BALTIMORE – Genomic sequencing has been adopted rapidly for clinical use in recent years, but its regulation is still taking shape in the US and in Europe, according to a discussion on the barriers and drivers for the implementation of clinical sequencing here at the American Society of Human Genetics annual meeting on Wednesday.
The session, part of a series organized by the American and European Societies of Human Genetics, included perspectives from three clinical researchers from the US and Europe and from a representative of the US Food and Drug Administration.
According to Wendy Chung, a clinical and molecular geneticist at Columbia University, genetic testing — including panel, exome, and whole-genome sequencing — for cancer and inherited disease diagnostics has recently expanded in the US as sequencing technologies have become cheaper and faster. However, researchers are still in the midst of studies to demonstrate the clinical utility and cost-effectiveness of such testing. "We are trying to fly the plane as we are building it," she said.
In that process, the lines between clinical research studies, which in some cases have returned results to participants, and clinical diagnostics can get blurred, she said, at least from a patient's point of view.
Addressing the concern from an audience member about the validity of variant interpretations by testing laboratories, she said that interpretations will improve over time as more variants are contributed to resources such as ClinVar and as errors in databases get corrected.
Scaling genomic testing to larger numbers of patients will require educational efforts, she said, both for healthcare providers and for patients and the public in general.
Meanwhile, as part of the Precision Medicine Initiative, the FDA has been looking into how to regulate clinical sequencing as it expands from targeted gene panels to exomes and whole genomes. "We are working on how we might approach regulation differently, in a more innovative way," said Liz Mansfield, deputy director of the Office of In Vitro Diagnostics and Radiological Health at the FDA.
The agency acknowledges that sequencing technology keeps evolving fast and is looking for a regulatory framework that will allow innovation to continue to grow, she said. "It is a very efficient technology that generates a lot of knowledge."
To that end, the FDA published a white paper last year and held a public meeting on NGS-based test regulation early this year.Â
Two upcoming public workshops in mid-November will discuss the use of a standards-based approach to evaluate the analytical performance of NGS tests and the use of curated databases to establish the clinical relevance of genetic variants, respectively, and the agency will publish additional white papers in the near future, Mansfield said. In addition, it will soon launch PrecisionFDA, a cloud-based open-source platform for evaluating bioinformatics workflows it has been building with its partner, DNAnexus.
Compelling laboratories to deposit clinical variants into databases is "an interesting idea," Mansfield said, though it is not clear this would be possible in the US.
On the other side of the pond, the European Society of Human Genetics has been lobbying against amendments to a proposed regulation on in vitro diagnostic medical devices that were made by a member of the European Parliament, according to Philippos Patsalis, head of translational genetics at the Cyprus Institute of Neurology and Genetics and a former health minister of Cyprus. In a statement last year, ESHG said that the amendments "will restrict the rights of patients and doctors to carry out essential genetic testing."
While ESHG welcomed the original regulation proposed by the European Commission that aimed to improve the quality, safety, availability, and oversight of IVDs in the European Union, it said that the amendments, which call for mandatory genetic counseling for all genetic tests, are too burdensome and unworkable and would limit the availability of genetic testing to patients.
Patsalis said that direct-to-consumer genetic testing has also been a controversial issue in Europe, where concerns have been raised about the absence of medical supervision, the accuracy of testing, access to counseling, and protection of privacy. He called on scientists and scientific societies to become "more proactive" on shaping the regulation of genetic testing.
David Barton, chief scientist at the National Centre for Medical Genetics in Dublin, Ireland, noted that up until now there has been no mandatory laboratory accreditation for human diagnostic laboratories in Europe. With regard to the regulation of laboratory-developed tests, there have been similar discussions in Europe and in the US, he said, while the issue of returning secondary findings has been treated with more caution in Europe and with more proactivity in the US.
Regarding gathering variant information in new databases such as ClinVar, he said that existing efforts for specific genes and diseases should not be ignored. "Nobody is an expert in the whole genome, but there are many experts for individual genes," he said.