Knowledge and Attitudes about Privacy and Secondary Data Use among African-Americans Using Direct-to-Consumer Genetic Testing.

INTRODUCTION: The rapidly expanding direct-to-consumer genetic testing (DTC GT) market is one area where narratives of underrepresented populations have not been explored extensively. This study describes African-American consumers' personal experiences with and perceptions about DTC GT and explores similarities and differences between African-Americans and an earlier cohort of mostly European American consumers. METHODS: Twenty semi-structured, qualitative interviews were held with individuals who self-identified as Black/African-American and completed DTC GT between February 2017 and February 2020. Interviews were transcribed and consensus-coded, using inductive content analysis. RESULTS: Participants generally had positive regard for DTC GT. When considering secondary uses of their results or samples, most participants were aware this was a possibility but had little concrete knowledge about company practices. When prompted about potential uses, participants were generally comfortable with research uses but had mixed outlooks on other nonresearch uses such as law enforcement, cloning, and product development. Most participants expressed that consent should be required for any secondary use, with the option to opt out. The most common suggestion for companies was to improve transparency. Compared to European American participants, African-American participants expressed more trust in DTC GT companies compared to healthcare providers, more concerns about law enforcement uses of data, and a stronger expression of community considerations. DISCUSSION/CONCLUSION: This study found that African-American consumers of DTC GT had a positive outlook about genetic testing and were open to research and some nonresearch uses, provided that they were able to give informed consent. Participants in this study had little knowledge of company practices regarding secondary uses. Compared to an earlier cohort of European American participants, African-American participants expressed more concerns about medical and law enforcement communities' use of data and more reference to community engagement.

Newborn screening for neurodevelopmental diseases: Are we there yet?

In the US, newborn screening (NBS) is a unique health program that supports health equity and screens virtually every baby after birth, and has brought timely treatments to babies since the 1960's. With the decreasing cost of sequencing and the improving methods to interpret genetic data, there is an opportunity to add DNA sequencing as a screening method to facilitate the identification of babies with treatable conditions that cannot be identified in any other scalable way, including highly penetrant genetic neurodevelopmental disorders (NDD). However, the lack of effective dietary or drug-based treatments has made it nearly impossible to consider NDDs in the current NBS framework, yet it is anticipated that any treatment will be maximally effective if started early. Hence there is a critical need for large scale pilot studies to assess if and how NDDs can be effectively screened at birth, if parents desire that information, and what impact early diagnosis may have. Here we attempt to provide an overview of the recent advances in NDD treatments, explore the possible framework of setting up a pilot study to genetically screen for NDDs, highlight key technical, practical, and ethical considerations and challenges, and examine the policy and health system implications.

Addressing ethical and laboratory challenges for initiation of a rapid whole genome sequencing program.

Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.

Exploring the use of a Comic for Education about Expanded Carrier Screening among a Diverse Group of Mothers.

Purpose: Expanded carrier screening (ECS) during prenatal care is an important test for identifying prospective parents' risk of inherited genetic diseases. However, barriers remain for effectively educating patients about ECS. Graphic medicine (i.e. comics) has grown as a mechanism for patient education. The purpose of this study was to explore attitudes and opinions of a comic to educate about ECS during prental care. Methods: Focus groups were conducted with pregnant women or women who recently gave birth (6 groups, n=54). The participants were all female, 44.4% Latino/Hispanic, 16.7% Bi-Racial/Other, and 43.3% reporting some college education or high school degree. Results: Most participants reported high enjoyment with the comic due to their relatability to the characters, simplicity of the story, description of medical outcomes in everyday terms and the exploration of multiple outcomes possible with ECS. In addition, participants reported that during pregnancy their reading habits increase as well as emotional reactions to the content and some participants stated they avoided reading information that may cause stress or anxiety. Conclusion: More research is needed to assess what features of the comic promote understanding and how that influences decisions and pre-test patient education for ECS. The use of graphic narratives may enable individuals to better understand medical information in general.

What Should Physician-Researchers Tell Patient-Subjects About Their Relationships With Industry?

An investigator's personal financial interest in technology under investigation or in the company sponsoring the research is a clear conflict of interest (COI). Such financial relationships are common, and ethical questions rightly emerge about COIs' capacity to compromise an investigator's approaches to research. This commentary on a case suggests that COI disclosure is appropriate during the process of facilitating patient-subjects' informed consent because it promotes informed decision making and motivates transparency. But COI disclosures are not always efficacious, nor are they sufficient to address the problem of research bias. This commentary argues that mitigation or elimination of COIs is a more effective strategy than disclosure.

Ethical concerns relating to genetic risk scores for suicide.

Genome-wide association studies (GWAS) provide valuable information in research contexts regarding genomic changes that contribute to risks for complex psychiatric conditions like major depressive disorder. GWAS results can be used to calculate polygenic risk scores (PRS) for psychiatric conditions, such as bipolar disorder or schizophrenia, as well as for other traits, such as obesity or hypertension. Private companies that provide direct-to-consumer (DTC) genetic testing sometimes report PRS for a variety of traits. Recently, the first well-powered GWAS study for suicide death was published. PRS reports that claim to assess suicide risk are therefore likely to appear soon in the DTC setting. We describe ethical concerns regarding the commercial use of GWAS results related to suicide. We identify several issues that must be addressed before PRS for suicide risk is made available to the public through DTC: (a) the potential for misinterpretation of results, (b) consumers' perceptions about determinism and behavior change, (c) potential contributions to stigma, discrimination, and health disparities; and (d) ethical problems regarding the testing of children and vulnerable adults. Tests for genetic prediction of suicidality may eventually have clinical significance, but until then, the potential for individual and public harm significantly outweighs any potential benefit. Even if genetic prediction of suicidality improves significantly, information about genetic risk scores must be distributed cautiously, with genetic counseling, and with adequate safeguards.

The Ethics of Artificial Intelligence in Pathology and Laboratory Medicine: Principles and Practice.

Growing numbers of artificial intelligence applications are being developed and applied to pathology and laboratory medicine. These technologies introduce risks and benefits that must be assessed and managed through the lens of ethics. This article describes how long-standing principles of medical and scientific ethics can be applied to artificial intelligence using examples from pathology and laboratory medicine.

Secondary Data Usage in Direct-to-Consumer Genetic Testing: To What Extent Are Customers Aware and Concerned?

INTRODUCTION: Customer data from direct-to-consumer genetic testing (DTC GT) are often used for secondary purposes beyond providing the customer with test results. OBJECTIVE: The goals of this study were to determine customer knowledge of secondary uses of data, to understand their perception of risks associated with these uses, and to determine the extent of customer concerns about privacy. METHODS: Twenty DTC GT customers were interviewed about their experiences. The semi-structured interviews were transcribed, coded, and analyzed for common themes. RESULTS: Most participants were aware of some secondary uses of data. All participants felt that data usage for research was acceptable, but acceptability for non-research purposes varied across participants. The majority of participants were aware of the existence of a privacy policy, but few read the majority of the privacy statement. When previously unconsidered uses of data were discussed, some participants expressed concern over privacy protections for their data. CONCLUSION: When exposed to new information on secondary uses of data, customers express concerns and a desire to improve consent with transparency, more opt-out options, improved readability, and more information on future uses and potential risks from direct-to-consumer companies. Effective ways to improve readership about the secondary use, risk of use, and protection of customer data should be investigated and the findings implemented by DTC companies to protect public trust in these practices.

Ethical and public health implications of genetic testing for suicide risk: family and survivor perspectives.

PURPOSE: Death from suicide has an estimated heritability of ~50%. Research may soon allow calculation of polygenic risk scores (PRS) for suicide death, which could be marketed directly to consumers. This raises ethical concerns. Understanding how consumers will utilize this information is urgent. METHODS: We conducted three focus groups involving suicide attempt survivors ("survivors") and family members of suicide decedents ("family members") to gauge their reactions to this technology. Questions focused on positive and negative implications of PRS results. Qualitative research methods were used to summarize studio results. RESULTS: Eight survivors and 13 family members participated. Both groups postulated benefits of suicide PRS, including prevention and reduced stigma. Their concerns ranged from increased stigma to adverse psychological effects. They suggested that suicide PRS should be accompanied by extensive education and counseling. Participants experienced no adverse effects. CONCLUSION: Many ethical, legal, and social implications of genetic testing for suicide risk are highly salient to community stakeholders. Our participants hoped that suicide PRS could have significant individual and community-level benefits, but had concerns about effects in several domains, including stigma, access to insurance and employment, and increased anxiety and depression.

Informed Consent for Genetic and Genomic Research.

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.

Cost-Effectiveness of Nusinersen and Universal Newborn Screening for Spinal Muscular Atrophy.

OBJECTIVE: To evaluate the cost-effectiveness of nusinersen with and without universal newborn screening for infantile-onset spinal muscular atrophy (SMA). STUDY DESIGN: A Markov model using data from clinical trials with US epidemiologic and cost data was developed. The primary interventions studied were nusinersen treatment in a screening setting, nusinersen treatment in a nonscreening setting, and standard care. Analysis was conducted from a societal perspective. RESULTS: Compared with no screening and no treatment, the incremental cost-effectiveness ratio (ICER) for nusinersen with screening was $330 558 per event-free life year (LY) saved, whereas the ICER for nusinersen treatment without screening was $508 481 per event-free LY saved. For nusinersen with screening to be cost-effective at a willingness-to-pay (WTP) threshold of $50 000 per event-free LY saved, the price would need to be $23 361 per dose, less than one-fifth its current price of $125 000. Preliminary data from the NURTURE trial indicated an 85.7% improvement in expected LYs saved compared with our base results. In probabilistic sensitivity analysis, nusinersen and screening was a preferred strategy 93% of the time at a $500 000 WTP threshold. CONCLUSION: Universal newborn screening for SMA provides improved economic value for payers and patients when nusinersen is available.

Experiences and lessons learned by genetic counselors in returning secondary genetic findings to patients.

Few studies have explored the real-world experiences and strategies of genetic counselors involved in the process of returning secondary findings (SFs). This study aimed to describe and categorize the experiences for the return of SFs from clinical sequencing. Semi-structured telephone interviews with 21 genetic counselors representing 56 incidences were conducted. A content analysis was conducted on the transcripts through an iterative, team-based approach. Four common categories emerged across all interviews. These included (a) the importance of pretest counseling for the return of SFs, (b) how primary test results influenced the level of importance placed on the SFs, (c) patients' emotional reactions from receiving SF results, and (d) how returning SFs changed future pretest counseling and consent. This study identified experiences and common practices by genetic counselors who returned SFs. More research is needed to assess how genetic counselors' specific strategies improve patient comprehension and medical actions.

Comparison of Video, App, and Standard Consent Processes on Decision-Making for Biospecimen Research: A Randomized Controlled Trial.

Obtaining informed consent for bloodspot research from newborn screening is particularly challenging due to the hectic environment of the postnatal period and the relatively abstract nature of future, unspecified research on the biospecimens. A randomized controlled trial was conducted in three Michigan hospitals to compare two different consent processes (video and interactive tablet "app") with standard brochure-based consent in the Michigan BioTrust for Health. Results indicated higher knowledge scores for the video and app groups as well as significantly higher scores on satisfaction, amount of information, and clarity with the information provided. More research is needed to find the right amount of information for informed decision-making, and additional feasibility studies are needed to assess implementation strategies.