Precision Medicine to Reduce Time Spent on Trial and Error Prescribing [Interview][Transcript]


Guest: Dr. Ajeet Singh
Presenter: Wayne Bucklar
Guest Bio: Dr Ajeet Singh MD is an Australian Academic Private Psychiatrist based in the Melbourne Area. In 2013 he was awarded his doctorate for work on antidepressant pharmacogenetics. He advises both government and industry groups on genetically guided prescribing – precision medicine. Ajeet is passionate about improving patient outcomes through tailored care.

Segment overview: For our Health Academy Series today, Dr. Ajeet Singh talks about genetically guided prescribing of antidepressants. He is a private psychiatrist at the Geelong Clinic and Senior Clinical Lecturer at the Deakin University School of Medicine, and also the founder of the GMHC Lobby Group. Dr. Ajeet Singh believes that precision medicine can reduce the trial and error process which many clinicians do when prescribing antidepressants.


Health Professional Radio

Wayne Bucklar: You’re listening to Health Professional Radio. My name is Wayne Bucklar and this is the Health Academy, our regular look at what’s happening in the academic world. And my guest today is Dr. Ajeet B. Singh. Now Ajeet is with the Geelong clinic and Deakin University School of Medicine where he is a psychiatrist. Welcome to Health Professional Radio Ajeet.
Dr. Ajeet B. Singh: Thanks for speaking with me.
W: It’s a pleasure to have you on. Now tell us what’s been getting your interest lately in the research world?
S: Well I’ve developed a very strong interest in what seems to be a really accelerating area at the moment “genetically guided prescribing” also to referred as “precision medicine.” And my interest began really out of a clinical need. So I became a psychiatrist back in 2005 and after about a year of working in practice was increasingly apparent to me that the way we prescribe medications to people that need them was very much “trial and error process” and this sort of got me interested in seeing if there were ways of reducing trial and error. And at that stage it was still relatively early days and investigating whether genetic variants could help predict who needed which medication at which dose. So that again really a several year process doing research, getting a doctorate all about trying to answer a clinical problem. And it’s a problem that still affects a lot of patients globally and it’s why it’s still a strong passion of mine.
W: Now it is the case I think it’s not that a lot of psychiatric prescribing is really about trying something and looking to avoid unpleasant side effects.
S: Yes. So I’m sort of based in a private practice setting and essentially what we deal with is people suffering with severe depression. Happily there’s a great many people when they have issue with depression, we get major dividends from lifestyle modification or psychological counseling. But there’s a group of people who have more severe persisting and handicapping cases of depression who present for help. And essentially the process is out of a collection of 15 to 20 odd medications there’s a trial and error process to see which medication works best for an individual. Sometimes you get a whole in one and the first medication at the first dose really makes a difference, sometimes it can take years. Equally there’s a group of patients where medications won’t be the be all and the end all and other issues be at damage from their childhood or too much stress in their life now, are require focus upon.
W: Now this is not a quick process for psychiatric medicines, is it? You can’t treat it like aspirin and take it now get an effect in 30 minutes time.
S: No. So one of the issues is the way we think these medications work it’s quite tricky. So seems to take at least a few weeks for them to begin to alter brain chemistry and the exact mechanism of how they work is unclear, I think reflecting just how complex a human brain is. But basically all you can discern in the first week is it somebody’s getting “side effects” and then basically just tell them to reduce the dose or stop it. But it takes at least a month to get a good signature if this they gonna improve, they can take up to 3 months to see if they recover and part of this drawn out process is the anti-depressant seems to alter chemical balances that can enable brain pathways to connect more strongly. A lot of people might have heard of “neuroplasticity” this idea that the brain is not locked in, it can actually recover and this process can take a few months. So the big issue with depression pills is you might start something and it might be a month before you know whether it’s working and you can see how very quickly 6 or 12 months can pass if you’re having trial and error through different set of pills or different doses.
W: So being able to more accurately predict what medications are going to work with which individual is obviously is a big advantage. What was the results of your research, where are we at?
S: So there’s been, it’s medical research is a process. And the early, at the earlier stages were association studies were there wasn’t a comparison between genetically guided prescribing and traditional non-guided prescribing. And the problem with association is there are all sort of factors that could mediate anything seeming outcome. So there were no firm conclusions, recently I’ve done work comparing whether genetically guided prescribing improve outcomes more than non-guided prescribing. And in a group I looked at we had a nearly doubling of the recovery rate over 12 weeks and the message that I took was looking at how we differ in our liver enzyme genetics and also genetics at the blood brain barrier. So early on in my career I’ve got the impression the brain itself was really tricky. So try to figure out kind of like the box that it comes in and a surprising thing about the brain is that it’s covered in this wrapping or membrane called the “blood brain barrier” which prevents medications getting in generally.
W: Uh huh.
S: And so it’s really looking at gene variants at that step as well as at the liver. Pretty much when you swallow a pill, most of it gets knocked out by your liver before it enters the blood stream. And then the fraction that gets into the blood stream, only a fraction of that can cross into the brain due to this blood brain barrier. And so there have been a specific thing that I focused on in my work.
W: You’re listening to Health Academy with Health Professional Radio. My name is Wayne Bucklar and I’m in conversation with Dr. Ajeet B. Singh who’s a private psychiatrist and an academic with Geelong Clinic in the Deakin University School of Medicine. We’ve been talking about prescribing and genetics. Now Ajeet, is genetics at a point where it is sufficiently detailed to be predictive?
S: So I think the big news in the last 5 years has been the exponential reduction in cost. So people can sort of remember back to around 2003 when the Human Genome Project was completed were they could have done the DNA sequence of one whole person, that cost about three billion US dollars.
W: (chuckles) Petty cash really, just petty cash.
S: (chuckles) As of last year the same thing can be done for USD$1,000. As of this week a single gene variant can be analyzes to USD$50 commercially.
W: Wow.
S: So what’s happened is the price point has really gotten low. And this is turbo charging not only commercial interest but research. So often research is a phase is a very tight budgets and competition for grants. What we’re seeing is a bigger infliction upswing in the amount of clinical research being done particularly comparing genetically guided prescribing to non-guided prescribing to see if this new method actually has real world merit or not.
W: Now even at $50, what’s involved in getting a gene study done? Is this a complex process for an individual?
S: So essentially you can either give a blood sample or just a spit sample. So a lot of the research I’ve done has been this really from a spit sample which you can collect in your office without any needles or people can go to their usual lab and get a blood test. And then there are certain companies that manufacture things called “Gene Chips” so basically what’s happening now is lots of labs globally have access to these sequencing machines. They just put your sample in this little Chip, plug it into the machine and then they get a result of your chip DNA profile. So things sort of reached that level of mass production and simplicity.
W: That’s an astonishing reduction in both cost and complexity in a very short period of time, isn’t it?
S: Yeah. And I think this is often we would become zealous about the area were interested in it can be lost in your own little world but earlier this year what got at a lot of attention was Barack Obama’s state of the Union Address. So January this year the one area of Science and Technology he highlighted was “Precision Medicine” this genetically guided prescribing. And a lot of the works has been done on genetically guided cancer treatment prescribing to get better survival but it’s also crossing over to all domains of medicine including antidepressant prescribing. And that was seen as a sort of lead indicator that this area is accelerating. And he pledged a quarter of a billion dollars with Bipartisan support to accelerate research in the area, he has pledged to have 1M American’s genotype have to hold genome done. The UK government last year pledged to do that for a hundred thousand. So it seems that we got trans-Atlantic race at the moment, with the UK and the USA leading the frontier.
W: And has your work reached the point where it’s something you can use in practice at this point?
S: So I’s say the evidence based at the moment in my view is suitable for earlier doctors. For at a level of evidence to reach routine prescribing guidelines that need to be the replicated, repeated, randomized, controlled trials. And so the evidence is not at that point yet but in the pipeline at the moment just in the antidepressant genetically guided prescribing, there are multiple randomized controlled trials in the pipeline. Now I’m anticipating by the end of next year we should see if we’ve got you know replicated, repeated, randomized, controlled trials coming through. At that point, I predict genetically guided prescribing will actually start to enter prescribing guidelines. It already has in psychiatry for one medication called “carbamazepine” – this is a medication used in epilepsy. But it’s also used in Bipolar Disorders and there’s a side effect called “Steven Johnson Syndrome.” It’s a catastrophic skin reaction which is more common in people with Asian ethnicity. So for people with an Asian ethnicity to have a $50 genetic test, we can predict if they’re at a very high risk of that reaction or not and make prescribing decisions. So that just entered routine prescribing guidelines and I think it’s the first wave of what’s gonna be a trend of genetically guided prescribing entering guidelines but again that evidence needs to be more mature.
W: And I guess Ajeet, given that the way you described some of the prescribing processes being trial and error to begin with – you don’t need to have a very strong rational for spending $50 if it’s going to improve what is really a random process anyway.
S: Yeah, well I think one of the things is also it’s one test per lifetime. So it’s not like getting repeated function test. Once we get your genotype, hopefully it doesn’t change overtime.
W: (chuckles)
S: So that also makes it attractive. I think the other thing is as the world faces lots of budget pressures, often new medical technology equals greater healthcare costs. With genetically guided prescribing we could take out enormous amounts of waste from the system and this is an example of a technology that could actually reduce total health spend. I think this is another reason why government is accelerating this area of work.
W: Yes. That’s a fact itself of a once a lifetime test is a thought that just haven’t occurred to me. Is there a downside that you see?
S: I think one of the perhaps early in any new medical technology is there can be people making claims way ahead of the evidence, either through commercial or academic ambition. And that’s something which regulators have to try and manage and early this year the FDA announced that they’re actually start to monitor companies offering genetic tests to make sure that they’ve got some robust evidence behind their claims. There had been a little bit of cowboy territory with companies were saying “We’ve got a genetic test for “XY zed” but in fact the science behind it was very flimsy and I think now government is starting to regulate the space. It will actually enhance the space because more credible tests will come through.
W: Yes, it’s an exciting time. But any where you get an exciting time you get a little bit of gold rush fever and there are always edges to be worried about.
S: Yeah, I think that’s right. And I often sort of reflect what is my core role and my role is to serve my patients. And so if we figure out better ways of helping people that are robustly empirically demonstrated – that’s the pathway forward. If we end up jumping the gun and exposing people to message that might not be in their best interest, we actually goes against our core intent as medical practitioners of trying to get optimal outcomes for our patients.
W: You’re listening to Health Professional Radio. My name is Wayne Bucklar and this is the Health Academy, our regular look at research and what’s happening within the academic world. My guest today is Dr. Ajeet Singh. Ajeet is a psychiatrist in academic at both the Geelong Clinic and Deakin University School of Medicine. Now Ajeet, I noticed recently in some research about you that you’ve been competing. I see that you’re a semi-finalist in a Biotech Start-up competition, tell us about that.
S: Yes. So I kind of stepped out of my comfort zone and so I often think of what happens in medical practice and academic medicine is we can sort of particularly at least in Australia be at very arm’s length to industry. But recently I’ve been reflecting on translational medicine, the concept of getting an idea, getting science to changing clinical practice. And I think one of the translational gaps is appropriate medical entrepreneurialism. I think a lot of medical practitioners consider entrepreneurialism as something to avoid. But I’ve made a deliberate decision to see whether we can get an evidenced based genetic guidelines report system up at running clearly indicating the strength and limits of the evidence and that’s in the early adoption phase. And with that in mind I ended a biotechnology start-up competition in Melbourne and got a lot further than I anticipated as a novice. But it was a great opportunity to learn a little bit about the different kind of language and thinking needed to actually birth something into reality beyond the academic alone.
W: And are you in a position to tell us what that idea was now? Or is it still secret and commercially sensitive?
S: No. So basically the idea is similar to as we discussed before is looking at gene variants at both liver enzymes and the blood brain barrier to guide the antidepressant prescribing. That really comes of the clinical trial which I’ve run the evidence of that and then making that available. But I’m very anxious that it’s not misrepresented. And that people visiting the website will be able to see that it’s based on this evidence and to have a dialogue with their doctor. I think one of the traps is anything that undermines a doctor-patient relationship, I think can back fire and I’m hoping to make this available but in a way that’s sort of enshrined and in the safe guards of the doctor-patient relationship, might help bring the technology forward somewhat.
W: Now your clinical and academic conservators and here’s completely at odds with the entrepreneurial IT world where you must over hype this, present this as being able to do everything from stop world hunger to colonize Mars and talk up the initial offering on the stock market. So I’m gonna have to give you lessons on how to do that, I think Ajeet.
S: (laughing) You know what I’m a believer that great products sell and maybe I’m employing reverse psychology.
Both: (laughing)
W: Perhaps, you’re well qualified to do that. Ajeet one of my favorite questions is about what’s coming over the horizon. Have you been looking you take off your conservative glasses for a moment and you look at where the next two years might be going, what’s the big thing you think in your area?
S: I think in the future getting your hold genome sequence will be so cheap that people will have the option of having it at birth or across entire populations. And I think if it’s used properly it will give people a heads-up on conditions they’re at above average who are risk of, which at one level could inflate anxiety but at another level could give people an opportunity to intensify, preventative and screening measures. So I could see a future where with no elevate risk of certain conditions, be their mental health, cancers other conditions. And then an opportunity to intensify preventative and screening opportunities. So I actually see a lot of good arising from the precision medicine space and genetics in general.
W: It will be interesting to see what the future brings in that area. Ajeet it’s been my pleasure to have you on this morning because it’s been a fascinating conversation. Thank you for joining us on the Health Academy on Health Professional Radio.
S: Yes it’s been a privilege and I thank you for the time.
W: Oh my pleasure. If you’ve just joined us, well then you just missed out on a fascinating conversation with Dr. Ajeet B. Singh, a psychiatric and academic from the Geelong Clinic and the Deakin University School of Medicine. However the good news is on our website we have a transcript at and there’s an audio archive both on SoundCloud and on YouTube. My name is Wayne Bucklar, this is the Health Academy on Health Professional Radio.

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