9 January 2017
The following post was written for Bill of Health, a blog by the Petrie-Flom Center at Harvard Law examining the intersection of law, healthcare, biotech, and bioethics. Adrian Thorogood is the Manager for the GA4GH Regulatory and Ethics Work Stream and an author on a paper recently published in Genetics in Medicine on legal responsibilities for the quality of data shared between laboratories, public variant databases, and physicians in clinical genomics.
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?”.
This question came up through our work with a database called the BRCAExchange.org, an international collaboration to share as much information as we can about how variants in the BRCA 1 and 2 genes influence breast and ovarian cancer risk through a single portal. The BRCA Exchange is supported by the Global Alliance for Genomics and Health (GA4GH), a public-private collaboration committed to demonstrating the value and feasibility of sharing genomic and health related data (read more about the Global Alliance and BRCA Exchange in our Perspective Paper here).
Members of the BRCA Exchange team asked us what legal risks databases might face if a laboratory submitted an improperly interpreted variant, or if database staff slip up when aggregating and sharing data over the web. Indeed, concern is bubbling across the genomics community over the recent lawsuit Williams v Athena. The plaintiff in the case alleges a laboratory was negligent in determining the clinical meaning of a variant. As a result, it is alleged that a young boy suffering from seizures received the wrong medication, leading to his death. While these allegations have not yet been established in court, the case hints at the stakes variant interpretation has for patients. It also raises questions about what legal duties fall respectively to laboratories and treating physicians in the genetic testing context, and what standard of care applies to laboratories interpreting the clinical meaning of a variant.
In the data sharing context, three parties may participate in genomic interpretation: the laboratory, the database, and the treating physician. Between the heavy regulation of laboratory processes and the legal duties physicians owe their patients, it is not clear that variant databases have legal responsibility for data quality. This may change as variant interpretation and database management standards solidify. As genome sequencing in the clinic and data sharing mature, it is likely that regulation will emerge for variant databases. Indeed, the US ClinGen variant database community has highlighted the importance of engaging with regulatory stakeholders to determine standards for variant interpretation and database management. The FDA recently proposed standards for variant databases as part of a scheme to regulate genomic diagnostic tests. Under this scheme, FDA-“recognized” variant databases could be relied on as evidence for a test’s clinical validity (see the GA4GH consultation response here).