Raw Reads is a series of refined, comprehensive transcripts of conversations on topics covered by Ion Genomics.
Is Grail’s Galleri test safe and effective? Do its risks outweigh its potential benefits?
The blood-based cancer detection test passed all three votes before the ten members of the Molecular and Clinical Genetics Devices Panel of the FDA’s Medical Devices Advisory Committee on Sept. 23.
The panel voted unanimously in favor of Galleri on the question of safety, but was split on the other two questions. The vote was closest, 6-5 in favor, on whether Galleri was effective at its proposed use of detecting multiple cancers early, and 7-2 in favor (with one abstention) on whether the rewards outweighed the risks presented by the test.
After hours of testimony and discussion, the ten panelists explained their reasoning behind each vote. Their comments reveal concerns about the use of the word “early” and broad questions about what other tests like Galleri will mean for the US healthcare system, as well as hopes for what these tests can do for detecting cancers for which there are not established screening methods.
These votes will guide FDA as it mulls approval for Galleri, though the agency is not bound by the results.
What follows is a refined, corrected, and annotated transcript of the video of the meeting posted publicly on YouTube; however, some comments were not attributable to a specific speaker and are noted that way.
Question One: Safety (10-0)
Unknown speaker
[...]We’re going to vote on all three and then we go around the room and discuss each one individually. [...] Question one: Is there a reasonable assurance that Galleri is safe for patients who meet the criteria specified in the proposed indication? [...]
Question two: Is there reasonable assurance that Galleri is effective for use in patients who meet the criteria specified in the proposed indication? [...]
Question three: Do the benefits of Galleri outweigh the risks for use in patients who meet the criteria specified in the proposed indication? [...]
I’m going to start with Dr. Ghosh and just state for your name how you voted and what influenced your vote. It could be short because you’re going to have to do it three times.
Aditya Ghosh (Internist physician, Mayo Clinic)
Aditya Ghosh Mayo Clinic. Yes. Uh, reasonable assurance that it’s safe. I think especially when put with uh when accompanied by uh adequate directions and warning against unsafe use. I think we’ve had extensive conversation too in terms of what that looks like and so really important in making sure that it’s appropriately rolled out and um that everybody’s aware of how it is intended to be used.
Kelly Hunt (Breast cancer surgeon, University of Texas MD Anderson Cancer Center)
Kelly Hunt. Yeah, I voted yes. I think as was stated previously, it’s safe. I believe it’s safe based on the data that we’ve seen and that along as an adjunct to appropriate cancer age appropriate cancer screening is safe.
Victor Van Berkel (Thoracic surgeon, University of Louisville)
I’m Dr. Van Berkel. Uh I also voted yes. Um I think this obviously the safety question covers a lot of territory. I think false reassurance is the largest issue leading to either ignoring symptoms or uh other screening guidelines. I think within the statement of safety, the part when accompanied by adequate directions and warnings carries a lot of weight. Um, and in that context, I think that it’s safe.
I do struggle a little bit with what to do with when it is obvious that the target audience will misinterpret the results. Just for the record, we didn’t talk about this, but this is evidenced by some of the public comments. There were a couple of physicians in the public comments who said, and you know, specifically something along the lines that this test not only finds cancer, but it rules it out, which this test clearly does not do. And there were two or three physicians, I don’t know if you guys read through all 180 of the comments there, but there were a couple people who definitely said that. And so, it’s not just patients that are going to misinterpret this, but physicians that are going to misinterpret this, but that’s not on the company, that’s on us. But with that in mind, I still think that they have done what they can as far as that goes.
Deborah Armstrong (Oncologist, Johns Hopkins University)
Um, Deb Armstrong, um, I voted yes. Um, I do think, uh, it’s safe. The biggest concerns, as we’ve talked about, um, are people being falsely reassured and not getting, um, recommended screening. Um, and then the very small number of people who have a false positive and the exposure they get to testing. Um uh but if I think if people are well informed, I think that’s an acceptable um that’s acceptable.
Jason Dominitz (Gastroenterologist, University of Washington and the VA)
Jason Dominitz, I also voted yes. Um echoing prior comments, you know, my biggest concern’s that the direct safety of the test itself is pretty clear minimum risk of the direct direct uh side effects of the test, but indirect uh risks are real uh in terms of false reassurance and false positives. And I think that may change with age. And I think it will be really important for us to think about an upper bound to minimize the risk to those who would not benefit from the test. And so labeling should consider things along the lines of, you know, intended for people for whom screening is appropriate. And there’s going to be a lot of people for whom screening is not appropriate. So we need to keep that in mind.
Charity Morgan (Biostatician, University of Alabama at Birmingham)
Charity Morgan. Like Dr. Armstrong. I was swayed by the low rate of false positives and the low number of invasive procedures in the false positives. Um the other possible risk that I was worried about was the impact on uh recommended screenings in people who are getting the tests, but we don’t have any evidence at this time that that is being effective. So what I’m left with in front of us today is evidence that we do see that this is a safe test.
Dan Makarov (Urologist, New York University)
Dan Makarov of NYU. I voted yes uh that I felt it was safe uh for reasons previously stated, but to summarize uh um uh low risk of false positive um and with uh you know appropriate uh guidance uh uh with restrictions of how it’s meant to be used and then also with uh with hope with my hope that there’s postmarket surveillance.
Lori Dodd (Statistician, National Institute of Allergy and Infectious Disease)
Lori Dodd and I voted yes for many of the reasons stated so I won’t go through them again.
Stan Lipkowitz (Senior Investigator, National Cancer Institute)
Stan Lipkowitz I voted yes and again for the same reasons. [...]
Dan Swerdlow (Radiologist, Georgetown University)
Dr. Swerdlow. Yeah, I voted yes. For the record, for the record, I voted yes. Um, for all the reasons uh previously mentioned, I do think there needs to be robust education of the practitioners who going to order this test so they really understand what it means uh more than just the label, but they probably should do an online course or something that gives them a good uh explanation of the data such as it is.
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Question Three: Benefits vs Risk (7-2)
Unidentified speaker
On question three, the panel voted seven yes, two nos, and one abstain that the benefits of Galleri outweigh the risk for use in patients who meet the criteria specified in the proposed indication.
Dominitz
Jason Dominitz. Well, you heard me talk about my heartburn over the answer to question two, but once I made a determination of yes for that and say if it was just a logical conclusion, but again, I have significant concerns and would like to see true outcome data, not necessarily mortality. I think that’s too high of a bar for a test like this. I mean, we don’t hold, you know, Cologuard to that standard. We randomized trial colonoscopy just recently, you know, hasn’t shown enough mortality benefit from colonoscopy, but we have other data to support that. But, you know, I think we have to be careful not to set too high of a bar, but I do think we need more outcome data for this test.
Morgan
Uh, Charity Morgan. Um, I did vote yes to this one. This one was a hard call as well. Not as hard as the last one. Um, honestly, you know, post approval studies could change my mind on this one, but um, you know, that with the absence of data to the contrary, I think what we have in front of us says that the benefits um, outweigh the risk at this point.
Makarov
I voted yes. I thought it was safe. I thought it was effective and the breakdown of risk risk benefit I thought was favorable one again, being driven a lot by cancers that don’t have um uh current screening protocols available and with the hope that there’s robust postmarket surveillance.
Dodd
Lori Dodd I voted no. You might wonder how I could vote yes on the other two and no on this one. Um but that’s because I took this to be a broader set of questions and and rather than reading the literal um label and the literal definitions of safety and effectiveness um you know do the benefits outweigh the risk? And in order to really address that, I felt like we needed to know more about clinical outcomes um and you know are these cancers that need to be treated? Some of them likely do, but how many of them don’t need to be treated? So, I would like to see more of those data before voting yes on this question.
Lipkowitz
So, I don’t know if this test is effective and you know, so that’s why I voted no, but that means that I don’t know if the risk and benefit where the risk and benefit come down. So, I abstain because I really just don’t know the answer to that question. and
Swerdlow
Yeah. Um so like Lori’s reasoning, I don’t know because we don’t have that data and I suppose someday it will become available but not right now. Um but I’m very concerned about the cost and implementation of this to the whole health care system. Um for things I discussed on the last question about number of providers, I see a lot of patients and providers twisting in the wind, not sharing, not sure what these results are actually going to mean. Uh as a contrast, lung cancer screening where everybody has to go through uh talk to doctors, get counsel, get understanding what these positive lung cancer screening tests mean. I know there’s a lot of backup for patients there. And in this case, I just don’t see that backup. And I see a lot of patients who are going to struggle to get their workups done because it’s not going to be convenient for them or it’s not going to get paid for by insurance or it’s simply not going to be cost effective to a system that’s already struggling.
Ghosh
Dr. Ghosh, I voted yes that the benefits of Galleri outweigh the risks. I think as the discussions and as everyone we’ve heard from on the panel you know there are certain things that you know Dr. Dominitz and I had brought brought up initially that at one point it’s you we wonder is that outside the scope of the conversation that we’re having today but I think it’s really important to say there’s a lot that goes into benefits and risks that are within scope and survival is definitely on there and the overall you know ability of this to um you know the overall ability of uh Grail to ensure that they have appropriate support uh for teams going forward uh when they’re rolling out this test is really important. Um, I think those were all kind of very valid points. I think I was weighing those against the risk of also not doing this. And when we say that there are cancers that we don’t currently have screening for, um, well, I don’t know if that’s true anymore.
You know, when we, you know, the cancer signal of origin, the things that we’ve seen and the fact that things like head and neck cancers, hematologic malignancies, um, some of the pancreatic malignancies, some of these that we know can be devastating to patients, the fact that there’s a blood test that could possibly capture them. And, you know, in terms of weighing that risk benefit ratio, I certainly think there is a lot of work that has to be done in order for us to definitively say stuff going forward. But when I weigh the risk and benefit of a test that could possibly give us something where we don’t currently have something um that’s just too much of a risk in my mind. So that’s why I weighed yes.
Hunt
Kelly Hunt I voted yes for a lot of the same reasons that have been articulated by Dr. Ghosh. And I also feel like the information that was provided about the algorithms that are utilized to help uh navigate the process of false positives and then also retesting for the negatives I think is very helpful in utilizing this test and then hearing from physicians who do utilize it. I think we learned the good and the bad part of that. So, I think the FDA can take a lot of that information to help in the labeling about how it should be utilized and what the yes means or what a positive test means and what a negative test means.
Van Berkel
Victor Van Berkel and I voted yes. I feel like Dr. Lipkowitz and I were thinking about this very much the same way and I seriously considered abstaining as well and then I chickened out. I guess I don’t know. Um, I feel like the only logically appropriate thing for me to say after saying yes and then no is that I’m not sure whether or not the risks are outweighed by the benefits. Uh I suppose the reason that I hedge towards yes is because I think that in the years ahead it probably will be proven to have the benefits outweigh the risks specifically when it comes to the tests that the cancers that we don’t have good tests for. Um I think even a marginally successful test if we can find uh more stage one or more early stage cancers in a in a in a population that we can’t screen for currently then that will end up having benefit. But I don’t know that that’s been proven yet. So perhaps my yes is a hopeful one rather than an accurate one.
Armstrong
I also voted yes. I don’t have a whole lot to add. I did think that the risk and my biggest concern would be the false um false positive and the rate is really quite low and I think that’s very reassuring to me. So, I think when you um um I think the benefits the potential benefits for this I think it but it is really potential at this point in time. So, um outweigh the risk. So, other than that, I don’t really have anything else to add.
Unidentified Speaker
I think uh at this point in time I’m supposed to summarize the vote. We had on the question of safety we had 10 yes and zero no. On the question of um effective we had six yes and four no. And then on the question of uh do the benefits outweigh the risks we had seven yes two no and one abstain. Um anything else anybody wants to contribute at this point in time? If not, um I’d like to thank everybody here. We take a lot of time out of our busy lives to do this. Um like to thank the FDA folks who’ve uh really put a huge amount of work in here and the sponsor um and the folks uh who um uh for the uh open public hearing both in person and online um many of which really were quite moving and remind us of the humanity that’s behind some of this. I think we’re ready to adjourn.