A consensus-driven conceptual framework from Canadian genetics experts describing four models for mainstreaming clinical genetic testing and the variables that determine which model fits specific clinical scenarios.
0:00Welcome to Base by Base, the paper cast that brings genomics to you wherever you are. Thanks for listening, and don't forget to follow and rate us in your podcast app. It's uh, it's great to be back for another deep dive today.
0:11Yeah, I'm really excited for this one. Imagine for a moment that you, or maybe like a close family member, are facing a severe, completely undiagnosed health issue. Oh wow. Yeah, that's a scary situation.
0:25Right. You go to your primary doctor and they tell you that you need a crucial medical test to understand what's going on, like a complex genetic test that could finally provide the answers you so desperately need.
0:36But then they drop the hammer. The wait time to even access the specialized clinic that can run this test is up to 3 years. Three years. I mean, that's just staggering. It's wild, but that is the stark reality in many healthcare systems right now.
0:50You know, over the last 2 decades, the cost of sequencing a genome plummeted from 1000000s of dollars to just a few hundred. Because of that, the demand for genomics informed care has skyrocketed. We know the DNA holds the answers.
1:03But here is the catch. The highly specialized workforce required to deliver that care simply hasn't grown to match it. Yeah, we're basically looking at a massive bottleneck. So spark your curiosity for a 2nd and ask yourself, how could this change?
1:19If the doctors you already see could safely and effectively run these advanced tests themselves. What really happens when we take highly specialized medicine out of the specialist's clinic? It represents, like, a really profound shift in how we fundamentally structure medical care.
1:35We're talking about rewiring the entire diagnostic pathway. Because if everyday doctors start ordering tests that used to require a specialist, you know, PhD level understanding that has massive implications for patient access.
1:47But I also introduces some profound questions about safety. Yeah, and accuracy too, I'd imagine. So today we celebrate the work of Michael P. Mackley, Kim M. Boycott, and an expansive collaborative team representing 20 distinct clinical genetic services across all Canadian provinces.
2:01And this was published in the Journal Genetics and Medicine in 2025 on behalf of the American College of Medical Genetics and Genomics. Which is huge. Yeah, it's basically a comprehensive framework trying to provide a blueprint for this exact wait time crisis you just mentioned.
2:18Okay, before we get into their solution, let's establish the players here. On one side, we have the genetics service, right? And on the other, we have non-geneticist clinicians. Who exactly falls into these 2 camps?
2:30So the genetic service is the highly specialized interprofessional team. They're the traditional gatekeepers of genetic testing. Like the geneticists themselves. Exactly. Medical geneticists? doctors with specialized residencies, along with genetic counselors, dietitians, nurses, and you know, the laboratory staff.
2:47Okay, the genome analysts and technologists. Right. They possess deep specialized knowledge. And on the flip side, the non-geneticist clinicians are your everyday doctors. So we're talking about, like, family physicians.
3:00Yeah, family physicians, pediatricians, neurologists, oncologists. These are the clinicians, seeing patients every single day who urgently need genetic testing. But historically, they've had to just, what, refer them into that bottleneck.
3:14Exactly. Straight into the bottleneck of that small, overburdened genetic service. Which leads directly to those three-year wait lists. I mean, people are just sitting in limbo while their disease progresses.
3:25So the medical field organically started doing something kind of mainstreaming to fix this. Yeah they had to do something. Just to define that for our listeners. Mainstreaming is the process of shifting parts, or maybe even all, of the clinical genetic testing process away from the specialists and over to the everyday doctors.
3:43Precisely. And mainstreaming actually has a very successful track record in cancer genetics, actually. Oh, really? In oncology. Yeah, because in oncology, time is of the essence. You absolutely cannot wait 3 years to figure out the genetic profile of a tumor.
3:57Right, that makes total sense. So because it was so effective in cancer care, it naturally started bleeding into nearly all other areas of medicine. But, and here's the core problem the authors highlight, it's spreading an absolute chaos right now.
4:13Okay, I have to challenge the word chaos there. If doctors are figuring out ways to get patients tested faster. Isn't that just like decentralized innovation? I mean, decentralized innovation is great, but in medicine, you cannot manage what you cannot measure.
4:28Right now, different hospitals are inventing their own workflows entirely from scratch. There is no standard language, no unified taxonomy. So like a hospital in Toronto might have a totally different system than Vancouver.
4:40Exactly. And if they're different, we have no way to compare them. Health systems can't evaluate if these models are actually improving patient access or if they're financially sustainable. Or I guess if they're inadvertently causing misdiagnoses.
4:53Yes, crucially that. Without a shared playbook, it's just fragmented guesswork. Okay, let's unpack this. How did the researchers tackle this chaos? Because bringing order to a fragmented medical system across dozens of specialties is no small task.
5:08No, it really isn't. They realize they needed a unified conceptual framework. So they convene a focus group at the Canadian College of Medical Geneticists. The CCMG annual scientific meeting in June 2024.
5:21And that was held in St. John's, Niffland, right? Yes, exactly. They brought together 33 frontline genetics experts. We're talking 26 medical geneticists, 4 resident physicians, a lab geneticists, and genetic counselors.
5:35Wow, that's a room full of heavy hitters. Yeah, and the goal was to hammer out exactly what mainstreaming looks like and build consensus framework that anyone, anywhere could adopt. It sounds like they had to map out a relay race, figuring out exactly where the baton is passed between the regular doctor and the genetics expert.
5:51That is a perfect way to put it. But getting 3 dozen specialized doctors to agree on a single framework sounds impossible. How did they actually build this? It took a highly rigorous, iterative process.
6:02The lead authors didn't just walk into the room with a blank whiteboard, you know. Right. would be a disaster. Yeah, they started with preliminary definitions. drafted from extensive literature reviews.
6:14They presented these drafts to the 33 experts. And then just debated it. systematically refined every single point. They solicited feedback, debated terminology, and continuously revised the definitions until there were absolutely 0 objections from the group.
6:30Zero objections from 33 doctors. That's actually incredible. It really is. And they ultimately broke the entire diagnostic journey into 4 meat sequential stages. Assessment, pretesting, laboratory, and post testing.
6:44Okay, let's make sure we understand those stages. The pretesting and laboratory stuff makes sense, like counseling, consent, running the sample. But what exactly falls under assessment? Well, the paper heavily uses the term phenotyping for this.
6:56Phenotyping. What does that actually mean for the patient sitting in the exam room? It's essentially the detective work of documenting observable traits. Let's say a patient comes in with a specific type of heart murmur.
7:07Okay. A regular doctor notes the murmur. But a clinical geneticist doing deep phenotyping, might notice that the heart murmur combined with, say, a slightly unusual curvature of the spine. Oh, I see, yeah.
7:21And maybe a specific wide set spacing of their eyes, points to a very specific genetic syndrome. Assessment is gathering all those clinical features and the deep family history to figure out if a genetic test is even warranted.
7:34Okay, here's where it gets really interesting, because the researchers use those 4 stages to map out 4 distinct models of mainstreaming. Yeah, going back to your reway race analogy, the moment that baton is passed dictates exactly which of the 4 models a hospital is using.
7:49Let's follow a pageant through these models to see how the races run. Say someone goes to their primary care doctor with a strong family history of early heart disease. In the most cautious approach, what the group called Model one or the 2 test model?
8:01What happens? In the 2 test model, the everyday clinician does the initial clinical assessment and gathers that family history. But they passed the baton very early. So before the test is even ordered.
8:14Exactly. The genetic service is the one that actually orders the genetic test before the patient ever steps foot in the specialized clinic. I mean, looking at this 1st model, honestly, it seems like a half measure.
8:25Why even bother having the primary doctor do the intake if the specialist still has to review the file and order the test anyway? Doesn't that just add an administrative step? It might seem like a half measure, but the logistical value is actually massive.
8:38Normally, that patient would wait 6 to 8 months just to sit in a geneticist office so they can ask about family history. Oh wow. Yeah. So by having the primary care doctor do that initial assessment, the patient bypasses the intake wait list entirely.
8:52The specialist just reviews the notes, orders the test, and care is accelerated by months. Okay, so it trims the fat off the waiting list. That makes sense. Moving down the spectrum to model two. The 2 result approach.
9:05Let's shift away from heart disease to cancer, since you mentioned this is common in oncology. How does a cancer patient experience this? In the 2 result model, the everyday doctor, the oncologist, in this case, holds baton much longer.
9:19They assess the patient, order the genetic screen for the tumor, handle the pretest counseling, and send this specimen to the lab. So they do basically everything up front. Right. The baton is only passed when the results come back.
9:31If the results reveal a highly complex, hereditary cancer, risk like, a BRCA mutation that affects the patient's siblings and children. Then the genetics team tags in. Exactly. The clinical genetic service steps in to deliver that complex news and manage the family follow-up.
9:47That makes perfect sense. The oncologist drives the immediate cancer treatment, but the geneticist steps in for the generational implications. Exactly. Now, Model 3 is called 2 navigation. And this is where the everyday doctor takes almost complete ownership.
9:59The paper highlights pediatricians screening for autism spectrum disorder as a prime example of this. Yes, and this is a really profound shift in pediatric care. If a child is showing signs of ASD, a regular pediatrician will now routinely order a 1st line genetic test.
10:16Right, what they call a chromosomal micro array. Exactly. They read the results and they disclose them to the parents. The genetic service is completely absent from this process unless the results are highly complex.
10:28Let's clarify 2 things there for the listener. First, what is a chromosomal micro array? And second, what makes a result so complex that a pediatrician would suddenly need to tag in a geneticist? Good questions.
10:39A chromosomal microwray is a test that looks for missing or extra chunks of DNA. It's not looking for a single typo in a specific word. It's more big picture. Yeah, it's looking to see its entire paragraphs or pages of the genetic instruction manual have been ripped out or duplicated.
10:54It's a fantastic, broad sweep tool. Okay, and what about the complexity part? The pediatrician would pass the baton. If the test reveals what we call a syndromeic cause. Syndromic, meaning it affects multiple systems in the body, not just the brain.
11:09Exactly. If the microoray shows a genetic deletion that causes autism, but also causes impending kidney failure and severe heart defects down the line. Oh man. It requires navigating a multi-system lifelong medical strategy.
11:23A general pediatrician will pass the baton to the genetics team to quarterback that massive coordination of care. Which brings us to the final approach, Model 4. The fully mainstreamd model. In our relay race, there is no baton pass.
11:39The everyday clinician runs the entire race from start to finish. That's right. The genetic service isn't routinely involved at all. This is currently used for conditions with very well understood clinical traits and known molecular causes.
11:51Like what, for example? Well, testing for hemocromatosis, for instance, a condition where the body absorbs too much iron. It's a very straightforward genetic mechanism. Okay, so a regular doctor can just handle that.
12:01Yeah, or you might see a nephrologist, a kidney specialist. who has taken a special interest in renal genetics. They independently manage all genetic testing for their kidney patients from assessment to long-term management.
12:14Interesting. What's fascinating here is how hospitals actually choose which of these 4 models to deploy. The framework identifies specific variables that push a testing scenario toward needing a specialist early on, or allowing the everyday doctor to handle it entirely.
12:30Let's dive into those variables. Because it can't just be based on how confident a doctor happens to feel that day, right? What mechanical or scientific factors dictate the model? It depends heavily on the disease and the test itself.
12:42One variable is whether the disease is isolated to a single system in the body or if it is multisystemic. So like we talked about with the syndromeic cause. Right. A single system disease, say a genetic form of early onset blindness, is much easier for an everyday ophthalmologist to mainstream.
12:59But a multi-systemic disease requires coordinating care across neurology, cardiology, orthopedics. That inherently demands the broad expertise of a clinical geneticist. Exactly. You also mentioned test complexity.
13:12I imagine there's a big difference between a simple cheek swab and something highly invasive. Absolutely. Are we talking about a simple blood draw to look at a static DNA archive, which is easy to mainstream?
13:23Or does the test require complex skin biopsies and RNA analysis? Why is RNA analysis so much harder? Because you aren't just looking at the hard coded DNA? You are looking at the active blueprints to sell as currently transcribing.
13:38It is highly dynamic and much harder to interpret. Oh wow. Yeah, if a test requires RNA analysis. It is almost certainly staying with the specialized genetic service. So what does this all mean? If I'm a patient navigating the healthcare system today, or if I'm a hospital administrator trying to clear a three-year backlog, what is the practical implication of defining these 4 models?
13:59For the broader healthcare system, this framework finally provides a standardized operational language. Administrators and clinical teams can now look at their specific workforce and intentionally design a mainstreaming program.
14:11They can actually plan it out. Right. They can say, our neurologists are completely comfortable handling Model 3 for these specific seizure panels, so let's shift that massive volume out of the genetics clinic.
14:22And they can track it properly now. Exactly. Because they are using standard definitions, they can accurately track data to ensure wait times are actually shrinking without increasing patient harm. Let me play devil's advocate here, because the idea of an everyday doctor ordering a massive genetic panel makes me incredibly nervous regarding patient safety.
14:41Okay, how so? Well, if a regular doctor orders a complex genetic test, what happens if they get a confusing result? Like a variant of uncertain significance? Doesn't this just create a dangerous situation where patients get misinterpreted results?
14:56Because finding a VUS is like finding a typo in a massive, highly technical instruction manual, you know the word is spelled wrong, but you have no idea if that typo is going to cause the machine to explode or if it's just a harmless error.
15:09Right exactly. You need an expert linguist to figure it out. If an everyday doctor tries to interpret a VUS, couldn't they needlessly terrify a patient or worse? Recommend a preventative surgery they don't actually need?
15:23This raises an important question, and it is exactly why the experts in the focus group debated the guardrails so extensively. So there are safety nets. Yes. The beauty of this framework is that it explicitly builds in Stacy Tripwires.
15:38Mainstreaming does not mean abandoning the everyday doctor on an island. How does that work in practice? In Model 3, for instance, getting a complex result, like a variant of uncertain significance acts as a hard stop.
15:49It immediately triggers a mandated referral back to the genetic service for expert interpretation. The everyday doctor is not allowed to guess. Okay, so the system acts as a safety net. The moment the instruction manual gets too technical, the expert linguist is automatically called in.
16:04Yes, the specialized clinical genetics services will remain absolutely vital players in resolving these uncertain variants. That's reassuring. Furthermore, the paper notes that the laboratory reports themselves are undergoing a massive redesigned to support everyday doctors.
16:20Really? Like making them easier to read. Exactly. Historically, lab reports were written by geneticists for geneticists. They were impenetrable walls of data. Now, laboratories are creating reports with clear synthesized language.
16:35Oh that's smart. Yeah, they're embedding educational resources right into the document, and explicitly stating recommended follow-up steps so that non-specialists can understand the clinical action plan without needing a PhD in molecular biology.
16:48That makes a ton of sense. The infrastructure of the system is adapting to support the people on the front lines. But, you know, no study is perfect and mapping out the future of an entire medical discipline isn't going to be flawless on the 1st try.
17:01Definitely not. What did the authors identify as the blind spots of this framework? Well, the authors were highly transparent about the study's limitations, particularly regarding representation. That initial focus group in St. John's was heavily dominated by medical geneticists.
17:15Right. You said 26 of them were geneticists. Yeah, so while they eventually expanded the authorship group to include other viewpoints, the foundational framework was built primarily by the specialists, the people who currently hold the power and the expertise.
17:28Which means they might have a blind spot regarding the reality of the everyday doctors they are trying to pass the work onto. Precisely. The authors explicitly state that for this to succeed in the real world, future iterations absolutely must deeply include the perspectives of genetic counselors.
17:47Why counselors specifically? Because counselors are critical. They actually have the scheduled time to explain the emotional and psychological weight of a genetic diagnosis to a family, unlike a primary care physician, who is often limited to, you know, a 15 minute appointment.
18:03And if you are asking a primary care doctor to suddenly manage complex genetic testing, You have to address their barriers, whether that's a lack of continuing education, a lot of time, or inadequate billing codes to compensate them for this highly complex work.
18:17You can't just dump the labor on them and expect the bottleneck to magically disappear. No, you really can't. The everyday doctors need a seat at the table to ensure these new mainstreaming models are actually viable in a busy, under-resourced family clinic.
18:31Mainstreaming genetic testing isn't a simple on or off switch, but rather a dynamic spectrum of collaboration between primary doctors and specialists. By using this framework to carefully pass the baton based on the patient's specific needs, and the doctor's expertise, healthcare systems can finally break the genetic testing bottleneck without sacrificing patient safety.
18:51If we connect this to the bigger picture. What does this mean for the future of your own primary care visits, and how much genomic literacy will we soon expect from every single nurse and doctor we see?
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