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?”. Continue reading

Transparency and Direct-to-Consumer Genetic Testing Companies

By Linnea Laestadius, PhD, MPP

Direct-to-consumer (DTC) genetic testing companies are now a fixture of U.S. consumer culture, with dozens of companies offering adults on-demand insights into their ancestry and health (sometimes loosely defined). While a compelling argument can be made for giving consumers the right to access information about their own genetic material, DTC-testing presents a range of legal and ethical concerns. Scholars and physicians have long been raising questions about the analytic validity, clinical validity, and clinical utility of these services. The FDA has increasingly worked to address these aspects of DTC-testing and has issued letters to multiple DTC genetic testing firms arguing that they are offering medical devices that should be subject to premarket review. Developments in this area continue to emerge and the FDA recently authorized marketing for 23andMe’s Bloom Syndrome carrier test, while also planning to exempt future carrier screening tests from premarket review.

These are clearly positive developments from the perspective of consumer protection, however, other aspects of DTC genetic testing remain largely unaddressed. Most notably, there are significant concerns about how firms handle consumer samples and data and how and if they use them for secondary purposes. To address this issue, Paul Auer, PhD, Jennifer Rich, MPH, and I set out to understand how transparent these firms are about their privacy, confidentiality, and secondary use policies. Recently published in Genetics in Medicine, this work offers an analysis of the terms-of-service and privacy policies of the top 30 DTC genetic testing firms that show up in a U.S. based web search.

While transparency about data practices varied across firms, a number of gaps appeared with regard to conveying information about the risks of data disclosure, the ultimate fate of samples and data, and use of data for research. Over the past decade, several major professional and governmental organizations have issued guidelines for transparency in these areas, including the American College of Medical Genetics and Genomics and the European Society of Human Genetics. At present, it does not appear that non-binding guidelines have been sufficient to encourage widespread compliance with best practices on these topics. Continue reading

Knowledge is Power, or Ignorance is Bliss?

By Kyle B. Brothers

You have a rare illness that seems to have a genetic cause. For years you have moved from geneticist to geneticist looking for the cause of your illness, hoping that by finding the precise genetic cause you will discover ways to alleviate your symptoms. You have had five or six genetic tests, but each one has turned up normal. Finally you visit a young geneticist fresh out of training, hoping that she will know of another test to try. She recommends the most comprehensive genetic test of all: whole genome sequencing (WGS). You are ready to immediately get this test when she poses a difficult question: WGS might reveal a cause for your illness, but it might also reveal that you are at risk for developing breast cancer, or schizophrenia, or Alzheimer’s disease. Which of these “incidental” findings do you also want to receive?

Until recently, this genomic “would you want to know” question has lived exclusively in the world of science fiction. Would you want to know what secrets your genome holds about your future? For example, would you want to know how you will die? If you knew what the future is likely to hold, would you feel fatalistic or empowered to take control of it? These questions have been the topic of compelling movies like GATTACA and classic novels like Aldous Huxley’s Brave New World. Continue reading

Considering stakeholders in policy around secondary findings in genomics

By Michael Mackley

It took nearly thirteen years and an army of scientists to generate the first sequence of the human genome. Now, patients around the world are having their genomes sequenced every day. Since the first sequence was unveiled in 2003, the cost of whole-genome sequencing (WGS) has dropped from almost $1 billion to less than $1,000—allowing WGS to enter routine clinical care, potentially transforming the way we diagnose and treat disease. Large national initiatives to read individuals’ genomes are helping to drive this transition; the UK’s NHS England is currently sequencing 100,000 genomes, and the USA has plans to sequence 1 million genomes in the near future. A 2015 study predicts that up to 2 billion people worldwide could have their genomes sequenced within the next decade—comparable to the current reach of the Internet. With so many genomes to be sequenced, it is imperative that laws and policy ensure that individuals, and society, are protected from harm. While larger pieces of legislation—such as those protecting against discrimination—are needed internationally, guidance and policies around routine management are also required.

One area of particular concern is that of ‘secondary’ (or ‘incidental’) findings. While WGS provides a valuable opportunity to learn about genetic contributions to disease (‘primary’ findings), it can also reveal genetic information that may not be relevant to the health condition affecting the patient or their family. This includes genetic changes associated with other health conditions—ranging from medically actionable findings, such as genetic predispositions to breast cancer where treatment is available, to non-actionable findings, such as genetic changes associated with an increased risk of Alzheimer’s. The American College of Medical Genetics and Genomics published recommendations suggesting a moral obligation to seek and return actionable secondary findings, fueling significant debate (1,2). Medical Genetics organizations from other countries (including Canada and Europe) have published more conservative guidelines restricting generation of secondary findings, at least until more evidence is available to support (or refute) clinical utility and assess wider impacts. Continue reading

Should healthcare systems implement routine recontacting services in clinical practice? Some legal and logistical considerations

By Daniele Carrieri, Angus Clarke, Anneke Lucassen, Susan Kelly

Advances in genetic and genomic medicine are resulting in better diagnosis and treatment of some health conditions, and the question of whether former patients should be recontacted is therefore timely. Recontacting patients to inform them of new information or new testing, that could be relevant to their health or that of their biological relatives is made more pressing by the increasing use of whole genome approaches in healthcare, where variants previously of unknown significance (VUSs) may now have known disease effects.  However, there is currently no consensus about whether or not healthcare professionals have a duty or responsibility to recontact former patients in light of this new information. There is also very little empirical evidence in this area. In a recent article published in Genetics in Medicine, we present the results of a survey of recontacting practices of clinical genetics services across the United Kingdom (UK). As far as we know, this is the first study that specifically explores current recontacting practices in clinical genetic services.

One of the questions of the survey asked was whether clinical genetics services should implement routine recontacting systems. The majority of genetic services were undecided for several reasons.  The main arguments given in favor of implementing such systems revolved around patient choice and the idea of keeping patients up to date.  The main arguments against pointed to the logistical difficulties of implementing recontacting systems and the possible legal implications of doing so, if that were seen as establishing a new standard of care without the additional resources required for this to be a sustainable activity. Continue reading

Genomic data sharing: How much oversight is necessary?

By Mahsa Shabani

Introducing data sharing practices into the genomic research has brought a number of concerns in research ethics and governance to the fore. For instance, research participants and the general public raised concerns about potential privacy issues in personal genomic data protection, as well as the scope of the secondary uses. In order to address such concerns, Data Access Committees (DACs) were seen crucial in the governance of main genomic databases such as the database of Genotypes and Phenotypes (dbGaP) and the European Genome-phenome Archive (EGA). Surprisingly, the component of access review, the structure, and the functionality of such committees have been barely scrutinized to date.

In a recent study published in Genetics in Medicine, we solicited the opinion of 20 DAC members and experts on genomic data access. Specifically, the interviewees were asked about the goals of access review and their experiences with reviewing the ethical and scientific aspects of proposals. The respondents unanimously agreed that the complexity of the access review should correspond with the concerns associated with genomic data sharing. In this regard, privacy risks often seemed possible, yet were not viewed as an imminent threat. The respondents could only recall a few examples of re-identification of genomic data in the past, yet could not promise full privacy protection given the evolving nature of the field. Regardless of the scarcity of such incidents, the controlled-access model is generally considered necessary to maintain public trust. As a DAC member put it: “I think the future of science depends upon high levels of public trust and you can only have high levels of public trust if people feel the data sharing is being managed.” Continue reading

Should a patient have a right not to know genetic information about him or herself?

By Benjamin E. Berkman, JD, MPH

While promising to eventually revolutionize medicine, the capacity to cheaply and quickly generate an individual’s entire genome has not been without controversy.  Producing information on this scale seems to violate some of the accepted norms governing how to practice medicine, norms that evolved during the early years of genetic testing when a targeted paradigm dominated.  One of these widely accepted norms was that an individual had a right not to know (“RNTK”) genetic information about him or herself.  Prompted by evolving professional practice guidelines, the RNTK has become a highly controversial topic.  The medical community and bioethicists are actively engaged in a contentious debate about the extent to which individual choice should play a role (if at all) in determining which clinically significant findings are returned.

In a recent paper published in Genetics in Medicine, my coauthors and I provide some data that illuminates this and other issues. Our survey of 800 IRB members and staff about their views on incidental findings demonstrates how malleable views on the RNTK can be.  Respondents were first asked about the RNTK in the abstract: “Do research participants have a right not to know their own genetic information?  In other words, would it be acceptable for them to choose not to receive any GIFs?”  An overwhelming majority (96%) endorsed the right not-to-know.  But when asked about a case where a specific patient has chosen not to receive clinically beneficial incidental findings, only 35% indicated that the individual’s RNTK should definitely be respected, and 28% said that they would probably honor the request not to know.  Interestingly, the percentage of respondents who indicated that they do not support the RNTK increased from 2% at baseline to 26% when presented with the specific case.  The percentage of people who are unsure similarly jumps, from 1% to 11%.

Continue reading

How broad can consent be?

By Nanibaa’ A. Garrison, Ellen Wright Clayton and Ingrid A. Holm

Based on today’s publication of the paper A systematic literature review of individuals’ perspectives on broad consent and data sharing in the United States in Genetics in Medicine. 

The recent Notice of Proposed Rule Making (NPRM) issued by the Office of Human Research Protections proposes to require researchers to obtain informed consent from virtually every patient and research participant for use of biospecimens for research. The proposed regulations also permit obtaining broad consent for future uses, without any IRB oversight unless individual results are going to be returned so long as an elaborate consent form is signed. The NIH Genomic Data Sharing Policy, which went into effect earlier this year, requires almost all investigators who receive NIH funding to seek broad consent from participants to allow their data to be shared with other investigators. Thus, in a short period of time, two major policies promoted broad consent for biobank research, changes in the practice of recruiting participants for research that make us take notice. They also raise new questions, including: What do research participants think about having their biospecimens and data shared, and about giving broad consent to do so?

Who is comfortable with Broad Consent?
The Electronic Medical Records and Genomics (eMERGE) Network’s Consent, Education, Regulation, and Consultation (CERC) working group set out to find some answers. As a part of this effort, we conducted a systematic review, which revealed that males, whites, older individuals, and more affluent individuals are generally pretty comfortable with broad consent that can be found here. By contrast, Asian and African American individuals are less comfortable with broad consent. Will these different levels of concern create a divide between those who will and will not participate? The consequences of lack of participation are clear – we will know less about how genetic variation in groups that do not take part affects health and less about how to provide optimal care. Continue reading

GIM: Informed consent for return of incidental findings in genomic research

In the second installment of our new collaboration with Genetics in Medicine, we are highlighting an article released last week discussing informed consent for the return of incidental findings in genomic research.

As whole-genome and whole-exome sequencing become increasingly common in medical research, the potential grows for identifying genetic findings that are unrelated to the main focus of the study (often called “incidental findings,” or “IFs”).  There is substantial debate about the duties associated with incidental findings, including whether researchers should or must search for them under ethical or legal frameworks, and whether and how to return the results to research participants.  One understudied aspect of the issue, though, is how informed consent should be obtained for the return of such findings, and this paper begins the task of addressing that question. Continue reading

GIM: 23andMe’s Patent for a Method to Obtain Designer Babies

In the first installment of our new collaboration with Genetics in Medicine, we are highlighting an article released yesterday discussing 23andMe’s controversial “designer baby” patent, which has already gotten quite a bit of attention.  Here’s the press release, and an exclusive commentary from Sigrid Sterckx, one of the article’s authors, can be found in a separate post immediately following this one.  Enjoy!

The controversial nature of a patent granted to the Direct-to-Consumer Genetics company, 23andMe, that lays claim to a broad method for allowing parents to select for specific traits in their offspring—such as lack of specific genetic diseases or eye color—is discussed in a Commentary published this week in Genetics in Medicine. The authors suggest that public trust is central to the continuing success of human genetics research, and urge all those engaged in human genetics research to be as transparent as possible about research goals and patenting activity.

The method described in the patent, issued by the United States Patent Office on 24 September 2013, is based on a computerized comparison of the genotypic data from the egg and sperm providers. The method does not guarantee that the desired traits will be present in the child, rather it selects for an egg and sperm pairing that increases the likelihood of those selected traits being present as compared to other possibilities. The characteristics that prospective parents could choose from include both disease-related traits and non-disease related traits (including eye color, personality characteristics, and athleticism).

Sigrid Sterckx and colleagues argue that a computerized process for selecting a specific egg and sperm pair to achieve a baby with a “phenotype of interest” has broad implications, and should have been given more serious consideration by the US Patent and Trademark Office and 23andMe. The authors suggest that the implications of this patent were not fully considered during the approval process, and that the Patent Office Examiner did not appear to question whether this technique was appropriate subject matter for a patent.

BoH Exclusive: Sigrid Sterckx comments on the media storm following Nature’s press release on her article announcing 23andMe’s patent for a method to obtain designer babies

[Posted on behalf of Sigrid Sterckx, as part of our collaboration with Genetics in Medicine]

Yesterday, 3 October, an article I wrote with three co-authors about a controversial US patent was published by the (Nature) journal Genetics in Medicine. The patent, granted last week to the Californian Direct-To-Consumer genetic testing company 23andMe, is entitled ‘Gamete donor selection based on genetic calculations’ (US Patent No. 8543339). It relates to a method by which prospective donors of ova and/or sperm may be selected so as to increase the likelihood of producing a human baby with characteristics desired by the prospective parents, the selection being based on a computerized comparison of the genotypic data of the egg provider with that of the sperm provider. The “phenotype of interest” prospective parents may have in mind can include, besides some disease-related traits, traits such as eye color, height, muscle development and personality characteristics. As quoted in the patent specification by way of example, prospective parents may indicate which of the three following choices they make: “I prefer a child with”: “longest expected life span”/“least expected life cost of health care”/“least expected cumulative duration of hospitalization.”

The press release issued by Nature on Monday 30 September quickly gave rise to several news reports. The company posted an announcement on its blog the next day, stating that the patent “relates to one of the tools we offer individuals as part of their genetic exploration. The tool – Family Traits Inheritance Calculator – offers an engaging way for you and your partner to see what kinds of traits your child might inherit from you”. However, anyone who looks at the patent and reads the claims will notice that this is not what the patent relates to. As mentioned above, it relates to a method to select gamete donors in order to achieve a child with the phenotype desired by the prospective parents. 23andMe admits that “the language of the patent extends beyond the calculator” but suggests that people need not be worried as: “At the time 23andMe filed the patent, there was consideration that the technology could have potential applications for fertility clinics so language specific to the fertility treatment process was included in the patent. But much has evolved in that time, including 23andMe’s strategic focus. The company never pursued the concepts discussed in the patent beyond our Family Traits Inheritance Calculator, nor do we have any plans to do so.”

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Welcome, Genetics in Medicine!

We’re pleased to announce a new collaboration with the American College of Medical Genetics and its journal, Genetics in Medicine (under the Nature umbrella).  We’ll be highlighting medico-legal articles, podcasts, and the like from GIM, and in some cases, offering blog-only commentary from GIM authors.

Stay tuned, but for now, take a look at these recent pieces:

Personalized medicine and genetic malpractice by Gary E. Marchant PhD, JD and Rachel A. Lindor JD

Minimizing liability risks under the ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing by Barbara J. Evans Ph.D., J.D.

Processes and factors involved in decisions regarding return of incidental genomic findings in research by Robert Klitzman MD, et al.

The undiscovered country: the future of integrating genomic information into the EHR by Joseph Kannry MD and Marc S. Williams MD (free full text)

Ethical, legal, and social implications of incorporating genomic information into electronic health records by Ribhi Hazin MD, et al.

Practical challenges in integrating genomic data into the electronic health record by Abel N. Kho MD, MS, et al.

Stakeholder engagement: a key component of integrating genomic information into electronic health records by Andrea Hartzler PhD, et al.