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Q&A: Ellen Wright Clayton on Physician Liability in the Age of Diagnostic Sequencing

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Ellen head shot_0.jpgName: Ellen Wright Clayton
Title: Craig-Weaver Professor of Pediatrics, Vanderbilt University Medical School;
Professor of Law, Vanderbilt University School of Law;
Co-founder, Center for Biomedical Ethics and Society, Vanderbilt University Medical School;
Faculty member, Vanderbilt Program in Human Genetics
Experience: Director, Center for Biomedical Ethics and Society, Vanderbilt;
Rosalind E. Franklin Professor of Genetics and Health Policy, Vanderbilt;
Attorney, Vinson and Elkins, Houston, Tex;
Visiting fellow, Institute for the Interprofessional Study of Health and Law, Houston, Tex.
Education: BS, Duke University; MS, Stanford University; JD, Yale School of Law; MD, Harvard Medical School

As more physicians are ordering next-generation sequencing gene panels, exomes, and even whole genomes to diagnose disease or guide cancer treatment, one question that has not been explored is how the physicians and/or the laboratories that provide such services will be held accountable for errors in the tests.

Already there have been cases of incorrectly annotated variants, and the sequencing technology itself may leave gaps in disease genes (see CSN 3/6/2013 and CSN 5/24/2011). In a sequencing study of 437 genes published in Science Translational Medicine, Stephen Kingsmore's group found that 27 percent of variants cited as disease causing were either misannotated or common polymorphisms.

In a study published in Genetics in Medicine, Ellen Wright Clayton, who holds joint posts at Vanderbilt University School of Law and Vanderbilt University Medical School, sought to address the question of how laboratories and physicians will be liable for reporting incorrect results or for missing a pathogenic mutation.

Clayton recently spoke with Clinical Sequencing News about the matter and how the recommendations by the American College of Medical Genetics and Genomics, which says that laboratories should return results from a list of 56 disease-related genes to physicians regardless of preference, complicates the matter even more.

Clayton is also the co-founder of Vanderbilt's Center for Biomedical Ethics and Society and has written extensively about the intersection of law, genetics, and ethics.

What prompted you to do this study?

I wasn't the instigator of this study, but once I got involved with it, I thought it would be helpful to have a general discussion about how a lawyer might approach [physician liability]. There are a lot of people in this field who are deeply concerned about liability. I noticed a lot of health care providers and researchers are worried about it.

In the study, you use the field of medical imaging to represent genomic sequencing. Why did you choose that field, and how are the two related?

What happened was, that first of all, I went to see if there were any [liability] cases about genetics at all. And there weren't any. There's been a lot of writing that has tried to compare imaging and genetics. I don't think they're completely comparable, but they've compared the two, particularly the work by Susan Wolf. [Editor's note: Wolf co-authored an opinion piece in Science, arguing against the recommendations of the American College of Medical Genetics and Genomics to return incidental findings (CSN 5/22/2013).]

So I thought we would look at the imaging cases, and there were a few.

What are the similarities and differences between genomic sequencing and imaging?

Let me start out with the differences. The differences are that, in order to look at a genomic sequence, to look at something other than what you're meant to look for requires considerable extra analysis. This has become really clear in the discussions following the ACMG recommendations with lots of people talking about how much time it takes to analyze those additional genes.

When you are looking at a film, radiologists, and to a somewhat lesser extent other physicians, are trained to look at the whole film. If something is there, the really important issue is to recognize that it's something meaningful and it needs to be responded to. But it doesn't take anything like the analysis that's required to take additional sequence information beyond what you were looking for and then trying to figure out whether its meaningful or not.

And the similarities?

The similarities are only that you do a film usually because there's something in particular you want to look at and there can be something extraneous to that. You do a genomic test because there's something you want to know and there can be data extraneous to that.

What did you find in your research, what are the implications for physician liability in the context of ordering sequencing-based tests?

I think the point that people need to recognize is that there's a pretty standard way that the legal system approaches this. They decide whether there's something the clinician ought to have recognized. The legal system decides that by looking at what the standard of care is for the clinician or who else is involved in the interpretative process. Then you look at what the standard of care is both for looking for it and also for analyzing and interpreting it.

Unless somebody who is unhappy because they didn't get something back is able to demonstrate that the clinician, in the case of genomic information, should have done initial analysis, should have recognized that there was something problematic, and should have returned it, unless they can show that all those elements are within the standard of care and that disclosure would have made a difference in long term outcome, then the possibility of liability is really quite low.

Now, the thing that's changed since we wrote that article is the ACMG statement [on incidental findings]. The ACMG made their recommendation that 56 genes be analyzed beyond the target and that those results be returned by the lab to the clinician. That potentially creates standard of care. Then the question becomes, what are clinicians going to do once they get these results?

So, the ACMG recommendation may have increased the likelihood that there will be more liability cases for errors in genomic tests or if something is missed in a genomic test?

You bet.

And will it be the labs that are held liable or the physicians?

The lab for sure. For the physician, ultimately what physicians do is going to define the standard of care. If physicians decide that they don't want to be returning these results or that there's more discretion involved, then that will be one thing. But, I think it's going to be pretty hard for clinicians, once additional results get put in the medical record, for them not to disclose it.

That is a point of great contention. As you well know, I've been very opposed to the new proposal by the ACMG. They keep saying that physicians can contextualize results. But I do worry that it dramatically limits their discretion.

I think one of [the ACMG's] concerns, and this is something they've told me on repeated occasions, is that one of their reasons for coming up with a list is to say that [labs] only have to look for those things and not anything else. I don't think that's apparent on the face of the paper, but I've heard that from a number of people. What they really want to get to is uniform practice, which becomes standard of care.

There has been a lot of debate in the field about the ACMG recommendations, with arguments both for and against the recommendations to return incidental findings.

Briefly, what are the main reasons why you are against the recommendations?

To give a quick list, first of all, there's nothing incidental about these findings. This is a deliberate decision to look for them. Number two, the fact that they don't ask consent, but rather say that the lab has to do them regardless, I think violates medical ethics. Three, the fact that they mean to report results for children, regardless of their parents, is a violation of pediatric ethics.

There are a lot of problems with this. But by far the most important one is that they don't give patients an opportunity to opt out of having this testing done. That is by far the biggest.

How will the ACMG recommendations impact standard of care, as diagnostic exome and genome sequencing become more common. And will that affect liability among the labs doing these tests and the physicians?

Laboratory practice is going to define what the practicing clinician knows, in general. Just like if a clinician gets a radiology report, the clinicians talks with the radiologist, tries to figure out what it means, and is then responsible for acting on it. As more and more sequence results get pushed to the clinicians, it's going to change the practice of physicians. I think that the big question that we have to ask here is how we decide what results people have to get.

I'm going to a conference tomorrow where the question is about the whole-genome sequencing of newborns. If all those results get returned, it's going to dramatically change the practice of medicine.

But I think what's going to happen here, is that the [laboratory technicians] and the medical geneticists will have to decide what's pertinent. Can you focus a clinical question for just what you want, or does it mean that you have to get all this other stuff? That's a huge change in medical practice. Huge. I think that if it becomes the case that in order to do whole-genome sequencing you have to get all this other stuff, you're going to find a lot of clinicians choosing to go with narrower tests. Because, the more that labs and clinicians decide to do, the more lawsuits there are going to be.

What are the next steps?

The main thing that we've already seen is that some labs are already giving people the option of getting the additional incidental findings panel or not. I'm a little agnostic about that, but it's better than saying you have to do it whether you want it or not, and that it has to be given to the clinician whether the patient wants it or not.

In the real world, if a lab gives a result to a clinician, it has to go in the medical record. It has to. So I think there needs to be several initial responses. One, is to make this a matter of choice. Two, is to talk about what the criteria are going to be. We have long-standing processes for figuring out how to make evidence-based criteria for all kinds of tests in medicine and they ought to be applied here. And then three, we have to deal with the kid issue and give parents choice. I think those are the things that have to be addressed in the near term.

A lot of geneticists are not happy with this.

I think the take-home message is this, if physicians start getting these results and start returning them, then they'll have to get them and they'll have to return them. Really what we ought to be insisting on is allowing people to decide what they want to get and the process of getting these tests. If there's not choice, then I think what you'll find is that people will back away from using this methodology.

Have you seen that happen already — physicians backing away from using exome sequencing?

Yes. I'm already seeing it with the physicians. Some physicians who were ordering exomes are now not.

The more people do, the more they have to do. That's how standard of care in medicine works. They need to be sure that it's in patients' interest to do what they have in mind if they're going to create a standard of care that demands [the return of those results].

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