Dr. Blair Bigham:
I'm Blair Bigham.
Dr. Mojola Omole:
And I'm Mojola Omole. This is the CMAJ podcast. So today, Blair, we're discussing a paper called, “Cost-effectiveness of pharmacogenomic guided treatment for major depression”.
Dr. Blair Bigham:
Yeah, at first I thought, "Oh no, an economic analysis that never sounds so stimulating for the audio waves." But man, this was really interesting and I guess it's rooted in my experiences in med school on my psychiatry rotation, which I actually loved a lot, but I knew it wasn't for me. I'm an emergency and ICU doctor, I do acute care medicine, so I like instant gratification. I like to defibrillate people and see their heartbeat restored. So to have to put someone on a medication and then not know if it's working for four weeks, six weeks, and I just couldn't handle that. And what's so interesting about this is we know that for some people, their body just has a different way of processing medications than others. And we've always known that it's almost a grab bag. Just pick an antidepressant, see if it works, and if it doesn't, try another one. How frustrating that must be. And so to go ahead and look at the pharmacogenetics of it, I had no idea how much you could predict and titrate and make clinical decisions based on these profiles.
Dr. Mojola Omole:
It's used already in cancer treatment and with medical oncologists, but this was the first time that I've seen it used in this scenario. And for me, having had loved ones and me, myself, also on antidepressants and having to try a few before I found one that worked, this was really interesting to me that this would be such a game changer for people who are suffering with depression and who are having a hard time finding medication that is going to help them with their symptoms.
Dr. Blair Bigham:
Absolutely. I have so many questions for our guests today. We're going to be speaking with two of the authors of the study. One is a mathematical modeler and research scientist who crunched the numbers to figure out if this is going to save money, and the second author is a genetic counselor and professor in both psychiatry and medical genetics. So clearly both of these people are smarter than us, Jola.
Dr. Mojola Omole:
I'm a surgeon. No one's smarter than me. This is really interesting and I'm looking forward to the discussion. Let's get into it.
Dr. Blair Bigham:
We have two authors of the study joining us. Jehannine Austin is a Professor of Psychiatry and Medical Genetics, and Shahzad Ghanbarian is a mathematical modeler and research scientist. Both are at the University of British Columbia. Thank you so much for joining us.
Shahzad Ghanbarian:
Thanks for having us.
Dr. Jehannine Austin:
Pleasure to be here.
Dr. Blair Bigham:
Jehannine, I want to step back for a minute because I am not a professor of psychiatry or in medical genetics. Tell us what is pharmacogenetic testing and why is it relevant in the treatment of depression?
Dr. Jehannine Austin:
Well, in the context of psychiatry, choosing a pharmacological treatment that works for a patient is a big clinical problem. So as you all know if you work in this space, lots of the time when a patient is in need because they are experiencing depression and a medication is prescribed to try and treat that, as much as half of the time, the first treatment we prescribe doesn't work. And obviously if somebody's in a state of psychiatric depression situation, that's not ideal. We want something that works better than that.
So pharmacogenomic testing is really about exploiting the idea that genetic variations that we each have influence how we respond to medications. So the idea is that perhaps if a medication is not working for you, it might be because you have genetic variations that mean that you don't metabolize it quite in the same way that other people would. So the idea behind this testing is that if we can test for those variations, then maybe that can help inform choice of medications so that people don't have to go through quite as much of this trial and error and the misery of things not working for them.
Dr. Blair Bigham:
So when I hear you describe it that way, I'm thinking back to medical school like cytochrome P450.
Dr. Jehannine Austin:
Oh, you got it.
Dr. Blair Bigham:
Is this what we're talking about?
Dr. Jehannine Austin:
That's exactly what we're talking about.
Dr. Blair Bigham:
Okay, perfect. So some people metabolize drugs more quickly and so they need a higher dose. Is that right? Or the drug wears off faster?
Dr. Jehannine Austin:
Yeah, of course. It's never quite that simple and straightforward. We're not talking about single genes or single variations or anything that straightforward, but that's the general idea. Yeah, so we're talking about not one variation in a gene. We're talking about multiple variations in genes. And so doing a panel test for those, which then provides you a composite picture or an overall idea of how somebody's metabolizing things.
Dr. Blair Bigham:
And then the results of that pharmacogenetic testing, it leads a physician to prescribe a different dose. Is that essentially where the clinical benefit comes from?
Dr. Jehannine Austin:
So what happens when you have a pharmacogenomic test done is it won't tell you, "Bingo, this is the medication that you should take." That is not what it will do in this situation. What it will do is it will provide a list of medications that might be more compatible with the patient's profile and a list of medications that are less compatible. And so these are not things that can be used just without any clinical judgment whatsoever. So that remains really important.
Dr. Blair Bigham:
Perfect.
Dr. Jehannine Austin:
So it helps you to choose a medication and to consider dose as well.
Dr. Blair Bigham:
Perfect. So you both have reviewed existing data on pharmacogenetics. What did you have a sense of what the research might show when you were specifically studying medications for depression?
Dr. Jehannine Austin:
So I think when we started this project, as a team, we knew that there were three main possible outcomes of this work. One, we would find that there was a lot of evidence that we should be implementing pharmacogenomic testing in our healthcare system now. Two, that we should absolutely not be implementing pharmacogenomic testing in our healthcare system now. And three, that we just don't know. Really, we should just need more evidence and we can't say one way or the other given the existing state of knowledge.
Dr. Shahzad Ghanbarian:
So there have been some studies, economic analysis, but none of them have been comprehensive enough. So there were a couple of economic models. They were not looking into the long-term benefit of pharmacogenomic testing. They did not have genetic makeup of the patient as one of the characteristics of the patient in their model. And also they did not have drugs specifically modeled. So that's why there was not enough evidence from an economic analysis perspective to provide to the decision makers.
Dr. Jehannine Austin:
And I think probably all of us were assuming that we would end up generating data that supported that third wave that we just didn't have enough data. So that was really what we were all expecting, I think, going into this.
Dr. Blair Bigham:
And what exactly did you find?
Dr. Jehannine Austin:
Not that.
Dr. Shahzad Ghanbarian:
So what we found is that if pharmacogenomic testing is implemented for a patient with moderate to severe major depression, in 20-year time horizon, the healthcare system will save around $1 billion and it also-
Dr. Blair Bigham:
With a B, one billion?
Dr. Shahzad Ghanbarian,:
Billion dollars. That's correct. And that would also improve the quality of life of the patient and a life year. So that would be higher survival for the patient with depression.
Dr. Blair Bigham:
So pharmacogenetic testing doesn't sound cheap to me. How does it save money?
Dr. Shahzad Ghanbarian,:
Yeah, there is a range for the cost of pharmacogenomic testing, it's between $300 to $2,500.
Dr. Blair Bigham:
Ouch.
Dr. Shahzad Ghanbarian,:
Yeah, and so in our analysis, we use the average cost, which is around $700. So yes, there is an upfront cost that the healthcare system should provide to allocate for this type of testing. But over time what happens is that there will be fewer patients that we call treatment resistant. And these patients are those that are expensive for the healthcare system. They have higher comorbidity, higher hospitalization rate, higher mortality rate. So having pharmacogenomic testing in place would reduce the number of patients with treatment resistant depression. That's around 37%. So that would cause fewer hospitalizations and fewer deaths and overall cost saving for the healthcare system.
Dr. Blair Bigham:
Give me a sense of the scope. How many people in British Columbia live with depression who could benefit from pharmacogenetic testing?
Dr. Shahzad Ghanbarian,:
So the prevalent rate is around 5%, and in our model, we included those who are eligible for pharmacotherapy. Not everyone chooses pharmacotherapy for treating their depression. So we included those patients and it's around 200,000 patients.
Dr. Blair Bigham:
Wow.
Dr. Mojola Omole:
Wow. That's impressive. What is considered moderate to severe depression in terms of what is this patient population? How is it different from everybody else who's in the world who has depression?
Dr. Jehannine Austin:
So I think one of the problems that we have when we think about depression is that because we've all had a down day, we think that might be what depression is all about and it's not. So there are actually clinical criteria for depression that a person has to meet in order to be diagnosed with this condition. So I, myself, have lived experience with depression. So I take medication every day because I struggle without it, essentially. So it's really about not just having one down day every once in a while, it's about being impacted in a significant way that interferes with your ability to live in the way that you would want to. So there's very specific clinical criteria for the diagnosis of these kinds of conditions.
Dr. Mojola Omole:
I guess my question was actually not just the diagnosis for depression, but what are we considering moderate to severe depression that would require pharmacogenetic testing? If we were to develop a criteria for, okay, which patient should get pharmacogenetic testing, how do we differentiate which patient would be the most benefit for it?
Dr. Shahzad Ghanbarian:
So, many of the clinical trials, they use HAM-D scoring criteria to score patients and then they identify patients, whether it's moderate or severe. And we use a similar approach in our study. So in our study, we know the distribution of severity for major depression in British Columbia, and we assign that to the patient. And in our study, those who get to the categories of moderate to severe received pharmacogenomic testing.
Dr. Blair Bigham:
So if a 37% reduction in people who have refractory depression, does that mean that right now, 1/3 of people with refractory depression, if you just got their dose right to suit their genetic profile, they'd get better. That seems like a pretty dramatic impact for people's lives.
Dr. Shahzad Ghanbarian:
That's correct. So what happens is that when patients get to this condition, then they are very challenging to treat. And by having pharmacogenomic testing in place, that would reduce the number of trial and error the patient is going to and therefore reduce the number of... That would avoid patients to get to the point that their condition is refractory.
Dr. Blair Bigham:
Jehannine, you're ready to jump in. Go for it.
Dr. Jehannine Austin:
Yeah, I just wanted to make sure that what Shahzad is saying is really heard, which is that what our data shows is that by using this kind of testing, we can prevent people from being diagnosed with refractory depression. It doesn't mean the same thing as what you were saying is that it would reverse course for a third of people who have refractory depression.
Dr. Blair Bigham:
So you got to catch it early. You got to get them on treatment early so that they don't evolve-
Dr. Jehannine Austin:
Exactly. It's about preventing going down that path.
Dr. Blair Bigham:
Normally when we look at a lot of research on this podcast, we're talking about numbers needed to treat that are nowhere near as optimistic as what you're talking about. I don't even care about the billion dollars in savings right now. This sounds like a substantial opportunity. Why hasn't this been done before?
Dr. Jehannine Austin:
So I think the reasons for which this has not been done before, so the first thing I think it needs is a sufficient body of literature about outcomes in order to generate the starting point for the modeling. And I would say we didn't really have enough of that until relatively recently. I would say another reason that this hasn't been done before is because the team required to do this in a meaningful way is incredibly diverse. So today, you're speaking together with me, I'm a genetic counselor by clinical training. I specialize in psychiatric conditions. Shahzad, you've heard about, is an expert modeler in the health economic space. And the team includes patient partners, people who treat people with psychiatric conditions in primary care and as psychiatrists, other health economists, do you know what I mean? The diversity of disciplines that we needed to bring together in order to effectively look at this question, I think, it's a bit special.
Dr. Blair Bigham:
Have you had any responses from, say, government or funders who have said, "Oh, let's pony up and put this money out on the table?" Or is this all something that right now, if I were on antidepressants and wanted to know why aren't they working so well, would I have to fund this myself out of my own pocket?
Dr. Shahzad Ghanbarian:
So it is not currently publicly funded in British Columbia, so patients are paying out of their pocket and some insurance companies are covering part of that cost. But yes, so right now it's out of the patient's pocket. What happens in the future, it depends on how the government would decide on that. And so we provided the evidence in terms of effectiveness and cost-effectiveness and we are passing that information to the government. But also, we are working on the next step, which is we are going to look at the implementation strategy to see who would be the best person to actually provide pharmacogenomic testing care to patients with major depression.
Dr. Mojola Omole:
So we've really focused on the economics of this testing. But beyond the cost savings, what does it actually mean for patients?
Dr. Shahzad Ghanbarian:
It means that there will be fewer trial and error process that they'd have to go through. The frustration that they are experiencing would be much less.
Dr. Blair Bigham:
The trial and error sounds so frustrating.
Dr. Shahzad Ghanbarian:
Yeah, so imagine you go for one medication, it's not working for you. You have to go back to see your physician and get another medication and it may not work for you again. And during this process, many of them give up and that's something that we heard from our patient partners and people that we have been talking to. So that's a very unfortunate situation.
Dr. Jehannine Austin:
Yeah, and remember that in this context, we're not just talking about a medication that doesn't clear up my rash. We're talking about a medication that I need because I am too depressed to participate in my life. So if you are already in that state, speaking as somebody who's been there, if you are already at the point where you need to go to the doctor to get medication for depression, you are in no condition where you can readily withstand the rigors of going through multiple rounds of medications not working and trying something new. I was one of the lucky ones. So for me, the first medication I tried was one that worked for me. But even then, I have some insight into what people live with because for the first seven days I had fairly overwhelming insomnia, nausea, vertigo.
And so I knew because I work in the psychiatry department, I have lots of psychiatrists who are friends. I knew that if I was lucky, that would peter out and I would actually start feeling therapeutic benefit. I was lucky that happened to me. But if those are the side effects that you are experiencing without any therapeutic benefits over a longer term than seven days, it's intolerable. It's genuinely intolerable. So that's what we're talking about here. That's, I think, why for all of us involved with the study, what we found is so powerful to us because not just because of the money as we've discussed, it's about the human element of this, what it means for people who live with these conditions.
Dr. Shahzad Ghanbarian:
We have done some other analysis that we haven't published yet, and it's from a societal perspective. It includes also how much money the patient and the society would save. And the amount of savings is much higher than the one that we reported in this study.
Dr. Blair Bigham:
A billion is an awful lot. What type of numbers are we talking about?
Dr. Shahzad Ghanbarian,:
Yeah, it's much higher. I cannot disclose the number. We haven't published yet. So to answer your question, that is the money that's going out of the patient's pocket for their treatment. So antidepressants are not fully covered, so patients are paying for part of that. Also, the main driver is the productivity loss. This patient, they cannot go to work and therefore that would cause some cost to the society.
Dr. Blair Bigham:
Oh, that's not part of your billion dollars? That's on top of it? Oh my-
Dr. Mojola Omole:
It's healthcare dollars, right?
Dr. Shahzad Ghanbarian:
No, the one that we reported is from a public payer perspective.
Dr. Blair Bigham:
Oh, wow. It's a no-brainer.
Dr. Shahzad Ghanbarian:
Yeah, it's a win-win situation, right? They will save money and then also the patients would benefit from this intervention. We call it no-brainer or dominant strategy in health economics.
Dr. Blair Bigham:
Of course you have a phraseology for no-brainer. I love that. Is there anywhere in the world that already does this? Has the UK figured this out? Has Australia figured this out? This seems like it should be on the front page of the New York Times.
Dr. Shahzad Ghanbarian:
So pharmacogenomic testing is partially covered for some conditions like cancer in other healthcare systems. For HIV treatment, the UK covered part of that, but to my knowledge, the coverage is not anywhere publicly funded for depression. Norway has partially covered, but if they are hospitalized, they will cover the cost of pharmacogenomic testing.
Dr. Blair Bigham:
Oh. Scandinavia is always ahead of us. They've always got it figured out.
Dr. Mojola Omole:
You've both made a compelling case for both the economic and the clinical effectiveness of doing pharmacogenetic testing with people who are living with major depressive disorder. Have there been any hints of how B.C. government has responded to your research in terms of future healthcare dollars expenditure?
Dr. Jehannine Austin:
So actually, we've been working really closely with our Ministry of Health here from the very outset of this study. So the reason that we did the study was because the Ministry of Health was interested in whether this is something that they should consider funding. So we've been working very closely together throughout and so obviously none of us know at this point what's going to happen in the future, but we do have very healthy, constructive, good lines of communication. And so we will see what happens, I suppose.
Dr. Blair Bigham:
I just want to clarify this billion dollars of savings over 20 years, that's just for British Columbia?
Dr. Shahzad Ghanbarian:
That's correct. We did our study using the data for British Columbia, the pass pay for British Columbia, so that's over 20-year time horizon for BC.
Dr. Jehannine Austin:
But what we don't know yet is although we know that there's costs that we can save by implementing this test, we don't yet know how best to implement it in the context of the healthcare system that we have in British Columbia. So our next phase of work that we hope to engage with is to actually study that, to examine the healthcare providers that could potentially be involved in implementing this work and figure out what works best from a variety of different perspectives in the context of the realities of our healthcare system.
Dr. Blair Bigham:
Got it. Thank you so much for joining us. This has been really interesting.
Dr. Mojola Omole:
Thank you.
Jehannine Austin:
Thank you so much.
Dr. Shahzad Ghanbarian:
Thank you too.
Dr. Blair Bigham:
It's always nice when we have a real big game changer to chat about. Yay.
Jehannine Austin is a professor of psychiatry and medical genetics at UBC and Shahzad Ghanbarian is a mathematical modeler and research scientist also at UBC. Jola, I have so many thoughts about our discussion today.
Dr. Mojola Omole:
So what are some of the thoughts that you're having, Blair?
Dr. Blair Bigham:
I know you're having just as many, very kind of you to Let me go first. Well, first of all, the impact that this could have on people's lives, sure, a billion dollars and maybe even more when we look at societal impacts, but 37% decrease in people with refractory depression. It blows my mind and it makes me wonder if pharmacogenetic testing can do this for depression, where else can we apply pharmacogenetic testing? It almost is like the AI question where AI is going to take over everything and change everything. I wonder if pharmacogenetic testing really has a way larger role to play in an efficient, effective healthcare system than we currently realize.
Dr. Mojola Omole:
100%, I think that that is part of what we talk about when we talk about precision medicine. Knowing that depression is one of the most common chronic illnesses that people have, that this and the impact on people's lives and their productivity and even from the cost savings of that, I think is really important. And although from the government point of view, it's an initial cost and we always think of the initial cost and not the downstream effects of multiple ER visits, multiple visits to the family physician. This, if we do the upfront cost part of preventative medicine, then the downstream effect is astounding.
Dr. Blair Bigham:
Yeah, we really are so reactive. This idea of nailing it right off the bat or early on in somebody's course of a disease obviously resonates.
Dr. Mojola Omole:
For sure. And I think part of it is that medicine is slightly rooted in this old-timey, let's just stir this up and see what happens. And this is really just saying, "You know what? We don't have to do that. We have the ability to predict and to know what is going to work for people when it comes to certain conditions and depression being so common." It would be very powerful.
Dr. Blair Bigham:
I also wonder how much there's this bias towards the traditional, what an old school person might say is a real disease. Cardiac catheterization is super expensive. It required giant labs to be built and very expensive wires, and it was implemented relatively quickly and totally changed care for people having STEMIs, for example. But I just wonder if there's less enthusiasm about using other new evolving technologies for mental health problems because of the stigma and low priority mental health often gets in a system that's always competing for dollars.
Dr. Mojola Omole:
And I would say, I think the other thing that drives the stigma and probably less dollars into pharmacogenetics is the fact that women are twice as likely to be diagnosed with depression. And so there is a lack of funding for diseases and conditions that affect predominantly cis women.
Dr. Blair Bigham:
Right. Fascinating, yeah. That's it for this episode of the CMAJ podcast. If you like what you heard, please do give us a five star rating wherever it is you get your podcasts. It goes a long way to helping us spread the word. The CMAJ podcast is produced for CMAJ by Neil Morrison at PodCraft Productions. Thanks so much for listening. I'm Blair Bigham.
Dr. Mojola Omole:
I'm Mojola Omole. Until next time, be well.