 Welcome everyone. This is the first event of the Health Care Professionals Genomics Education Week supported by the National Human Genome Research Institute and the Inter-Society Coordinating Committee for Practitioner Education in Genomics. My name is Tracy Weiler and the session that we are delivering today is entitled Direct-to-Consumer Genetic Testing Updates and Cases. And this is with a group of individuals who are members of the Direct-to-Consumer Genetic Testing Project Group. So the learning objectives for our session today are to describe the current Direct-to-Consumer Genetic Testing or DTCGT landscape and to apply DTCGT results to a patient scenario with the following types of results. Disease risk results, carrier risk results, and pharmacogenomics results. If you have any questions throughout the session, you are welcome to use the Q&A button on your Zoom and we have a couple of panelists here today who will be answering the questions in the Q&A via text or also we might be able to answer them live later on during this session. The session is going to run from 12 to one Eastern time. I know we have people from around the world so you may be in a different time zone, I'm sure many of you are. We will be staying on the call for another 30 minutes or so beyond the hour if people have additional questions that they would like answered. Okay, our panelists today are all members as I said at the DTCGT Project Group of ISCCPAC. We have clinical geneticists and genetic counselors and pharmacy, farm D people and PAs and medical school educators as well. So we have a wide swath of expertise here today. None of us have any financial disclosures at all and just to give you a brief overview of the ISCCPAC you can go to this website genome.gov slash ISCC to find out more information about the ISCCPAC in general and the direct to consumer genetic testing working group. The last thing I wanted to say before I turn the mic over to our next presenter is that there is a direct to consumer genetic testing FAQ for healthcare professionals. So if you go to genome.gov and just look for the DTCGT FAQ you can find a whole bunch of information about DTC in healthcare practice. And on that note I am, oh all of a sudden my my slides are going backwards. The last thing I wanted to say before I turn the mic over is that we do appreciate your feedback on this event on this webinar and there is a QR code here and if you leave the call early and leave the zoom early this will appear and we would really appreciate your feedback on this presentation. It will also, it doesn't matter when you leave the webinar you will get this link. And so let's start with an introduction of direct to consumer genetic testing when Park is a physician associate and she will lead us off. Good afternoon everyone and I'm really excited to be here with you. My name is Dr. Wynn Park. I'm the president founder of the Society of PAs in genetics and genomics and we're going to talk about genetic testing models. So genetic testing can be a little confusing for people. It's easy to break things down though if you look at the different types of testing and if you look at different factors specifically who's ordering the test looking at how consent is obtained, how the results are given, and then how the results can be clinically applied. So we'll start with clinic based genetic testing and that one's pretty straightforward. That one is a test that is ordered by a healthcare professional and because of that the healthcare professional obtains consent excuse me and then the results come to the healthcare professional which allows them to integrate it directly into clinical care of the patient and those results can be used clinically. There's kind of an intermediate category that is a consumer initiated but provider mediated category in which the consumer orders the test but it's and sometimes it's done through a commercial company but there is a healthcare professional who's employed by that lab and they sign off on the test. Consent is usually obtained directly from the consumer sometimes with sometimes without the healthcare professional assisting with that and then the result gets sent directly to the consumer which sometimes they may have optional access to a healthcare professional afterwards and oftentimes those results can be used clinically as well. What we'll be talking about today though are direct consumer genetic tests. In these cases a healthcare professional is not involved. The consumer orders the test. The consent is obtained on usually on the website directly to the consumer with written information. There's not really explanation given beyond the written explanation and then the results come directly to the consumer and usually they need to be confirmed before they can be used or applied clinically. So these are the differences between the main differences between the tests and so looking at the methodologies that's another way that we can distinguish between the different types of tests and these are really you can distinguish between the three major categories according to the American College of Medical Genetics and Genomics and the Association of Molecular Pathology recommendations for their variant interpretation. So starting with a clinic based genetic testing this can be done either through single genes or gene panels either genome or exome sequencing can be ordered, chromosomal microarray, karyotyping we can look at pharmacogenomics or the effects of your genetic background on your ability to metabolize different medications. Also you can review methylation and trinucleotide copy number analysis. In the consumer mediated or a consumer initiated provider mediated these tend to rely more on gene panels and are usually not as extensive as what you can see in the clinic based genetic testing and also there's a can be a focus on pharmacogenomics. Now in direct to consumer testing however it can be more limited we're looking more at primarily SNP based testing or single nucleotide based testing or genome sequencing and again there can be a focus on pharmacogenomics. Next slide. It's interesting. There we go. Oh no you're fine. And so as we talked about ACMG and AMP they have different consensus recommendations for variant interpretation. As I said only the direct to consumer does not have recommendations for variant interpretation use in clinical or very limited I should say there's I think there's only one or two cases. In terms of the consensus recommendations for variant interpretation in direct to consumer there are three different or I'm sorry five different types pathogenic likely pathogenic variant of uncertain significance likely benign and benign. Now we use these consensus recommendations in both clinic based and in the consumer mediated with provide or consumer ordered and provider mediated but these categories and these consensus recommendations for variant interpretation are not used in direct to consumer genetic testing as will be demonstrated in case examples that we will be discussing later. So to help start with some of our cases I'd like to introduce Hewan Lee for our next case the next slide please for our first case presentation. So Hewan Lee is a genetic counselor and assistant professor. Thank you so much Dr. Park. So hello everyone my name is Hewan Lee is she her pronouns I'm really excited to talk about our first case. So in this first case we have a 29-year-old young woman who uses she her pronouns and who's done direct to consumer testing and plans to start a family. She has some concerns about two variants that were detected and she is disclosed that she's adopted and has no biological family health history. Now while DTC is not ideal in a clinical situation this can be very meaningful the directed consumer testing can be very meaningful for many patients who are adopted donor conceived or don't have access to their family health history. And so this test can be really sometimes the only connection that patients have to their biological family and so adoptees in general don't have the bio advantage of knowing generations of family health history and their risks for certain diseases. And so many are turning to direct to consumer testing as a way to open the door and to get clues on their own health risks. So this can be a conversation starter a first step for a proactive patient. And additionally if they have children or they're planning to have children finding out any risk information for adoptees can be very helpful for future reproductive risks. And so for this case in particular here we've highlighted the variant that was found in the LDLR gene. Next slide please. And so this is just a hypothetical example of what a direct to consumer test report might look like and so I usually try to look at it in a couple ways like what are we seeing and what are we missing. So we're seeing here a short overview of hypercholesterolemia or FH and how it's associated with high cholesterol and risk for cardiovascular disease. And so we see that one variant is detected in the LDLR gene out of 24 different variants that the company tests for. And we can see in the bottom and fine print that we put on there that it's just the LDLR gene is one of four genes. But then we want to say well what are we missing. And so one thing a consumer might look at and think about as well you know are the 24 variants in the LDLR gene only or could they be in any other different gene. We can't really find that out by looking at this. We are also missing the name the exact name of the variant. And so we'd have to look for the fine print to get any information about it. A patient might even wonder as well what am I at risk for FH or is it okay just to have one variant. What if I had two or three or four so it doesn't really contextualize what a one variant might be. And we know for FH in many cases it can be autosomal dominant. And so having one variant could really be clinically actionable for disease risk. And then the report essentially is missing the next steps for consumers. So when a variant is detected in direct to consumer testing it may or may not be clinically actionable. So Dr. Park previously discussed how the direct to consumer testing standards and guidelines are very different than the clinical genetic testing with how the interpretation of a variant occurs. But you know when a patient brings in this information especially with FH we don't want to ignore you know potentially clinically actionable information for that patient and their family member's health. Next slide please. So now we're going to actually ask you what would you do. We really would love to have some audience engagement. And so I'm going to read the question about some potential next steps options for what this patient could do or what you would do as a provider. And then I'll start the polling. So first is what would you do. And I'm going to read through this disregard the results because it's not clinical grade testing order a fasting lipid profile order sequencing of the LDL R gene order a gene panel for FH order whole genome sequencing and or consult with the genetics professional. And so if we could please launch the first poll please choose all that you would apply. Great we're getting some good results here. Thank you so much for participating we're having over 50% of our audiences participating now looks like order a fasting lipid profile is in the lead here also order a gene panel for FH consult with the genetics professional I love seeing that we'll just run this for maybe five more seconds wonderful. Okay so let's wrap this up and I would love to be able to share the results with everyone and you can also put in the Q&A your response and why you would choose a few answers. Great so we can see here that the number one question or the number one answer of what you could do would be order a fasting lipid. Then it looks like the next one is consult with the genetics professional and then we have a gene panel for FH that's great. Okay so thank you so much for participating in that next slide please. Okay so now I'm going to introduce and hand this over to Dr. Haria Ayubie. She's a clinical geneticist and medical educator at Texas Tech University Health Center at El Paso thank you. Hello everybody so we started by figuring out why the patient pursued the dark consumer genetic testing and found out that it was really the lack of her personal history and the fact that she wants to start a family is the reason that she pursued the dark consumer genetic testing. Next we looked at the report and determined what are we seeing and it indicated a risk for a genetic condition. Now we need to determine if additional tested may be needed to confirm or refute the result and this may or may not be covered by their health insurance. So in this case a good starting point would be a lipid panel because it's something that you can order as part of national guidelines and recommendations and would give you some guidance as to whether or not the patient's variant is contributing to their elevated cholesterol. The second step would be to consider clinical genetic testing since this genetic test result could predispose to elevated cholesterol and even in some individuals actually even if it is confirmed to be truly pathogenic if it's confirmed that it is truly associated with elevated cholesterol not everyone manifests elevated cholesterol and we call that variable penetrance. If she does not demonstrate elevated cholesterol it may have reproductive implications as they are planning to start a family. So let's assume her lipid panel came with elevated cholesterol LDL more than 190. The next step would be ideally to send genetic testing. Now because as Dr. Park talked about and our genetic counselor He-Won talked about that the familial hypercholesterolemia and elevated cholesterol may be caused by pathogenic variants in different genes I would choose to order a gene panel because she had elevated cholesterol and this way it would be more informative. As for the family planning aspect of it I would ideally want her to see a preconception genetic counselor or a specialist who has some expertise in preconception genetic counseling so that she may be able to pursue clinical grade carrier genetic testing for being a carrier. Next slide please. So here her familial hypercholesterolemia panel came back with a pathogenic variant and notice the difference here between this hypothetical clinical grade report versus the dark consumer genetic test report. The report shows you the gene followed by followed by where exactly the nucleic acid change is and the exact annotation. In the interpretation section it tells you more about this genetic change tells you more information about its frequency in the general population whether there's been any evidence to support it in the literature or not and here it is classified as pathogenic. Next slide please. So with that ideally for this patient you would have after ordering the lipid panel you would order a gene panel because her lipid panel was elevated. Now had her lipid panel been not elevated with elevated cholesterol maybe I would just send for the LDLR gene given that it is unlikely to be covered by insurance and this way there would be less of a cost incurred by the patient and while a geneticist or a genetic counselor would be helpful to to walk you through these results but being the only genetics professional in El Paso Texas I don't think it's feasible for every patient who pursues dark consumer genetic testing to be evaluated by a genetics professional and with that we'll open it up for questions. We do have one question on what happens when a patient cannot pay for the test Haria do you want to take that one? So if you're trying to order a clinical grade genetic testing ideally you would try to go through the patient's insurance in order to and this is where it becomes a problem and when it starts with genetic test results without any companion alteration however if the patient has elevated LDL cholesterol then ideally insurance would cover that test result. Now laboratories that offer clinical grade genetic testing also offer payment plans for patients who are who really want to proceed with the genetic testing that being said it's a conversation to have with your patient whether or not paying out of pocket is is reasonable for them or not and whether not pursuing genetic testing would be an option as well and here you know with elevated cholesterol many people have elevated cholesterol and we go send genetic testing for every single person so potentially you might if the patient is unable to afford the testing you might not send it based on that conversation that you're going to have with your patient. I think we've answered all of the live questions oh hold on one more one more just came in. Do you routinely recommend DTC genetic testing for patients who have no family history info available? He won do you want to take that one? Yeah that's a great question so I think routinely you know it really depends on a person's personal history if they have any conditions that might warrant genetic testing or other preventative health measures. Sometimes when patients would come to see me I was in cancer and they didn't have a family health history we would order usually a larger panel but there's a lot of considerations to to think about you know if people how much information the person wants how much they're comfortable with if they have biological children or wanting biological children sometimes people would come for gender affirming care and they had no family history they wanted to know if they carried you know a BRCA or other high risk variant so there are definitely situations where I think genetic counselors and other genetics professionals are willing to consider you know genetic testing but if someone is very healthy and they don't have you know any personal histories then you know it really warrants a larger conversation to figure out what's the right path what makes sense what's covered what isn't and then go through the informed consent process to make sure that patient is very comfortable with that. Thanks. Thanks everyone I think we've answered all of the live questions so we can move on. Thank you Heimann I would agree with you I wouldn't particularly recommend consumer genetic testing because again the only test for select variants and if they are concerned about a cancer risk or other you would want a more comprehensive test that that is clinical grade rather than barred consumer but an alternative may be consumer-initiated physician mediated with that we are going to move on to the pharmacogenomics aspect of this case because we are going to start medications for our patient and as it happens your direct consumer genetic test also includes for macronomic test results and our clinical pharmacists with expertise with for macronomics Dr. Roseanne Gamal is going to present the next section. Thank you so much Dr. UVA as she said my name is Roseanne Gamal and I'm an associate professor of pharmacy practice at Massachusetts College of Pharmacy and Health Sciences in Boston and so in this section you'll talk about the pharmacogenomics so again pharmacogenomics is a field of study that lies at the intersection of pharmacology and genomics and it's all about how our genes influence medication response. Next slide please so we're still with the same patient as we were in the first part of the case but now we're going to focus on the pharmacogenomic aspects of her direct-to-consumer genetic testing in particular there was a variant detected in a gene called SLCO1B1 which relates to statin medications that are used to treat high cholesterol. Next slide please so in this case as you know we've already discussed it's recommended you know in this best practice would have been to have ordered a lipid panel for this patient so let's say we did this for her and we see that her LDL cholesterol is very elevated at 320 milligrams per deciliter and if we go to the current clinical guidelines for the treatment of high cholesterol we see there's a recommendation to pursue high intensity statin therapy in order to bring that level down and reduce her overall cardiovascular risk and so the question at hand is which the patient may very well have is you know will the genetic test results impact my treatment in any way. Next slide please so if we take a closer look at her direct-to-consumer pharmacogenomic test report what you may see is a table that may look like this that contains several genes that relate to medication response you know oftentimes these genes relate to specific medications are surely not relevant for all medications but you also see that there is an indication of what variants may be detected in these genes and what those variants mean for the overall protein function for those for those different proteins that are encoded by those genes and again focusing on that last gene result there SLCO1B1 we see that the patient does carry a variant in that gene that does have an impact on that protein function specifically it results in a decreased function of that protein so we'll go to the next slide please and we'll look at well how does this gene and this this protein that's encoded by the SLCO1B1 gene relate to statins so I'll direct your attention first to the left side of the screen where we're looking at a situation where there's no variants in the SLCO1B1 gene we have a normal functioning protein the protein in this case is what we call a drug transporter which is responsible for basically think of it as as a door that that opens and allows the statin medication to travel from the bloodstream into the liver and it's in the liver where that medication will be broken down and cleared from the body so again on the left hand side if we have a situation where there's there's no variants in that gene that gene is working properly we have an SLCO1B1 transporter that's working well and that can readily transport again those statin medications from the blood to the liver where it can be broken down and cleared from the body now if we direct our attention to the right hand side we have the case that where we see our patient is presenting in that she has a variant in one of her copies of the SLCO1B1 gene so what does that mean for her well that means that SLCO1B1 transporter is not working as well and in this case we go with the door analogy you think about it the door is kind of just slightly open not fully open just a little bit open so it allows some statin medication to go through but not as readily as a normal functioning protein would and the clinical consequence of that is that you can have a buildup of that statin medication in the bloodstream and if that concentration gets too high it can lead to adverse effects and notably with the statin medications the adverse effect that we're concerned with is muscle pains and weakness something called myopathy which we may see with statin therapy so this specific variant and SLCO1B1 can lead to a higher risk of statin associated myopathy in patients we'll go to the next slide please and at this time I'm going to hand it over to my colleague Dr. Christine Formia who's also a clinical pharmacist who specializes in pharmacogenomics thank you great thank you Dr. Gamal appreciate that now that Dr. Gamal has covered the important information about the the patient case we're going to go into another patient into another question so what is the next best step for the clinician to take one disregard all of the direct to consumer pharmacogenomic test results two use all of the direct to consumer pharmacogenomic test results to guide prescribing three determine whether the direct to consumer pharmacogenomic test is FDA cleared for clinical use or four order confirmatory clinical testing from a CLIA certified lab would you please launch the poll please is the polling launched oh thank you very good all right I'm going to give it a few seconds here for you all to participate in the polling okay looks like we've got two big contenders here number three and number four and we have about 60 participation thank you maybe just a couple more seconds here okay great we have I'm going to close it here in about two more seconds all right thank you well what we see here is the we're going to share the results and the looks like from our polling question we had a very neck and neck response selecting number three and four from our our participants today thank you let's close that poll appreciate that and next slide please the answer that we're looking for for the next best step for the clinician is number three to determine whether the direct to consumer pharmacogenomic test is FDA cleared for clinical use and this is important because this has really been over the past few years this has really been changing up so um where were we where we were at a few years ago would have been number four but where we're at today this has changed up and let's we'll talk a little bit more about this in this next section next slide please so as I said this things have changed in the recent recent times and what where we are today is that direct to consumer genetic tests including pharmacogenomic tests typically require confirmatory clinical testing prior to use in medical decision making like I said this is changing the environment in the landscape keeps changing up here we have two important exceptions at this time the first is 23 and me sip 2c 19 test results for which are paired with copitagral and citalopram on patient reports can be used clinically now and the second key exception is 23 and me's s lco 1b 1 test which is paired with simple statin on the patient reports this is the second exception so these two are the only two tests for pharmacogenomics direct to consumer testing that can be used for medical decision making currently now the next point to know is that the clinical significance of the pharmacogenomic variants detected on these direct to consumer tests can be researched using evidence-based resources and the first resource is c pic or the clinical pharmacogenetics implementation consortium now c pic is an international group that supports implementation of pharmacogenomic tests through evidence-based peer reviewed guidelines the second example next thank you is farm gkb this stands for the pharmacogenetics knowledge base it is a publicly available and comprehensive resource that contains extensive knowledge about drug and gene information and it's particularly helpful for healthcare providers and researchers next please and the third available resource is fda or food and drug administrations tables for pharmacogenomics the first is a table for pharmacogenomic biomarkers and the second is a table for drug gene associations now all three of these resources are freely accessible to the public they're you know use these great these web access websites to find more information and they're freely available on the internet to use for patient care next slide please great now that we've now that we've gone through that important information we have verified in fact that the patients directed consumer pharmacogenomic test results are from 23 in me so we know that we can document the two fda cleared results on the patient's report remember that's a sip to c 19 and the s l c o 1 b 1 results and we can put them into the patients chart in the electronic health record now now that we have that portion we know this we can go through and use the c pic guidelines for therapeutic care for the patient as we recall the patient had a very elevated cholesterol level the ldl was 320 milligrams per deciliter and they need high intensity so some very intense therapy to bring down that cholesterol level so we're going to focus on the left side of this algorithm and as we move down the algorithm we can see that there's increasing risk for that myopathy that muscle pain and weakness and aching that can happen with with using increased doses and being very intense with that therapy for this patient next slide please and with that we'd be happy to answer questions in the chat thank you and actually just to clarify the questions put your questions in the q&a oh yes thank you so a couple questions are coming up and the first one is what would the normal doses be christine can you answer that one i don't have the the numbers right here i would be using the medication doses that are listed in the drug and the drug labeling at this point that would be the starting point these would be the higher doses for this particular patient case rose would you be able to have you have additional information for the question yeah i'll just add that there's this different standard doses that associate with the different intensities of statins you can see some examples there of what are the doses for what's a low intensity statin regimen versus moderate and high intensity and this is a figure that we're showing from the c pic guideline for satins that shows the different intensity sands with the doses and then categorized based on the risk for that statin associated myopathy based on that decrease function result and so this gives you an idea of what those doses are here okay we have another question um about some other genes that impact statins so would you also consider abcg2 and sip2c9 that's a great question um and in your right that there are those other genes relate to other statins specifically abcg2 relates to resuva statin and sip2c9 relates to fluva statin and c pic provides guidelines for the interpretation of those results and use of those results to guide those specific statin therapies in the case of direct to consumer pharmacogenomic testing at this time those genes are not included on direct to consumer testing and so we really just have the slco1b1 results to go off of but certainly if the patient has had clinical pharmacogenomic testing and has those results then we can certainly include them as part of our decision-making process and following up on that there's another question do you know of any other any genes that are being considered to be added to the clinically clear list i'm not aware of any that are particular you know queued up at this time so um but perhaps dr. gamma is aware so 23 and me has been fda cleared to return i think it's eight total genes um as part of their panel currently they're just returning um three genes and two of those three genes are clinically cleared so i'm not aware of like kind of what's up next for kind of clinical clearance for for use in medical practice directly um but know that there are other genes that 23 and me has been cleared for generally to return back they just haven't done so at the present time presumably in the near future okay and there's another um someone's asking for some clarification primarily about the previous one but i think it relates to this as well are you saying that commercial test results from companies like um um one ohm and gene site need to be retested by an fda cleared lab so so no um so one ohm and gene site um don't offer direct to consumer genetic testing in the truest sense in that you know when we there was a slide um but which outlined the different models and so um it is possible for a consumer to go through the consumer initiated provider mediated testing so for example go on the one ohm website as a consumer say i want to do pharmacogenomic testing and then they employ physicians who then sign off on those results those are considered clinical results that can be used directly um so what we're talking about here is a true kind of direct to consumer with no healthcare professional involved no healthcare professional ordering these tests um and so in that case that's when there could potentially be the need for confirmatory testing if there's not specific fda clearance for it but the other models you know whether ordered through a healthcare provider directly or if a patient initiates to the company and they have a healthcare provider that signs off on the test those are all considered you know clinical grade testing that can be used directly without confirmatory testing we have a question um that's asking about algorithm how many algorithms are there did you say there were only two and i don't have the more context for that question okay so they're in terms of the algorithm that we were following could you go back one slide please great yes thank you so this particular algorithm is provided within the cpik guidelines and this is with information about slco1b1 but there are as we heard there was a question about adding when there's clinical information clinical testing fda um you know approved laboratory testing results available we have some other genetic variables that can be considered so there are additional algorithms that can be incorporated with this genetic and medication information with this particular algorithm we are only looking at slco1b1 and that the high intensity statin therapy on the left-hand side so again this is in the context of our directed consumer pharmacogenomic test results and what we've talked about with this particular patient case focusing on this piece of the algorithm for what we have and what is fda clear to use for this patient care and also to clarify that this is a decreased function variant in slco1b1 very important thank you so much dr weiler and then the next question about that the next steps is what are the clinical steps that are done to decide the management once a pharmacogenetic variant is detected yeah so once you know what the variant is again first step is that you ask yourself can you use this clinically is this fda clear and we went over those you know specific examples here so once you know it's cleared for use we recommend going to those evidence-based sources for guidance namely the clinical pharmacogenetics implementation consortium the website's there for your reference c pic pgx.org there is a list of those peer reviewed evidence-based guidelines they're freely available and they are designed to tell clinicians or and help them understand how do you interpret these genetic test results and what do they mean for medication therapy does that mean a change in dose does that mean a change in drug therapy does that mean we can use the standard dose when we're when we're looking at these different medications so c pic is kind of a great resource to start with and as also was mentioned the us fda has a pharmacogenomics guidance and some of some labels of some medications as well and so they may have some additional information that would be helpful for clinical care um in that middle resource farm gkb that's kind of like a clearinghouse for all of this information so you really didn't know what to start you could search farm gkb for the gene of interest and medication of interest and they would pull in what are those available resources and guidelines that can help you answer that clinical question to add to that um when you want to choose a genetic testing uh company one resource that i like to use is the genetic testing registry uh by the national institute of health which is a central location for voluntary submission of genetic information my laboratories and they include the test purpose methodology validity usefulness and laboratory contacts and that would enable you to order clinical grade for macogenomic test for your patient um to confirm um any dark consumer dark consumer for macogenomic results um outside of what we talked about outside the exceptions that we talked about and even i'll just add to even if you have a clinical um result back from direct to consumer testing like the slco 1v1 result note that other clinical tests may test for additional variants that were not included on the direct to consumer test and so it is possible to get additional information back um from a different test again depending on what variants were covered compared to the ones that were covered on the direct to consumer testing okay there are some questions about um links um there are some are on that slide and another question came up about um so what percent of the 23 and me report is now FDA approved whether it's all of it 10 percent 30 percent um does the 23 and me report state which variants are FDA approved that's a good question and this is just in general i believe not just for pharmacogenetics so i can speak to the the pharmacogenomics piece of it again i think there's eight genes that are FDA clear you know for for 23 and me to report back currently they're reporting back three genes and two of those three genes no longer require confirmatory clinical testing for use um so that's the pharmacogenomics piece of it i'm not sure if someone else on the panel might be able to speak to actually i as far as i know i don't think anything else um it can be used directly clinically but yes i'll defer to my colleagues on the panel for that information so so the FDA um they have received marketing authorization by the FDA um for accuracy reliability and consumer comprehension but you cannot use them clinically without conformatory clinical genetic testing and um that's and you're going to see that on the report too um with the exception of the pharmacogenomic variants um as they pertain to the medications that op gamma and um doctor for me i talked about that being said there are other dark consumer genetic companies that are offering um additional um results again um you need to confirm those results through a clinical laboratory before you act on them um and there is a there is a difference between um and this might change with time but at present time um these reports from dark consumer genetic testing companies typically have a a a sentence or two saying please talk to your health care professional before implementing any changes um in your medications or um any um making any new medications or lifestyle changes based on these results and in speaking of director consumer genetic testing more broadly i would say that um you need to be cautious as health care providers and as consumers in terms of the um way as we said that the variants are not reported um according to the consensus recommendations and um frequently they are testing a very small proportion of variants um and there are there can be hundreds of variants that are associated but they may only be testing three and so that's not helpful for you as a health care provider or you as a consumer to definitively be able to say anything clinically about reports from director consumer genetic testing especially um when they're not um clinically validated so another really great point just came up in the q and a and this is about how understandable the languages of the reports for um for general physicians so the question is our DTC pharmacogenetic lab reports typically written at the level of understanding to family medicine physicians due to as we all know limited genetics professional access i would think patients would discuss these results with primary care physicians before they are referred to genics professionals and that is absolutely true that's a key reason of having this session so it's somebody like to address that specifically for the DTC pharmacogenetic lab reports rosanne or pristine sure i'll take a hit i'll take a swing at that one um the most of the results are if they're direct to consumer the information that's there is geared towards the patient it's these are um readily accessible and that language is very um accessible for general consumers however when we start talking about clinical grade pharmacogenomic testing though because those tests are typically ordered by health care providers such as family medicine um health care providers genetic counselors there's a higher level of um discussion based on the genetics and the medication interactions and they are at a higher medic um level of understanding and it can be um and the reason for that is because these tests are being ordered by medical providers so it's a higher level of of language and um expected understanding and interpretations and it's expected that the health care provider will take that information and then translate that and share that in those discussions with the patients that they're interpreting the results for and interpreting those those key genetic variants and those implications for medications with the patients so there is a difference there between the two different types of testing and it's also important to know that the health care providers getting that understanding is important using those third part those resources we shared earlier to get a good understanding of some of those genetic variants that are out there to be able to share that at a patient appropriate level with patients and they're with their result delivery so dr for me you're you're suggesting that the some of the reports might be at a higher level and you're referring folks to like primary care physicians to the resources to really have a better understanding of how to interpret the results that are in a particularly focusing on the clinical grade so some of those when we have confirmatory testing does that make sense those the laboratory where the provide patients go to the providers remember we talked about the this uh doctor um doctor um i think we talked about this earlier in the slide doctor park showed us where we have those situations where patients go to the providers and the providers health care providers order those clinical grade tests those are the ones that are going to be at a higher level because the providers involved and they're ordering them we we're talking more specifically about direct to consumer that is going to be more general and i think that's at the level that can be understood by a general audience and that's what fda has set forth as having general accessibility to that information for direct to consumer is my understanding thank you and just to follow with what as was said before that sometimes that the direct to consumer reports while they may be you know a more understandable they also do not they're also lacking a lot of information they don't provide everything so to keep that in mind and there's a question could you comment on the high frequency of false positives in direct to consumer testing in general yeah i can i can hop in on that so in general a lot of the research that's done on some of these false positives with direct to consumer testing is really talking about third party interpretation services so a consumer would do a direct to consumer test download their raw data and then upload it to a third party interpretation service and there were a few studies out there that saying up to 40 percent he's pretty high level so a variance are actually a false positive so sometimes i've seen patients come in with the like 80 pages from their third party interpretation and saying oh my gosh i have so many variants that i'm at risk for and so what we first have to do is really talk about the education event saying you know a lot of the times those third party interpretations are are incorrect because they're using different standards and guidelines and even the direct to consumer testing um and then compared to clinical grade so we'll kind of go over and talk about saying maybe some of the highest points take a look at it if we do have family health history try to contextualize it and if the patient is willing then have a discussion about clinical grade genetic testing to really try to confirm um and kind of you know assuage those doubts and worries um another thing i think the question was talking about um costs associated with DTC um in general they can be more affordable than some of the clinical grade genetic testing um i don't have a you know a ballpark i'm coming from the cancer world i'm thinking you know two to three hundred um but also there are some clinical grade genetic testing that can be very affordable depending on income um and equity is definitely you know something that we talk about um sometimes people will say well it was a really a lot easier for me to just go to a store and get this test and then start this process then try to wage and get to see a genetic counselor etc so you definitely can understand that it can provide some access but again we always say with that caveat that you know it's not as comprehensive it's only looking at this much of a gene it's really not being applied with the same standards as clinical genetic testing so again great first step good for a proactive patient um but definitely would want to have the discussion with the with the genetics professional to talk about comprehensive testing um and kimon can you also add to that the question that also asks about health equity yes yes yes when i was talking about access yes so i think yes some of that um because it can be cheaper than clinical grade testing it is definitely more you know accessible and affordable but it's really important to sort of have your patient or have people sort of weigh the costs and benefits like do they know what they're signing up to um you know they may not want to have the biological relative um connection there they may that might open too many doors for their health thing they may think hey great i don't have a BRCA variant i'm not going to get breast cancer but we know with many tests it's only looking at just a few variants and it's not looking you know comprehensively at the gene so yes there's some health equity there um as far as access and affordability but i would argue that that is at a cost at really not getting a fuller picture which might enrich and help a patient down the line gain some more you know access to to preventative treatments which would be another you know health equity um issue i i would agree with you know um um kimon you know it's it's important to remember that here our cases had positive results and or a variant that was detected and we figured out what the result and and whether or not we should proceed with confirmatory genetic testing clinical clinical genetic testing but the result could come back negative right or say after or undetected which may be true negative but it could also be a false negative or an uninformative result because art consumer testing is not comprehensive and is limited a finite number of variants for specific conditions carrier risk or pharmacopneumic tests so this could result in falsely assurance and in fact individual could be at risk for a genetic condition a carrier risk that they could pass on to their offspring or some medication response um with that um art consumer um you know clinical rate genetic testing that is ordered by a healthcare professional uh typically um would almost always would provide you access to a genetic counselor or other genetic specialists who could help you with um not only ordering um a test but determining the results if you don't have adequate expertise with genetic testing um alternatively um you know consumer-annihniated, physician-annihniated can be um an a a an affordable avenue for some patients um that being said unfortunately we do see discrepancy in genetic testing um in referral to genetics in general um with underrepresented individuals not being as well represented in our genetics clinics and and that applies to you know as it would be expected with healthcare and um and that's something that we all strive to improve on um and would want access to all. So there are a couple questions that I think are are um somewhat related um and so maybe a couple of you might want to chime in on this so the first is do you have a sense for how many clinicians are using this data and then how often do you see primary care physicians ordering more specifically pgx tests pharmacogenetics tests and my experience is that they don't want to due to lack of understanding so how many clinicians are actually using the data and particularly for pharmacogenetics how often are they um are they ordering it? I don't have good numbers um he won do you have any experience? I mean I think from a genetic counseling perspective if I've seen it used in the prenatal and the cancer setting I'm sure in other settings as well um if a patient brings in their direct consumer testing and they say you know I have this variant I have concerns about it we often have a discussion you know of how accurate is it you know most likely we confirm it with genetic testing we ask about family health history if there is any um and sometimes there are a few of those consumer initiated provide you know physician mediated um tests that people can bring in and we say okay that's great you know we don't have to retest you on this this looks like a real variant but that's that's pretty that's probably more uncommon um but we definitely take them seriously um I know sometimes providers will say oh gosh I don't know what to do with this or but I always want to reframe the situation and say this is a great first step it is opening the door it is a conversation starter that patient is interested in engaged and proactive and so even though if this might not be the right test or it might be in the direction that you know isn't appropriate for them we can still talk with them and see what their you know interest fears hopes are with this testing and this health information and Kathy so I deployed a study for a survey to PAs in a nationwide survey and I would say that 25 to 30 percent of PAs had had patients who came to them with direct consumer genetic testing with questions and so patients are coming to clinicians for this also a program that's going on in the VA is called the phaser program which is related to precision oncology and more pharmacogenomics within the VA so there are more providers within the the VA that are being encouraged to order pharmacogenomic testing and to use it in a clinical setting but in general I think the feeling and part of the reason why probably a lot of people are attending our session today is because a lot of people have questions about director consumer genetic testing and how it can impact on as people have said both how do we care for our patients but also how it impacts on health equity and then from a pharmacogenomic standpoint I think you know due to the you know relative lack of education really in pharmacogenomics among primary care physicians we really don't see it yet a standard of care in many primary care practices that being said there are some centers across the country that have implementation projects they're leading in the implementation of pharmacogenomics and they have robust educational efforts to help get their physicians up to speed with testing and that often makes them more comfortable and more apt to be ordering testing or being more comfortable with the results but yeah this issue of education is a big reason why we're all here today while we're having this healthcare professionals genomics education week because this technology exists these tests exist they have the potential to really help with improved patient care and we need to make sure we're getting our healthcare professionals up to speed with the latest science so that we can help optimize patient outcomes so education really is key to all of this and I would agree with everything that Dr. Gamble said additionally keeping in mind that the landscape is changing with these directed consumer pharmacogenomic test results and over time we have gone from absolutely none no did that variance could be we're FDA cleared to a slow changing now we have two two particular genes that can be used and we talked about those today so again just being aware that as as time changes as we're moving so is so is the target so just to also keep that in mind as well to communicate with other healthcare professionals and keep asking questions and joining in with groups like this to learn what's new and best for patients applying to patient care and for those of you interested in learning more about pharmacogenomics and educational offerings we do have a pharmacogenomics day as part of this week tomorrow and there are several sessions it's all focused on pharmacogenomics including one that we're going to be talking about a new pharmacogenomics learning series for healthcare professionals that's going to be free to everyone and offered for CE credit as well for a small fee for the credit but yes it be available for anyone interested to learn more about pharmacogenomics if you're interested feel free to check out the sessions tomorrow as well thank you so much Dr. Gamble Dr. Formia and thank you for all the work you're doing this on this you know education work that you're doing to help out physicians this is really fantastic and I just want to note that it is five after the hour and we are all willing to to hang out and then answer more questions so if you'd like to stay with us Tracy do you want to say anything about the time or should I just keep going with questions for right now keep going with questions okay okay so you're all welcome to stay with us if you have the time to stay and we'll have a bit more of a discussion so then someone is bringing up a really important point kind of coming back to the to the health equity issue and so this attorney is saying that one could argue that the provider initiated physician order testing approach actually improves health equity these tests are moderate in terms of costs around three hundred dollars and they don't require an office visit which is helpful for patients who live in rural settings or have disabilities that impact mobility on the flip side they tend to be accessed more by individuals with relatively higher education and familiarity with these types of tests and I'll also point out that while three hundred dollars is less expensive than a lot of other tests this is not covered by insurance and many other tests are covered by insurance so when we talk about health equity I would argue that this is not very accessible for for many folks so we have to keep that in mind too but would others like to chime in and say something about this I would agree that the consumer mediated or consumer initiated provider mediated is more accessible in one respect unless in another we really you know and really I think partly the accessibility is an issue of of do we even know it exists right for so many folks they don't even recognize that this is an option for them so it's partly an education thing you know and the more knowledge we can convey to both providers as well as their patients the the better off everybody's going to be above in that respect I would also argue that sometimes there can be language accessibility issues when it comes to these provider initiated and and sorry consumer initiated and provider mediated tests because sometimes you know first there's the education piece but then also the ability to to communicate the results in a way that makes sense culturally I think is a piece that it's more helpful to have when you have genetic counselors and genetic professionals within the community themselves that those that's a much better option yeah I would I would like to add on to that too I think those are all great points and especially the point about having an interpreter or having language services for the letter and for the you know the consult additionally the cascade testing which we know is really important for our case with FH but for many cases if it's something that can be passed on to biological children it's really important to have that discussion between a provider and a patient to say okay like do you have any biological children or what siblings or what your family how do you think they would feel let's provide a letter let's get that letter translated into these different languages for you so those are all ways of access and equity that we can as providers help out and then I think something that you know maybe hasn't been addressed particularly is there a lot of psychosocial concerns that can occur during you know any kind of testing but with genetic testing and trying to really figure out one's risk as well as communicating it to others and your support people and you know even for people who are doing direct to consumer testing if they do the kind where they find biological family that can also have a lot of impact emotionally and psychosocially that they bring to you at the provider that has to deal with a whole landscape of things so we want to really support and educate people that if you're going to be doing you know direct to consumer testing and in clinical genetic testing as well that you know to have a really good support from your provider and others. Thank you. Before we finish there's a couple of there's some summary points here that we would like to make to kind of close out the session and I think Dr. IUBA is is going to present this. Can you hear me well? I know I've had some microphone issues. So you know wrap up recognize that there is a difference between direct to consumer initiated decision mediated or providing mediated and clinical genetic testing and that only clinical genetic testing consumer-initiated position mediated or consumer genetic testing can be used right away for clinical decision making except for the only exception which the only exception is the pharmacogenomic DTCGT result that has FBA5N clearance which is the CIPPC-19 for clippy de viril and CETALEPRAM for 23andMe and SLCO1B1 Marcin-Vistatin test result. Now when a patient is interested in pursuing direct to consumer genetic testing or have pursued direct to consumer genetic testing figure out why they are why they want to pursue the test are there any underlying health concerns any personal family or medication history that clinical grade genetic testing is warranted recognize that individuals with limited family history may be interested in genetic testing to understand their health predispositions. When reviewing the DTCGT report determine what are you looking at and recognize that there are limitations to the test and there are limitations of the report that is issued by the direct to consumer genetic testing company. Additionally, patients may use their raw data put it at third party analysis interpretation services and those reports may yield from the results. If you have direct to consumer genetic test report in front of you and a variant is detected the result is positive. Look it up find out what does this mean does this mean it's a risk for genetic condition that they pass this on to their offspring is the supremacic result and determine whether or not confirmatory clinical genetic testing is warranted and discussed with the patient how they would like to proceed and whether or not understand that this could may not be covered by their health insurance. That being said any genetic test result is considered private information cannot be it's covered by the genetic information and discrimination act it cannot be accessed by employers except for certain for the federal government military and health insurance cannot discriminate against you but if you take out a life insurance disability or long-term policy they can look at your genetic test results that's why when you proceed with genetic testing it's useful to have a conversation with a professional with expertise in genetics to talk about all of those different aspects. That being said we're still here to answer questions and we really appreciate your feedback about the session. If there are no more questions in the Q&A we thank you for attending today we are very appreciative of your interest in direct to consumer genetic testing and how it applies to clinical care because it's not it's not an easy thing there's some complexity there. So thank you and we really encourage your feedback on the with the QR code. And please attend more events this week for lots more wonderful information about about medical genetics and genomics and stay tuned tomorrow for more info about the pharmacogenomics. You can go to the genome.gov website and look for all of the the relevant health care professionals genomics education week offerings are listed there. Okay thank you very much.