Toward Realizing the Promise of AI in Precision Health Across the Spectrum of Care.

Significant progress has been made in augmenting clinical decision-making using artificial intelligence (AI) in the context of secondary and tertiary care at large academic medical centers. For such innovations to have an impact across the spectrum of care, additional challenges must be addressed, including inconsistent use of preventative care and gaps in chronic care management. The integration of additional data, including genomics and data from wearables, could prove critical in addressing these gaps, but technical, legal, and ethical challenges arise. On the technical side, approaches for integrating complex and messy data are needed. Data and design imperfections like selection bias, missing data, and confounding must be addressed. In terms of legal and ethical challenges, while AI has the potential to aid in leveraging patient data to make clinical care decisions, we also risk exacerbating existing disparities. Organizations implementing AI solutions must carefully consider how they can improve care for all and reduce inequities.

Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association.

A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research, prevention, and care of individuals and populations. Nevertheless, several challenges exist, and few artificial intelligence tools have been shown to improve cardiovascular and stroke care sufficiently to be widely adopted. This scientific statement outlines the current state of the art on the use of artificial intelligence algorithms and data science in the diagnosis, classification, and treatment of cardiovascular disease. It also sets out to advance this mission, focusing on how digital tools and, in particular, artificial intelligence may provide clinical and mechanistic insights, address bias in clinical studies, and facilitate education and implementation science to improve cardiovascular and stroke outcomes. Last, a key objective of this scientific statement is to further the field by identifying best practices, gaps, and challenges for interested stakeholders.

Principles for Health Information Collection, Sharing, and Use: A Policy Statement From the American Heart Association.

The evolution of the electronic health record, combined with advances in data curation and analytic technologies, increasingly enables data sharing and harmonization. Advances in the analysis of health-related and health-proxy information have already accelerated research discoveries and improved patient care. This American Heart Association policy statement discusses how broad data sharing can be an enabling driver of progress by providing data to develop, test, and benchmark innovative methods, scalable insights, and potential new paradigms for data storage and workflow. Along with these advances come concerns about the sensitive nature of some health data, equity considerations about the involvement of historically excluded communities, and the complex intersection of laws attempting to govern behavior. Data-sharing principles are therefore necessary across a wide swath of entities, including parties who collect health information, funders, researchers, patients, legislatures, commercial companies, and regulatory departments and agencies. This policy statement outlines some of the key equity and legal background relevant to health data sharing and responsible management. It then articulates principles that will guide the American Heart Association's engagement in public policy related to data collection, sharing, and use to continue to inform its work across the research enterprise, as well as specific examples of how these principles might be applied in the policy landscape. The goal of these principles is to improve policy to support the use or reuse of health information in ways that are respectful of patients and research participants, equitable in impact in terms of both risks and potential benefits, and beneficial across broad and demographically diverse communities in the United States.

"Extremely slow and capricious": A qualitative exploration of genetic researcher priorities in selecting shared data resources.

PURPOSE: Genetic researchers' selection of a database can have scientific, regulatory, and ethical implications. It is important to understand what is driving database selection such that database stewards can be responsive to user needs while balancing the interests of communities in equitably benefiting from advances. METHODS: We conducted 23 semistructured interviews with US academic genetic researchers working with private, government, and collaboratory data stewards to explore factors that they consider when selecting a genetic database. RESULTS: Interviewees used existing databases to avoid burdens of primary data collection, which was described as expensive and time-consuming. They highlighted ease of access as the most important selection factor, integrating concepts of familiarity and efficiency. Data features, such as size and available phenotype, were also important. Demographic diversity was not originally cited by any interviewee as a pivotal factor; when probed, most stated that the option to consider diversity in database selection was limited. Database features, including integrity, harmonization, and storage were also described as key components of efficient use. CONCLUSION: There is a growing market and competition between genetic data stewards. Data need to be accessible, harmonized, and administratively supported for their existence to be translated into use and, in turn, result in scientific advancements across diverse communities.

Abortion Policy in the United States: The New Legal Landscape and Its Threats to Health and Socioeconomic Well-Being.

Policy Points The historic 2022 Supreme Court Dobbs v Jackson Women's Health Organization decision has created a new public policy landscape in the United States that will restrict access to legal and safe abortion for a significant proportion of the population. Policies restricting access to abortion bring with them significant threats and harms to health by delaying or denying essential evidence-based medical care and increasing the risks for adverse maternal and infant outcomes, including death. Restrictive abortion policies will increase the number of children born into and living in poverty, increase the number of families experiencing serious financial instability and hardship, increase racial inequities in socioeconomic security, and put significant additional pressure on under-resourced social welfare systems.

An ethics framework for consolidating and prioritizing COVID-19 clinical trials.

Given the dearth of established safe and effective interventions to respond to COVID-19, there is an urgent ethical imperative to conduct meaningful clinical research. The good news is that interventions to be tested are not in short supply. Unfortunately, the human and material resources needed to conduct these trials are finite. It is essential that trials be robust and meet enrollment targets and that lower-quality studies not be permitted to displace higher-quality studies, delaying answers to critical questions. Yet, with few exceptions, existing research review bodies and processes are not designed to ensure these conditions are satisfied. To meet this challenge, we offer guidance for research institutions about how to ethically consolidate and prioritize COVID-19 clinical trials, while recognizing that consolidation and prioritization should also take place upstream (among manufacturers and funders) and at a higher level (e.g. nationally). In our proposed three-stage process, trials must first meet threshold criteria. Those that do are evaluated in a second stage to determine whether the institution has sufficient capacity to support all proposed trials. If it does not, the third stage entails evaluating studies against two additional sets of comparative prioritization criteria: those specific to the study and those that aim to advance diversification of an institution's research portfolio. To implement these criteria fairly, we propose that research institutions form COVID-19 research prioritization committees. We briefly discuss some important attributes of these committees, drawing on the authors' experiences at our respective institutions. Although we focus on clinical trials of COVID-19 therapeutics, our guidance should prove useful for other kinds of COVID-19 research, as well as non-pandemic research, which can raise similar challenges due to the scarcity of research resources.

Industry Compensation to Physician Vascular Specialist Authors of Highly-referenced Aortic Aneurysm Studies.

BACKGROUND: Industry payments to physicians may influence their attitudes toward medical devices and products. Disclosure of industry compensation by authors of scientific manuscripts usually occurs at the authors' discretion and is seldom audited as part of the peer review process. The purpose of this analysis was to characterize industry compensation among highly cited research articles related to aortic aneurysm. METHODS: A Web of Science search for English language articles published from 2013-2017 using the search term "aortic aneurysm" identified publications for this study. The top 99 most-cited publications were abstracted by author. Physician authors with reported industry compensation from 2013-2016 were identified using the ProPublica Dollars for Docs search tool (linked to Centers for Medicare and Medicaid Services Open Payments data), based on provider name, medical specialty, and geographic location. Statistical analysis included descriptive statistics and categorical tests. RESULTS: The 99 articles had 1,264 unique authors, of whom 105 physicians (8.3%) received industry compensation during the study period. Fourteen of the 105 authors self-reported having received industry compensation. The remaining 91 authors (86.7%) did not disclose their industry-reported compensation. Industry payments during the study period totaled $6,082,574 paid through 13,489 transactions from 169 different manufacturers. In-kind items and services were the most common form of payment (65.3%). The median transaction amount was $58.32. [$138.34]. Food and beverage accounted for the largest number of transactions (N=9653), followed by travel and lodging (N=2365), consulting (N=513), and promotional speaking (N=436). Consulting accounted for the most total dollars over the study period ($1,970,606), followed by travel and lodging ($1,122,276), promotional speaking ($972,894), food and beverage ($568,251), royalty or license ($504,631), honoraria ($452,167), and education ($428,489). Royalty and license payments had the highest median transaction amount ($15,418. [$29,049]), and was the only category with a median transaction amount greater than $5,000. In contrast, several categories had median transaction amounts under $50, including food and beverage ($32. [$77]), gifts ($34. [$86]), and entertainment ($30. [$69]). No significant difference in payment amounts by medical specialty was identified (P=0.071). CONCLUSIONS: Only 8.3% of physician authors of highly cited aortic aneurysm studies received industry compensation, but 86.7% of those physician authors receiving payments did not disclose industry compensation within the manuscripts. Potential bias associated with industry compensation may be underestimated and conservatively biased based on author self-reporting.

Coronavirus Disease 2019 (COVID-19) Clinical Trial Oversight at a Major Academic Medical Center: Approach of Michigan Medicine.

Clinicians, eager to offer the best care in the absence of guiding data, have provided patients with coronavirus disease 2019 (COVID-19) diverse clinical interventions. This usage has led to perceptions of efficacy of some interventions that, while receiving media coverage, lack robust evidence. Moving forward, randomized controlled clinical trials are necessary to ensure that clinicians can treat patients effectively during this outbreak and the next. To do so, academic medical centers must address 2 key research issues: (1) how to effectively and efficiently determine which trials have the best chance of benefiting current and future patients and (2) how to establish a transparent and ethical process for subject recruitment while maintaining research integrity and without overburdening patients or staff. We share here the current methods used by Michigan Medicine to address these issues.

"My Research Is Their Business, but I'm Not Their Business": Patient and Clinician Perspectives on Commercialization of Precision Oncology Data.

BACKGROUND: Genetic sequencing and precision oncology have supported clinical breakthroughs but depend upon access to vast arrays of research specimens and data. One way for academic medical centers to fund such infrastructure and research is "commercialization" of access to specimens and data to industry. Here we explore patient and clinician perspectives regarding cancer specimen and data commercialization with the goal of improving such processes in the future. MATERIALS AND METHODS: This qualitative analysis was embedded within a prospective precision oncology sequencing study of adults with head and neck cancer. Via semistructured dyadic interviews with patients with cancer and their doctors, we assessed understanding and concerns regarding potential commercialization, opinions regarding investment of profits, and perspectives regarding the return of information directly to participants from industry. RESULTS: Several patient- and clinician-participants did not understand that the consent form already permitted commercialization of patient genetic data and expressed concerns regarding who would profit from the data, how profits would be used, and privacy and access. Patients were generally more comfortable with commercialization than clinicians. Many patients and clinicians were comfortable with investing profits back into research, but clinicians were more interested in investment in head and neck cancer research specifically. Patients generally supported potential return-of-results from a private entity, but their clinicians were more skeptical. CONCLUSION: Our results illustrate the limitations of mandatory disclosures in the informed consent process. The voices of both patients and their doctors are critical to mitigate violations of privacy and a degradation of trust as stakeholders negotiate the terms of academic and commercial engagement. IMPLICATIONS FOR PRACTICE: Further education is needed regarding how and why specimens and data in precision oncology research may be commercialized for both patients and providers alike. This process will require increased transparency, comprehension, and engagement of involved stakeholders.

Industry compensation and self-reported financial conflicts of interest among authors of highly cited peripheral artery disease studies.

OBJECTIVE: Industry compensation to authors may influence the interpretation of study results. Scientific journals often require author disclosure of a relevant financial conflict of interest (FCOI) but seldom quantify compensation and leave reporting up to the author's discretion. Professional and public concerns related to potential bias introduced into medical research by FCOI have arisen, especially when physician compensation from manufacturers is not disclosed. Little is known, however, about the prevalence of industry compensation to authors of related publications, payment amounts, or how this information compares with self-reported FCOI. The objective of this study was to compare industry compensation and disclosed FCOI among highly referenced publications related to treatment of peripheral artery disease, a disease that affects approximately 8.5 million Americans and is often treated with medications and devices. METHODS: "Peripheral artery disease" was used as a Web of Science search term to identify publications from 2013 to 2016, excluding review articles, conference proceedings, book chapters, abstract publications, and non-English language publications. The top 99 most cited publications were abstracted for self-reported FCOI by author. Industry compensation to authors was queried using a ProPublica Dollars for Docs custom data set based on Centers for Medicare and Medicaid Services Open Payments data. Providers practicing in the United States in any of the following specialties were included: cardiology, cardiothoracic surgery, vascular and interventional radiology, or vascular surgery. Payment transactions were matched to physician authors on the basis of provider name, specialty, and geographic location. Statistical analysis included descriptive statistics and categorical tests. Descriptive statistics are reported as frequency (percentage) or median (interquartile range). RESULTS: Among 1008 vascular specialist authors identified, 218 (22%) self-reported FCOI. Fifty-six physician authors had compensation reported to the Centers for Medicare and Medicaid Services by industry during the study period. Among those identified as recipients of industry compensation, 28 (50%) self-reported FCOI. Industry payments to the 56 authors totaled $11,139,987, with a median total payment of $18,827 (interquartile range, $152,084) per author. Food and beverage was the most frequently identified nature of payment (n = 8981 [74%]), promotional speaking involved the largest total amount of payments ($3,256,431), and royalty or license was the highest median payment ($51,431 [$72,215]). Physicians reporting FCOI received a total of $9,435,340 during the study period vs $1,706,647 for those who did not report any FCOI. Median total payments were higher among authors reporting FCOI vs not ($81,224 [$324,171] vs $9494 [$43,448]; P < .001). CONCLUSIONS: Nondisclosed author compensation from industry is relatively uncommon among highly cited peripheral artery disease research studies but may be associated with substantial payments. These results suggest that self-reported FCOI does not provide a comprehensive overview of industry compensation. Reporting all payments rather than only those deemed relevant by the author might provide a more complete and transparent report of potential FCOI, allowing independent assessment of relevance in interpreting study findings.

Genetic data partnerships: academic publications with privately owned or generated genetic data.

PURPOSE: Access to large genetic data sets, many of which are privately owned, is essential to precision medicine and other research protocols. Academic researchers are increasingly capitalizing on this privately held data. Our goal is to understand these private-academic "genetic data partnerships." METHODS: We analyzed publications using human genetic data generated or held by major private genetic testing companies that were indexed in PubMed between 2011 and 2017. RESULTS: We found that (1) the number of publications using private genetic data is increasing over time (from 4 in 2011 to 57 in 2017); (2) there are two main models of data-sharing, including researchers using existing private data held by industry (n = 172) or researchers sending in new samples for analysis (n = 6); (3) 45% of the publications were supported at least in part by the National Institutes of Health; and (4) the type of contributor consent is not disclosed/unclear in the publication almost half (43%) the time. CONCLUSION: Privately held or analyzed genetic databanks offer academic researchers the opportunity to efficiently access large amounts of genetic data. But more transparency should be encouraged, if not required, to ensure the proper notification of contributors and to further understand the use of public research funds for private collaborations.

Analysis of state laws on informed consent for clinical genetic testing in the era of genomic sequencing.

This article assesses the adequacy of informed consent to clinical genetic testing laws based on an examination of 15 states with institutions that had been involved in a National Institutes of Health-supported Clinical Sequencing Exploratory Research Consortium project. We identified relevant statutory provisions through a legal search engine and included statutes that describe the informed consent requirements for clinical genetic testing and/or the protections for genetic material, information, or data. We found that statutory definitions were often limited in problematic ways, such as focusing only on variants known to be associated with disease or negative health effects or associated with asymptomatic disease. Some statutes required complex levels of detail if applied to genomic technologies and set confusing disclosure standards for current use and future access. Others had exceptions from informed consent requirements for future research use, limited requirements for the destruction of specimens as opposed to derived data, or linked key definitional components to the evolving concept of "identifiability." Further reform and research are needed to ensure that state law protections advance as rapidly as the science they aspire to enable.

Revisiting Expectations in an Era of Precision Oncology.

As we enter an era of precision medicine and targeted therapies in the treatment of metastatic cancer, we face new challenges for patients and providers alike as we establish clear guidelines, regulations, and strategies for implementation. At the crux of this challenge is the fact that patients with advanced cancer may have disproportionate expectations of personal benefit when participating in clinical trials designed to generate generalizable knowledge. Patient and physician goals of treatment may not align, and reconciliation of their disparate perceptions must be addressed. However, it is particularly challenging to manage a patient's expectations when the goal of precision medicine-personalized response-exacerbates our inability to predict outcomes for any individual patient. The precision medicine informed consent process must therefore directly address this issue. We are challenged to honestly, clearly, and compassionately engage a patient population in an informed consent process that is responsive to their vulnerability, as well as ever-evolving indications and evidence. This era requires a continual reassessment of expectations and goals from both sides of the bed.

From in vivo to in vitro: How the Guatemala STD Experiments Transformed Bodies Into Biospecimens.

Policy Points: While most scholarship regarding the US Public Health Service's STD experiments in Guatemala during the 1940s has focused on the intentional exposure experiments, secondary research was also conducted on biospecimens collected from these subjects. These biospecimen experiments continued after the Guatemala grant ended, and the specimens were used in conjunction with those from the Tuskegee syphilis experiments for ongoing research. We argue there should be a public accounting of whether there are still biospecimens from the Guatemala and Tuskegee experiments held in US government biorepositories today. If such specimens exist, they should be retired from US government research archives because they were collected unethically as understood at the time. CONTEXT: The US Public Health Service's Guatemala STD experiments (1946-1948) included intentional exposure to pathogens and testing of postexposure prophylaxis methods for syphilis, gonorrhea, and chancroid in over 1,300 soldiers, commercial sex workers, prison inmates, and psychiatric patients. Though the experiments had officially ended, the biospecimens collected from these subjects continued to be used for research at least into the 1950s. METHODS: We analyzed historical documents-including clinical and laboratory records, correspondence, final reports, and medical records-for information relevant to these biospecimen experiments from the US National Archives. In addition, we researched material from past governmental investigations into the Guatemala STD experiments, including those of the US Presidential Commission for the Study of Bioethical Issues and the Guatemalan Comisión Presidencial para el Esclarecimiento de los Experimentos Practicados con Humanos en Guatemala. FINDINGS: Identified spinal fluid, blood specimens, and tissue collected during the Guatemala diagnostic methodology and intentional exposure experiments were subsequently distributed to laboratories throughout the United States for use in ongoing research until at least 1957. Five psychiatric patient subjects involved in these biospecimen experiments died soon after experimental exposure to STDs. The same US government researchers working with the Guatemala biospecimens after the exposure experiments ended were also working with specimens taken from the Tuskegee syphilis study. CONCLUSIONS: There should be a complete public accounting of whether biospecimens from the Guatemala and Tuskegee experiments are held in US government biorepositories today. If they still exist, these specimens should be retired from such biorepositories and their future disposition determined by stakeholders, including representatives from the communities from which they were derived.