Returning personalized, genetic health test results to individuals of African descent or ancestry in precision medicine research.

Today, many epidemiological studies and biobanks are offering to disclose individual genetic results to their participants, including the National Institutes of Health's All of Us Research Program. Returning hereditary disease risks and pharmacogenetic test results to study participants from racial/ethnic groups that are historically underrepresented in biomedical research poses specific challenges to those participants and the health system writ large. For example, individuals of African descent are underrepresented in research about drug-gene interactions and have a relatively higher proportion of variants of unknown significance, affecting their ability to take clinical action following return of results. In this brief report, we summarize studies published to date concerning the perspectives and/or attitudes of African Americans engaged in genetic research programs to anticipate factors in disclosure protocols that would minimize risks and maximize benefits. A thematic analysis of studies identified (n = 6) lends to themes centered on motivations to engage or disengage in the return of results and integrating research and care. Actionable strategies determined in reaction to these themes center on ensuring adequate system and health education support for participants and personalizing the process for participants engaging in return of results. Overall, we offer these themes and actionable strategies as early guidance to research programs, and provide recommendations to policy makers focused on fair and equitable return of genetic research results to underrepresented research participants.

Equity, diversity, and inclusion at the Global Alliance for Genomics and Health.

A lack of diversity in genomics for health continues to hinder equitable leadership and access to precision medicine approaches for underrepresented populations. To avoid perpetuating biases within the genomics workforce and genomic data collection practices, equity, diversity, and inclusion (EDI) must be addressed. This paper documents the journey taken by the Global Alliance for Genomics and Health (a genomics-based standard-setting and policy-framing organization) to create a more equitable, diverse, and inclusive environment for its standards and members. Initial steps include the creation of two groups: the Equity, Diversity, and Inclusion Advisory Group and the Regulatory and Ethics Diversity Group. Following a framework that we call "Reflected in our Teams, Reflected in our Standards," both groups address EDI at different stages in their policy development process.

A survey of United States adult privacy perspectives and willingness to share real-world data.

Objective: Real-world data privacy is a complex yet underexplored topic. To date, few studies have reported adult perspectives around real-world data privacy and willingness to share real-world data with researchers. Methods: Relevant survey items were identified in the literature, adapted and pilot tested among a small convenience sample, and finalized for distribution. The survey was distributed electronically in April 2021 among adults (≥18 years of age) registered in ResearchMatch (www.researchmatch.org). Microsoft Excel was used to assess descriptive statistics across demographical items and four privacy-related items. Results: Of 402 completed responses received, half of respondents (∼50%) expressed willingness to share their prescription history data and music streaming data with researchers and unwillingness to share real-world data from several other sources. Most (53-93%) of participants expressed concern with five statements reflecting the sharing and use of their digital data online. Most participants (71-75%) agreed with four statements focused on individual measures taken to protect their personal privacy and disagreed (77-85%) with two statements centered on not being concerned about sharing or 3rd party access to their personal data online. Conclusions: Our observations indicate an important yet unmet need to further explore and address real-world data privacy concerns among US adults engaging as prospective research participants.

An Assessment of Perspectives and Concerns Among Research Participants of Childbearing Age Regarding the Health-Relatedness of Data, Online Data Privacy, and Donating Data to Researchers: Survey Study.

BACKGROUND: The June 2022 US Supreme Court decision to ban abortion care in Dobbs v Jackson Women's Health Organization sparked ominous debate about the privacy and safety of women and families of childbearing age with digital footprints who actively engage in family planning, including abortion and miscarriage care. OBJECTIVE: To assess the perspectives of a subpopulation of research participants of childbearing age regarding the health-relatedness of their digital data, their concerns about the use and sharing of personal data online, and their concerns about donating data from various sources to researchers today or in the future. METHODS: An 18-item electronic survey was developed using Qualtrics and administered to adults (aged ≥18 years) registered in the ResearchMatch database in April 2021. Individuals were invited to participate in the survey regardless of health status, race, gender, or any other mutable or immutable characteristics. Descriptive statistical analyses were conducted using Microsoft Excel and manual queries (single layer, bottom-up topic modeling) and used to categorize illuminating quotes from free-text survey responses. RESULTS: A total of 470 participants initiated the survey and 402 completed and submitted the survey (for an 86% completion rate). Nearly half the participants (189/402, 47%) self-reported to be persons of childbearing age (18 to 50 years). Most participants of childbearing age agreed or strongly agreed that social media data, email data, text message data, Google search history data, online purchase history data, electronic medical record data, fitness tracker and wearable data, credit card statement data, and genetic data are health-related. Most participants disagreed or strongly disagreed that music streaming data, Yelp review and rating data, ride-sharing history data, tax records and other income history data, voting history data, and geolocation data are health-related. Most (164/189, 87%) participants were concerned about fraud or abuse based on their personal information, online companies and websites sharing information with other parties without consent, and online companies and websites using information for purposes that are not explicitly stated in their privacy policies. Free-text survey responses showed that participants were concerned about data use beyond scope of consent; exclusion from health care and insurance; government and corporate mistrust; and data confidentiality, security, and discretion. CONCLUSIONS: Our findings in light of Dobbs and other related events indicate there are opportunities to educate research participants about the health-relatedness of their digital data. Developing strategies and best privacy practices for discretion regarding digital-footprint data related to family planning should be a priority for companies, researchers, families, and other stakeholders.

The Aetion Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation Initiative: Oncology.

Legislative and technological advancements over the past decade have given rise to the proliferation of healthcare data generated from routine clinical practice, often referred to as real-world data (RWD). These data have piqued the interest of healthcare stakeholders due to their potential utility in generating evidence to support clinical and regulatory decision making. In the oncology setting, studies leveraging RWD offer distinct advantages that are complementary to randomized controlled trials (RCTs). They also permit the conduct of investigations that may not be possible through prospective designs due to ethics or feasibility. Despite its promise, the use of RWD for the generation of clinical evidence remains controversial due to concerns of unmeasured confounding and other sources of bias that must be carefully addressed in the study design and analysis. To facilitate a better understanding of when RWD can provide reliable conclusions on drug effectiveness, we seek to conduct 10 RWD-based studies that emulate RCTs in oncology using a systematic, protocol-driven approach described herein. Results of this investigation will help inform clinical, scientific, and regulatory stakeholders on the applications of RWD in the context of product labeling expansion, drug safety, and comparative effectiveness in oncology.

A Survey of Research Participants' Privacy-Related Experiences and Willingness to Share Real-World Data with Researchers.

BACKGROUND: Real-world data (RWD) privacy is an increasingly complex topic within the scope of personalized medicine, as it implicates several sources of data. OBJECTIVE: To assess how privacy-related experiences, when adjusted for age and education level, may shape adult research participants' willingness to share various sources of real-world data with researchers. METHODS: An electronic survey was conducted in April 2021 among adults (≥18 years of age) registered in ResearchMatch, a national health research registry. Descriptive analyses were conducted to assess survey participant demographics. Logistic regression was conducted to assess the association between participants' five distinct privacy-related experiences and their willingness to share each of the 19 data sources with researchers, adjusting for education level and age range. RESULTS: A total of 598 ResearchMatch adults were contacted and 402 completed the survey. Most respondents were over the age of 51 years (49% total) and held a master's or bachelor's degree (63% total). Over half of participants (54%) had their account accessed by someone without their permission. Almost half of participants (49%) reported the privacy of their personal information being violated. Analyses showed that, when adjusted for age range and education level, participants whose reputations were negatively affected as a result of information posted online were more likely to share electronic medical record data (OR = 2.074, 95% CI: 0.986-4.364) and genetic data (OR = 2.302, 95% CI: 0.894-5.93) versus those without this experience. Among participants who had an unpleasant experience as a result of giving out information online, those with some college/associates/trade school compared to those with a doctoral or other terminal degree were significantly more willing to share genetic data (OR = 1.064, 95% CI: 0.396-2.857). Across all privacy-related experiences, participants aged 18 to 30 were significantly more likely than those over 60 years to share music streaming data, ridesharing history data, and voting history data. Additionally, across all privacy-related experiences, those with a high school education were significantly more likely than those with a doctorate or other terminal degree to share credit card statement data. CONCLUSIONS: This study offers the first insights into how privacy-related experiences, adjusted for age range and education level, may shape ResearchMatch participants' willingness to share several sources of real-world data sources with precision medicine researchers. Future work should further explore these insights.

Practical Considerations and Recommendations for "a Revised Hippocratic Oath for the Era of Digital Health".

The Hippocratic Oath (the "Oath") is a longstanding body of ethical tenets that have undergone several amendments to accommodate changes and evolutions in the practice of medicine. In their recent perspective entitled, "A Revised Hippocratic Oath for the Era of Digital Health," Meskó and Spiegel offered proposed amendments to the Oath to address both challenges and needs that follow digital health implementation in clinical practice. In this commentary, we offer additional thoughts and considerations to Meskó and Spiegel's proposed amendments to accomplish two goals: (1) reflect on the shared goals and values of all digital health stakeholders and (2) drive home the focus on affirming patient choice, autonomy, and respect.

Report From the Field: Public Health Equity Through Innovative Multisector Data Sharing.

CONTEXT: Data sharing across sectors for the purpose of driving health equity is a particularly innovative yet emerging concept in public health practice and research, although the extent to which public health entities engage in multisector data sharing and initiatives is currently underexplored. This practice report examines the nature and extent to which public health entities are sharing data across sectors in ways that are innovative and supportive of their organizational missions to promote community health equity and well-being. PROGRAM: As a program office of the Robert Wood Johnson Foundation, Data Across Sectors for Health (DASH) seeks to promote and support data sharing systems leveraged toward equitable improvements to health. IMPLEMENTATION: We pilot tested, revised, and disseminated the 2021 All In National Inventory, a survey implemented to scan the environment to track progress and challenges in the field of data sharing, and feed lessons learned back into communities to cultivate further public health innovations involving shared data and infrastructure development. EVALUATION: Use case development, engaging communities to cocreate shared data systems. DISCUSSION: Findings show public health plays a pivotal role in innovation to share data across sectors to serve as a community health improvement foundation. While public health often leads these initiatives to improve health and promote health equity, national data suggest there is much room for improvement in incorporating equitable data sharing practice.

Selecting Privacy-Enhancing Technologies for Managing Health Data Use.

Privacy protection for health data is more than simply stripping datasets of specific identifiers. Privacy protection increasingly means the application of privacy-enhancing technologies (PETs), also known as privacy engineering. Demands for the application of PETs are not yet met with ease of use or even understanding. This paper provides a scope of the current peer-reviewed evidence regarding the practical use or adoption of various PETs for managing health data privacy. We describe the state of knowledge of PETS for the use and exchange of health data specifically and build a practical perspective on the steps needed to improve the standardization of the application of PETs for diverse uses of health data.

Pulse Oximeter App Privacy Policies During COVID-19: Scoping Assessment.

BACKGROUND: Pulse oximeter apps became of interest to consumers during the COVID-19 pandemic, particularly when traditional over-the-counter pulse oximeter devices were in short supply. Yet, no study to date has examined or scoped the state of privacy policies and notices for the top-rated and most downloaded pulse oximeter apps during COVID-19. OBJECTIVE: The aim of this study was to examine, through a high-level qualitative assessment, the state and nature of privacy policies for the downloaded and top-rated pulse oximeter apps during the COVID-19 pandemic to (1) compare findings against comparable research involving other mobile health (mHealth) apps and (2) begin discussions on opportunities for future research or investigation. METHODS: During August-October 2020, privacy policies were reviewed for pulse oximeter apps that had either at least 500 downloads (Google Play Store apps only) or a three out of five-star rating (Apple Store apps only). In addition to determining if the apps had an accessible privacy policy, other key privacy policy-related details that were extracted included, but were not limited to, app developer location (country); whether the app was free or required paid use/subscription; whether an ads disclosure was provided on the app's site; the scope of personal data collected; proportionality, fundamental rights, and data protection and privacy issues; and privacy safeguards. RESULTS: Six pulse oximeter apps met the inclusion criteria and only 33% (n=2) of the six apps had an accessible privacy policy that was specific to the pulse oximeter app feature (vs the app developer's website or at all). Variation was found in both the regulatory nature and data privacy protections offered by pulse oximeter apps, with notable privacy protection limitations and gaps, although each app provided at least some information about the scope of personal data collected upon installing the app. CONCLUSIONS: Pulse oximeter app developers should invest in offering stronger privacy protections for their app users, and should provide more accessible and transparent privacy policies. This is a necessary first step to ensure that the data privacy of mHealth consumers is not exploited during public health emergency situations such as the COVID-19 pandemic, where over-the-counter personal health monitoring devices could be in short supply and patients and consumers may, as a result, turn to mHealth apps to fill such supply gaps. Future research considerations and recommendations are also suggested for mHealth technology and privacy researchers who are interested in examining privacy implications associated with the use of pulse oximeter apps during and after the COVID-19 pandemic.

Integrating Patient-Reported Outcomes Into Clinical Genetic Testing for Familial Hypercholesterolemia.

Patient-reported outcomes (PROs) and PRO measures (PROMs) are often used to help clinicians and researchers understand patients' personal concerns, feelings, experiences, and perspectives following the implementation of an intervention. Notably, PROs and PROMs can inform health systems, health policy, and payers on the utility of clinical genetic testing based on each patient's personal values, perspectives, and potential health behaviors subsequent to testing. In this topic synopsis, we discuss the underexplored role of and implications for PROs and PROMs following genetic testing for familial hypercholesterolemia (FH), an autosomal dominant genetic disorder of cholesterol metabolism that can lead to highly premature fatal and nonfatal myocardial infarction and stroke. We also discuss why the use and consideration of patient perspectives, via PROs and PROMs, are critical to the process of optimizing patient care across various FH treatment contexts. As expert clinician groups consider the latest evidence when establishing recommendations for FH genetic testing, there is a ripe opportunity for clinicians and researchers to explore the value and utility of PROs to inform and possibly improve care for patients diagnosed with FH.

Patient-Reported Outcomes following Genetic Testing for Familial Hypercholesterolemia, Breast and Ovarian Cancer Syndrome, and Lynch Syndrome: A Systematic Review.

BACKGROUND: Patient-reported outcomes (PROs) and PRO measures (PROMs) are real-world evidence that can help capture patient experiences and perspectives regarding a clinical intervention such as genetic testing. OBJECTIVE: To identify and capture methods and qualitative PRO themes among studies reporting PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome. METHODS: A systematic review was conducted via PubMed/MEDLINE, EMBASE, and Yale University's TRIP Medical Databases on articles published by April 2021. RESULTS: We identified 24 studies published between 1996 and 2021 representing 4279 participants that reported PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome. Studies collected and reported PROs from validated PROM instruments (n = 12; 50%), validated surveys (n = 7; 26%), and interviews (n = 10; 42%). PRO themes ranged across all collection methods (e.g., psychological, knowledge, coping and satisfaction, concern about stigma/discrimination, etc.). CONCLUSIONS: Important gaps identified include (1) most studies (n = 18; 75%) reported PROs following genetic testing for breast and ovarian cancer, and (2) populations reporting PROs overall were largely of White/Caucasian/Northern European/Anglo-Saxon descent. We offer recommendations and describe real-world implications for the field moving forward.

African American Nurses' Perspectives on Genomic Medicine Research.

Background: There is a lack of African American (AA) community engagement in genomic medicine research. Recent popular interest in the experience of AAs, such as that of Henrietta Lacks, has perhaps prompted interest in research on how AA nurses can provide strategies to better engage AA communities in genomic medicine research. Methods: The authors conducted one-on-one semi-structured interviews with 11 National Black Nurses Association (NBNA) chapter leaders from 8 different US states, representing 782 NBNA members. Results: Our results quantified NBNA chapter leader agreement on known themes from the literature, captured newly emerging themes, and produced a set of actionable strategies to help overcome barriers to AA engagement in genomic medicine research that fall under 6 themes: (1) engagement, support, information dissemination, and implementation recommendations in general and to address health disparities; (2) addressing language barriers; (3) addressing research implementation barriers; (4) getting physicians to participate; (5) overcoming privacy concerns; and (6) nursing education recommendations. Conclusions: Actionable strategies presented herein can help researchers better engage AA communities in genomic medicine research.

Engaged genomic science produces better and fairer outcomes: an engagement framework for engaging and involving participants, patients and publics in genomics research and healthcare implementation.

Genomic science is increasingly central to the provision of health care. Producing and applying robust genomics knowledge is a complex endeavour in which no single individual, profession, discipline or community holds all the answers.  Engagement and involvement of diverse stakeholders can support alignment of societal and scientific interests, understandings and perspectives and promises better science and fairer outcomes. In this context we argue for F.A.I.R.E.R. data and data use that is Findable, Accessible, Interoperable, Reproducible, Equitable and Responsible. Yet there is a paucity of international guidance on how to engage publics, patients and participants in genomics. To support meaningful and effective engagement and involvement we developed an Engagement Framework for involving and engaging participants, patients and publics in genomics research and health implementation. The Engagement Framework is intended to support all those working in genomics research, medicine, and healthcare to deliberatively consider approaches to participant, patient and public engagement and involvement in their work. Through a series of questions, the Engagement Framework prompts new ways of thinking about the aims and purposes of engagement, and support reflection on the strengths, limitations, likely outcomes and impacts of choosing different approaches to engagement. To guide genomics activities, we describe four themes and associated questions for deliberative reflection: (i) fairness; (ii) context; (iii) heterogeneity, and (iv) recognising tensions and conflict. The four key components in the Engagement provide a framework to assist those involved in genomics to reflect on decisions they make for their initiatives, including the strategies selected, the participant, patient and public stakeholders engaged, and the anticipated goals. The Engagement Framework is one step in an actively evolving process of building genomics research and implementation cultures which foster responsible leadership and are attentive to objectives which increase equality, diversity and inclusion in participation and outcomes.

A Qualitative Study to Develop a Privacy and Nondiscrimination Best Practice Framework for Personalized Wellness Programs.

Employers in the United States (US) increasingly offer personalized wellness products as a workplace benefit. In doing so, those employers must be cognizant of not only US law but also European Union (EU) law to the extent that the EU law applies to European immigrants or guest workers in the US. To the extent that wellness programs are implemented in either public health or employment contexts within the US and/or EU, sponsors of these programs can partner with direct-to-consumer (DTC) genetic testing companies and other digital health companies to generate, collect, and process sensitive health information that are loosely or partially regulated from a privacy and nondiscrimination standpoint. Balancing claims about the benefits of wellness programs are concerns about employee health privacy and discrimination and the current unregulated nature of consumer health data. We qualitatively explored the concerns and opinions of public and legislative stakeholders in the US to determine key themes and develop privacy and nondiscrimination best practices. Key themes emerged as promoting a culture of trust and wellness. Best practices within these themes were: (1) have transparent and prominent data standards and practices, (2) uphold employee privacy and nondiscrimination standards, (3) remove penalties associated with biometric outcomes and nondisclosure of sensitive health information, (4) reward healthy behavior regardless of biometric outcomes, and (5) make program benefits accessible regardless of personal status. Employers, DTC genetic testing companies, policymakers, and stakeholders broadly should consider these themes and best practices in the current absence of broad regulations on nondiscriminatory workplace wellness programs.

A Global Review on the Utility of Genetic Testing for Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism that affects an estimated 1/250 persons in the United States and abroad. FH is hallmarked by high low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. This review summarizes recent global evidence showing the utility of FH genetic testing across diverse populations. Clinical and other qualitative outcomes following FH genetic testing were improved FH diagnosis, treatment initiation or continued treatment, treatment modification, improved total or LDL cholesterol levels, education on lifestyle management, and genetic counseling. This summary of evidence should be considered by those seeking overall evidence and knowledge gaps on the utility of FH genetic testing from a global perspective and for certain ethnic and age populations. These findings can be used to inform insurance policies and coverage decisions for FH genetic testing, policy recommendations to reduce the clinical and public health burden of FH, clinical practice and guidelines to improve the management of FH populations, and ongoing research involving FH genetic testing. We conclude that further investigations are needed to examine: (1) non-clinical outcomes following FH genetic testing; (2) patient-reported outcomes following FH genetic testing to convey patient experiences, values, and goals; and (3) clinical outcomes following FH genetic testing in non-Caucasian and pediatric populations in the United States and abroad.

What motivates the sharing of consumer-generated genomic information?

Genomic medicine is an emerging practice that followed the completion of the Human Genome Project and that considers genomic information about an individual in the provision of their clinical care. Large and start-up direct-to-consumer genetic testing companies like Ancestry, 23andMe, Luna DNA, and Nebula Genomics have capitalized on findings from the Human Genome Project by offering genetic health testing services to consumers without a clinical intermediary. Genomic medicine is thus further propelled by unprecedented supply and demand market forces driven by direct-to-consumer genetic testing companies. As government entities like the National Human Genome Research Institute question how genomics can be implemented into routine medical practice to prevent disease and improve the health of all members of a diverse community, we believe that stakeholders must first examine how and scenarios in which stakeholders can become motivated to share or receive genomic information. In this commentary, we discuss consumers three scenarios: satisfying personal curiosity, providing a social good, and receiving a financial return. We examine these motivations based on recent events and current avenues through which have engaged or can engage in genomic data sharing via private, secure (e.g. centralized genomic databases and de-centralized platforms like blockchain) and public, unsecure platforms (e.g. open platforms that are publicly available online). By examining these scenarios, we can likely determine how various stakeholders, such as consumers, might prefer to extract value from genomic information and how privacy preferences among those stakeholders might vary depending on how they seek to use or share genomic information. From there, one can recommend best practices to promote transparency and uphold privacy standards and expectations among stakeholders engaged in genomic medicine.