Assessment of the current status of real-world pharmacogenomic testing: informed consent, patient education, and related practices
Original Research
Lucas Pereira, Cyrine-Eliana Haidar, Susanne B. Haga, Anna G. Cisler, April Hall, Sanjay K. Shukla, Scott J. Hebbring,
Emili J. W. Leary
Frontiers in Pharmacology, 8 February 2024
Abstract
Introduction
The practice of informed consent (IC) for pharmacogenomic testing in clinical settings varies, and there is currently no consensus on which elements of IC to provide to patients. This study aims to assess current IC practices for pharmacogenomic testing.
Methods
An online survey was developed and sent to health providers at institutions that offer clinical germline pharmacogenomic testing to assess current IC practices.
Results
Forty-six completed surveys representing 43 clinical institutions offering pharmacogenomic testing were received. Thirty-two (74%) respondents obtain IC from patients with variability in elements incorporated. Results revealed that twenty-nine (67%) institutions discuss the benefits, description, and purpose of pharmacogenomic testing with patients. Less commonly discussed elements included methodology and accuracy of testing, and laboratory storage of samples.
Discussion
IC practices varied widely among survey respondents. Most respondents desire the establishment of consensus IC recommendations from a trusted pharmacogenomics organization to help address these disparities.
Category: Genomic Medicine/Gene Editing
The Need to Consider Context: A Systematic Review of Factors Involved in the Consent Process for Genetic Tests from the Perspective of Patients
The Need to Consider Context: A Systematic Review of Factors Involved in the Consent Process for Genetic Tests from the Perspective of Patients
Research Article
Frédéric Coulombe, Anne-Marie Laberge
AJOB Empirical Bioethics, 8 January 2024
Abstract
Background
Informed consent for genetic tests is a well-established practice. It should be based on good quality information and in keeping with the patient’s values. Existing informed consent assessment tools assess knowledge and values. Nevertheless, there is no consensus on what specific elements need to be discussed or considered in the consent process for genetic tests.
Methods
We performed a systematic review to identify all factors involved in the decision-making and consent process about genetic testing, from the perspective of patients. Through public databases, we identified studies reporting factors that influence the decision to accept or decline genetic testing. Studies were included if they reported the perspective of patients or at-risk individuals. All articles were thematically coded.
Results
1989 articles were reviewed: 70 met inclusion criteria and 12 additional articles were identified through the references of included studies. Coding of the 82 articles led to the identification of 45 factors involved in decision-making and consent, which were initially divided into three domains: in favor of, against or with an undetermined influence on genetic testing. Each factor was also divided into three subdomains relating to the informed choice concept: knowledge, values or other. The factors in the “other” subdomain were all related to the context of testing (e.g. timing, cost, influence of family members, etc), and were present in all three domains.
Conclusions
We describe the network of factors contributing to decision-making and consent process and identify the context of genetic testing as a third component to influence this process. Future studies should consider the evaluation of contextual factors as an important and relevant component of the consent and decision-making process about genetic tests. Based on these results, we plan to develop and test a more comprehensive tool to assess informed consent for genetic testing.
Informed Consent In Genetic Research
Informed Consent In Genetic Reasearch
Ljupco Chakar, Aleksandar Stankov, Goran Pavlovski, Natasha Bitoljanu, Viktorija Belakaposka Srpanova, Ana Ivcheva, Rosica Siamkouri, Zlatko Jakjovski
Journal of Morphological Sciences, 27 December 2023
Abstract
Recognizing the ethical, legal, and social implications (ELSI) of genetic testing becomes crucial for physicians in the face of complex medical issues, as they are increasingly expected to counsel their patients regarding the medical, psychological, and social responses arising from genetic information. Genetic medicine, with its extreme complexity and the potential repercussions on an individual’s life, raises important questions in the ethical, deontological, and legal realms of medicine, playing a primary role in personalized medicine. The aim of this paper is to underscore the significance of informed consent and to provide insights into the ethical procedures associated with genetic testing.
Editor’s note: The Journal of Morphological Sciences is a publication of the Brazilian Society of Anatomy and the Panamerican Association of Anatomists.
Ethical considerations for genetic research in low-income countries: perceptions of informed consent, data sharing, and expectations in Nicaragua
Ethical considerations for genetic research in low-income countries: perceptions of informed consent, data sharing, and expectations in Nicaragua
Iris S. Delgado, Abigail Outterson, Vaishnavi Ramesh, Alda Gabriela Amador Sanchez, Alfonso César Boza, Damaris Lopez-Pilarte, Juan José Amador Velázquez, David J. Friedman, Daniel R. Brooks, Madeleine K. Scammell, Catharine Wang
European Journal of Human Genetics, 5 December 2023
Open Access
Abstract
Genetic research presents numerous ethical, legal, and social implications (ELSI), particularly when the research involves collaborations between investigators in high and low-income countries. Some ELSI issues are universal, and others are specific to context and culture. This study investigates perceptions of genetic research in Nicaragua, Central America, where local and U.S. based researchers have collaborated for over a decade. A total of 43 residents from northwestern Nicaragua, a region with high mortality rates attributed to chronic kidney disease of non-traditional causes (CKDnt), were interviewed, including research participants in ongoing studies (n = 36), health professionals (n = 3), labor leaders (n = 2), and family members of research participants (n = 2). Questions focused on informed consent, data-sharing, and post-study expectations. Audio recordings of interviews conducted in Spanish were transcribed and translated into English. English transcripts were coded and analyzed using NVivo 12 software. The lack of familiarity with terms in the consent form presented a barrier to participant comprehension of key elements of the genetic research study, raising concerns about the validity of informed consent. Research participants often viewed their participation as access to health care. Health professionals emphasized the importance of long-term partnerships between foreign-based researchers and local health institutions. Leaders and family members recommended that they be informed of research studies and allowed the opportunity to consent, as they felt the benefits and risks of research also apply to them. Our findings identified genetic research practices to be improved upon in order to be more responsive to the contextual realities of collaborators living in low-resource settings.
Spotlight Article
This month we are spotlighting The Lived Experience of Pediatric Gene Therapy – A Scoping Review by Kimberly et al. In this Human Gene Therapy article the authors assess empirical research examining the lived experience of both patients and caregivers participating in pediatric gene therapy trials. Their scoping review underscores a serious gap in the literature leading to an examination of narrative accounts from trial participants and their families, and areas where further research in necessary. The authors note that:
[p. 4]
“…When making a decision about whether to enroll a child in a GT clinical trial, caregivers must weigh factors such as: the inability for most treatments to be repeated or re-dosed; uncertainty around the durability, efficacy, and safety of an experimental treatment; risk of a child’s disease progressing if they wait for an approved treatment or more safety data; and efficacy of existing approved alternative treatments… The confluence of these factors within a high-stakes decision-making framework creates a unique ethical context for pediatric rare disease patients and their parents and caregivers. The progressive nature of many of these diseases also adds a time constraint to participation…
[p. 16]
The field of pediatric GT research… has an important and timely opportunity to better understand how patients and their parents/caregivers choose whether or not to consider GT, and their lived experience of participating in clinical trials. Pediatric patients’ own perspectives are almost completely absent from the literature, marking an important area for future research efforts. Such insights from further research will inform more patient- and family-centered clinical trial design and can help to ensure that clinical trial design and implementation reflect patients’ and families’ values, their priorities, and their goals for care. This scoping review lays a foundation for future research in this space.”
The Lived Experience of Pediatric Gene Therapy – A Scoping Review
Laura Kimberly, Cara Hunt, Katherine Beaverson, Emma James, Alison Bateman-House, Richard McGowan, Jennifer DeSante-Bertkau
Human Gene Therapy, 15 November 2023
Abstract
Little is known about patients’ and families’ lived experience of participating in pediatric gene therapy (GT) clinical trials. Currently, pediatric GT research targets a broad range of indications––including rare and ultra-rare diseases––which vary in severity and in the availability of alternative therapies. Pediatric GT differs meaningfully from adult GT because the decision to participate involves a dyad of both the child and parent or caregiver/s. It is critical to understand patients’ and caregivers’ perceptions and experiences of the social, emotional, physical, and logistical burdens or benefits of participating in such trials, and how they weigh and prioritize these factors when deciding whether to participate. We conducted a scoping review of the current literature in this subject area with objectives to a) provide an overview of existing literature, b) identify gaps and areas for further research, and c) better understand the lived impact of pediatric GT research on patients and their parents/caregivers. , Four themes emerged, including 1) weighing risks and benefits 2) timing of GT trial participation 3) value of clear communication, and 4) potential impact on quality of life. Notably, our sample surfaced articles about how patients/parents/caregivers were thinking about GT – their understanding of its safety, efficacy, and risks – rather than accounts of their experiences, which was our initial intention. Nevertheless, our findings offer useful insights to improve the informed consent process and promote a more patient- and family-centered approach. Moreover, our findings can contribute to patient advocacy organizations’ efforts to develop educational materials tailored to patients’ and families’ expressed informational needs and perspectives, and can inform more patient- and family-centered policies from GT clinical trial sponsors.
Ambivalence and regret in genome sequencing
Ambivalence and regret in genome sequencing
Editorial
Alisdair McNeill
European Journal of Human Genetics, 21 November 2023
Excerpt
…Consent conversations relating to genome sequencing for children are recognised as being potentially problematic. Given the vast number of potential outcomes of genome sequencing (e.g. no diagnosis, incidental finding), it has been disputed if ‘informed’ consent can be achieved. A qualitative study of medical geneticists views on consent for genome sequencing in paediatrics provides useful insights. One view was that truly informed consent for genome sequencing in paediatrics is not possible. The need for more genetics professionals and better information resources for families was recognised. A further issue around informed consent in genetics is around that of reuse of genetic information and data in research projects…
Consumer Genetics: What About Informed Consent?
Consumer Genetics: What About Informed Consent?
Research Article
Matt Artz, Doug Henry, Carolina Severiche Mena
Human Organization, 17 November 2023; 82(4) pp 394–404
Abstract
With the dramatic rise in Direct-to-Consumer Genetics has come increasing concern for the potential abuse of consumer health data, often presumed confidential. Companies exchange and monetize their customers’ DNA in a competitive marketplace, obtaining consent through complex legal contracts that consumers must sign. However, drawing on ethnographic data, we show that this consent is rarely “informed.” Particular concerns include lack of contractual knowledge, misunderstanding of the potential benefits and risks, privacy, and low genetic literacy.
Editor’s note: Human Organization is the Journal of the Society for Applied Anthropology, “founded in 1941 to promote the investigation of the principles of human behavior and the application of these principles to contemporary issues and problems.
Uncertain futures and unsolicited findings in pediatric genomic sequencing: guidelines for return of results in cases of developmental delay
Uncertain futures and unsolicited findings in pediatric genomic sequencing: guidelines for return of results in cases of developmental delay
Research
BMC Medical Ethics, 11 November 2023
Candice Cornelis, Wybo Dondorp, Ineke Bolt, Guido de Wert, Marieke van Summeren, Eva Brilstra, Nine Knoers, Annelien L. Bredenoord
Open Access
Abstract
Background
Massively parallel sequencing techniques, such as whole exome sequencing (WES) and whole genome sequencing (WGS), may reveal unsolicited findings (UFs) unrelated to the diagnostic aim. Such techniques are frequently used for diagnostic purposes in pediatric cases of developmental delay (DD). Yet policy guidelines for informed consent and return of UFs are not well equipped to address specific moral challenges that may arise in these children’s situations.
Discussion
In previous empirical studies conducted by our research group, we found that it is sometimes uncertain how children with a DD will develop and whether they could come to possess capacities for autonomous decision-making in the future. Parents sometimes felt this brought them into a Catch-22 like situation when confronted with choices about UFs before undergoing WES in trio-analysis (both the parents’ and child’s DNA are sequenced). An important reason for choosing to consent to WES was to gain more insight into how their child might develop. However, to make responsible choices about receiving or declining knowledge of UFs, some idea of their child’s future development of autonomous capacities is needed. This undesirable Catch-22 situation was created by the specific policy configuration in which parents were required to make choices about UFs before being sequencing (trio-analysis). We argue that this finding is relevant for reconfiguring current policies for return of UFs for WES/WGS and propose guidelines that encompass two features. First, the informed consent process ought to be staged. Second, differing guidelines are required for withholding/disclosing a UF in cases of DD appropriate to the level of confidence there is about the child’s future developmental of autonomous capacities.
Conclusion
When combined with a dynamic consent procedure, these two features of our guidelines could help overcome significant moral challenges that present themselves in the situations of children undergoing genomic sequencing for clarifying a DD.
‘It’s a nightmare’: informed consent in paediatric genome-wide sequencing. A qualitative expert interview study from Germany and Switzerland
‘It’s a nightmare’: informed consent in paediatric genome-wide sequencing. A qualitative expert interview study from Germany and Switzerland
Johanna Eichinger, Bettina Zimmermann, Bernice Elger, Stuart McLennan, Isabel Filges, Insa Koné
European Journal of Human Genetics, 29 September 2023
Open Access
Abstract
The use of genome-wide sequencing (GWS) in paediatrics has added complexity to informed consent (IC) and pretest counselling because of the vast number and interpretation of potential findings, and their implications. However, empirical data from continental Europe on these issues remains limited. This study therefore aimed to explore the experiences and views of medical geneticists working with children in Germany and Switzerland regarding the challenges of obtaining valid IC in paediatric GWS. Qualitative interviews with 20 medical geneticists were analysed employing reflexive thematic analysis. In the interviews, many medical geneticists questioned the validity of parents’ IC due to the enormous amount of relevant information given and the variety and complexity of the possible test outcomes. Key barriers identified included familial implications, administrative challenges and struggles with non-directiveness. Medical geneticists’ suggestions for improvement included increasing the number of genetics professionals and better information material, which is crucial as GWS becomes a diagnostic standard in the early care pathways of children. An adjustment of aspirations from still existing ideal of traditional fully IC to appropriate IC seems to be needed. Such a more realistic and ethically sound adaptation of the requirements for IC can lead to better ‘informedness’ and improve the validity of the consent. This might also help reduce the moral distress for the medical geneticists involved.
Evaluation of CTRL: a web application for dynamic consent and engagement with individuals involved in a cardiovascular genetic disorders cohort
Evaluation of CTRL: a web application for dynamic consent and engagement with individuals involved in a cardiovascular genetic disorders cohort
Matilda A. Haas, Evanthia O. Madelli, Rosie Brown, Megan Prictor, Tiffany Boughtwood
European Journal of Human Genetics, 14 September 2023
Open Access
Abstract
There has been keen interest in whether dynamic consent should be used in health research but few real-world studies have evaluated its use. Australian Genomics piloted and evaluated CTRL (‘control’), a digital consent tool incorporating granular, dynamic decision-making and communication for genomic research. Individuals from a Cardiovascular Genetic Disorders Flagship were invited in person (prospective cohort) or by email (retrospective cohort) to register for CTRL after initial study recruitment. Demographics, consent choices, experience surveys and website analytics were analysed using descriptive statistics. Ninety-one individuals registered to CTRL (15.5% of the prospective cohort and 11.8% of the retrospective cohort). Significantly more males than females registered when invited retrospectively, but there was no difference in age, gender, or education level between those who did and did not use CTRL. Variation in individual consent choices about secondary data use and return of results supports the desirability of providing granular consent options. Robust conclusions were not drawn from satisfaction, trust, decision regret and knowledge outcome measures: differences between CTRL and non-CTRL cohorts did not emerge. Analytics indicate CTRL is acceptable, although underutilised. This is one of the first studies evaluating uptake and decision-making using online consent tools and will inform refinement of future designs.
Center for Informed Consent Integrity 