16 Minutes on the News: The Opioid Crisis

0:00:03 Hi, everyone. Welcome to the A6NZ podcast.
0:00:06 I’m Sonal, and I’m here today with the fourth episode
0:00:08 of our new short form new show, “16 Minutes,”
0:00:10 where we cover recent headlines
0:00:12 the A6NZ way offering expert takes
0:00:14 on the trends involved in more.
0:00:16 You can follow the show in its own feed
0:00:18 in your favorite podcast player app.
0:00:21 Our other episodes cover multiple news items and topics,
0:00:23 but this week, we’re doing two separate,
0:00:26 but short, deep dives connected to recent headlines.
0:00:28 One on eSports gaming and the future of entertainment,
0:00:30 which you can find in this feed,
0:00:33 or at a6nz.com/16minutes.
0:00:34 And this episode,
0:00:38 which is on a sad but important topic, the opioid crisis.
0:00:39 Just to quickly sum up,
0:00:42 the issue of the opioid crisis has been around for years,
0:00:44 which is at this prescription opioid epidemic
0:00:46 that resulted in nearly 100,000 deaths
0:00:50 from 2005 to 2012, and what makes it even sadder
0:00:52 is that it just proportionately affected people
0:00:54 from regions that are underserved economically,
0:00:56 for instance, Native American tribal regions,
0:00:58 towns in West Virginia, and so on.
0:01:00 For what opioids are, as a reminder,
0:01:01 remember the word opium?
0:01:03 There are a class of drugs that include
0:01:05 heroin, fentanyl, pain relievers like OxyContin,
0:01:07 Vicodin, Codine, Morphine,
0:01:08 and most of those are pain relievers
0:01:11 that are legal and available by prescription.
0:01:13 This crisis has been around for years, but here’s the news.
0:01:15 The Washington Post and the publisher
0:01:17 of the Charleston Gazette Mail,
0:01:18 which is a West Virginia paper,
0:01:21 one of the regions that’s most impacted by this crisis,
0:01:24 waged a year-long legal battle and won a court order
0:01:28 for access to the Drug Enforcement Administration’s database,
0:01:29 which is this Automation of Reports
0:01:32 and Consolidated Orders, it’s the ARCOS database.
0:01:35 And basically, the Washington Post’s work helps visualize
0:01:38 how much specific drugs went to individual states
0:01:41 and counties, and who the top distributors,
0:01:43 manufacturers, and pharmacies that were involved.
0:01:46 And according to the Post, high-level findings,
0:01:49 just three companies manufactured about 88% of the pills,
0:01:52 and just six companies distributed 75% of them.
0:01:54 And over the past couple of weeks,
0:01:55 a number of lawsuits have been filed
0:01:56 as a result of those findings.
0:02:00 Arizona just filed a case against a maker of oxycontin.
0:02:02 Unusually, they did it directly at the Supreme Court level,
0:02:05 while towns and cities are suing pharmacies
0:02:07 like Walmart, CVS, and Walgreens.
0:02:09 In fact, nearly 2,000 cases have been brought
0:02:11 as reported by the New York Times.
0:02:14 And their headline for that story, by the way,
0:02:16 was so perfect and so starkly sad.
0:02:21 3,271 pill bottles, a town of 2,831.
0:02:25 So that’s a high-level summary of what’s going on,
0:02:27 what’s in the news.
0:02:29 I’d like to now welcome A-6 and Z-Bio,
0:02:32 general partners Jorge Conde and Vijay Pandey
0:02:34 to talk about their views on this
0:02:35 from their vantage point.
0:02:36 Welcome, guys.
0:02:37 – Thank you.
0:02:39 – So one bit of color from that New York Times story
0:02:42 that is just so vivid and heartbreaking.
0:02:45 One county in Ohio resorted to a mobile morgue
0:02:47 just to handle all the corpses from people
0:02:50 who died from overdoses, which is so sad.
0:02:51 And as with all such things,
0:02:54 science and technology is not living a vacuum
0:02:56 and plays out against a broader structural context.
0:02:58 So I want to acknowledge that,
0:03:00 that we’re going to be focusing on a specific angle,
0:03:02 but really this is a huge problem
0:03:04 on so many different levels.
0:03:06 So first of all, can you just quickly summarize
0:03:08 the crisis from your point of view?
0:03:10 Why opioid? What’s going on here?
0:03:12 – Well, first of all, opioids, as you said,
0:03:13 are opium-based drugs.
0:03:16 And it’s probably worth a moment to talk about
0:03:19 kind of how they work and why there’s a problem.
0:03:23 Opioids basically target a receptor class within cells
0:03:24 called the opioid receptors.
0:03:25 And there’s three main classes.
0:03:27 And the three main classes
0:03:29 all have slightly different functions.
0:03:31 And by the way, as we learn more biology,
0:03:34 but I think identified another 15 or 20 subclasses
0:03:34 of these things.
0:03:36 So the biology as you can imagine is complex,
0:03:38 but essentially what happens with an opioid
0:03:43 is that it targets one or usually many of these receptors.
0:03:47 And that has the pain numbing or pain killing effect.
0:03:49 It also hits some of our,
0:03:51 essentially our pleasure-seeking centers.
0:03:53 So it has the addictive effect.
0:03:54 – Right, hence the addiction.
0:03:55 – And by the way,
0:03:58 it also hits other important receptors that are necessary
0:04:00 for sort of our physiological function.
0:04:02 Most notably, one of the subclasses of receptors
0:04:04 is responsible for sending the signal to your brain
0:04:05 that you need to breathe.
0:04:06 – Whoa, I had no idea.
0:04:07 – Yeah, no.
0:04:10 So a lot of people that overdose and die from opioids,
0:04:12 really what they die from is forgetting to breathe.
0:04:15 And in fact, like the recovery drug Naloxone,
0:04:18 it basically competes for the drug off that receptor.
0:04:20 So the person actually comes back and remembers to breathe.
0:04:23 So the drug itself is incredibly powerful.
0:04:25 And I think one of the important things to remember
0:04:28 is that addiction isn’t weakness.
0:04:30 It’s not lack of willpower.
0:04:32 It’s actually a weakness of the biology
0:04:34 that the opioids target.
0:04:36 In fact, I remember when I was in graduate school,
0:04:39 I took a pharmacology class and the lecturer
0:04:41 at the beginning said,
0:04:42 if I took this classroom,
0:04:44 a very accomplished, intelligent driven,
0:04:46 responsible graduate students, medical students,
0:04:48 and gave everyone a dose of heroin,
0:04:49 a significant proportion,
0:04:52 a significant majority of this class
0:04:54 would be hopeless addicts tomorrow.
0:04:55 So a big part of the problem here
0:04:59 is that this is a very, very powerful class of drugs.
0:05:01 And what’s really tricky about opioids
0:05:03 is that a more powerful drug
0:05:04 is not necessarily a better drug.
0:05:06 – First of all, thank you for acknowledging
0:05:09 that this is not necessarily a choice that people make.
0:05:11 That’s really important, that it’s biology.
0:05:13 But you also mentioned heroin in that example.
0:05:14 That one is an illegal one,
0:05:16 which is of course a class of opioid,
0:05:17 but most of these are prescribed.
0:05:20 So I’m curious for how that plays out.
0:05:23 – First of all, biology is a very dynamic system.
0:05:26 And so if you take a drug, any drug, really,
0:05:28 you start to, or you tend to develop tolerance
0:05:29 for it over time.
0:05:31 And it can happen via various mechanisms,
0:05:33 but one of the mechanisms that’s believed
0:05:35 to be the case in opioids is that
0:05:37 as you essentially take the drug,
0:05:39 your receptors essentially become accustomed to it.
0:05:41 And so it actually changes the dynamic of the receptors
0:05:43 and people describe it as, you know,
0:05:45 if you take opioids for a long time,
0:05:47 you are quite literally changing your brain.
0:05:51 And so the result of that is if you’re taking a drug,
0:05:53 and especially for relieving pain,
0:05:56 you may need more and more of that drug to relieve pain.
0:06:01 If that particular opioid also happens to target or hit,
0:06:02 one of the receptors associated
0:06:06 with what’s linked to addiction over time,
0:06:08 you’re gonna seek more and more of it.
0:06:11 So it just becomes a truly biological dependence
0:06:13 at the cellular level for these drugs.
0:06:14 – Well, you know, it’s important to consider
0:06:16 why patients are getting these in the first place.
0:06:19 – Right, quite honestly, if this is of kind of,
0:06:20 the biology of it is that you become more addicted
0:06:22 as you take it, why are they getting it?
0:06:26 – And there’s two reasons, which is somewhat of a shift.
0:06:29 So one reason is that there’s been a recent shift in policy
0:06:31 that essentially no pain is acceptable.
0:06:33 So, you know, they often ask you
0:06:34 if you’re in the ER or something like,
0:06:36 what’s your pain from zero to 10?
0:06:38 And it’s not that everyone’s saying 10,
0:06:40 and then they get fentanyl.
0:06:42 It’s the belief that no pain is acceptable.
0:06:44 And this is actually very much an American thing.
0:06:47 In other cultures, you know, you may be under extreme pain,
0:06:50 but you’ll get T or you’ll get maybe Tylenol
0:06:52 or something, something very different.
0:06:55 And it’s just understood that you have to sit with the pain.
0:06:57 The second thing that’s just the healthcare system now
0:07:01 is so strained that if, let’s say you have major back pain
0:07:03 and you should maybe be seeing physical therapy
0:07:05 or maybe you should be seeing a doctor
0:07:08 for musculoskeletal, it may take you four weeks,
0:07:09 six weeks to see that doctor.
0:07:11 It takes time to see an expert.
0:07:13 Yeah, but you could get the prescription immediately.
0:07:14 So some of this is tied to healthcare access.
0:07:17 Yeah, but then, you know, puts them in this bind
0:07:19 where they really should be getting physical therapy
0:07:22 or something like that, and they are on this path.
0:07:24 The third thing is that often the alternatives
0:07:26 are harder short-term, like physical therapy
0:07:28 is a lot of pain.
0:07:30 And so this is just, it’s available,
0:07:33 it’s thrown on you by a doctor and it’s easy.
0:07:35 You put those things together.
0:07:38 That’s the match on the, that lights the fire.
0:07:41 So this is very helpful for helping break down the biology
0:07:43 and the science behind this.
0:07:46 It plays out against broader structural factors,
0:07:48 cultural factors, political factors.
0:07:50 This is a really big important topic.
0:07:53 And I have to ask, who’s to blame?
0:07:56 Like the interesting thing is that the news,
0:07:58 there’s all these lawsuits happening to these pharmacies
0:07:59 and now the pharmacies and distributors,
0:08:00 they’re coming back and saying,
0:08:02 well, what about the impact of doctors
0:08:03 and criminal drug dealers?
0:08:05 Politicians, they are the ones who are trying
0:08:06 to hide the database.
0:08:08 There’s so many different players going around here.
0:08:10 I want you guys to tell me, like, who’s to blame?
0:08:12 I mean, embedded in the question is part of the answer.
0:08:15 I think really what we have is a massive systemic failure.
0:08:16 I mean, you talk about manufacturers,
0:08:19 you talk about distributors, you talk about pharmacies,
0:08:20 you talk about prescribing physicians.
0:08:22 And ultimately you talk about patients
0:08:24 and their families and their caregivers
0:08:27 and sort of the communities that support them.
0:08:29 And then you also talk about the politicians,
0:08:30 you know, the public health agencies.
0:08:34 I think the systemic failure here is pretty broad.
0:08:35 So we can start from the very beginning,
0:08:39 which is we do need better opioids.
0:08:40 We do need better pain killing drugs.
0:08:42 We need, as Vijay mentioned,
0:08:45 to be more thoughtful about how and when we intervene
0:08:47 with pharmacologic drugs, forward pain.
0:08:51 One of the things that you can do with an opioid
0:08:53 is you can try to design something
0:08:55 that is only hitting the right receptor.
0:08:56 This goes back to your earlier point about there being
0:08:58 15 types of receptors that are now being discovered.
0:08:59 You can get more and more precise.
0:09:00 Exactly.
0:09:01 So now that we can engineer cells
0:09:02 and we can work with cells,
0:09:05 we can find very precise ways to understand
0:09:09 what molecules are interacting with what parts of the cell
0:09:12 and design molecules that are hitting just the right notes
0:09:13 that are gonna be more targeted.
0:09:16 So there is the potential for a better opioid.
0:09:19 By the way, to date, most of the attempts to improve it
0:09:22 have been to address the ways to not tamper with it
0:09:24 so you can overdose on it.
0:09:26 But the reality is you can get a better molecule
0:09:27 if we understand what’s driving the biology.
0:09:29 So that’s the first step on the manufacturing side.
0:09:33 The second one is, yes, the distributors and the pharmacies,
0:09:35 I mean, the biggest problem is that this is a very ad hoc,
0:09:39 disjointed system that we have here in the United States.
0:09:39 Like healthcare system.
0:09:40 The healthcare system.
0:09:42 And so I think a lot of what you’re relying on
0:09:44 in terms of the crisis is that there aren’t really
0:09:47 the checks and balances and the alert systems
0:09:49 that one would expect in place
0:09:51 that doesn’t require sort of a human being to say,
0:09:54 this employees flag one particular shipment.
0:09:56 But that one particular shipment
0:09:58 or that one particular prescription obviously
0:10:01 doesn’t catch the systemic problem as it’s evolving.
0:10:04 And so you’re really missing the force for the tree.
0:10:05 – Is that a place that tech can help?
0:10:07 – It’s an absolute place that tech can help
0:10:08 because I mean, first of all,
0:10:10 a lot of this is by requirement
0:10:14 that you have to inform the public health agencies
0:10:18 if there is the suspected overuse of a controlled substance.
0:10:20 And so instead of requiring on people to voluntarily do that,
0:10:22 you could deploy technology-based systems
0:10:24 that essentially do that automatically.
0:10:26 – In fact, one of the quotes in the “New York Times” article
0:10:28 came from a Walgreens official who said
0:10:30 that he was the one who was tasked with monitoring
0:10:32 the orders said his department, I quote,
0:10:34 was not equipped for that work.
0:10:35 I mean, that seems like an obvious place
0:10:37 that tech could literally do what you’re describing.
0:10:39 – And it’s a place that tech could do it far better.
0:10:40 – Exactly, no, that makes great sense.
0:10:41 – You have to understand, I mean,
0:10:43 what’s going on in a lot of these places,
0:10:45 it’s post, it’s fax machines.
0:10:48 It’s something where the things that we take for granted
0:10:50 that sort of just coordinate our daily lives
0:10:52 could be put in here
0:10:54 and could really have a significant impact.
0:10:57 – Okay, so let’s go back to the systemic players and failures.
0:10:58 We have manufacturers, distributors.
0:11:00 Let’s continue breaking each one of those down.
0:11:01 – On the manufacturer side,
0:11:03 there’s really two issues here.
0:11:05 One is we do need better drugs as we talked about.
0:11:08 And number two, and I think this is a very important point,
0:11:10 is a lot of times in companies
0:11:13 as they’re commercializing drugs,
0:11:15 obviously the goal is to grow revenue.
0:11:18 And that can sometimes create perverse incentives
0:11:21 to drive usage where perhaps there shouldn’t be usage.
0:11:23 And I’m not saying that’s necessarily the case here,
0:11:25 but that’s something that I’ve seen happen,
0:11:28 unfortunately, across the industry over time.
0:11:29 The second issue is the distributors.
0:11:31 The distributors are obviously responsible
0:11:33 for moving product through the channel.
0:11:35 They of course have incentive
0:11:38 to move more product through the channel.
0:11:40 And so, if there are no controls in place,
0:11:42 if the right tensions aren’t there
0:11:44 between how things are prescribed
0:11:45 or how things are reordered
0:11:47 or how things are pulled through the system,
0:11:49 that could also create a perverse incentive
0:11:50 from a distributor standpoint.
0:11:52 And I think you show some of the concentration
0:11:56 of what happened in the case of this particular opioid,
0:11:58 episode of the opioid crisis as you’ve laid it out.
0:12:00 So we do need checks against the distributors as well.
0:12:02 When you get to the pharmacy,
0:12:04 the pharmacy is where the rubber meets the road, right?
0:12:06 Is these are where the prescriptions are getting picked up,
0:12:07 we’re getting shipped to at least.
0:12:12 And so, if you don’t have a manual control system there,
0:12:14 I actually think that the biggest problem
0:12:16 is just lack of an alert system.
0:12:20 If I go in today to pick up a prescription,
0:12:22 there’s no real system that would raise flags,
0:12:25 at least not efficiently, at the system-wide level.
0:12:27 It tends to happen very episodically,
0:12:29 as the story itself has shown.
0:12:32 And then finally, there’s the physician prescription challenge.
0:12:33 Because patients are in pain,
0:12:36 the physician may not want them to tolerate pain,
0:12:38 so it may be more likely to offer this,
0:12:39 to offer immediate relief.
0:12:41 Two, you get to the point where,
0:12:43 if you have to wait weeks and weeks and weeks
0:12:46 to see a specialist or to get therapy or to get treatment,
0:12:48 this is a fast-to-fix, short-term solution
0:12:50 that eventually might become a longer-term problem,
0:12:54 obviously, as addiction becomes an issue.
0:12:57 And the third one is, and these are all related points,
0:12:59 but physicians, for the most part,
0:13:02 don’t have the right control systems
0:13:05 to do really effective medication management.
0:13:07 So, my treatment of you is very episodic.
0:13:09 I come, I see you, you describe pain,
0:13:10 I will prescribe something.
0:13:12 I may look in the notes and go back
0:13:14 and see what had happened in the past,
0:13:16 but I’m not really following this day-to-day.
0:13:18 And this, by the way, applies across all health problems,
0:13:21 all health, medication management,
0:13:23 medication reconciliation is a massive problem
0:13:25 across the entire healthcare system.
0:13:26 The particular challenge here, of course,
0:13:28 is that this is the one area
0:13:31 where a more powerful drug leads to more usage
0:13:33 rather than less usage.
0:13:34 And that’s what makes it so difficult
0:13:35 when you can’t reconcile, you know,
0:13:38 patient usage is happening over time.
0:13:40 – Well, and there’s ways that we could work
0:13:41 within the existing system.
0:13:43 Like, one thing you could imagine is a PBM
0:13:44 that is more involved-
0:13:45 – A Pharmacy Benefit Manager.
0:13:46 – Yeah, Pharmacy Benefit Manager,
0:13:48 that’s more involved with clinical care,
0:13:50 where they’re just, they’re not the doctors,
0:13:52 but at least they’re better interfacing with the doctors,
0:13:54 such that you can at least have sanity checks,
0:13:56 like there’s no reason why a patient would need this.
0:13:59 And this way you can’t shop around to multiple pharmacies
0:14:00 because you’ve got the same PBM.
0:14:01 And it is that layer.
0:14:04 And I think as you start to get smarter PBMs,
0:14:06 these problems would be very naturally addressed,
0:14:08 not just for the opioid crisis,
0:14:09 but it would be true for patients
0:14:11 that have sometimes two or three drugs
0:14:12 to treat the same condition,
0:14:14 or three drugs that are actually
0:14:15 gonna interfere with each other.
0:14:16 Those are sometimes very difficult
0:14:17 because in the medical system,
0:14:20 you’ve got the endocrinologist and the cardiologist
0:14:23 and the psychiatrist, each prescribing,
0:14:25 or without really any coordination.
0:14:27 – And you know, to that exact point,
0:14:29 we have a problem in the healthcare system
0:14:30 of getting things deprescribed.
0:14:31 – What do you mean by that?
0:14:34 – Well, the patients might be taking a medication
0:14:35 for an acute condition.
0:14:37 And you know, I saw the physician,
0:14:38 and the physician told me to take this medicine
0:14:39 for a condition accident.
0:14:41 – You broke your arm and you need back again.
0:14:44 – Or you may have a heart condition
0:14:45 that is going through an acute episode.
0:14:48 Any number of things that I’m on 10 different medications,
0:14:50 it could be that the condition
0:14:52 for which this one drug was given to me
0:14:54 has since been alleviated, has since been addressed.
0:14:55 – But that information doesn’t get plugged back
0:14:56 into the system.
0:14:57 – Yeah, and I don’t know to stop taking it.
0:14:58 So I might be taking a medication
0:15:00 that I don’t need for a long period of time.
0:15:02 And if somebody doesn’t do the reconciliation
0:15:03 that we just described,
0:15:04 I could be on many medications
0:15:05 that not only interfere with each other,
0:15:06 which is a problem,
0:15:07 but that I may not even need,
0:15:08 which is a different problem.
0:15:10 – So that kind of addresses it
0:15:12 at the sort of structural logistical level
0:15:14 of the healthcare system.
0:15:16 Now, back to the point you brought up
0:15:18 about the biology and some of the pain management.
0:15:19 I mean, there’s obviously alternatives
0:15:21 like TENS devices and all kinds of things
0:15:23 that could potentially scale in the future to address pain.
0:15:24 But now let’s go to what the fixes are.
0:15:26 Obviously there’s social societal things
0:15:27 that need to be addressed,
0:15:30 but what can tech and science help with here?
0:15:31 Are there any other future directions
0:15:33 from your vantage point on the biocide?
0:15:35 Clearly there’s technology to address the transparency,
0:15:37 the pre-BMs, the pharmacy benefit managers,
0:15:40 closing the loop, everything from manufacturer’s distribution
0:15:41 to prescription.
0:15:42 What are some of the other things?
0:15:44 What are some of the interesting directions you see
0:15:45 to help address this?
0:15:47 – Well, there are efforts to develop
0:15:50 digital therapeutics, VR type applications.
0:15:51 – And by the way, digital therapeutics
0:15:54 is in like apps and things like technology
0:15:56 that can actually act as if a drug
0:15:58 in helping people to better outcomes.
0:16:01 – Exactly, that can help you get you into a state of mind
0:16:03 that might help alleviate the pain, right?
0:16:05 So, you know, if you can find different ways
0:16:06 to address the pain issue,
0:16:08 whether it’s physical therapies
0:16:10 or something maybe novel like, you know,
0:16:14 quite literally having a VR virtual reality type experience
0:16:15 or having an application on your phone
0:16:18 that helps you meditate or calm down
0:16:19 that might address some of the pain issues,
0:16:20 you may not be as dependent
0:16:22 on getting on the opioids in the first place.
0:16:23 – I’ve read a ton of papers actually
0:16:25 that VR has already proven to be effective
0:16:28 in helping with PTSD, post-traumatic stress disorders
0:16:30 with veterans coming back from wars
0:16:33 or, you know, people who are suffering severe depression.
0:16:34 It’s just, it’s really amazing that it can help.
0:16:37 – Well, you know, I think often we are worrying
0:16:39 about the consequences without thinking about the source
0:16:42 or you made a great point about how addiction
0:16:43 is a natural consequence.
0:16:45 There are other recent studies that talk about
0:16:47 sort of a little deeper about why this is so.
0:16:50 So the famous one is called the rat park study
0:16:52 where they actually had rats in a cage
0:16:53 which is kind of like in jail
0:16:56 and given the choice between food or opioid,
0:16:57 they’ll take the opioid
0:16:59 until eventually they kill themselves.
0:17:00 But if you give them access to rat park
0:17:01 where they can play and be social
0:17:04 and sort of just live their normal happy lives,
0:17:06 then actually given the same choice,
0:17:08 they would choose food and not the opioid.
0:17:12 We know that social determinants are a key part of healthcare.
0:17:15 It’s just not wrapped into a fee for service kind of system
0:17:17 where no one’s job is to take care of these things.
0:17:20 But we could take care of the root causes of this
0:17:22 which are beyond just about prescribing drugs
0:17:25 but thinking about healthcare as a societal issue.
0:17:27 I think then we can actually really have a huge impact.
0:17:31 – And there are several efforts ongoing now to use technology
0:17:35 to help try to pull in all of those stakeholders
0:17:37 in the community that can have such a big impact
0:17:39 on some of these social determinants of health.
0:17:42 Without that is another example of a fragmented system,
0:17:45 a very analog system is you’re doing this with call sheets
0:17:47 and coming up with referral names
0:17:48 and calling and trying to get appointments
0:17:51 and inbound visits and things like that.
0:17:52 And it’s all necessary
0:17:54 because this requires human intervention
0:17:56 but the coordination shouldn’t also be human.
0:17:58 So I think technology has an opportunity here
0:18:00 to have a massive impact on how we coordinate
0:18:02 all of these stakeholders to the people
0:18:03 that may be more susceptible
0:18:06 given some of these social determinants are more supported.
0:18:08 – Right and it just goes back to the bottom line for me though
0:18:09 which is technology is social
0:18:11 and it lives in a broader cultural context
0:18:12 that clearly plays.
0:18:14 Well, thank you so much Jorge and Vijay
0:18:17 for joining the A6NZ Podcast 16 Minutes.
0:18:18 – Thank you.