Issues & Insights

Opioids: Bad Science, Bad Policy, Bad Outcomes

There’s an old joke about the drunk who’s hunting for his lost keys under the lamppost, not because he thinks they’re there, but because the light is good. Well, that’s what the feds and state governments are doing to try to quell the epidemic of opioid addiction and overdoses.

The problem is quite real, but legislators and regulators are making incorrect assumptions and adopting flawed strategies. And then, there are some flawed clinical studies and statements by the U.S. surgeon general that conspire to create misunderstanding of the landscape. 

For a start, the problem isn’t currently prescribed opioids, such as fentanyl, morphine, oxycodone, and hydrocodone. A study published earlier this year in the New England Journal of Medicine found that from 2012 to 2017, a time when the overdose death rate was markedly accelerating, the rate of opioid prescriptions in patients who had not previously used opioids fell 54%, a decline driven by a decreasing number of prescribers.

More evidence was provided by a February article in the journal JAMA, which concluded that “under current conditions, the opioid overdose crisis is expected to worsen — with the annual number of opioid overdose deaths projected to reach nearly 82,000 by 2025, resulting in approximately 700,000 deaths from 2016 to 2025.”  But here’s the rub: In the predictive model, preventing prescription opioid misuse alone would have only a modest effect — a few percent — on lowering overall opioid overdose deaths in the near future.

In spite of such findings indicating that the crux of the problem is not physician-prescribed opioids but illicit fentanyl and its analogs smuggled from abroad, like the drunk in the parable the feds and state governments are looking in the wrong place.

The extant problem has been exacerbated by the law of unintended consequences and the law of supply and demand. As a result of federal policies, some of our most important and potent analgesics, including fentanyl, morphine, and hydromorphone, which are commonly used in patients with advanced cancer and for pain control after surgery, are now in shortage, according to the FDA. All of these drugs had their manufacturing quotas reduced by the DEA, as if, in any case, it’s the government’s business to tell companies what and what not to manufacture.

The feds misunderstand the role of opioids in providing relief from significant pain — such as from kidney stones, sciatica, cancer, or broken bones, which can be excruciating — but they are not entirely to blame. Academics have also contributed — for example, a 2017 article in JAMA Network by Chang et al.  The study is so poorly designed that we can only conclude that the investigators intended to get a desired, albeit inaccurate, result — namely, that acetaminophen (brand name: Tylenol) and ibuprofen (brand name: Advil) are as effective pain relievers as opioids alone or opioids in combination with acetaminophen.

If they were real, these findings would be hugely important, because opioids could be supplanted by widely used, over-the-counter analgesics. For that reason, it is worth enumerating the flaws — or, more precisely, tricks — in the study.

The study included four groups of people in pain (416 total) who were seen at either of two emergency departments at the Montefiore Medical Center in the Bronx between 2015 and 2016. The four groups that were compared:

  • Group 1 received 400 mg of ibuprofen plus 1,000 mg of acetaminophen
  • Group 2 received 5 mg of hydrocodone and 300 mg of acetaminophen
  • Group 3 received 5 mg of oxycodone plus 325 mg of acetaminophen
  • Group 4 received 30 mg of codeine and 325 mg of acetaminophen

There are several problems with the study design:

1. Dose.

It appears that the study was designed to compare the analgesic power of the highest permitted dose of ibuprofen and acetaminophen with the lowest effective doses of hydrocodone and oxycodone. That’s not playing fair. If this trial had been performed with realistic, instead of barely therapeutic, opioid doses we would expect to see very different results.

2. Selection criteria. The study group was limited to patients with acute extremity pain — “pain originating distal to and including the shoulder joint in the upper extremities and distal to and including the hip joint in the lower extremities.” If the patients had been experiencing really intense pain from, say, kidney stones or severe sciatica, ibuprofen and acetaminophen would hardly touch it.

3. Opioids to the rescue for some. Approximately 18% of the patients received “rescue analgesia.” In other words, when the initial treatment failed, the patient was given oxycodone or morphine. A total of 73 patients didn’t get adequate relief from either ibuprofen/acetaminophen or low-dose opioids, but the authors do not indicate which therapy failed.

4. We wonder why those patients were given insufficient pain medicine in the first place. And we believe that the rescue data indicate that opioids are superior for pain relief: The 73 did not get “rescue acetaminophen” because a) some of them had already been given the maximum dose, and b) literature reviews have shown that acetaminophen is pretty worthless as an analgesic.

We can’t help wondering why anyone in an emergency room with “moderate to severe acute extremity pain” would agree to be part of a study in which three-quarters of the patients weren’t going to receive an opioid. We suspect that there’s not a compos mentis physician in the world who would volunteer to be a patient in such a study.

Thus, the Chang et al study appears to have been more about ideology than medicine. And just this month, we had a painful sensation of déjà vu — courtesy of no less a personage than Dr. Jerome Adams, the U.S. surgeon general. On July 3, he tweeted:

We’d like very much to hear directly from the patients, especially those with significant post-operative pain who were given Tylenol.

A day later, Adams was at it again:

Does Tylenol relieve pain better than morphine? Count us as skeptical. Adams was referring to a 54-person randomized clinical trial of pain control following rib fractures, which are notoriously painful. The trial, which was conducted in an emergency department in Iran, compared intravenously administered Tylenol (,1000 mg) and morphine (0.1 mg per kilo of body weight). Supposedly, the result was that Tylenol relieved pain as well as intravenous morphine in patients with rib fractures — but even a cursory reading of the article, which was published in the obscure journal Emergency (Tehran), reveals that it demonstrates no such thing.

Basically, that study found that 30 minutes post-administration of drug, the mean pain score on a scale of 1-11 was 5.5 for the morphine-treated patients and 4.9 for the Tylenol-treated patients. That supposed difference was the entire basis for Adams’ claims of equivalence of Tylenol and morphine — except that the data aren’t even close to being statistically significant: p = 0.23. (Statistical significance would be p<0.05.) In plain language, one cannot conclude from this study that Tylenol is equivalent to morphine.

There were many other deficiencies in the design of the study. For example, there was no control group, so it can’t be determined whether the observed reductions in pain score were due to drug or to a placebo effect. Also, the initial pain score of both groups was supposedly “the same,” but with p = 0.19, this may or may not be true. It can’t be determined whether the group that received began the study with more pain, less pain, or no difference, confounding the interpretations of the results.

Moreover, the success rate (defined as a three percentage-point reduction in pain score) was 80% for Tylenol and 59% for morphine. That difference also fails statistical significance: p = 0.09. Even the authors acknowledge that. Thus, from this study, there is simply no evidence that Tylenol and morphine are equivalent — something that Adams should have known.

Perhaps more baffling about the study is that when there was a treatment failure after 30 minutes (inadequate pain relief), morphine was given as a rescue therapy. This automatically skews the results. It’s like saying “Tylenol works as well as morphine except when it doesn’t.” Nor do the authors tell us how often rescue therapy was given.

Finally, there was this: “Presentation of side effects was similar in both groups.”

That is hard to explain. We’ve been hearing for a decade how dangerous opiate analgesics are, but there was no difference in side effects between the Tylenol and morphine groups? The fact that the patients who received morphine did not report nausea or dizziness suggests that morphine was either not used at all, or used at a sub-therapeutic dose.

The surgeon general’s claim that intravenous Tylenol works as well as morphine was unsupported and irresponsible. (He has subsequently deleted the tweet.)

The evidence continues to accumulate that the government’s opioid policies — and pronouncements — need adult supervision.  We are not optimistic that it will materialize.

Henry I. Miller, a physician and molecular biologist, is a senior fellow at the Pacific Research Institute. He was the founding director of the FDA’s Office of Biotechnology. Josh Bloom is the director of chemical and pharmaceutical science at the American Council on Science and Health. He has a Ph.D. in chemistry.

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  • I have taken oxycodone for over 10 years, 25 mgs a day, yet, have never had any addiction or withdrawal problems with it. When a person can forget to take his meds he’s doesn’t have addiction problems and I often do that. But here’s one of the issues with it. Before all this censorship crap started I found several independent studies done on it, mostly from Europe, that were not linked back to the CDC or big pharma in any way that I could find. My mother had become highly addicted to morphine by that time so I wanted to look into why. These studies stated that opioids when mixed with the compounds found in a drug like Xanax made the opioids twice as strong and 2 to 3 times more addictive to the study subjects. I have never really had any problems with meds, in that regard, except gabapentin, which was addictive to me so I spent 2.5 months weaning off of it. It was the only drug to ever do that to me and being a child of the 70’s, I’ve tried many drugs, recreationally, back in the day. It no longer helped and was seriously messing with my vision and memory and after the CDC, finally, admitted how it works, I could see why. How many millenials and many women, in general, “just can’t cope” with the stress of everyday life out there and are taking Xanax to help them? A crap ton, that’s how many. Big pharma knows this and so do many doctors but I suspect many don’t but just follow the drug company suggestions for treatment. I have never taken or needed anything like Xanax but my mother did and started that with oxycodone at the same time, too and, eventually, went on to morphine and fentanyl before she died from her COPD. She, by nature, could become addicted to damn near anything, even if only in a mental sense but much was physical, as well. I’m the exact opposite. Most meds do not work on me without really high doses but I don’t want to be in a position when I’m on my own death bed where nothing can help with pain because of built up immunities so I limit myself to a way lower dose that what would help me, at this time. Each person is different in how they react to these things. I wish I had saved those studies because I recently did a mild search for them, again and could not find them, which only figures, these days. If you have to take pain meds for whatever reason, avoid anti-depressant drugs, learn to deal with a certain amount of pain and most importantly, learn to deal with the realities of everyday life. We all have our problems and most of how that is dealt with can only be done in your own mind. These drugs really don’t help with that as well as you think. Key word…”think”. Sorry about the wall of text but I’m limited in time.

  • I’m a 100% Disabled Vet. I have chronic back and other pains. Last year a ER Doctor reduced the dosage of hydrocordone and the number of doses to three day at a time. Though I was told to take it three times a day, I endure pain because I m afraid I might get hooked, and only take it when I have too. Also the Tyenol the major part of the pill is dangerous to my liver.
    VA and Civilian Doctors won’t prescribe Oxycontin, which I took in the hospital, after knee replacement even though it delivers the best pain relief and will not damage the liver etc.
    My Son who has a broken back, a vertebrae broken on both sides with nerve endings in the break, even after surgery and radio ablation, he comes home from part tiem job, that is really too much for him, and lies around and sometimes he can’t help but cry from the pain and sleep is ellusive. The Doctors won’t prescribe anything to help with pain, saying they were trying to get him off pain killers with radio ablation. he has never been “on” pain killers.
    So it appears from here that some Politicians are trying to make an me for themselves, by “fighting opioid addictions” and lumping chronic and sever pain sufferers as drug addics who must be condemned, and their medications taken away. Suffering continual and constant pain is not noble. It is hell and shortens lives even more! But this appears to be what they think is righteous! They want to stop real Drug users and the Drug Culture then stop email order etc, from China and Asia.
    There is no logical reason to not prescribe Oxycontin, and ever reason to prescribe it .A little relief would be great. Addiction, I don’t know anything about that except the few who were prescribed it liked not hurting..

    • Yea, a lot of their attitudes towards folks like us is what really pisses me off. They seem not to want to consider this side of the coin. Not cool. Also, something I forgot to mention about those studies I found is that oxycodone alone is really not very addictive. It’s when mixed with other compounds that it gets more so.

      Contin, from what I know, is not a time release form of oxy and is the main reason it’s not prescribed for chronic pain. Being short term, too many would require more, too soon and that can sometimes lead to addiction. The codone form will, eventually, not last very long, either. As it is, it would take 40 mgs to give me the 50% relief that I was getting, last year but I’m avoiding that as long as I can for the reasons previously stated. I’ve seen too many, lately, suffer a lot on their death bed because of having taken such high doses before that time came and now they’re screwed for relief, unless they want to go all out coma or worse.

      Like many have said, though, I do not like taking all the extra Tylenol along with the oxy. Just a harmless buffering powder should be good enough for long release but noooo….not offered and folks wonder why I don’t trust big pharma.

      Also, be careful with anything VA, with the wrong doctor you could wind up way over prescribed and find yourself in one of their nursing homes unable to carry on a conversation, like a friend of mine is now because he was prescribed 3 times the amount of oxy, xanas, valium and morphine than my addicted mother was on her death bed. He’s lucky (maybe?) that when he couldn’t feel all his organs shutting down that he passed out in front of his family and they got him to the emergency room when they did. Another hour and he’d been dead. Most of this started from the oxycontin they gave him when he injured himself in Assghanistan, as he often called it. He actually had fewer problems than I do but took waaaaaaaay too much med for it because the VA would rather appease a drug addiction than actually help a person. It’s easier, less expensive on their end and keeps the big pharma partners happy. Yea, we’re all thoroughly screwed by all the systems we and they create for us to live by.

  • A study of 54 patients would be rejected by the FDA. Too small a database and, as noted, not statistically significant. Probably paid for by Tylenol.

  • Hey, it doesn’t matter if it means shortages or if people overdose, you can’t let druggies get high!! Who cares how many of them die? Who cares if people in pain can’t get their medicine, we can’t have junkies taking drugs for fun!! Better the whole world die than one person recreationally use opiods!

  • As a survivor of esophageal cancer and a disabled vet with back and neck nerve issues, I am really frustrated with this scheme that demonizes and, basically, slanders anyone who receives enough relief with opioids to live a life of reduced pain.

    Opioids, when not abused, provide relief and a semi-normal life for people who benefit from them.

    Politicians will do anything they can with the least amount of effort to look like they are doing “something”..
    So instead of building the wall and cutting off the importation of illegal opiates, they attack and belittle those who suffer in pain because we have little political voice while cutting off the supply of illegal drugs (and thus resulting in reduced illegal invasion) is politically “difficult”.

    To me, this blocking of patients to have sufficient pain management is a violation of the Americans with Disability act, the right of the people to obtain necessary medical care and an unconstitutional infringement into the patient / doctor relationship.

  • The truth is there are far more deaths caused by alcoholism. Setting aside the deaths caused by automobiles and related injuries due to consumption, the economic losses are staggering. Disease related costs need to be added as well.
    We tried prohibition without success.
    It is almost impossible now to receive adequate pain control now that physicians are obligated to reduce their prescribing or come under scrutiny.

    • My rights as a gun owner seem to have the same damn issues with “perception”. Ignorance is truly rampant in this country, if not outright stupidity.

  • The FDA and the CDC need to retract those inaccurate guidelines that have caused this storm of ignorance from the DEA and doctors on how Opiods work for All Pain Patients. Suicide rates have increased eversince these guidelines were implemented , so many of us are dying of constant pain with no relief, and everyday we live in this prison with no hope for a better future because the Gov decided to Infringed on my rights as a patient so now I no longer receive adecuate care from the VA to control my excruciating Pain.

  • Any addiction or misuse considerations for elderly patients would appear ridiculous on closer examination . We have an aging demographic . It is only reasonable to conclude that greater amounts of painkillers will continue to be utilized . If the practicing physician is unable to relive pain and add to the quality of live – What The Hell is he good For !
    Saving life to be in pain with deteriorating quality !

  • Of course the source of the problem is not over-prescription – that’s an excuse – as in blame others or circumstances instead of the decadent character of the drug addicts.

    To irrational humanists, everything is the fault of circumstances, never the fault of the genetic degenerate.

  • Right on the money. That’s why the AG removed his tweet. Either, didn’t think anyone would notice or that anyone would challenge him? Can’t argue with truth and facts and like you said he should have known better. Seems he’s been caught several times making inaccurate comments but each time he’s caught and bombarded he changes his tact, only to try it again? Is he believing someone whispering in his ear, not thinking before he tweets or really just that clueless?

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