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

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143694/1/ajmgc31608_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143694/2/ajmgc31608.pd

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 medicineâ personalized responseâ 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 everâ evolving indications and evidence. This era requires a continual reassessment of expectations and goals from both sides of the bed.New challenges are faced in this era of precision medicine and targeted therapies. Clear guidelines, regulations, and strategies for implementation are needed. Patients with advanced cancer may have disproportionate expectations of the personal benefit of participating in clinical trials. The informed consent process must address this issue directly and honestly. This era requires a continual reassessment of both patient and physician expectations and goals.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142968/1/onco12322_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142968/2/onco12322.pd

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

BackgroundGenetic 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 MethodsThis 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.ResultsSeveral 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.ConclusionOur 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 PracticeFurther 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.To better understand perspectives on cancer specimen and data commercialization, interviews of patients participating in a prospective precision medicine cancer sequencing study were conducted, along with corresponding interviews with the patients’ referring doctors. This article reports the results and aims to improve the consent process for biospecimen and health data sharing and commercialization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156136/2/onco13272.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156136/1/onco13272_am.pd

Respecting Autonomy and Enabling Diversity: The Effect of Eligibility and Enrollment on Research Data Demographics

Many promising advances in precision health and other Big Data research rely on large data sets to analyze correlations among genetic variants, behavior, environment, and outcomes to improve population health. But these data sets are generally populated with demographically homogeneous cohorts. We conducted a retrospective cohort study of patients at a major academic medical center during 2012–19 to explore how recruitment and enrollment approaches affected the demographic diversity of participants in its research biospecimen and data bank. We found that compared with the overall clinical population, patients who consented to enroll in the research data bank were significantly less diverse in terms of age, sex, race, ethnicity, and socioeconomic status. Compared with patients who were recruited for the data bank, patients who enrolled were younger and less likely to be Black or African American, Asian, or Hispanic. The overall demographic diversity of the data bank was affected as much (and in some cases more) by which patients were considered eligible for recruitment as by which patients consented to enroll. Our work underscores the need for systemic commitment to diversify data banks so that different communities can benefit from research

Ethical, legal, and social implications of learning health systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141917/1/lrh210051-sup-0001-Supplementary_info.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141917/2/lrh210051.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141917/3/lrh210051_am.pd

Voluntary workplace genomic testing: wellness benefit or Pandora\u27s box?

Consumer interest in genetic and genomic testing is growing rapidly, with more than 26 million Americans having purchased direct-to-consumer genetic testing services. Capitalizing on the increasing comfort of consumers with genetic testing outside the clinical environment, commercial vendors are expanding their customer base by marketing genetic and genomic testing services, including testing for pharmacogenomic and pathogenic variants, to employers for inclusion in workplace wellness programs. We describe the appeal of voluntary workplace genomic testing (wGT) to employers and employees, how the ethical, legal, and social implications literature has approached the issue of genetic testing in the workplace in the past, and outline the relevant legal landscape. Given that we are in the early stages of development of the wGT market, now is the time to identify the critical interests and concerns of employees and employers, so that governance can develop and evolve along with the wGT market, rather than behind it, and be based on data, rather than speculative hopes and fears

Consumer Perspectives on Access to Directâ toâ Consumer Genetic Testing: Role of Demographic Factors and the Testing Experience

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137391/1/milq12262.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137391/2/milq12262_am.pd

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

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144269/1/milq12318.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144269/2/milq12318_am.pd

Something of an Adventure : Postwar NIH Research Ethos and the Guatemala STD Experiments

The STD experiments in Guatemala from 1946-1948 have earned a place of infamy in the history of medical ethics. But if the Guatemala STD experiments were so “ethically impossible,” how did the U.S. government approve their funding? Although much of the literature has targeted the failings of Dr. John Cutler, we focus on the institutional context and research ethos that shaped the outcome of the research. After the end of WWII, Dr. Cassius Van Slyke reconstructed the federal research contracts process into a grant program. The inaugural NIH study section recommended approval of the Guatemala STD experiments at its first meeting. The funding and oversight process of the Guatemala research was marked with serious conflicts of interest and a lack of oversight, and it was this structure, as opposed to merely a maleficent individual, that allowed the Guatemala STD experiments to proceed. We conclude that while current research regulations are designed to prevent the abuses perpetrated on the subjects of the Guatemala STD experiments, it takes a comprehensive understanding of research ethics through professional education to achieve the longstanding ideal of the responsible investigator, and ensure ethical research under any regulatory scheme

Consuming Genomics: Regulating Direct-to-Consumer Genetic and Genomic Information

This Article is one of the first to analyze the effect of the 23andMe Warning Letter on the industry, to focus on the bifurcation of genetic interpretation and information as an independent medical device, and to analyze future regulatory approaches available to FDA. Part II of this Article offers an overview of public access to genetic information: the significance of genetic information, the transition from discrete genetic testing to large-scale genetic testing and genomic sequencing, and the movement of genetic interpretation from the clinic to DTC. This Part will also discuss government scrutiny of the DTC genetic-testing industry. Part III of this Article will conduct a deeper examination of the agencies poised to regulate DTC genetic testing. This Part analyzes FDA’s Untitled and Warning Letters and highlights four major insights for the industry going forward. But, although FDA is best-positioned to regulate the industry, it is not the only agency with the power to engage. Several other federal agencies—such as the U.S. Federal Trade Commission (FTC) and the U.S. Centers for Medicare and Medicaid Services (CMS)—can also influence access to, and the validity and utility of, DTC genetic testing. Finally, the Supreme Court’s recent decision in Myriad, invalidating patents on human genetic material, eliminates a potential barrier to DTC genetic testing and suggests a way in which the U.S. Patent and Trademark Office (PTO) can help ensure continued access to certain types of genetic interpretation. Part III will clarify the ways these agencies can support access to valid and useful genetic information and will highlight their limitations in this rapidly evolving field. State law provides an additional layer enhancing federal protections. Part IV considers the particular challenges associated with regulating bifurcated genetic data and interpretation entities. Entities that merely provide genetic data are likely to remain unregulated both because they do not satisfy FDA’s definition of a medical device and because FDA officials have explicitly disclaimed interest in their regulation. Entities that interpret genetic data and provide associated medical information, even without access to the underlying biological sample, give rise to a different analysis. Here, comparisons to FDA regulatory approaches taken with WebMD and mobile medical devices will likely fall short, whereas the approach taken with regulating software might be helpful—but even then, regulation of DTC interpretation services will face serious First Amendment scrutiny. Part V offers a risk-based stratification approach to regulate largescale genetic and genomic information as a medical device—treating interpretation of large-scale genetic data and genomic sequences as a compilation of smaller products as opposed to a single device. This would allow FDA to continue its regulatory focus on genetic interpretation that carries the greatest possible risk to the consumer (such as analyzing genes associated with diagnosing a predisposition to breast cancer for which individuals could seek out risky medical interventions such as mastectomy) without allocating time and energy to genetic interpretation that carries little to no risk (such as analyzing genes associated with earwax type). FDA has made clear that it will treat DTC genetic tests, including individual components used to produce patient-specific information, as medical devices falling under its regulations—and that labeling these devices as for educational or research use only while marketing them for health-related indications or knowingly selling them to companies will not shield the manufacturer from enforcement. Also, although FDA might consider some genetic tests as falling into lowerrisk regulatory categories, a manufacturer’s decision not to validate or substantiate individual tests might result in an entire genetic or genomic interpretation device being classified in a higher-risk regulatory category, thereby requiring full FDA premarket approval. However, as companies continue to bifurcate into entities that produce data- or information-only products, including entities that provide Internet-based, open-source genetic and genomic interpretation, FDA will face increasing difficulty enforcing its medical device regulations as typically done. If FDA and the DTC industry approach large-scale genetic and genomic interpretation as a compilation of discrete genetic tests, they can address the riskiest aspects of the product without allowing the evolving field to overwhelm current quality assurances and without limiting consumer access to accurate and valid genetic information