Debunking the Standard Narrative on the "Opioid Epidemic": A Response to Vox

This post will be a response to the standard narrative on the "opioid epidemic" using this Vox piece by German Lopez as a foil. I should make very clear that I am not picking on Vox or Mr. Lopez here. They have a lot of company. I see a lot of irresponsible and inaccurate reporting on the so-called opioid epidemic. Details are wrong, important facts and details are omitted, wild speculation is indulged, and selective use of "experts" is made to tie everything into a standard narrative. Also, this isn't personal. I have tried not to add any gratuitous barbs or insults to this piece. If the Vox piece got something badly wrong, or if Mr. Lopez suggests some policy change that would have horrible consequences, I try to point these things out as matter-of-factly as I can. This can feel like a personal attack even if done carefully, so I've tried to be aware of this. I hope Mr. Lopez finds his way to my piece and it influences his reporting.

 The title of his piece is "The Opioid Epidemic Explained", the subtitle (tagline?) is "The opioid epidemic could kill as many as 650,000 people in the next decade. Here’s how it got so bad." Both the title and tagline are incredibly misleading.

Lopez opens with this:

If nothing is done, we can expect a lot of people to die: A forecast by STAT concluded that as many as 650,000 people will die over the next 10 years from opioid overdoses — more than the entire city of Baltimore. The US risks losing the equivalent of a whole American city in just one decade.

Link preserved. If you open that link, you will find an article with the title "STAT forecast: Opioids could kill nearly 500,000 Americans in the next decade." 650,000? 500,000? What's going on here? Read the STAT piece. There are ten different scenarios, and Lopez picked the worst case scenario to sensationalize his story. Lopez links to the piece, and does say "as many as 650,000 people will die" over the next ten years. But why lead with the highest plausible estimate, rather than a mid-range estimate? The middle scenarios give you numbers in the 350,000 - 400,000 range. Still scary, I suppose, but why exaggerate? A careless reader will anchor to the 650,000 figure and not remember that it's an extremely pessimistic and unlikely scenario. And why sum across an entire decade anyway? A more valuable piece of information might be something like "risk per legal prescription" or "risk per user." (We'll get to that later.) It is incredibly bad "public health" analysis to sum up a risk across a huge population to get a large number, then build your case on how big that number is. It's even worse to sum across multiple years. Why stop at 10 years, anyway? Why not sum up 20 or 30 years and make it a cool million? Why not sum up across an entire century? If America had three times the population, and thus three times the expected number of overdose deaths, would the problem be three times worse? If some hypothetical future society with one trillion people had the same rate of opioid overdose mortality, would it be three thousand times as big a problem? I don't think so. The relevant measure of risk is per user per year (or some other relevant time period). This piece is off to a bad start.

From the next paragraph:

In 2015, more than 52,000 people died of drug overdoses in America — about two-thirds of which were linked to opioids. The toll is on its way up, with an analysis of preliminary data from the New York Times finding that 59,000 to 65,000 likely died from drug overdoses in 2016.

Once again, he anchors the reader to an irrelevant number: 52,000. A careful reader will pull out his calculator, multiply 52,000 by 2/3 and get the figure of 34,667. Then he immediately jumps back to a total number of drug overdoses for 2016, in a post that's supposedly about the opioid crisis. Why is he adding together cocaine, methamphetamine, and benzodiazepine-related deaths? Again, a careful reader will remember to multiply by 2/3, but why doesn't Lopez just say clearly what the relevant numbers are? It's as if I were writing a piece about vehicle-related fatalities by adding together auto fatalities and gun deaths, then said, "About half of these are auto-deaths."

The actual figure, by the way, is 33,204. That's adding together prescription opioids, methadone, synthetic opioids, and heroin, avoiding double-counting (most deaths involve multiple substances). And if you remove suicides and likely suicides, you get 29,490. Drug overdose data suffers from a similar problem to the one faced by "gun death" statistics, in that suicides are included in the total. This isn't the fault of the statistics, of course, but rather the fault of sloppy reporting that adds unlike things together to get an inflated total. Of the 52,623 drug overdose deaths in 2015, 5,215 were suicides and 2,979 were of "undetermined intent." Ninety-four were "murder." (Arguably some fraction of "undetermined intent" should be added in when tabulating "accidental deaths, but this number hasn't risen over the last 15 years so it's not really part of the trendline we're interested in.) I don't think it's fair to blame suicides on opioid over-prescription. You can argue that despondent addicts are giving up on life and killing themselves, but then you're speculating wildly about whether that person would have died if not for the causal factor we're interested in. See my thorough breakdown of the 2015 overdose deaths here.  I actually warn my readers near the beginning of the post:

"I suspect you will see a lot of news stories starting with “There were 52,600 drug overdoses in 2015…” If you see such a story, scan it to see if it gives a breakdown by “accidental vs intentional.” If it doesn’t, that’s a big warning sign that the author didn’t do their homework.

This warning certainly applies to the Vox piece. Anyone who is actually curious about this important topic can download the data from the CDC's website and dissect it however they like.

The Vox piece then gives the standard narrative explanation of how we got here:

Over the past couple of decades, the health care system, bolstered by pharmaceutical companies, flooded the US with painkillers. Then illicit drug traffickers followed suit, inundating the country with heroin and other illegally produced opioids that people could use once they ran out of painkillers or wanted something stronger. All of this made it very easy to obtain and misuse drugs.

The author should have told his readers that this is a wild guess. There is no convincing proof that the new heroin users are former prescription opioid addicts. Or, at any rate, there is no convincing evidence that prior prescription opioid use caused subsequent heroin use. The great fallacy in this "opioid epidemic" narrative is that the heroin users and prescription opioid users are the same population. In 2015, 85 million people used prescription opioids legally, and there were ~200 million legal prescriptions. By contrast, there were half a million heroin users. But there were comparable numbers of deaths in both categories (~13,000 from prescription opioids and 12,000 heroin deaths, or 18,500 heroin deaths if you add the "heroin" and "synthetic opioids" together to capture the fact that some dealers have been mixing fentanyl in with heroin). Some relevant numbers in my piece here, once again from the CDC's website. Deaths per legal opioid user are in the 0.015% range; deaths per heroin  user are probably somewhere in the 1% to 3.5% range. In other words, the prescription opioid deaths are a very small risk applied to a very large population. The heroin-related deaths are an extremely high risk applied to a relatively small population (about half a million users according to survey data, but see caveats in my piece about the size of the population of heroin users). These are very different issues with very different underlying social causes. It makes little sense to add them together just because the chemical mechanism is the same. The "opioid epidemic" isn't a thing. It's several things.

The Vox piece now weaves a narrative of irresponsible doctors prescribing way too many opioids. There are several drivers of this trend. There was a change in philosophy on how pain should be treated. Pharmaceutical companies developed new opioids and supposedly bamboozled impressionable doctors into over-prescribing them. There is no doubt that the sheer tonnage of opioids prescribed increased; the government tracks these figures and they are certainly rising. See the chart at the bottom of this page. But it's not at all clear that the expansion of opioid prescribing was inappropriate. Second-guessing doctors prescribing pain medicine is a very dangerous business. If Mr. Lopez is wrong, but the force of his argument nonetheless determines the course of US drug policy, he may be damning many people to unnecessary suffering. He says it himself in the Vox article:

On the patient side, there were serious medical issues that needed to be addressed. For one, the Institute of Medicine has estimated that about 100 million US adults suffer from chronic pain. Given that the evidence shows opioids pose more risks than benefits in the majority of these cases, patients likely should obtain other treatments for chronic pain, such as non-opioid medications, special physical exercises, alternative medicine approaches (such as acupuncture and meditation), and techniques for how to self-manage and mitigate pain.

I've seen the 100 million figure before. I don't know if it's right or not, but if it's even the right order of magnitude this is a huge problem. We should not be placing any restrictions on how doctors treat these patients, who according to the 100 million figure comprise almost a third of the US population. That's not to say 1/3 of us are constantly walking around in agonizing pain, but rather that a third of us have occasional flare-ups of intractable pain. It is downright cruel to take treatment options of the table.

It's a bit amusing that Lopez so cavalierly dismisses prescription opioids for chronic pain and then suggests acupuncture and meditation, which are basically placebo treatments.  Of course opioids work for pain management. People can feel the relief almost immediately. People have used opium for thousands of years. In Montana, where it's hard for chronic pain sufferers to get the treatment they need, many pain patients flee the state to get their necessary prescriptions. (From the link: “My pain, it’s all from my waist down,” he said. “It’s like being boiled in oil 24 hours a day.”) Many pain doctors are getting fed up with idiotic politically motivated restrictions on their practice, which condemns many of their patients to endless suffering. Some pain patients have committed suicide after being cut off from their only source of relief. Mr. Lopez is making it sound like it's so very easy, like if we'd just prescribed less opioids we wouldn't have these problems. Not so. You're always going to have this false positives/false negatives trade-off. There isn't a simple "make fewer mistakes" lever. There isn't a magic "accurately identify appropriate candidates for opioids" button. Greater accuracy isn't an option. The people making the call (doctors) have the highest possible level of education. They possess the most information they could plausibly obtain about the patient's medical history. They are constantly doing continuing education for new trends in medicine. (I dearly hope they aren't looking to Vox for their information.) We can't descriminate more accurately on a systematic basis, we can only change the discrimination threshold. You can prescribe opioids more freely, knowing that a few more people who don't need them will get them. Or you can prescribe opioids more restrictively, knowing that more people who actually need them won't get them. A false negative is way more costly than a false positive here. We should be willing to tolerate a lot of false positives. The "downside" of being too permissive is that some people who use opioids because they enjoy them get to indulge their vice. [Edit 9/26/2017: I should clarify, I am not knocking either acupuncture or meditation for pain sufferers who feel like these treatments work. I would expect placebo treatments to be pretty effective for pain management. It's possible that the effectiveness of opioids is partially a placebo effect, too. I believe pain is one of the more subjective symptoms in medicine, and we should default to believing people who say they suffer from it. We should also default to believing people who say they have found a solution to it.]

It reminds me of journalists and economists who complain about all the "unnecessary medicine" provided in the United States, as if we can just categorize all medicine as "necessary" and "unnecessary" and then stop doing the unnecessary stuff. The problem is that these things are never certain. Nothing is "100% necessary" or "100% unnecessary." Rather, the best we can do is have some confidence level: "I'm 10% sure this is necessary" or "I'm 95% sure this is necessary." And then establish some sort of threshold, as in "We'll do everything that's at least 50% necessary." (This threshold should vary with the relative costs of false positives and false negatives, of course.) Mr. Lopez can correctly say that there is a lot of unnecessary opioid prescription, but he hasn't really given us a better means of discriminating "necessary" from "unnecessary", nor has he made the case that the threshold should be made more restrictive.

The Vox piece says:

And in other cases, the doctors involved were outright malicious — establishing “pill mills” in which they gave away opioids with little scrutiny, often for hard cash.

How "malicious" it is to sell something to willing buyers. The downside is that people who want to get high get to.

Another section of the piece starts with the title "Heroin and Fentanyl made the crisis much worse." Again, referring to it as the crisis incorrectly collapses heroin, fentanyl, and prescription opioids into a single problem. Lopez tries to connect this to opioid prescriptions, but I think he fails. From the piece:

A 2014 study in JAMA Psychiatry found 75 percent of heroin users in treatment started with painkillers, and a 2015 analysis by the CDC found people who are addicted to painkillers are 40 times more likely to be addicted to heroin.

If you read the study, it says nothing about the causal link between prescription painkillers and subsequent heroin use. Recall that there were 85 million prescription opioid users in 2015. If any of them subsequently become heroin users, they will be counted in the 75%. When I had some serious oral surgery done in 2001, I was prescribed some hydrocodone. If at any point in my life I become a heroin user, I will be counted in the 75%. [Edit 9/26/2017: This is incorrect; the 75% figure refers to past opioid abuse, not legal use. The first sentence of this paragraph holds up pretty well under this correction. According to the detailed tables of the SAMHSA survey from 2014, there were ~36 million prior non-medical users of prescription opioids. "Prior" meaning lifetime, not past year or month. Still a very large pool of people for the 75% figure to arise from.] This is much like the argument, popular among drug warriors, that marijuana is a gateway drug because most users of hard drugs start with marijuana. There are simply so many current and past prescription opioid users that most heroin users will probably have had past experience with these drugs, but that says nothing at all about a causal link. Indeed, the vast majority of prescription opioid users never go on to use heroin, so the causal link is dubious.

Although prescription opioid overdose deaths have really hit middle-aged and older Americans in their 40s and up, there’s evidence that heroin and fentanyl are much more likely to hit younger adults in their 20s and early 30s — creating a divide in the epidemic by age.

I'm not quite sure where he's going with this. For the record, the average age of someone who died of heroin in 2014 was 38. The average age of someone who died of prescription opioids in 2014 was 44. The users skew much younger than the average overdose death, implying that age is a huge risk factor in overdose deaths.

There are some good statistics in the Vox piece. Lopex points out that a huge fraction of opioid deaths (heroin and prescription painkillers) are really multi-drug interactions. I wish he'd have made a much bigger deal out of this. Take a look at my dissection of the 2015 overdose deaths (also linked to above). He refers to a couple of studies, but actually anyone can pull the data off the CDC website and do their own dissection. It's public information (although every death record is anonymous). If these deaths are multi-drug interactions, then the policy implications are much milder than "keep drugs away from people." Rather "let them have their drugs but remind them not to mix certain drugs" would suffice. "Get high, but do it this safe way..." is an easier sell than "don't get high." Only a small percentage of drug overdose deaths are single-substance overdoses (~14% of prescription opioid poisoning deaths, ~25% of heroin deaths, ~1% of benzodiazepine deaths). If we can get these people to stop mixing substances, we'd save a lot of lives. Lopez should have fixated his attention on this.

I'll step away from directly quoting and responding to the Vox piece and make a couple of observations.

Prescription Opioid Abuse Isn't Increasing!

There's all this talk about a prescription opioid epidemic. Gee, if only the government kept statistics on rates of drug use, broken down by drug category. Oh, wait, they do! Here is a figure from page 7 of the SAMHSA's Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health (link).

It's basically flat. It's even decreasing for younger demographics. Opioid epidemic busted? Okay, so maybe "past month use" isn't indicative of overdose risk. Maybe it's just a subset of these who are really dangerous users who wind up killing themselves. If only they kept track of some other statistic indicating a more severe problem with prescription pain relievers. Oh, wait, they do that, too! Here is page 26 of the same document:

Once again, is't basically flat, and probably decreasing for the younger demographic. And just for good measure, here are some charts from the Monitoring the Future survey, which only covers 8th, 10th, and 12th graders. See page 31 of this document:

Admittedly this is a restricted age demographic, very different from the population of people who are actually dying from prescription opioids. But it confirms the notion from the SAMHSA survey that youth use rates are falling. And the "availability" question is telling. It appears to be falling, indicating that these substances are harder to get than a decade ago for this age demographic. (The discontinuity in the curve represents a methodology change where the survey question was re-worded, so interpret the charts with that in mind).

I have heard people dismiss the survey data. The argument goes something like, "If someone has a prescription, they're not going to count themselves as 'misusing.'" There's some kind of reporting error in the survey. People either don't even consider themselves to be "misusing" their opioids, or they know damn well they are misusing but are reluctant to say so on a government survey. I am sympathetic to this, but I find it really implausible that this would completely mask a trend of increasing painkiller abuse. Prescription opioid overdose deaths roughly tripled from 1999 to 2014, but the number of self-reported abusers is totally flat? Prescription opioid deaths basically flat-lined around 2010, presumably because of political responses to the so-called crisis. Wouldn't the "under-reporting" story imply that there should be an increase in self-reported painkiller misuse around this time? I could imagine under-reporting skewing the drug use statistics, but it's hard to swallow the idea that this reporting bias completely masks a trend, then also masks a flattening in that trend. I can buy that there's some reporting bias in these statistics, but it's hard to swallow the idea that the bias adjusts to hide any kind of movement in opioid use. Whatever kind of bias is being proposed by the people who dismiss the SAMHSA statistics, propose a mechanism for this bias and be consistent about how it works. And keep in mind Mr. Lopez actually cites and links to the SAMHSA summary. he somehow missed that the trendline for this statistic is flat, or he didn't see fit to share that with his readers.

Lopez points out that:

About 2.1 million people are estimated to have an opioid use disorder in America — and experts widely agree this is, if anything, an underestimate.

The link is to the 2016 SAMHSA survey summary report (my link above is to the 2014 version). Actually, that report says: "In 2016, an estimated 1.8 million people aged 12 or older had a pain reliever use disorder, which represents 0.7 percent of people aged 12 or older." That report, which I hadn't seen until just today, actually does not include the charts displaying the trend in prescription painkiller misuse and substance use disorders from 2002 to present (the charts shown above in this post). Why not? Why weren't those charts updated for the most recent report. Well, the 2014 version says, "The estimated 1.9 million people aged 12 or older in 2014 who had a pain reliever use disorder (Figure 31) represent 0.7 percent of the people aged 12 or older." The number of people with a substance abuse disorder regarding painkillers decreased by 100,000 people in the last two years. Is SAMHSA trying to disguise a decline in a widely publicized problem? Shame on them if they are.

I can find a similar duo of quotes about declining "past month use". The 2014 report says: "The estimated 4.3 million people aged 12 or older in 2014 who were current nonmedical users of pain relievers represent 1.6 percent of the population aged 12 or older." The 2016 report says: "An estimated 3.3 million people aged 12 or older in 2016 were current misusers of pain relievers, which represents 1.2 percent of the population aged 12 or older." Once again the chart is missing from the 2016 version of the report; if it were there it would show a sharp decline in past month painkiller misuse in 2016. Past month recreational use of prescription painkillers decreased by a million people, and the government is disguising this decline? My best non-cynical explanation for removing the charts is that 2015 was the first year that they started asking about "illicit painkiller use" and "any painkiller use" (previously they had just asked about illicit use). But then they should show the graph but have a footnote about the methodology change, like the Monitoring the Future report does. Failing to disclose this to the report's readers is just disgraceful.

By the way, the SAMHSA survey shows declining rates of cocaine use from 2006 to present, which is in line with declining numbers of cocaine overdose deaths. It also shows a probably real increase in heroin use, which once again corroborates the increase in heroin overdose deaths. So we can't just go dismissing the drug survey figures out of hand because "people lie about their drug use on government surveys." These surveys are apparently tracking some real trends.

Lopez might have taken this opportunity to at least remark on the statistics that contradict his narrative.

But, while were in the business of doubting government statistics...

Doubts About The Death Statistics 

There are many things that give me pause about the death statistics themselves. They could be overstated, or understated for all I know. Determining the cause of death is fundamentally a matter of opinion. If you read Karch's Pathology of Drug Abuse, the standard medical textbook on the topic, it's like every other sentence is a warning about assigning a drug-related cause of death. I urge Lopez and other curious readers to pick up a copy and read it thoroughly. See several excerpts from the chapter on opioids here and from the chapter on cocaine here. Also, see comments that  Steven Karch made for Radley Balko's great series in the Huffington Post on this topic here. From the textbook:

Not one single control study, even in animals, has ever shown that postmortem drug concentrations accurately reflect drug concentrations at the time of death, but a goodly number have shown quite the opposite to be true, chiefly because of the problem of postmortem redistribution (Pounder et al., 1996; Hilberg et al., 1999; Moriya and Hashimoto, 1999; Drummer and Gerostamoulos, 2002; Flanagan et al., 2003; Ferner, 2008). Postmortem redistribution is defined as the movement of a drug down a concentration gradient after death.

This is just one quote of many. It's like every other line he's reminding the reader, "Hey, it's really hard to determine the cause of death. You can't simply do it based on postmortem drug or metabolite concentrations, which unfortunately is standard practice." Seriously, read through it. Parts of it are feel like they are from a text on the philosophy of causal inference. I suspect that, with a lot of people on high-dosage opioids walking around, a few of them randomly drop dead from other causes and get labeled a "drug overdose" by an unwary medical examiner. The examiner might be ignorant or simply busy and has a handy explanation that allows him to move on. It's certainly the case that people who die of drug overdoses have a lot of other illnesses and medical problems, which end up on the death certificate. This indicates that some other causes of death contributed, or perhaps were actually the primary cause. (If an opioid user wouldn't have died but for their sleep apnea, which cause is "primary"? It's almost a philosophical question. But sheer navel-gazing aside, there are also implications for who should and shouldn't get opioids if these other illnesses are overdose risk factors.) The people who die of drug overdoses also tend to be older than the using population in general. It's likely that a lot of these people are sick or old and die for reasons other than their opioid prescription, but the handy explanation is too easy to pass up. And there is plenty of other evidence for a spurious trend in drug overdose deaths: categories that were empty in 1999 but populated in 2014, the ICD-9 to ICD-10 changeover in 1999, the promiscuous use of the generic drug overdose category (as in they couldn't actually blame the death on a particular substance), etc. I'm not suggesting that the entire trend is spurious, just that some proportion of it is not real.

This is one of my pet peeves about these opioid epidemic stories: taking the death totals at face value. A body is a body; there is  no doubt that these counts represent people who actually died. But the cause of death is always in question. If thousands of these deaths have the wrong cause of death assigned to them, then we will draw incorrect conclusions if we simply add them up and take them at face value. People like to have facts and numbers to support their story. That's understandable. Statistics feel a lot like facts, immutable nuggets of unimpeachable truth. But if the underlying data are bad, any summarizing, averaging, trendline-fitting, regression analysis, or other statistical magic will give you garbage. I wish people would be a lot more skeptical about these death figures.

Alternative Narrative

My simple story is this: there is some very low probability of overdosing on prescription opioids. The tonnage of opioids prescribed roughly tripled from 1999 to 2015, and so did the number of opioid overdose deaths. The risk per legal prescription did not change. Contrary to the standard narrative, we did not see an increase in illicit use of painkillers despite this massive expansion in their legal use. We have more people exposed to a particular risk, a risk whose magnitude did not change over the past decade and a half. It's as if we were doing a certain surgery, which always carries some trivial cause of death, three times as much as we were in 1999. Then somebody tabulated some statistics and showed that, OMG, death rates from that surgery have also tripled! The surgery needs to be evaluated by the following criterion: Is the risk worth the benefits for the individual undergoing surgery? Summing the deaths from surgery complications across 300 million people simply does not give you a statistic that is relevant for public health policy. If the surgery is deemed worthwhile, it doesn't matter if the "death total" is large, or if it's increasing or decreasing over time. The surgery is either worth doing at the individual level or it isn't. There were about 0.5 deaths per kilogram of opioid prescribed in 1999, and there were about 0.5 deaths per kilogram of opioid prescribed in 2014. This is an unchanging risk being applied to a larger population.  Lopez tries to make the case that the expansion of prescription opioids was unnecessary, but he ultimately fails to make this case. Plainly a lot of chronic and acute pain sufferers are better off with prescription opioids, and neither Vox nor anyone else has established a sorting mechanism better than doctor's judgment for deciding who does and does not get these drugs.

The recent spike in heroin deaths is related to very cheap "heroin". The price drop is due to drug dealers spiking their heroin with fentanyl and stronger synthetic opioids. These opioids are sometimes hundreds of times stronger than heroin and are poorly mixed into batches of drugs that get sold as heroin. So people take something far stronger than they intended and end up overdosing. The increase in heroin deaths showed up very late in the game. The increase in synthetic opioid deaths showed up even later. I would have expected to see heroin deaths increasing steadily since 1999 if prescription painkillers were turning people into heroin addicts, but it's flat from 1999 to 2007 (green line below). The causal link here is dubious. See the trends for different drugs in the chart below:

A much fuller exploration of alternative narratives here. My basic explanation is that the prescription opioid overdoses aren't mostly coming from addicts with serious drug problems (though clearly some of them are). They're mostly coming from normal people with legal prescriptions who occasionally do something incautious, like take painkillers with alcohol or benzodiazepines or imprudently take more than the recommended dosage. It's a boring story without a bad guy, and it denies the news-consuming public their craving for a good drug scare. But in my opinion it's the most likely explanation. Not every social problem is a moral panic with an identifiable villain.

I certainly don't disagree with everything in the Vox piece. Sure, make naloxone, the antidote for an opioid overdose, more available. Sure, spend some money on drug treatment programs. (I'm skeptical...do these drug treatment programs even work?) But the basic underlying narrative is simply mistaken.