children with down syndrome smiling

Many Families with Down syndrome Children Would Consider Gene Modification, but with Serious Concerns

By Marsha Michie, PhD and Megan Allyse, PhD

Scientists and bioethicists have been talking a lot recently about CRISPR/Cas9 and related technologies to alter genomes. But the voices of patients and families, especially those with genetic conditions, haven’t been nearly as audible in these conversations about so-called “gene editing”—despite calls for these voices from the National Academies and others.

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23 and me boxes

You Received Genetic Test Results from Direct to Consumer Companies or from Research – Will Your Doctor Be Happy to See You?

By Ellen W. Clayton

You recently responded to a TV advertisement by a direct to consumer (DTC) genetic testing company because you wanted to find more of your relatives. The company also offered to send you your genomic data.  Although not what you originally had in mind, you decided to send the data to another DTC company for interpretation to learn more about your health. Unfortunately, you were told that you are at risk for a condition you had never heard of.  Even though the company sent some educational information, you quickly decided to call your doctor for more information and to start prevention or treatment.

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What’s in a name? Why metaphors matter for genetics research

By Mildred K. Cho, PhD

In 2017, the US FDA approved a gene therapy for the first time. However, it’s important to remember that the term “gene therapy” has been an optimistic misnomer for nearly 30 years, since the first clinical trial of a gene-based intervention was initiated in 1990.  Although the FDA has now approved a handful of gene-based therapies, there are concerns about the viability of the approach in actual clinical practice.

Because of the decades-long struggles of the technology to live up to its hype, the term “gene therapy” has been heavily criticized for encouraging the “therapeutic misconception” and for conveying unwarranted “therapeutic optimism.” In addition, there is evidence of how clinical trial participants and investigators both overestimated benefits from research but also how research was framed as treatment.  As a result, many recommended the alternative term “gene transfer” to more accurately represent the purpose and benefit of the intervention.  We may never know exactly how much the use of the term “gene therapy” contributed to potential bias in perceptions of effectiveness and intent, but it does highlight the potential impact of language on the ethical conduct of research.

Similarly, the rhetoric surrounding the genetic “revolution” has been justly criticized. Our research published in Genetics in Medicine, the peer-reviewed journal of the American College of Medical Genetics and Genomics (ACMG), suggests that researchers and advocates should not only avoid hyperbole, but also be more cautious and reflective about the use of metaphors.  We asked patients in a Northern California health system to tell us what the word biobank made them think of, and received a range of notable responses.  Some people associated the term with financial banks or gold mines, and others expressed suspicion of commercial motives of pharmaceutical or insurance companies for collecting and using biosamples.  Others associated the term with computers or databases, and some may have been misled by the association of biobank with the concept of electronically-accessible information, saying that a benefit of a health system’s research biobank-linked database was that patients could look up personally-relevant information in it directly and therefore not have to see a doctor. Read More

Genomic Screening: What’s Age Got To Do With It?

By Margaret Waltz, PhD, R. Jean Cadigan, PhD, Anya E. R. Prince, JD, MPP, Debra Skinner, PhD, and Gail E. Henderson, PhD

Age is an important consideration in medical screening, but calls for population based preventive genomic screening programs do not mention an upper age limit. Should such programs employ upper age limits, as occurs in other clinical screenings, on the assumption that older individuals would not benefit clinically? To address this question, our Genetics in Medicine paper analyzed data from GeneScreen, a research study of preventive genomic screening aimed at adults. We focused on how the researchers who designed the study and 50 individuals who joined the study understood and valued age in relation to screening.

GeneScreen used a screening panel of 17 genes associated with 11 rare conditions for which treatment and/or prevention options were available, like Hereditary Breast and Ovarian Cancer, Lynch Syndrome, and Long QT Syndrome. GeneScreen researchers initially suggested an upper age limit, reflecting the assumption that older individuals were unlikely to clinically benefit from the results. One clinician worried that without an upper age limit, GeneScreen might reinforce the desire for screening among older adults and the misconception that screening “does a lot of good when you’re 80.” This was reconsidered when they discussed familial benefit. As one researcher said, participation “might not actually save the 80-year-old that we test, but [it] could save his grandchildren.” The recognition of familial benefit motivated the decision to not exclude adults based on age.

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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.

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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