Dna test infographic. Genome sequence map, chromosome architecture and genetic sequencing chart abstract data. Molecule structure genetic test.

Ethnic Identity and Genomics Research: Toward Creating Culturally Sensitive Policies and Practices

By Erin Turbitt and Megan C Roberts

Genomic discoveries are rapidly entering healthcare, further propelled by large nationally funded initiatives such as the “All of Us” program. However, minority groups risk not benefiting from these discoveries to the same degree as individuals of European descent. This is because most genomics research involves European descended individuals and genomic databases largely consist of data from these studies. Read More

Image of Normal blood cells next to a sickle blood cell, colored scanning electron microscope image.

Recharting the Course of Sickle Cell Disease – Who will Benefit?

By Vence L. Bonham and Anitra Persaud

Scientific advancements in gene therapy and the implications of leveraging this technology to develop new curative therapies are at the forefront of medical research. Sickle cell disease (SCD), the most common genetic blood disorder, stands center stage. Last month, 60 Minutes aired a segment showcasing the story of a patient at the NIH Clinical Center who is on her journey to a cure of sickle cell disease (SCD) with the help of an experimental gene therapy.

Preliminary clinical trial findings suggest that gene therapy has an acceptable level of safety and can help individuals with the disease produce normal red blood cells instead of the sickle-shaped ones that underlie the physiological basis of the disease and its complications. Given these promising results, there is hope that gene therapy may catalyze a turning point for the SCD population, a community that has long suffered the debilitating effects of not only their disease, but of longstanding neglect within the medical system and research enterprise. Read More

Precision Medicine’s Impact on the Doctor-Patient Relationship

By Paul S. Appelbaum and Gil Eyal

Healthcare is now entering a much-anticipated era of “precision medicine” (PM), an effort characterized “[b]y taking into account individual differences in lifestyle, environment, and biology” to “accelerate research and improve health”.

The extent to which these goals are achievable and generalizable has been extensively debated, but often lost in the discussion is the likely impact of PM on the doctor-patient relationship, still the primary means of delivering medical care. As we and our colleagues noted in our recent commentary in Genetics in Medicine, multiple changes are looming in both the doctor’s and the patient’s roles. Here we highlight just two of them: the proliferation of uncertainty and its downloading to the patient; and the diminution in the control and authority of the physician. Read More

Precision Medicine for All? The Need for Disability Inclusion

By Maya Sabatello

Stakeholders’ engagement is key to achieving the promises of precision medicine research. It is needed in order to establish a sufficiently powered cohort of diverse groups that will allow tailoring disease diagnosis, treatment, and prevention to individual variability in genes, environment, and lifestyle. It is also needed to ensure that research priorities are in sync with the health needs of participants and for curtailing health disparities in the US.

Cognizant of these issues, precision medicine initiatives, including are increasingly investing time and resources to engage potential participants in their studies. the All of Us Research Program (AoU) is exemplary in this regard, focusing in particular on racial and ethnic minorities as well as Native Americans who have been historically underrepresented in genomic research.

But what about people with disabilities?

This question may seem to be off target. After all, persons with disabilities have long been prime targets of genotyping, and their enrollment in genomic research is ongoing.

Read More

Navigating the Research-Clinical Interface in Genomic Medicine: Challenging the Traditional Dichotomy Between Research & Clinical Care

By Susan M. Wolf & Wylie Burke

Translational genomics challenges the traditional view that research and clinical care are distinct activities that should be governed by separate norms, rules, and law. Beginning with the Belmont Report and emergence of regulations governing the conduct of research with human participants, the conventional view has been that there are fundamental differences between research and clinical care, necessitating distinctive ethical frameworks, regulatory oversight, and legal analyses.

However, a new paper published in Genetics in Medicine reports the first empirical test of this conventional dichotomy in the context of genomics. The paper analyzes empirical data collected by surveying investigators conducting major NIH-funded genomics research projects in the NHGRI/NCI-supported Clinical Sequencing Exploratory Research (CSER) Consortium. Those investigators report their actual practices, experiences, and attitudes in navigating the research-clinical interface. These results reveal how the research-clinical boundary operates in practice and cast serious doubts on the adequacy of the conventional dichotomy. Read More

Sharing Data for 21st Century Cures – Two Steps Forward…

By Mary A. Majumder, Christi J. Guerrini, Juli M. Bollinger, Robert Cook-Deegan, and Amy L. McGuire

The 21st Century Cures Act was passed with support from both sides of the aisle (imagine that!) and signed into law by then-President Obama late last year. This ambitious legislation drives action in areas as diverse as drug and device regulation and response to the opioid epidemic. It also tackles the issue of how to make data more broadly available for research use and clinical purposes. In our recently published GIM article, “Sharing data under the 21st Century Cures Act,” we examine the Act’s potential to facilitate data-sharing, in line with a recent position statement of the American College of Medical Genetics and Genomics. We highlight a number of provisions of the Act that either explicitly advance data-sharing or promote policy developments that have the potential to advance it. For example, Section 2014 of the Act authorizes the Director of National Institutes of Health to require award recipients to share data, and Section 4006 requires the Secretary of Health and Human Services to promote policies ensuring that patients have access to their electronic health information and are supported in sharing this information with others.

Just as relevant, the Act takes steps to reduce some major barriers to data sharing. An important feature of the Act, which has not been extensively publicized, is its incorporation of provisions from legislation originally proposed by Senators Elizabeth Warren and Mike Enzi to protect the identifiable, sensitive information of research subjects. Senator Warren, in particular, has been a vocal advocate of data sharing. Arguably, one of the biggest barriers to sharing is public concern about privacy. The relevant provisions address this concern chiefly via Certificates of Confidentiality. Among other things, the Act makes issuance of Certificates automatic for federally-funded research in which identifiable, sensitive information is collected and prohibits disclosure of identifiable, sensitive information by covered researchers, with only a few exceptions such as disclosure for purposes of other research. These protections became effective June 11, 2017. While NIH has signaled its awareness of the Act, it has not yet updated its Certificates of Confidentiality webpage. Read More

How should we organize consent to research biobanking in the hospital?

By Alena Buyx, MD PhD

Ever wondered what happens to the biological material you leave behind when you check out of the hospital? Nothing much, is the usual answer. However, the little bits of blood, tissue, and urine are potentially valuable for medical research; miniscule amounts of it may already allow sophisticated analyses, including genetic ones. Thus, in an approach termed ‘healthcare-embedded biobanking’, healthcare providers have started collections of leftover patient materials to create resources for future research.

However, unlike traditional research, healthcare-embedded biobanking is not done with a clear research question in mind. The materials are simply left-overs from diagnosis or treatment and, at the time of collection, the scientific projects for which they may be used eventually are entirely unclear.

This approach leads to an ethical conundrum. Established research ethics frameworks found here and here require that patients be asked for their consent and that they are given  all the information they need to make an informed decision about whether to donate their material (and its associated data) or not.  This includes, in particular, the research goals as well as the potential benefits and risks. However, this provision of information is not possible in healthcare-embedded biobanking: the risks and benefits can only be described in very broad terms, and the goals and timing of future research are usually unknown. Indeed, the materials may even not be used at all. Read More

Contracting to counter gene patents – a 21st Century solution to access and innovation

By Sarah Ali-Khan and E. Richard Gold

As Precision Medicine becomes a reality, molecular tests are an increasingly critical part of patient care. While patients and their physicians would like to maximize access, they have confronted a roadblock in the form of patents covering genes and methods of diagnosis. Many hoped that the landmark 2013 Supreme Court of the United States decision in Myriad v AMP spelled the end of these patents, but the number of gene patents has actually increased since that decision. This is because, while limiting the availability of patents over genomic DNA, the court decision was narrow, leaving substantial grey zones such as over cDNA or where the patent covers a sequence of DNA used in a particular way. Patent agents have been assiduous in exploiting these grey zones to file for and obtain patents over molecular tests. This development points to continued adverse consequences of gene patents not only in the US, but around the world. Our recently published GiM article Gene patents still alive and kicking: their impact on provision of genetic testing for Long QT syndrome in the Canadian public health-care system’, not only examines the impact of gene patents in one country, Canada, but shows how 21st Century contracting can provide a nuanced and pragmatic means to enabling both access and innovation around patented genetic tests.

In Nov 2014, in the first Canadian instance of a public interest ‘test case’ in intellectual property and public health, The Children’s Hospital of Eastern Ontario (CHEO) challenged five patents held by Transgenomic Inc. over a genetic test for Long QT Syndrome (LQTS), a potentially fatal cardiac disorder most commonly striking in children and youth. Widely reported, settled in March 2016, and named as one of the year’s cases having the most impact on intellectual property, the case produced the CHEO Public Health Access Agreement. The Agreement does not itself alter law– gene patents remain valid in Canada. Rather, it constitutes a contractual agreement between parties to the litigation, allowing for efficient, no-cost test implementation. The Agreement explicitly states that Transgenomic will freely grant a license to test the LQTS-associated genes to any entity providing services within Canada’s public healthcare system. That is, except for a marginal private market, all LQTS in Canada can now be provided free. Read More

Genetic counselors, genetic interpreters, and conflicting interests

By Katie Stoll, Amanda Mackison, Megan Allyse, and Marsha Michie

The booming genetic testing industry has created many new job opportunities for genetic counselors. Within commercial laboratories, genetic counselors work in sales and marketing, variant interpretation, as “medical science liaisons” to clinicians, and providing direct patient care. Although the communication skills and genetics expertise of the genetic counselor prepare them well for these roles, they also raise concerns about conflicts of interest (COI).

Why are genetic counselors leaving clinics and hospitals for industry jobs? Alongside greater job flexibility and taking on new challenges, a big reason is better pay. Hospitals and clinics have difficulty competing with the higher salaries at commercial labs because of continuing challenges in insurance reimbursement. Apart from limited preventive care covered under the Affordable Care Act, genetic counseling is inconsistently covered by private payers. Medicaid reimbursement for genetic counseling is state-dependent, and Medicare does not recognize genetic counselors as reimbursable health care providers at all.

Genetic counselors’ primary objective has historically been to help patients navigate difficult medical genetic information and decisions, supporting their autonomy.  But as laboratory employees, they must also navigate their employer’s financial interests, including increasing the uptake of genetic testing. In this changing landscape, can the profession of genetic counseling maintain the bioethical principles of beneficence, informed consent, and respect for autonomy that have been its foundation and ethos? Read More

Public Variant Databases: Data Share with Care

By Adrian Thorogood, BCL, LLB

If every individual has millions of unique variants in their DNA, how can clinicians be expected to tease out a handful of disease causing mutations from a haystack of inconsequential variants? To aid their cause, public human genomic variant databases have sprung up to catalog variants that cause (or do not cause) disease. These databases aggregate, curate and share data from research publications and from clinical sequencing laboratories who have identified a  “pathogenic”, “unknown” or “benign” variant when testing a patient.

International sharing of variant data is “crucial” to improving human health. To inform patient diagnosis or treatment, it is essential that data be accurate and up to date. If variants are collaboratively interpreted by laboratories, databases and treating physicians, who is ultimately responsible for the quality of data? If one actor in the chain does a shoddy job of interpreting variants, resulting in harm to patients, who could be liable? This is the question I pose with Professors Bartha Knoppers and Robert Cook-Deegan in a recent article in Genetics and Medicine: “Public Variant Databases: Liability?”. Read More