Which Arm of the Trial Would You Pick?

For years, critics of opioid guidelines have argued that the absence of evidence on long term efficacy of opioids wasn't a sufficient reason to declare such long term use "medically unnecessary." Advocates of opioid therapy have been frustrated by the notion that because we didn't have a randomized clinical trial (RCT) showing the drugs to be helpful, we all assumed them to be harmful. While practical experience led to this totally plausible conclusion, detractors still saw hypocrisy in our dependence on documented medical evidence... that still didn't exist.

That RCT has finally arrived.

The study is to be published soon, but Dr. Erin Krebs recently presented her findings at the 2017 meeting of the Society for General Internal Medicine in Washington, DC.   You can read a synopsis and commentary in one of my favorite monthly medical newsletters, The Back Letter (subscription required).  Here's the key take-away:

Opioids provided no advantage in terms of function at the 12-month follow-up mark, and patients in the opioid wing of the study actually reported marginally more pain at 12 months than those in the non-opioid group.  

There are really two key points there: the first, that opioids don't appear to increase functionality, is obvious to most of us who have been living and breathing this issue for the last decade.  The second, though, refutes the most fundamental argument of opioid advocates - that the drugs at least control pain.  Turns out, they don't do a good job of that either.  To sum up, the opioid creates the exact opposite of its intended effect: it fails to increase function and instead actually increases pain.

Perhaps the most interesting characteristic of the study was its design.  It was randomized (patients are chosen by chance to participate in one or more clinical interventions - in this case, opioids for pain relief) and controlled (the clinical intervention was compared to a standard practice - sometimes placebo, sometimes not - as in this case - a non-opioid drug regimen).

But it wasn't blinded.  A blind trial indicates that the participants don't know which arm of the study they've been assigned to.  In this study, patients getting opioids knew they were getting opioids and patients not getting opioids knew they weren't getting opioids.  To me, that makes the results even more compelling.  Patients who knew they were receiving opioids to manage their pain still reported higher pain levels at the 12-month mark.  And patients who knew they were not getting opioids still reported increased functionality vs. the opioid group.

Apparently, there was some ethical debate regarding this study before its launch. It was assumed by some that such a trial would be impossible because people in chronic pain would simply refuse to join the non-opioid arm of the trial if that's where they were randomly assigned.  Further, some assumed it would be unethical to not provide opioids to people in chronic pain - that by instituting a non-opioid control group, patients would be deprived of necessary medical care.

As it turns out, the arm of the trial some ethicists assumed would be, in the first place, impossible to fill, and secondly, inhumane... well that's the arm of the trial you actually wanted to be in.

Michael
On Twitter @PRIUM1

Detox and Marshmallows: Dealing with Addiction

On Monday, NPR's Morning Edition ran two pieces back-to-back that while ostensibly not intended to be related, nonetheless struck me as providing important insights into opioid misuse and abuse.  

The first story (read and/or listen here) was about the potential perils of Do-It-Yourself detoxification from drugs of addiction. While there's plenty in this story for the schadenfreude crowd ("he says his stomach cramps felt like 'having Freddy Krueger inside you trying to rip his way out.'"), I was struck by the comments of a doctor interviewed for the story:

So can detoxing on your own be the solution? In most cases, the answer is no. 

In fact, a growing movement within the field of addiction medicine is challenging the entire notion of detox and the assumption that when people cleanse themselves of chemicals, they're on the road to recovery. 

"That's a really pernicious myth, and it has erroneous implications," says Dr. Frederic Baurer, president of the Pennsylvania Society of Addiction Medicine.

"Detox" does not equal "treatment."  Treatment may, of necessity, start with detox, but without counseling and the potential use of other medications, recovery is rare.  In fact, the relapse rate from detox alone is upwards of 90%.  We have to do more than just detox if we want long term results for injured workers suffering from addiction.  

The second story (read and/or listen here) was about marshmallows.  More accurately, it was about a child psychology experiment involving marshmallows.  In the the 1960s, a Stanford psychologist named Walter Mischel designed this experiment to study children's self-control.  Kids ages 3 to 5 have a marshmallow placed before them. Then researchers give the child the following instructions: You can eat the marshmallow now, but if you can wait for me to return, you'll get two marshmallows.

More than half of kids dig in.  And among those who don't gobble up the treat but instead exercise self-control, there appears to be a correlation to superior future academic performance and achievement.  (The story is interesting because new research deploys the experiment outside of western culture for the first time and the results are interesting, if not concerning).

The objective of the experiment is to study a psychological phenomenon called "delayed gratification."  Can one put off immediate gratification in return for greater, albeit delayed, reward?  Even among 3 to 5 year olds, the delay creates physical and emotional distress.  They whine, they squirm in their seats, their heart rates go up, they feel real stress.

Am I comparing a 4 year old who eats the first marshmallow to an opioid addict who can't go a day without a fix?  Absolutely not.  Addiction is a disease and it requires treatment.  It's not a simple failure of willpower.

Rather, I'm comparing the 4 year old who eats the first marshmallow to some insurers, employers, government regulators and politicians who want a simple, cheap, fast, pop-the-balloon solution for an injured worker who has been on opioids for 10 years.  Relying on detox alone is like gobbling up that first treat.  Instead, we need to squirm, face hard choices, make investments in sound treatment, and exercise patience.  

We could use a little more delayed gratification in the fight against opioid misuse and abuse.

Michael
On Twitter @PRIUM1