 Okay, I'm going to talk a little bit about the last eight or nine months of my life that's been involved with the issue of who gets to decide whether genetic testing is reimbursed or covered, which is actually the same or similar question, not the same but a similar question to who decides whether there's sufficient clinical utility in genetic testing to make it worthwhile for private insurance companies or for federal agencies to pay for it. This is a very complicated issue and I describe it a little bit like the old expression about making sausage. You do not necessarily want to know how it's being done, but you do need to deal with it. These are my disclosures of limitation. There's an enormous amount of rumbling and noise of various kinds. It sounds like elephants trumping through the room. Okay, I'm an officer and shareholder at Invite, which is a publicly traded company covered by SEC rules. I'm on the National Advisory Council for HGRI. I've been involved in negotiations with medical insurance companies to bring Invite a network so I can only speak in generalities about what is a heterogeneous and complex ecosystem. And most of what I'm going to be telling you is primarily anecdotal evidence based on many hours of conversation with various pairs and pair groups. So here's a sausage factory and he's saying, you're right, I really didn't want to know how it's made because that was incredibly boring. As far as anecdotes go, I love the fact that there's an enormous amount of feedback. Wait, wait, please. Okay, good. Feedback is better. Can you still hear me? Yes. Okay, good. So anecdotes and data. Here's two conflicting quotes. The plural of anecdote is data, Raymond Wolfinger, 1969 and 70. And after that, the plural of anecdote is not data with a number of people, all of which actually post date Wolfinger. And so you can take your pick as to whether you like Wolfinger's version or Brinner's version. But what I'm going to be talking to you about today are anecdotes. So who ultimately decides about whether genetic testing is going to be paid for? Well, ultimately, it's the payers, which also includes the federal payers. However, it's a very complex ecosystem of what I call four P's, which are payers, patients, providers, those are the positions, genetic councils, etc., and the purveyors. And that means the laboratories. But even this is just a very small picture of everyone who's involved because behind the payers are the employers who are a major source of the funding for payers. They cover their employees and have to pay for medical insurance. For the patients, they're patient advocacy groups that to a greater or lesser extent have an impact on this ecosystem. For the providers, I think professional guidelines are a major channel by which providers have input into the system. But also both laboratories and providers have a crucial role to play in evidence development. And of course, patients and purveyors can often work together to attempt to develop evidence. And also providers, by constantly ordering genetic tests that they think are medically indicated, even though the insurance companies consider them to be investigational, once that it becomes a tsunami of denied claims, the insurance companies have to start paying attention and taking notice of what's going on. So you can see that there's a lot of interaction among the four P's. So payers, they're very homogeneous in their level of knowledge and sophistication. I've been actually quite shocked by how little some people in tremendous positions of authority within some of the very large insurance companies how little they know about genetics or genetic testing, while in other cases they're fairly sophisticated. Some of the payers use Palmetto Maldiak system as an evaluation system for deciding on whether a test has analytic and clinical validity and to some extent clinical utility. Private insurance, there are some tech assessment groups, but for many of them they consider these to be either advisory or they don't pay any attention to them at all. And it's entirely up to the private payer to decide that. I heard repeatedly from my conversations with payers that they feel they've been had, or they've been burned in the past by new technology in general and from laboratories in particular by code stacking. And of course this all went away with the change in CPT codes from particular procedures like we're doing 15 PCRs and a DNA extraction and a gel and a this and a that, to we're doing this test or that test or this panel or that panel. But this is really just an in its infancy. And anyone who wants to know how infantile it is, just take a look at the most recent Medicare announcement on what they are deciding to do about hereditary breast and ovarian cancer panels versus the testing of just two genes, BRCA1 and 2, which are part of some of the larger panels. There is not a lot of logic and not a lot of rationale in what they're doing. They're very worried about the cost of testing, but even more so on the misuse of test results, in particular, whether VOSs are going to trigger unnecessary and expensive downstream testing and procedures. I heard this over and over again that they're afraid to open the floodgates to testing, first because they think it's going to cost them a lot and to some extent they're fighting the last war because of the code stacking and the fact that genetic testing has cost thousands and thousands of dollars in the past and this cost has now come down substantially and will continue to come down. But more so than that, they're worried about the downstream radiological tests, procedures, fine needle biopsies, electrophysiological tests and on and on and on that may be triggered by genetic testing that is misinterpreted or misused by providers who are not that sophisticated in using genetic testing. In addition, the payers do respond to professional guidelines. They want to see them and they also respond to the pressure of a tsunami of unpaid claims. If they're seeing over and over again that the providers that have patients in their network who are ordering a certain test over and over again and are writing letters of medical necessity, they will take notice, but it takes hundreds to perhaps even a thousand such before they will consider changing their policy. They are under financial pressure from the employers who wish to keep the health premiums down, but also I should mention that the employers also want to be also have a certain amount of market power with the payers and that the payers do want to be able to keep these employers in their system, not have them to go off and contract with another payer and so being responsive to those employers, not just keeping costs down, but also giving their employees something that the employers consider to be a perk is of value. They are looking to partner with labs and with others to provide what they consider utilization, management of genetic testing. This is sort of an interesting new development based on the very long standing experience with utilization management on the pharmacy side. They're interested in trying to apply that to genetic testing as well. I think there are many laboratories that feel a little bit uncomfortable with putting themselves in the role of utilization management for payers because the laboratories want to stay firmly on the side of or to be in the camp of the providers and the patients. They don't want to be viewed too much as being direct allies of the payers. At the same time they want to work with payers and have the genetic testing be something the payers are comfortable with. This is a tango. This is a dance that is going on now I think quite extensively. Also the payers are experiencing a lot of financial stress from the Affordable Care Act and they have a mandate to reduce administrative costs from the Affordable Care Act. I think you can see the recent wrath of mergers and acquisitions that are going on in the payers with SIGNA and UMANA for example. I think it's a clear indication that the payers are starting to consolidate and grow in size in response to the financial stress that they're feeling. Payer coverage with evidence development. I hear this over and over again from people who say why can't the payers help us develop evidence. I just want to give you a direct quote from the head of which insurance company but a chief medical officer at a very large insurance company that's not our job to finance your business development. Now on the labs where the payers they survive by selling tests and so there's a financial incentive to develop evidence but very limited resources to do so. I was asked specifically at a meeting of a group of payers I won't say which where I was describing our attempts to provide genetic testing using genes that had clear clinical validity that these were not genes of unknown significance and that these were genes in which there was evidence that there was not only clinical validity but clinical utility it would change provider behavior to have the results of this genetic testing. And one of the people in the audience said but how many studies have you done to show that there's economic benefit to the payer community for doing these tests. The suggestion being the implication being that it was the laboratory's responsibility to carry out medical economic tests of experiments medical economic trials of genetic testing in order to demonstrate to the payers that the payers would be saving money if these tests were done. And I think that there are very few payers that can do that and of course there is a perverse benefit of patent protection for testing that it did incentivize evidence development. I you know maybe ACLU God forgive me for saying this but I think it is true that to a significant not complete but to a significant extent a lot of the evidence that was developed over the last 20 years on the role of genetic testing in the management of redditary breast and ovarian cancer and breast cancer developed because of resources that were put into this by a laboratory that had a monopoly on that testing and were able to monopolize on that monopoly in their pricing and their profit. There's also I think among the labs an unfortunate tendency to claim low VOS rates and I think they're doing that either from hubris thinking that they can really interpret rare variants about which we know very little better than we really can or also using it unfortunately I think as a marketing ploy and this really this over calling really feeds payer paranoia. They are upset enough about VOS's and their misuse they're particularly upset when the VOS's are actually being interpreted as likely pathogenic or pathogenic which really does trigger a lot of downstream costs. I just want to point out for example this article by Andresa Dallanjama a very I think influential and interesting article that arose out of the eMERGE group where there was a discordance between long QTS genotypes and the EHR based phenotypes in an unaffected cohort from EMR and that this was designed to simulate incidental findings of long QT genotypes and the idea was to ask if you do stumble upon genotypes that appear to be pathogenic or pathogenic in a group of patients who ostensibly were not referred because of what sounds like a long QT type phenotype or event what do you find? What I find and their interpretation was that there was very low predictive value of the genotype in these unaffected individuals by looking at the medical record and seeing whether these individuals have anything to suggest a long QT they actually found that they did not and that this was probably due to a lack of penetrance but I'd like to point out that it could also mean misclassification of the variants by the three laboratories to whom the variants were sent for interpretation. There could also be false negative phenotyping based on the medical record the medical record has its limitations however I think the misclassification of variants by the three laboratories really needs to be kept in mind as a possibility. For one thing there were very few of the variants in which there was complete concordance on the interpretation and I think we all know that this is a major challenge in the field and it causes the payers I'd say real heartburn. Now the providers or academic researchers they play an extremely important role in evidence development assessment partnerships with labs have and can be very fruitful particularly in clinical utility and medical economic studies that the labs are in no position to carry out themselves they do not have direct access to the patients and these are and economic studies require having your fingers into the medical records and the ordering and the billing of these patients and there's an alphabet soup of NHGRI and NIH initiatives you're all aware of they're very valuable but I have to say that for many of the payers these carry the taint of the ivory tower about them and I think Terry went and spoke at a group recently I think she was very well received in describing some of the NIH initiatives so I think this is a changing landscape in there the payers willingness to pay attention to some of these sorts of studies. I have two minutes left and I'm going to say this underscores the special role of integrated systems in evidence development places like Geisinger or Intermountain Kaiser where they can gather the sort of economic data that I think is necessary and providers I think we have a real problem with professional guidelines we need up-to-date professional guidelines that speak with one voice and any of you who have been working in this field on the cancer side versus the cardiology NCCN is really an important although it's expert opinion to a large extent whereas in cardiology genetics there's a cacophony of guidelines some of which are more than five years old and it's much harder to make a case for guidelines on the cardiology side patients I find often have an adversarial relationship they may experience substantial bureaucratic procedures and a string of denials despite paying substantial premiums and fundamentally I think much of this arises from a lack of agreement between patients and payers as to what constitutes clinical utility these two groups have a very different view so I'm ending here just to say I think there's a complex ecosystem of the four P's and there is no one pathway to the development of reimbursement for genetic testing it takes a coordinated effort which is at this point not very well coordinated and with that I'll stop thank you Great thank you Bob Rita's going to type what I'm saying quickly so we don't type this Rita it's too long so we asked Bob to speak because we felt it was important for everybody to understand the ecosystem that we're actually working in as clinicians because these tests can't be used in large degree unless they can be reimbursed and we need the evidence to be able to do that so we wanted to give you that perspective I think we can type and ask one question or two Wendy make it simple and quick and then Callum so do you think it would be possible for payers to get interested in a possible new type of insurance product whereby people who have enough means to drive here and oh she's typing it okay so new new insurance product negotiated price for people who can pay interest or not by payers Rita is typing yeah well for payers to get new insurance product negotiation prices to pay well I think there's a couple of things on the horizon one of course is that the cost of the genetic testing is going down and that's the impact of next generation sequencing and improvement in laboratory and software the other is I think there is a role to play in patient pay where you basically bypass the payers and set the price so low that patients believe that they're getting real value and they are willing to pay this cuts out people of low socioeconomic levels this cuts out people who do not have available resources and for them I think abandoning the payers in order to have patient pay is I think an abandonment of an obligation that we have so I do think it's possible to get I mean for example the BRCA 1 and 2 test now being offered is a well over $2,300 reimbursement from Medicare whereas a panel Medicare is offering to pay something in the high $600 so there's already been a huge drop in the price and I think this is only going to continue however getting the price down is only one part of it cleaning up the VUS issue and relieving them of the worry of downstream is still a big issue thank you wait a second hunt and pack fifth p pharma about combining genomics with therapy oh yes quite a bit and excuse me just a second I'm sorry I just have to step for a second yes we spoke into pharma about combining genomics with therapy they're obviously very interested in this and I think we really need to start a movement in the rare disorder community where we make it very clear that patients with rare disorders should know their genotypes I think the possibility of having crossover of drugs from one disorder to another because of the mutation in that gene rather than which gene it is is a real possibility and this is something that pharma is really quite interested in great thank you thank you all bye bye now bye all right well that was interesting thank you for your patience we'll send Bob flowers later so yeah that's right so I think at this point did you want to close this Carol? yeah sure I think we do have the next panel so and we're pushing past noon so I think we'll go ahead and break for lunch we'll reconvene at at 1 p.m. and Rex will take over the chair we'll have a panel discussion and lots of time to follow up on this presentation and the questions that may not have been dealt with in a previous session so thank you to everyone for speaking and for commenting and we'll break for lunch