Video and Transcript Available - FDA Changes to Laboratory Developed Test Regulation: Livestreamed Expert Panel

What: Live from the annual conference of the Association for Diagnostics & Laboratory Medicine (ADLM, formerly AACC), experts will discuss how FDA oversight of laboratory developed tests will hinder patient care.

Who: 

         Geoff Hollett, PhD, American Medical Association
         Meghan Delaney, DO, MPH, Children's National Hospital
         Sarah Braswell, Caregiver and Patient Advocate
         Dennis Dietzen, PhD, DABCC, FADLM, Washington University School of Medicine
         Olivia Braswell, Patient

When: July 30, 2024 at 5:30 PM ET

Where: Newswise Live Zoom Room (address will be included in follow-up email)

A laboratory developed test is a new or significantly modified test that is developed, validated, and used by highly trained laboratory medicine professionals within a single clinical laboratory in response to a specific patient care need. Most laboratory developed tests are created because no Food and Drug Administration (FDA)-approved test is available, and they are often used to diagnose rare conditions, such as inherited genetic disorders in newborns.

Laboratory developed tests are already subject to rigorous oversight by the Centers for Medicare & Medicaid Services. However, the FDA has now released a final rule bringing laboratory developed tests under FDA oversight as well. This duplicative regulation will force many labs to stop performing these essential tests, which could harm patients by significantly delaying diagnoses and care.

In this special session, experts from ADLM, the American Medical Association, and the Children’s Hospital Association will discuss how the FDA’s new rule will impede healthcare professionals’ ability to provide quality patient care. Attendees of this session will also hear from a caregiver and patient advocate on the importance of laboratory developed tests in diagnosing medical conditions. The session will close with the speakers taking questions directly from the audience. 

Transcript

Announcer: Please welcome the President of the Association for Diagnostics and Laboratory Medicine, Dr. Octavia Peck-Palmer.

Dr. Octavia Peck-Palmer: Thank you. Good evening everyone, and welcome to our special session on how FDA oversight of laboratory developed tests will affect patient care. I am pleased to welcome representatives from the American Medical Association and the Children's Hospital Association and two special patient advocates to today's conversation. We are all here to share experiences with patients having a life altering diagnosis with laboratory developed tests like the stories we just heard in the video. And it's because of stories like these that we, as ADLM, are passionate about the science and the advocacy required to bring the patient's perspective to policy makers, regulators and other medical professional organizations and the public, most labs are aware of and have been working within their institutions on how to respond to the FDA final rule on the regulation of laboratory developed tests and this rule places an enormous clinical, financial, and human burden on clinical laboratories. ADLM believes that if the ruling remains unchanged, it will severely reduce patient access to essential testing. It will take our continued collective action as a medical community to ensure that appropriate patient centered regulations govern these tests and in the future. As a quick reminder of how we got here, I wanted to share with you a few of the notes on past FDA activities. In 2022 the FDA sought and failed to obtain congressional authority for overseeing laboratory developed tests. This led to them publishing a proposed rule in October of 2023 claiming oversight over laboratory developed tests. Then, of course, in May, the FDA published a final rule asserting its authority to regulate laboratory tests as it currently stands. The rule is meant to be phased in over four years. This started July 5th, 2024. ADLM has been actively engaged in attempting to work with the FDA and with Congress to mitigate the negative impact of this FDA rule on patients in the United States. And we know that laboratory developed tests are already subject to rigorous oversight under CMS and ADLM believes that any reform to laboratory developed tests should be made by updating CLIA legislation. However, as already noted, the FDA has been trying for years to place this test, these tests under dual FDA and CMS oversight, despite the fact that this additional regulation would be duplicative and burdensome for clinical laboratories. As we've continued to work for patient access to vital tests, it is important for us to have some evidence that we can use to reach out to regulators and policy makers. And to that end, in early April, we began our first of a series of surveys that have gone out to labs across the country to get more detailed information on just exactly how will the FDA regulation of laboratory developed tests impact patient care. We have concluded two surveys so far, and the third is currently live. You will see a slide at the end of this presentation with details on how to access the survey yourself. I wanted to share some key findings from these first two surveys. First of all, many labs don't have the staff or the financial resources to comply with the FDA rule, and because of this, many labs are likely to discontinue or scale back the number of types of laboratory developed tests they perform. And of course, it will lead to patients having difficulty accessing vital testing. So specifically, what will that mean for patients? Well, that is what this session is intended to uncover. And today you will hear from colleagues in the physician community on how the FDA rule will impact physicians' ability to care for their patients, and you will learn from our colleagues working in children's hospitals about the most vulnerable of our patients, children, and how they will suffer under this rule. And we will also have a patient advocate who will share her story about the important role of laboratory developed tests and how they played a role in diagnosing and treating her own daughter's condition. We'll end with a panel discussion where you can ask our speakers and panelists your questions about the FDA role and its impact. Now I'm pleased to turn the mic over to Dr. Jeff Hollett of the American Medical Association, who will share the physician's perspective on how the FDA rule could impact patient care. Dr Hollett is a Senior Science Policy Analyst. Please join me on the stage.

Dr. Jeff Hollet: Hello and thank you to ADLM for the invitation to come and speak on such an important topic. My name is Jeff Hollett. I'm a Senior Science Policy Analyst with the American Medical Association. And first, I'd like to just begin by reflecting on who I'm here representing. So the American Medical Association is the member organization for America's physicians. That means we have members in every state and in every practice setting that you can imagine: rural, urban, academic medical centers, federally qualified health centers and on. In the context of LDTs, this also means that our members represent specialists across the spectrum. We represent the primary care physicians that use LDTs to begin a patient's diagnostic odyssey. We represent the specialists who use LDTs to guide cutting edge care. And we also represent the pathologists, where LDTs are truly the meat and potatoes of what they do every day. So when we're talking about LDTs and our membership, the main theme that comes up over and over and over again is uncertainty, one of the worst words that can come up in the clinic. I don't know. Maybe these words really hurt our patients. And one of the quotes that really stuck with me in discussing LDTs with our members is that it's a tough time to be a physician, but it's a great time to be a lawyer right now. So when we're talking to our members, we get a lot of questions like, why now? We know that laboratory testing is safe and it's effective, and it's overseen by highly trained board certified physicians and other laboratory professionals. You know, for those that have been following this issue for a while now, you know that this is not a new issue, and that Congress has been looking at laboratory oversight modernization for years, with the valid and vital act and some of the omnibus bills that have been going through Congress in the past year, but comparatively, the FDA rule was developed at lightning speed with minimal input from the public. And I think some of the folks in the policy space can get, you know, a little jaded and say that Congress isn't going to pass anything. It's so sclerotic. You know, everything's a partisan battle. But if you actually look at what was going on around laboratory modernization, you know, this was a bipartisan issue. There was support in the Senate and the House, among Democrats and Republicans that some laboratory modernization may be beneficial to patients, but the reason why it has struggled to get across the finish line isn't because of some partisan fight, but instead because this is an incredibly complicated issue that needs to be done deliberatively and slowly and making sure that people don't fall through the cracks, and that our patients get the care that they need. Also, as we emerge from the COVID pandemic, we often talk about public trust, and what does it mean for medicine to be trustworthy? And one of the key concerns that our members are telling us is, what message does this rule send to the public? Can you trust the test that your physician is currently providing to you? And we think that this is a really dangerous message to be sending. Additionally, enforcement discretion is not a rule. It can change at any time. And in fact, the FDA has already argued that they have been exercising enforcement discretion over LDTs since the 70s, and we all saw how quickly that they changed their mind on that in the past year. And for physicians who are trying to open their practice or figure out where they're going to practice, you know this, this has a lot of implications. And anytime there is uncertainty, anytime there is a question of, oh gosh, I don't know, is this going to be covered? Am I out of compliance by providing this test? Is this test even going to be available to my patient? Anytime those questions creep into the physician's head, that means that there will be abstention, while some will be able to have the resources to figure out and navigate this rule, many will not, and that means that tests will not be offered. Patient care will get worse, and practices will close. I will also note that this isn't just a rule that's being developed in a vacuum. Physicians are currently facing an existential crisis for things like burnout, where one in two physicians is saying that they have experienced significant burnout and a decrease in their satisfaction. This also is caused by things like Medicare payments going down for the fifth time in a row, or for other entities such as regulatory agencies, but also increasingly, judges, legislators and payers encroaching into the clinic and telling physicians and their patients what they can and cannot do. These all lead to substantial dissatisfaction for physicians, which trickles down to patients. There's also significant consolidation in the medical community right now, with over two thirds of all hospitals and nearly half of all physicians being associated with an increasingly smaller and smaller number of large healthcare providers, meaning that smaller practices are rapidly going extinct. So moving forward, some of the unanswered questions that our members and the AMA have is, will the LDTs rule allow for physicians to provide the highest level of care to their patients. You know, LDTs, as they formerly stood, allowed for physicians to practice at the top of their license, similar to how a physician is able to prescribe a medication off label if there is evidence for its use. LDTs allow for physicians and laboratory professionals to diagnose and to treat when there is evidence for their use and FDA approval is far too slow for the rapidly evolving rate of diagnostic medicine. It only takes a short walk around this expo hall to see how rapidly there are developments in the technology and the biomarkers that are critical for patient care. One of our members relayed to me that in the time in which their laboratory submitted a gene panel test to New York state regulators for LDTs approval, by the time they received their approval, they were now on the eighth generation of this test and dramatically altered what genes were offered, what populations were being offered, and the diagnoses associated with this, meaning it was far, far too slow to be responsive to the needs of our patients and to be aligned with good science. We are also concerned about a physician's need to serve their communities. FDA approval is slow, but it's also expensive, so only the most profitable tests are likely to be pursued for FDA approval. What that means is that people that look like me are going to do really well, people who are an adult, people of European ancestry and people with more common diseases are more likely to be served by FDA approved tests, and more likely and less likely to require an LDTs. We're also concerned, like I mentioned before, around trust and what it means to be trustworthy, and as smaller as smaller labs close, that means that samples are going to be sent out of local communities and more and more towards larger, faceless entities that may have questionable track records in the communities that they're seeking to treat. We've seen over and over again out of the covid pandemic that the most trustworthy person in medicine is an individual's personal physician, the person that sits in the room with them, the person that sends their kids to the same school as them, the people that understand what their life looks like, and they are far less likely to be interested in sending their incredibly important, sensitive samples to a company that they don't know anything about and also doesn't know anything about them. And then finally, they're really concerned about the dollars and cents. Are they going to be able to keep the doors open and the lights on? Patient care costs will go up. Practice Management costs will go up. Risk to physicians and their patients will go up. And as such, burnout will also go up. As was mentioned before, there's also significant concern over who is going to be doing this regulatory work, while some of the folks in this room may feel that they have a good grasp on it, there's not exactly a large workforce out there that's ready to go, and the small and highly specialized group that's going to be required are going to be incredibly competitive, and many of our smaller practices are concerned that they are simply not going to be able to afford regulatory professionals to help them navigate this thicket. And I'll close by reflecting on the importance of advocacy, so for groups like ADLM and the American Medical Association and the importance of your voice to be represented. While there were some carve outs that were made in the FDA rule from October to May, they weren't great, but they were made because of voices such as your own. And this is unlikely to be the last time that we hear anything about LDTs, so I encourage folks to reach out to their members of Congress, to the associations and organizations that they belong to, to make sure that your voices are being heard, because it is incredibly important. Thank you.

Dr. Peck-Palmer: Thank you. Dr Hollett, it is now my pleasure to introduce you to our next speaker, Dr Megan Delaney, please join us on the stage. Dr Megan Delaney is the chief of pathology and immunology medicine and the president of the medical staff at Children's National Hospital in Washington, DC. She is also a professor of pathology and pediatrics at George Washington University. Today, Dr Delaney will be sharing her perspectives on the impact of the FDA rule and how it would play out on children's health. And as a representing voice and a physician, she'll share those thoughts. Thank you.

Dr. Megan Delaney: Thank you so much, and thanks for joining us this evening for this special session. So, children's hospitals, let me begin there. So, children's hospitals account for fewer than 2% of hospitals in the United States, but they care for over one half of children admitted to hospitals, and in particular, children's hospitals provide care for the most serious illnesses that affect our children. The other thing I want to talk about with the children's hospitals, these are patient centered research oriented institutions, and they lead discovery in pediatric health. They really form the cornerstone of innovation for children's medicines, drugs and laboratory tests. They are nonprofit institutions with a charitable mission and a duty to serve the children of our entire nation and our referral centers from the community surrounding them. Children's National Hospital, where I am, is one of the oldest pediatric hospitals in the United States. It's over 150 years old. And at Children's National I run the laboratory. Let me tell you about the laboratory. So in a pediatric laboratory, it looks very similar to all laboratories and hospitals around the country, but we have to specialize in many different ways to take care of patients that are not adults and that are spanning the age range of human development. So as a physician, my job there is to make sure that we have all the accurate testing that our children need, and these span from having IVD approved tests that we've purchased from manufacturers, IVD approved tests that we've modified to be able to use in children, and then LDTs that we developed de novo for our patient population. And in my experience, in my years of running laboratories in pediatric hospitals, there's no difference in how these tests perform for our patients. They're accurate and they're effective for our patients and for our physicians. So I really want to focus tonight on the impact on children. So children, as we know, are not just little adults. They're constantly growing and developing, and their health care needs are different than those of adults. Medications, therapeutics, devices and equipment, all are different if you are a patient who was just born and came to this world, or if you're 14 years old or 7 years old. How old you are, how large your body is and your physiology are all different for all different age ranges of human development. Also, thankfully, most children are healthy, but when children have diseases, they're often in the category of rare diseases, and these types of tests that we need for these diseases are often LDTs, and that's because there's nothing available on the market. According to the GAO, half of the estimated 30 million people in the world, in the US, I'm sorry, the US with rare diseases are children and many pediatric related diseases and diagnosis there are no FDA approved tests. So LDTs fill this gap because there are no other tests available to monitor and diagnose them. Over the history of our country and of modern medicine as it's developed, children have often been left behind in the development of new pharmaceuticals, which are usually developed for adults, and the same situation exists for laboratory tests through the small market and highly specialized nature of pediatric disease. In addition, the relatively small population and unique aspects of studying children are barriers to doing clinical large clinical trials to develop new tests. So children's hospitals like mine, we fill the gap with pediatric diagnostics by either developing tests from scratch that are needed for our patients, or, and we have to perform extensive validation work, including determining the reference range for these tests for all of the different age ranges for the patients that our physicians treat. I'm going to talk about a couple of examples. So for an impact on children, one that's very important is tests for diseases and diagnosis that are related or discovered in infancy and childhood. Now our video, you heard about newborn screens. So after a baby is born, they all have a newborn screen. In the United States, each state has its own newborn screening test, but babies are usually born in adult hospitals, where the mom delivers the baby and then that newborn screen is sent. But as you heard in all of those examples, they also need a confirmatory testing, and they need it right away. And what often happens is that confirmatory testing actually is sent from the adult hospital to a pediatric laboratory like mine, where we can perform that critical confirmatory test so they can make treatment decisions. The FDA rule will not allow pediatric laboratories to support nearby birth hospitals with confirmatory pediatric lab testing without premarket FDA approval. In addition a few more examples, so, for tests that are not done by adult focused laboratories. So the most common cancer in children is leukemia. It's a blood cancer. And the flow cytometry test for leukemia diagnosis is done at my hospital every day, and we can render that diagnosis within hours, so that the Pharmacy can compound the chemotherapy and start the therapy for that child that day. These kinds of tests are all LDTs. Also tests for pediatric rare and orphan diseases. So sticking with the idea of pediatric cancer, one of the most common pediatric cancers in toddlers is called neuroblastoma. And the test that we use to monitor that disease, and you can see it here with a long name, it's a VMA HVA test. We use that, we'll… very, very few labs in the country perform that test, but pediatric cancer centers will perform that test. So while there are exclusions in the FDA rule, these enforcement discretion for unmet needs and grandfathering are temporary measures. So what my concern is that as the laboratory equipment is upgraded, like we all do every few years, and supplies change, or an IVD approved test comes on the market, pediatric laboratories will be left in a place of uncertainty if their tests are no longer under enforcement discretion anymore. So the pediatric laboratory community has really been coalescing around their concern for their patients with the new FDA rule. Many of us got together and tallied up how many tests we have, and it's a great number. Most of us offer 5 to 15% of our performed test types are LDTs, and some are more than 20%. However, it's important to also think about that. Doesn't sound like that many, but getting them through the FDA as approval process would be an enormous burden, and this is because you need to understand where pediatric health care is paid for in the United States. So the Medicaid, on average, provides health insurance to cover half of the children at the Children's Hospital's patients, and depending on the payer mix, it might be closer to three quarters to 80% of children in a region might be covered by Medicaid. So many of these LDTs that I'm talking about that we run might be reimbursed by Medicaid for $9 to $25 and we might only run them a few 1000 times a year. So to think about that and then put it in the context of potentially needing to put them through an FDA approval process, or even just the first parts of the FDA approval process that will start in years one and two, is a significant burden for these tests that we can perform at low cost to make sure our patients have the diagnostics that they need. So in addition to being a major payer for children's hospitals, Medicaid is really the backbone of children's health care, especially for children of underserved populations. And we also think that this will therefore have an outward, a larger impact on Medicaid enrolled children, and this will already exacerbate the healthcare inequities by populations. For example, black children in America are significantly more likely to have elevated blood lead levels compared to white children, but access to accurate laboratory testing for lead, is an LDT as well, and the only confirmatory tests that can measure this are LDTs. So the pediatric laboratory community has assessed the impact, and we are very concerned about how this will eventually, over time, decrease access both at hospitals like mine, which is a referral center, but also at medium or smaller sized hospitals that might care for the local pediatric population and then eventually refer when they need to higher level of care. If you're a smaller lab, it's going to be even harder to meet these regulations. So in conclusion, I am concerned about the long term impact the FDA rule will have on laboratories that perform testing for children in the United States. This rule is going to slow innovation that supports new therapies and overall decrease lab test access for children. And I believe that we must work together to find a way to improve healthcare in America for our children and not make it harder to provide. Thank you.

Dr. Peck-Palmer: Thank you. Dr Delaney, I am very happy now to introduce a special speaker in our lineup for today. This is Sarah Braswell. Sarah Braswell is a parent advocate and works with multiple regional and global advocacy groups for special needs children, especially those with a focus on Down’s Syndrome. Sarah is a devoted wife and a mom of two wonderful children, Olivia, her seven year old daughter who has Down’s Syndrome and BJ, her six year old son. Professionally, Sarah works in learning and development for a leading tech company in the Washington DC metro area. Please welcome Miss Sarah Braswell to the stage.

Ms. Sarah Braswell: So I'm in the ER, the OR, sorry, and my first child is being delivered. And the doctor says it looks like she has Down's, before I have even laid eyes on my child. And that's my first start to the journey of my daughter being diagnosed with Down’s Syndrome. She was born in an adult focused hospital where they outsourced most of their pediatric needs. She did get the typical newborn screenings. Then they wanted her to have a diagnosis for sure of Down’s Syndrome. So they called the pediatrician, our pediatrician that we have selected said, “I don't work with kids with special needs.” Don't even have an official diagnosis yet. So then we're off to a great start. I had to find another pediatrician who then performed the karyotype test and we received a diagnosis of trisomy 21, thirteen days after birth. And I do want to note that I did the NIPPIT test and the only results that came from that was a genetic specialist asking if me and my husband were related. It's a whole other story. 

So how has this diagnosis impacted me and my family?

First, it's a complete mental shift. I had to say goodbye to what I envisioned for my child's life, for our life, and mentally prepare myself how our life will move forward. 

Next, DIY education. Down’s Syndrome is not one of those diagnoses that you can fit in a box, and all the children are going to be the same, the issues that they're going to have are going to be the same. It's just not there. I took it upon myself and Google to figure out what is Down’s Syndrome, how is this going to affect my child, how can I advocate for my child? And you know that is a rabbit hole in itself, but there's not anything out there when you get that diagnosis for parents on next steps. So after I did a little DIY education, the doctors, the therapies, and more tests started coming in. 

With Down’s Syndrome, we know they have cardiac issues. We know that they are delayed. So you need PT, OT, speech, feeding therapy, you name it. We have been there with every specialist and every therapy. And finally, a big impact I was not aware of was financially. 

You have to pay every time you go to the hospital. My insurance only allowed two therapies a month. She needed two a week. I had to take off work to take her to therapies, take her to the specialist. There's things where I get to specialists and there's a charge. At this point, I don't even know what the charge is. I'm just paying it because it's my child. There are my spouse's impacts financially where eventually we decide that for our family that I wouldn't work. So naturally that's an impact as well. And the last thing about financial impact I want to mention is - children with special needs are not allowed to have a lot of money in their account when they turn 18 if we want social security. So even as I'm trying to advocate for my child and I want them to make sure that they're set up in case something's wrong with me, I can't even have more than $12,000 in an ABLE account, which is special needs accounts, which will always be taxed. 

And then finally, I said, okay, I always heard people with Down’s Syndrome have a less life expectancy, let me get life insurance. She was denied life insurance, and they told me blatantly, call back in 10 years and we'll think about insuring her. 

So the next way that the Trisomy 21 diagnosis impacted us was as services that she would get. 

So the screenings. There's also what Children with Down’s Syndrome, we hear a lot that the viruses and bacteria that they get – impact them really fast. So anytime we need any type of blood work when she was sick, everything was stat. Everything was always fast. So I don't think that's anything official, but that's just how it has impacted us there when we need a diagnosis. 

Children with Down’s Syndrome also have a 10 to 20% increase in getting leukemia. So one time, one to two times a year, if we do blood tests, the CBC twice a year, we test for cancer, we test for thyroid issues, we do immunization titer tests because the immunizations don't work as well on children with Down’s Syndrome. So we do that annually. AAI tests for the next and multiple sleep studies every year. 

Also government assistant programs. 

So respite, simple things like needing diapers. I had to get on Medicare to get her diapers to fit her because she had outgrown the typical diapers you find in Target. A lot of those are based on income. And it's really based on state, but that can affect you as well. But again, I wouldn't even have those steps to take if I didn't have that diagnosis. 

The level of care. So even though she has this diagnosis of Down’s Syndrome, I still have to go annually and tell them like what she can do, what she's able to do, what she can't do, her level of care, just for those services to continue. But again, I wouldn't be able to even have those services available to me without that initial diagnosis. 

Education. You automatically get IEP with the diagnosis of Down’s Syndrome. But with that IEP comes a blanket, just a blanket IEP, which it doesn't necessarily mean it meets her needs. So sometimes it's not always the good things, the services you get, the IEP is great, but people just kind of check that box and say, okay, she has Down’s Syndrome, she's going to be delayed versus really looking at her abilities. 

How this diagnosis has impacted our state today and her future. So as Octavia mentioned, I have another son. Automatically, I had more tests. I can't even tell you how many tests I had or what they're called, but I was treated as this child is automatically going to have Down’s Syndrome. Also, they put me on steroids right away. They made me have a C-section and had to be delivered early, all because my child, that had nothing to do with this current child, had Down’s Syndrome. 

The siblings in my family are affected in a way where she does have Down’s Syndrome and we realize that. So a lot of our world is her world. How we interact, how we go to restaurants, if you know I'm chasing her because she's a eloper, that my son is affected by that. He might not get the attention that he deserves or needs because of that diagnosis. 

And lastly is life planning. As I mentioned before, we don't have life insurance for her right now. We're trying to figure out like what's her care? What is it going to be next? Because she does have Down’s Syndrome, and I'm not going to be here forever. And that's just scary. So coming up with a detailed plan with a lawyer - when my child's only seven, That's not to me typical of what most parents have to go through. But with this diagnosis, I feel that's very important for our family. 

And also just our day to day activity. It's summertime right now. What camps can she go to? Because it's limited in that way. Are we going to be able to have a teacher that's going to work with her because she has Down’s Syndrome? I have to get special access to even get on the plane to come here. So all those things impact our daily life and will continue to impact our life. 

So thank you for having me today. 

I'm going to pass it over to Octavia, the ADLM president, to start the panel discussion.

Dr. Peck-Palmer: So I just want to say before we bring out our next guest, that thank you so very much to the speakers. Thank you, Sarah, for being so open that your diagnosis, which came about by a clinical laboratory test, then has continued to lead you through how your family is now navigating life with Olivia and how special Olivia is. 

Now I'm delighted to welcome the chair of ADLM's Policy and External Affairs Core Committee, Dr. Dennis Dietzen. And later we will welcome our youngest and our cutest panelists and patient advocate, Olivia Braswell. 

Dennis, please join us on the stage. 

Okay, before we get started, I encourage you to send us your questions by using the QR code that you see on the screen. I'm going to get my questions. 

All right, everyone's got the QR code up. I'll go ahead and get started. 

And I'll start with you first, Dr. Hollett. You shared with us that you represent a host of individuals who understand the impact that the FDA regulation will have on patient care. Extend out to me more about the work that your group is doing to advocate, and give us some examples in which we can continue to advocate.

Dr. Hollett: Gosh, I mean, there are significant opportunities. I mean, the major one that I would focus on is communication to the regulators and those that oversee the regulators. So that being the FDA and to Congress. While there isn't anything active in Congress right now that would deal with LDT regulations, there absolutely have been indications from some members that there is an appetite or certainly concern over the way in which LDT regulations were rolled out and how Congress had been historically looking at it. 

So for folks in the room or for folks that are engaged in policy and advocacy. Those would be the two obvious places to start. There are significant concerns and there are lots of folks receptive to listening.

Dr. Peck-Palmer: Thank you. I'm going to move to Dr. Delaney now. Dr. Delaney, you actually lead a laboratory that performs testing, laboratory developed tests. Can you talk to me about the experience of the individuals that develop the laboratory tests? And then how do we actually voice that information to the FDA or our policymakers so that they truly understand that these are individuals that are fully trained to do this work.

Dr. Delaney: Yeah, thank you. I think some of those individuals are here in the audience today. They do an amazing job. So laboratory staff, all of the managers and the leadership of a laboratory like mine are trained and certified to know how to make a test when we need to, or to modify a test. And really, it really comes back down to validation and to making sure that the test performs to the specifications that our patients need. And that takes a lot of work. I think one of the parts about getting people outside the lab to understand what the lab does, is to invite them in to show them - I haven't ever done a lab tour that someone didn't leave going, that was the coolest thing I've ever seen. Because people know about getting their blood drawn or giving a sample, But then what actually happens and how the answers come, really bringing that to light I think so to the advocacy inviting people to do tours and to see how a laboratory works. We are very regulated, we take great care that everything, all of our results are accurate. And whenever we sense any question, it's investigated to its fullest and remedied. So I think that people in the United States should feel great about laboratory testing. And I do have significant concerns about adding additional burden of regulation, because I do not think it will improve the quality that's already very high quality laboratory testing.

Dr. Peck-Palmer: I want to piggyback upon that because someone in the audience, Dr. Delaney, said, “for pediatric tests, has there been a review or a breakdown of potential FDA risk classifications to understand the impact?” So if we do not have a specific test, has the FDA actually identified what the risk would be not being able to diagnose this disease?

Dr. Delaney: I am not aware that they have. I will say that the rule from October till its re-release in May, there were some clauses added that did appear that the FDA was trying to improve things for pediatrics because it is recognized, especially if you look at drugs in pediatrics. It's what we're about to embark on is what happened with drugs that there's not enough FDA approved medicines for children. And we will go down that road if we put this type of regulation in for children. So I'm not aware of an analysis and as I shared in my comments that we, the directors of laboratories at pediatric hospitals have ourselves started to do those types of analyses. And as I shared with those numbers, they're pretty significant portions of our menu that would be impacted. And that while some of those,  enforcement discretion might help at the beginning, as time goes on they will come into effect and we will slowly see a decrease of access to laboratory testing for children.

Dr. Peck-Palmer: Thank you. I'm going to jump to Dr. Dennis Dietzen for one second because this is a good question. Dr. Dietzen, what is the FDA's reasoning behind the additional regulation on LDTs?

Dr. Dietzen: I mean, they think it's a really good idea because they've held up an example of a couple of dozen tests that they see as insufficient. And they feel like, that if they had a chance to review those, that those tests would not be on the market. You know, when you really dig down into the criticism of those tests, FDA oversight would not really be the salve that takes them off the market. A lot of times they are implementation of the tests in the laboratory that CLIA already oversees. So it is unclear. And that's one of the more frustrating pieces of this is that what is the problem we are trying to solve? And they cannot - I cannot put my finger on what that problem is at this point. 

So I think there are some really high profile things like the Theranos debacle that the FDA latched on. I think that kind of agitated them and they felt like they could have stopped that, but that was fraud. It was illegal and different rules would not have helped that.

Dr. Peck-Palmer: Exactly, thank you. So then I must follow up with this. The question is, what are the chances that the recent ruling will be overturned?

Dr. Dietzen: I think we are hopeful. I think the tide of events that have happened since the guidance was finalized. So there is a single lawsuit at this point filed in federal court, over to effectively nullify the decision, the recent Supreme Court decision to nullify what's known as Chevron deference. So this was a policy where courts were supposed to defer to regulatory agencies that were the experts and were making the rules. And the Supreme Court said not so much - that the courts could now intervene and kind of put a leash on some of those regulatory agencies. So that's a good thing. But I think we're hopeful that the rule would get nullified, but the problem is we can't pretend like it's going away. So we still have to prepare ourselves for what might come. 

Dr. Peck-Palmer: Ms. Braswell, the question came in for you. You mentioned that a laboratory developed test provided that official diagnosis that you needed for Olivia to just access vital services that you needed for her. Can you elaborate on how important that was in order to get the diagnosis and how did that then lead to those services that you shared with us?

Ms. Brasswell: Yes, those services are critical to my life and I know for other special needs parents as well. One example is that during a sleep study, we found out she had sleep apnea. And she was in daycare. Well, guess what, I can't go to daycare on oxygen. So without that diagnosis, I would not be able to get into a medical daycare or special needs daycare that allowed me to work because of the financial burden. I had to work for some time. So that is one of the services that was available because of that diagnosis, but also automatically depending on the state, we'll get Medicare, which allowed me to get respite care and allowed me, like outside services, additional to my insurance for PT, OT, and speech. Other services is simple things like camps that she just needed diagnosis for that to come free, which is very beneficial to families who may not be able to afford those things.

Dr Peck-Palmer: Thank you. So that test really impacts your whole life and the opportunities that she has. 

I want to go back to Dr. Delaney. The question here is how do you see the new LDT ruling impacting innovation of new assays and how does that impact pediatric care for the child as they transition to their lifespan?

Dr. Delaney: Yeah, so if you think about where we are today with immune therapies, cancer therapies, I mean, modern medicine can cure or really make people's lives much longer and live with cancer for a very long time. And that's true in pediatric care. And if you think about all the tests that the patients that are getting those therapies need, it's many. So there's many that are the FDA approved ones, but there's many that are LDTs. Patients might not know which one is which, but to get through a trajectory of that kind of care for organ transplantation, cancer care, treatment of these lifelong conditions, they're having many tests throughout their lives. And where we are today, 40 years into, where modern medicine is, is based on CLIA and how we have had tests regulated that allows, especially our referral centers and our cancer centers to develop a new test when there's a new treatment. So they can do those things in parallel. But can you imagine if then you have to wait years to have the test approved while the therapy is marching along? You really need the diagnostics and the therapies to be developed in parallel. And the time concern is an enormous concern for all patients, but absolutely in particular for children. If you think about the cancers we can cure now with CAR T and immunotherapy, the tests that are done to monitor those diseases and those therapies are LDTs.

Dr. Peck-Palmer: Thank you, Dr. Delaney. And you actually answered the second question, which is what other tests or diagnoses come from laboratory developed tests. And so thank you for walking us through those other tests. Thank you. 

I think I want to go back to Dr. Dietzen. So the question is coming in asking about, you've got a small company and they're working on a new or a modified LDT test and now this ruling has come very confusing. How are they supposed to innovate during this time that the ruling is in place and how do they remain profitable? 

Dr. Hollett: I don't know if you can give them the answer to that last part.

Dr. Dietzen: Well, I think you hit on a key issue. I think one of the things that diagnostic manufacturers see is that there's this dichotomy in the way that these tests are treated. LDTs are not regulated through the FDA. We can, we build, I mean, we spend a lot of time on these things, we invest in these things, but then there are similar tests, maybe not the same tests that do go through an FDA approval process. And that's far more expensive and far slower. So that's not helpful. 

So the real answer to the question is not for the LDT rule to go away, it's more to find a rational sort of regulatory environment that involves the FDA, also involves CMS, that us in the laboratory, we can -  there's some of the things that I do, there is an FDA test, kind of, but it doesn't work perfectly. So I have to change it, or I have to develop something totally different to do it. So I think the answer to that question is we need a playing field that's level for everybody that allows everybody to innovate at the same rate, and everybody will benefit from that sort of thing. That's the way I would answer that question. 

The profitability thing, I don't know. I'm going to leave that one alone.

Well, the FDA actually made all LDT folks manufacturers when the rule was finalized. So, you know, I'm working on listing on the New York Stock Exchange now.

Dr. Peck-Palmer: Wonderful. Thank you. Dr. Hollett, you know, I'm going to give you this question. 

The question here is - they're asking, “who's going to bear the risk of the medical malpractice if clinicians are unable to provide appropriate care due to the lack of testing due to the LDT removal?” What does your association think about that?

Dr. Hollett: I mean we're deeply concerned – I can assure you on that. But I think that ultimately comes back to our major concern is that uncertainty, right, Is that I don't think anyone knows definitively who will bear that risk. You know, as Dr. Dietzen alluded to, there are some concerns around things that may have, say, higher false positive rates or things of that nature that may have been the genesis for this rule. And you could argue that those diagnoses would also be subject to things like medical malpractice if the wrong diagnosis was arrived at. But I don't think a lot of folks are talking about the reverse in what is happening if a test is never offered in the first place, right? Because that is also going to cause clinicians to arrive at the wrong diagnosis. And frankly, no one has an answer, or at least certainly I have not heard a convincing answer about what happens to patients and physician risk in treating something where there's so many unknowns.

Dr. Peck-Palmer: I'm going to jump back to Dr. Delaney. This question came in, It says, “given that the FDA finalized rule grandfathers existing test, why would current menu offerings be affected?”

Dr. Delaney: So I haven't lived through what it's like to go through the implementation that we're all about to live through, but my concern about grandfathering is - so I'm, I'm glad that there's grandfathering there, so I'm glad about that. But if you go up and look at the expo right - we're all looking, as laboratorians we're all looking at the next instrument we're going to purchase, the replacement, the improvement. And that once the test is changed, which is the nature of our work, we're always changing, that it will fall out of enforcement discretion. That's the concern. And that really will be an impact on, I believe pediatric hospitals in particular, because we also have this higher proportion of tests that are lab developed tests.

Dr. Peck-Palmer: Dennis, for you, do you think the recent announcement of the retirement of the director, Dr. Shuren impacts FDA's focus on and the abilities to manage this change?

Dr. Dietzen: I got asked that question this morning in our session this morning too, and my answer was I hope so. 

Dr. Peck-Palmer: Wonderful. So, Ms. Braswell, I have a follow-up question for you. When did you first learn about laboratory-developed tests? And can you share with me how you've communicated or actually provided awareness to others and the public so that they understand the need to get laboratory-developed tests?

Ms. Braswell: I'm going to be honest, I knew nothing about it before Olivia's diagnosis. How I let other families, I'm an advocate within hospitals and within Down’s Syndrome communities. I let them just telling them aware of what type of tests are available there. So if it's a first time mom to a child with Down’s Syndrome, these are the different LDT’s that you need to check for or that a doctor has informed me about and letting them know what's out there, what's available, because unfortunately, a lot of times the pediatricians might not know or what to recommend. So as an advocate, I share with other special needs families, especially Down’s syndrome families of what tests are available and what they should look into.

Dr. Peck-Palmer: Wonderful, thank you. Let's go to Dr. Dietzen. So The FDA said that CMS has claimed that they themselves do not have the expertise to more effectively regulate LDT’s. What is ADLM's answer to the claim that CMS does not want the oversight?

Dr. Dietzen: I think CMS speaks the truth. The expertise in lab-developed tests lies in the developers. It doesn't lie at the FDA. It doesn't lie within CMS. So the answer to that is if we're going to hand it to one or the other, there's got to be resources and there got to be experts there, but will those - who are the experts that are going to judge the work that we do, from years of training and education about pathology and analytical chemistry, how is that going to happen? 

We - just as an aside, we just finished building on the day before the guidance was finalized, by the way, we just finished building a new LDT for an amino acid profile. And I'm sitting through the entire development process. I'm thinking how would I present this to the FDA as a 510k, or as a de novo submission, or as a PMA? You know, when I've got a biologic marker that will diagnose an exceedingly rare metabolic disease, and there's probably one or two kids in our clinic that might be affected by this, how do I present that to the FDA? And how will the FDA look at the performance of that and decide if it's okay to do that? Cause I had trouble deciding what was adequate in that situation. 

So those are the kind of confusing things I think when there's delocalized expertise and the expertise on a lot of these disorders is distributed all over the country in different laboratories. So the quick and dirty answer is that the FDA doesn't have the resources or the expertise and CMS doesn't have the resources or the expertise.

Dr. Peck-Palmer: Let's see, there's a follow-up question to that - How are we to prepare on the monitoring that will take place on these LDTs once we get to that year two and three if we have to look ahead?

Dr. Dietzen:

The question is, it's the profitability question again, right?

Dr. Peck-Palmer: Back to that.

Dr. Dietzen: Yeah. These tests, by and large, don't make anybody any money. So we operate on a shoestring. We do things as efficiently as we possibly can. And if we have to expend more resources, an administrator might come down to the laboratory and say that we can't support this anymore. And that's the point at which we would have to stop doing it and refer it out. 

Often folks have asked me when we will stop doing them. And my answer is typically when somebody comes in the lab and grabs my pipette from my cold dead hands, I will stop. And somebody might do that. And that's what it's going to take. And I think that's what we're looking at. There are some, and it may not be everything that we do, but there may be some things that are less profitable than others that we may be forced to give up. 

Dr. Delaney: Going off of that, if you think about, well, then we'd send it out, but what if there's no place to send it? Right? Especially for the small population tests, especially children, that means then that the referral labs that we all count on would have had to take it through the FDA because they can't go under the single health system enforcement discretion. And so they have to get it through the FDA and you just describing what it would be like to sit there and explain to them. That's what goes through my mind and makes me think that ultimately the access for children, for people with rare diseases and for the innovation that we all have come to depend on in our country will be tampened down. 

Dr. Peck-Palmer: I want to go back to this, Dennis, because I know that PEEC has done a lot of work in this area and know that even Vince Stein, our own staff member, prepares us, provides us with information so that we can be a voice concerning this. And so the question really is around that. How do individuals find this template email so that they can address those concerns? And is there a distribution list of regulators that they can send emails to?

Dr. Dietzen: Yeah, so I mean the association and with the help of staff, which is indispensable for organizing this and making it happen. There's a number of advocacy tools that we have at our disposal. You know the board of directors is on the Hill. Frequently we talk to folks in the congressional offices. Individuals I think can do a couple of different things.

One is we will tee up an email for them and it will be targeted to them and it will tell them who their representatives are, who their representative is, and who their senators are and tee that message up. The message, I think there, is less important than actually just sending the message because what it does is it amplifies the message that we are on the ground doing - Peak is on the hill as well. 

The second thing is, if you're in a hospital system - particularly an academic medical center I think we've heard a lot from the FDA, for example, and from Congress that academic medical centers in their home states, in their home jurisdictions are really influential. They're major employers. They are major drivers of the economy in those places. So what they say matters. And I'm sure all of your institutions have a government advocacy office. So find it, find the people in it, and tell them what's happening.

So that's further and I think it's all about amplifying the message, using as many tools as we can get to and amplifying the message as much as possible.

Dr. Peck-Palmer: This is a question for anyone in the panel. The individual says,  “will the FDA ban the new equations for estimated glomerular filtration rate or cholesterol because are they perceived as LDTs?” I see Dr. Dietzen laughing, so.

Dr. Dietzen: I hadn't heard that one before.

I don't think they're going to go there. Mathematical equations I think are exempted here. So, and then maybe not. I don't know.

Dr. Peck-Palmer: So another question here is - this goes to you, Dr. Delaney. Similar to the question to Dr. Hollett, how will this rule also affect your overall mission as a children's hospital?

Dr. Delaney: Our mission will not change. We're always going to be there for the kids, and we're going to keep performing the tests until they take the pipettes out of our hands. But really, there are enforcement discretion that allow things to continue with some increasing amount of regulation over the next few years. And so we're going to be learning, getting ready each year for each - to try to keep as much possible that we can continue to provide. As I mentioned in my comments, though, that health care is not in a great place right now, after the pandemic, there's not excess funds to bear increased costs. So over time, I do fear, especially the smaller hospitals and those that are not focused on the care of rare diseases in children - would be the ones that might say they can't perform it anymore. I do think hospitals like mine will continue to do everything they can to continue to perform as much as we can and we will see how it goes. 

Dr. Dietzen: I think that attitude is pretty common amongst children's hospitals. We are going to try to keep doing everything that we can do. Yes. Because the mission is still the same. It'll be harder, it'll be more expensive, but we're going to try and do it.

Dr. Peck-Palmer: This goes along the expense. So I'm going to give it to you, Dr. Dietzen. And it says, “can you comment on the possibility that in light of the FDA regulation, insurance companies might also limit the coverage for LBT putting additional burden on labs and patients?”

Dr. Dietzen: Yeah, I mean, we're already at a disadvantage from a reimbursement standpoint. So you could imagine an insurance company taking a stance that a test if it's not FDA approved, we're not going to pay for it. So I think that's a real possibility and a real risk, and it'll just exacerbate the lack of profitability that these tests have. So that's scary.

Dr. Peck-Palmer: Yes. I have to piggyback this question. This is a really good question. It needs to go to you, Dr. Dietzen. And it says, “how does this ruling actually impact clinical chemistry training programs? And will it reduce the research component, or will new trainees have to now learn how to get through the FDA process?”

Dr. Dietzen: Had not thought of that. 

I think it will have an impact. I think our trainees, they need to develop a broad set of skills. And if negotiating with the FDA now needs to become a didactic session, then so be it. But I don't know who's going to teach me the problem, because I don't know how to interface with the FDA and not many people in our institution don't know how to interface with the FDA. 

So yeah, I think it'll impact. And, a lot of research projects - you know this, are born out of a need, a perceived need in the patient population. And we decide we need to build something. And we grab a trainee by the neck and drag them into the lab, and teach them how to do it. And this is how they learn. And this is how we propagate LDT’s from one generation to the next generation. So, yeah, it'll have an impact.

Dr. Hollett: Yeah, I would piggyback on that in that for medical students, which the AMA also represents, is that is a major decision that they are dealing with now too, is that, you go through medical school and you're set to choose your residency or your specialty. I can't imagine that there are many medical students sitting there right now thinking that pathology looks pretty attractive. I mean, I think there is going to absolutely be a lapse in applications to residency programs and specialized physicians, certainly.

Dr. Peck-Palmer: I want to stay then with you, Dr. Hollett. Does the final rule actually convey misinformation that laboratory medicine is not a practice of medicine and how do we overcome this?

Dr. Hollett: That's, Oh boy.

Yeah, I don't know if I would go so far as to say that it's misinformation. I think there are certainly folks that can disagree as to what the role of a clinical pathologist is. And the AMA, I think, and certainly some of our other member organizations would disagree that LDTs are not within the scope of practice for a pathologist, whether or not that goes to misinformation. You know, disagreeing minds can not necessarily go that far. 

But yeah, I think that it certainly absolutely does match the training that our physicians have in developing these tests and validating this test and being the experts. As Dr. Dietzen alluded to earlier, this expertise doesn't exist with the regulators, it exists with the clinicians and the laboratory staff, right? These are the folks that are best positioned to understand, similar to how physicians prescribe medications off label, right? That is within a clinician's training to understand a drug's indications, its safety profile, and what is medically appropriate. And I think that that is true for laboratory-developed tests as well.

Dr. Peck-Palmer: Yes, that we do embody and are trained to actually perform that testing. So clinical chemists and the like have that training. Thank you. 

So this is a question to anyone in the panel says, “does selling LDTs come with the liability, now that the FDA has deemed us to be manufacturers of medical devices?”

Dr. Dietzen: I don't know that we have any more liability than we already have today. I don't know that, I mean, I'm not a lawyer. Sometimes I think it would be good to get a law degree now to understand some of this stuff, but we're already, I mean, we're already liable. We already have a lot of insurance at our back. Because we do, I mean, a lot of these LDTs are rare, they're high risk sorts of things. So yeah, we understand the liability going into it, but I don't know that this increases. I think the only way it would increase it is if we are either intentionally or unintentionally now not complying with a new set of regulations that maybe we don't fully understand and appreciate. So maybe there is a little extra liability there. Possibly.

Dr. Peck-Palmer: Wonderful. Question here. Why don't we have, to any one on the panel, why don't we have several lawsuits challenging the FDA? Why only the ACLA? And do you foresee more individuals having their own or joining with the ACLA?

Dr. Dietzen: I don't know the answer to that exactly, but it takes deep pockets to file such a lawsuit, and it takes a lot of deep pockets to litigate such a lawsuit. So I am not surprised that there aren't more. I think a lot of us are sitting back waiting to be asked to support the single lawsuit that has been filed and we will do so. So, yeah, I don't know, I don't exactly know why there aren't more. I would like there to be more because you play, you roll the dice and the more dice you have, the more chances you have to win. So, yeah, I'm not sure why there aren't more. It was largely predicted that ACLA would file this lawsuit. So I think maybe everybody else took a step back and let it happen and then they're going to watch it play out. That's my personal opinion as to why.

Dr. Peck-Palmer: Ms. Braswell, we talked a lot about and you shared with us that the initial diagnosis is helping you receive these services. Let's say that tomorrow there's no LDT test available for you. What do you do consistently? You shared there are some tests that you get monthly, yearly, how is that going to impact you, your whole family and Olivia?

Ms. Braswell: The biggest impact it would have is if, God forbid, she had cancer and I didn't know. Yes. Like, and I didn't have a test, any diagnosis, the longer you wait the more sick somebody could get. So not having access to those tests right away would be very scary as a mom. Just waiting and not knowing, things have come up in her CBCs that she didn't have any signs of. So if I didn't have that test, I would have no idea of what she needed next.

Dr. Peck-Palmer: Expand on that a little bit, Sarah, when you go to the doctor, what does it look like? How do you know what tests to order? 

Ms. Braswell: I don't know every test to order, right? Right. But I will say, I'm that mom who comes in the room. I don't care how much it is. Give me every test because I don't want to hear - it's because she has Down’s Syndrome. And I think that's the biggest takeaway. A lot of times I will have physicians or other people in the medical field tell me it's just because she has Down’s Syndrome. Now I need you to have a test to prove that it's something like her DNA or genetics is not making her cough all night. So having those tests and them proving to me what her sickness or illness is, wouldn't be possible without the tests. And not accepting those blanket statements.

Dr. Peck-Palmer: Question, are you aware - for anyone on the panel, are you aware of larger academic institutions having conversations with smaller labs to maybe make a hub as we move forward with this FDA rule to ensure that certain large hospitals actually have testing available as we progress through this ruling?

Dr. Delaney: So the exclusion about the singular healthcare system is pretty specific. It's about if all of the physicians ordering are credentialed under a single medical staff. And so we are, as Jeff said, having a lot of consolidation of hospital systems in our country. But if they're all under one medical staff, you could have a number of hospitals that could all use that same laboratory. So I think that that's a benefit that was put in in that exclusion. However, remember what I said about the grandfathering, as the tests change, it still could change, or if there's an FDA approved test that comes online, But I think that that is true. 

Now for a singular hospital though, and like a pediatric hospital like mine, we have our pediatricians, but the pediatricians in the local community are not credentialed. And so we wouldn't be able to provide that for them. So we are worried about the fragmentation of how we regionally support the practices and the smaller hospitals around us. 

Dr. Peck-Palmer: I think Olivia is telling us when we can come out and see you all. So let's go ahead. I think you'd love to meet Olivia. Can we do that now?  Wonderful.

Hi, Olivia. Are you going to wave to everybody?

Ms. Braswell:

Hi. Okay, let's go sit.

Dr. Peck-Palmer: Wonderful. Olivia, we talked a lot about you today and we're so happy to see you. Yeah. You're so pretty with your beads. I love it. Thank you. These are all of my friends and we've been talking about laboratory-developed tests. Tell them hi one more time.

I want to thank all of you, everyone in here, for this engaging conversation about how patient care will be impacted if the FDA rule on laboratory-developed tests moves on. I hope you've learned as much as I have, and I want to remind you that ADLM's third survey on laboratory-developed tests is now active, And so if you take a look at your screen, you'll see the QR code. Also the website where you can go to. Please share your feedback with us and have a great evening.