danya F. Vears, Pascal Borry, Julian Savulescu, Julian J. Koplin
American Journal of Bioethics, 5 October 2020; pp 12-23
Abstract
Background
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.
Methods
We conducted semi-structured interviews with 31 GHPs across Europe, Australia and Canada to identify some of these challenges.
Results
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.
Conclusions
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

Informed consent for genetic testing in hematology
Jonathan M. Marron
Hematology, 4 December 2020; 1 pp 213–218
Open Access
Abstract
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

Informed Consent for Genetic and Genomic Research
Overview
Jeffrey R. Botkin
Current Protocols in Human Genetics, 17 November 2020
Abstract
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

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
Open Access
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.

Participant Reactions to a Literacy-Focused, Web-Based Informed Consent Approach for a Genomic Implementation Study

Participant Reactions to a Literacy-Focused, Web-Based Informed Consent Approach for a Genomic Implementation Study
Research Article
Stephanie A. Kraft, Kathryn M. Porter, Devan M. Duenas, Claudia Guerra, Galen Joseph, Sandra Soo-Jin Lee, Kelly J. Shipman, Jake Allen, Donna Eubanks, Tia L. Kauffman, Nangel M. Lindberg, Katherine Anderson, Jamilyn M. Zepp, Marian J. Gilmore, Kathleen F. Mittendorf, Elizabeth Shuster, Kristin R. Muessig, Briana Arnold, Katrina A.B Goddard, Benjamin S. Wilfond
AJOB Empirical Bioethics, 26 September 2020
Abstract
Background
Clinical genomic implementation studies pose challenges for informed consent. Consent forms often include complex language and concepts, which can be a barrier to diverse enrollment, and these studies often blur traditional research-clinical boundaries. There is a move toward self-directed, web-based research enrollment, but more evidence is needed about how these enrollment approaches work in practice. In this study, we developed and evaluated a literacy-focused, web-based consent approach to support enrollment of diverse participants in an ongoing clinical genomic implementation study.
Methods
As part of the Cancer Health Assessments Reaching Many (CHARM) study, we developed a web-based consent approach that featured plain language, multimedia, and separate descriptions of clinical care and research activities. CHARM offered clinical exome sequencing to individuals at high risk of hereditary cancer. We interviewed CHARM participants about their reactions to the consent approach. We audio recorded, transcribed, and coded interviews using a deductively and inductively derived codebook. We reviewed coded excerpts as a team to identify overarching themes.
Results
We conducted 32 interviews, including 12 (38%) in Spanish. Most (69%) enrolled without assistance from study staff, usually on a mobile phone. Those who completed enrollment in one day spent an average of 12 minutes on the consent portion. Interviewees found the information simple to read but comprehensive, were neutral to positive about the multimedia support, and identified increased access to testing in the study as the key difference from clinical care.
Conclusions
This study showed that interviewees found our literacy-focused, web-based consent approach acceptable; did not distinguish the consent materials from other online study processes; and valued getting access to testing in the study. Overall, conducting empirical bioethics research in an ongoing clinical trial was useful to demonstrate the acceptability of our novel consent approach but posed practical challenges.

A qualitative study on aspects of consent for genomic research in communities with low literacy

A qualitative study on aspects of consent for genomic research in communities with low literacy
Research Article
Daima Bukini, Columba Mbekenga, Siana Nkya, Lisa Purvis, Sheryl McCurdy, Michael Parker, Julie Makani
BMC Medical Ethics, 12 June 2020; 21(48)
Open Access
Abstract
Background
Low literacy of study participants in Sub – Saharan Africa has been associated with poor comprehension during the consenting process in research participation. The concerns in comprehension are far greater when consenting to participate in genomic studies due to the complexity of the science involved. While efforts are made to explore possibilities of applying genomic technologies in diseases prevalent in Sub Saharan Africa, we ought to develop methods to improve participants’ comprehension for genomic studies. The purpose of this study was to understand different approaches that can be used to seek consent from individuals with low literacy in Sub-Saharan African countries in genomic research to improve comprehension.
Methods
Using qualitative study design, we conducted focus-group discussions, in-depth interviews and participant observations as data collection methods. This study was embedded in a hospital based genomic study on Sickle Cell Disease at Muhimbili National Hospital in Tanzania. Thematic content analysis was used to analyse the transcripts and field notes.
Results
Findings from this study show that literacy level has little influence on understanding the research details. According to the participants of this study, the methods used to provide information, the language, and time spent with the study participants were the key factors influencing understanding. The availability of group sessions held before individual consent to allow for a detailed questions and answers format was agreed to be the best method to facilitate the comprehension.
Conclusion
The quality of the consenting process of participants will be influence by a number of factors. The type of research consented for, where the research will be implemented and who are the potential study participants are amongst the factors that need to be assessed during the consenting. Measures to improve participants’ comprehension need to be developed when consenting participants with low literacy level in genomic studies.

The genomic data deficit: On the need to inform research subjects of the informational content of their genomic sequence data in consent for genomic research

The genomic data deficit: On the need to inform research subjects of the informational content of their genomic sequence data in consent for genomic research
Dara Hallinan
Computer Law & Security Review, July 2020; 37
Abstract
Research subject consent plays a significant role in the legitimation of genomic research in Europe – both ethically and legally. One key criterion for any consent to be legitimate is that the research subject is ‘informed’. This criterion implies that the research subject is given all relevant information to allow them to decide whether engaging with a genomic research infrastructure or project would be normatively desirable and whether they wish to accept the risks associated with engagement. This article makes the normative argument that, in order to be truly ‘informed’, the research subject should be provided with information on the informational content of their genomic sequence data. Information should be provided, in the first instance, prior to the initial consent transaction, and should include: information on the fact that genomic sequence data will be collected and processed, information on the types of information which can currently be extracted from sequence data and information on the uncertainties surrounding the types of information which may eventually be extractable from sequence data. Information should also be provided, on an ongoing basis, as relevant and necessary, throughout the research process, and should include: information on novel information which can be extracted from sequence data and information on the novel uses and utility of sequence data. The article argues that current elaborations of ‘informed’ consent fail to adequately address the requirements set out in the normative argument and that this inadequacy constitutes an issue in need of a solution. The article finishes with a set of observations as to the fora best suited to deliver a solution and as to the substantive content of a solution.