Over the last few weeks/months, I have been blogging about what is the science behind MME’s. Our DNA was not discovered until 1953 and was not completely “mapped” until 2003 and the CYP-450 liver enzyme system was identified in 1963, but there is some 50 odd separate and distinct enzymes in the entire CYP-450 system.
According to this article by Dr Dinerstein, the “MME System” seems to have evolved in a very haphazard manner. Much like the game that many kids play, some shares a story and the story is passed from friend to friend and by the time that the store gets back to the person that started it … the story has probably CHANGED dramatically.
There has been a number of “players” with a anti-opiate agenda. Physicians for Responsible Opioid Prescribing (PROP) and some of its members seem to be a driving forced behind the CDC 2016 opiate dosing guidelines being published. One has to suspect who was actually behind these guidelines. The CDC did not publish the proposed guidelines, did not allow for a public comment period and tried to keep all those participating on the committee behind these guidelines remained ANONYMOUS. Their attempt to keep the members of the committee anonymous FAILED…and it became clear that many on the committee had a anti-opiate agenda. In hind sight, it would appear that the Veterans Admin and the DEA pounced on these guidelines “before the ink had dried on the paper it was printed”
Since 2016, it appears to me that the DEA has moved from looking from “dead bodies” that could be attached to a prescriber’s practice to file charges, to finding someone in a practice’s pt base that are good con artist and is a addict or diverter.. they can be easily identified by data mining various state’s PDMP… then promising the “bogus pt” a “get our of jail free” card for promising to testifying specifics that DEA tells them against the prescriber…
Lately, the DEA is going after prescribers for violating some (non defined) standard of care and best practices… and thus providing controlled substances without a valid medical necessity, which – according to the DEA – makes the prescriber in violation of the Controlled Substance Act.
I have recently checked numerous FDA approved literature for the prescribing of the medication. I did word searches for “MME” and there is NO REFERENCE to MME for all of these opiates. So, does that mean that the FDA DOES NOT RECOGNIZE the “MME system” ? Why is it that the FEDERAL DRUG ADMINISTRATION does not recommend a reference to MME… they only recommend doses in MGS/micrograms. There is published LD50 on meds – that is the mgs given to a number of pts… that 50% will DIE… the problem with opiates is that LD50 will increase with opiate tolerant pts who have taken opiates over a longer period of time and/or taken high doses over a long period of time.
When the FDA approves a new medication, there is a recommended range of mgs and frequency of dosing and a specific disease state that the clinical trials have shown to help manage. Physicians are free to use the medication “off-label” both for indication and dose range. The prescriber is assuming the risk – of harm to a pt – for giving a med for diseases not indicated for and/or doses above what the FDA/Pharma considers a “safe dose”…
You don’t see the FDA going after prescribers for prescribing meds/doses “off-label”… that is what law firms are for … if a pt is harmed.
And this is just the first “dent in the DEA’s war on drug armor” that showed up this week…
Here is what could be the second “dent in their armor” The Curious Case of Dr. Xiulu Ruan
Most would consider the answer a straightforward no and the case simple enough to not require the high court’s time. But the opioid epidemic is anything but straightforward or simple. And the ensuing implications of a ruling in favor of Dr. Ruan will reverberate far beyond the original intent of the question – through the entire opioid epidemic and all the layers of policy and laws designed to curtail opioid abuse.
The question, like most things at the intersection of healthcare and law, appears simple enough, but is insidiously complicated. Good faith, as it is defined in the Controlled Substance Act, the law used to indict and convict Dr. Ruan, is a poorly constructed term, defined through vague, clinically irrelevant wording.
It is precisely through these ambiguities that the term good faith has been manipulated to represent anything but its original intent. Now it is understood through a legal interpretation of clinical behavior, defined by federal prosecutors who presume that by reducing opioid prescriptions, we will reduce the number of opioid related mortality.
But in heeding such misguided notions, federal prosecutors have similarly misinterpreted the definition of good faith, to one that is outside of its medically appropriate meaning. Good faith is not just a characterization of a singular action, but of one clinical action relative to another, to be examined within a broader context of patient care.
To understand this, we must begin where most physicians start their careers – by pledging an oath to patients. Most nascent physicians swear upon either the Hippocratic Oath or the Oath of Maimonides. In the latter, there is a distinct line that encapsulates a requirement for all physicians:
“May I never see in the patient anything but a fellow creature in pain.”
It implies that a physician by nature must implicitly trust patients unless proven otherwise. But trust cannot be afforded blindly; it must be balanced with oversight. Good faith is defined through the series of clinical actions within the context of a patient encounter that forms this balance.
For example, although access to care must be the default course of action for any physician, that access must be balanced with oversight, whether that is urine drug screens, imaging studies, or a review of a patient’s prescription history.
Law enforcement, not versed in pain management or addiction medicine, simply views the prescribing of opioids as a drug deal exchange. This is why prosecutors focused less on clinical decision-making and more on specific acts, or purported red flags, that inductively insinuate a physician behaved in a criminal manner with criminal intent.
Clinically, it has been proven that access to care improves quality of care. Instead of simply cutting off patients from medically necessary medications and incurring patient harm in the process, healthcare providers must continue to provide access to patient care while addressing the risks of abuse.
Access to healthcare is the essence of healthcare. The very concept of emergency care ensures access to care for all patients at all hours. Should every patient who presents to the emergency room with pain be denied medications unless they have legal verification to justify a prescription for opioids?
When we clarify the definition of good faith, we are actually clarifying the balance between access to care with its oversight – which translates into the courts as a comparative analysis of two legal interpretations – that of good faith with mens rea.
Mens rea is, true to topic, also a complex concept and derived from common law. It requires that the accused demonstrate criminal intent in order to be convicted of a particular crime, which modern courts have distilled into four component classifications.
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1. Acting purposely – the defendant had an underlying conscious object to act
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2. Acting knowingly – the defendant is practically certain that the conduct will cause a particular result
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3. Acting recklessly – the defendant consciously disregarded a substantial and unjustified risk
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4. Acting negligently – the defendant was not aware of the risk, but should have been aware of the risk
This may the point in the 52 yr war on drugs/pts for the community to put their dollars together to start by challenging the CDC, if they have/had the statutory authority to even generate those 2016 opiate dosing guidelines ? Challenge the “MME system” itself as to being established without any valid science behind it. It was reported that the 2016 guidelines were established using studies that were mostly rated “3” or “4” as to the quality of data and conclusions… where “1” is good/excellent and “3-4” is poor/crappy”… If one reads the new 211 page 2022 proposed CDC opiate dosing guidelines, they state in there that they are using the same “quality standards” that was used on the 2016 guidelines.. There is only 5 authors on the 2022 version and one hold over from the original committee Dr Chou and if you look at the 20 pages of references… ONE WHOLE PAGE …lists reference where Dr Chou was one of the authors on all of those same references.
I believe that there are 37 states that have codified the CDC dosing guidelines at the state level.
I am seeing many references to Einstein’s definition of INSANITY…. with the proposed 2022 guidelines.
With so many entities finding their favorite sentence, paragraph, page out of the 40 odd pages of the 2016 guidelines and declaring that their policies and procedures are following the 2016 guidelines… just imagine just how many new policies and procedures that could come out of 211 pages of the new proposed 2022 guidelines.
Just think of all the uncontrolled “snatch/grab” in many large cities where local District Attorney is refusing to prosecute any what use to be called “shoplifting” but now only those stealing more than $950 in Los Angeles & San Francisco to really be seen as a CRIME. I think that it was Walgreens has closed some 15-18 stores in bay area because of all the massive shoplifting. Look at all the shooting/killings in big cities, because local District Attorneys are imposing no bail on criminals and putting them right back on the street in < 24 hrs…
In 2021 our country averaged abt a COP SHOT/KILLED EVER DAY… abt 126% INCREASE OVER 2020 and yet ONLY ONE DEA AGENT was shot/killed in 2021 while trying to confiscate money from someone on a cross country TRAIN. https://abcnews.go.com/US/wireStory/shots-fired-amtrak-train-arizona-custody-80400081
According to the opinions of some of the Supreme Court Justices… in the above article, the DEA is/has criminalized the Controlled Substance Act… to justify their actions and justified their budget. While we have a TSUNAMI of illegal Fentanyl coming across our SW border.
NO ONE FEARS chronic pain pts… prescribers, pharmacists/pharmacies – particularly chain pharmacies, hospital system, Insurance/PBM industry. They do fear the DEA – because the DEA visits their HQ’s and threaten/intimidate them …. to fine them … often tens/hundreds of millions of dollars… for practicing medicine and treating chronic pain pts … in doses that the DEA have declared are “outside of -undefined – standard of care and best practices”.
These “badge carrying criminals” are causing people to be left to live/exist in a torturous level of pain, chronic pain pts are dying prematurely from under/untreated pain and committing suicide because they can no longer tolerate the torturous level of pain and see no alternatives to stop their torturous level of pain. What may be even worse is that there is no real accounting of the number of “dead bodies”.
Last night, President Biden’s state of the union https://www.ksdk.com/article/news/nation-world/joe-biden-state-of-the-union-text/507-3827f3f9-1884-487a-8802-99ac7ff48293 he stated
“First, beat the opioid epidemic. There is so much we can do. Increase funding for prevention, treatment, harm reduction, and recovery. Get rid of outdated rules that stop doctors from prescribing treatments. And stop the flow of illicit drugs by working with state and local law enforcement to go after traffickers.”
I don’t think that Biden was talking about getting rid of outdated laws that stop prescribers from prescribing meds for TREATMENT… that TREATMENT has nothing to do with treating PAIN. Biden is an attorney, who was around when the Controlled Substance Act was signed into law and most likely his mindset is aligned with the DEA’s agenda that prescribed opiates directly leads to addiction, which leads to buying illegal opiates off the street and end up ODing/dying.
In the history of the 52 yr war on drugs/pts, it may be the first time that the facts supporting the war, may never been at its weakest level of supporting/justifying it existence going forward. If the community continues its history of infighting, continues its history of starting petitions, continues its history of writing/calling your members of Congress, and continue its history of failing in putting their dollars together and hiring a law firm to challenge the validity of the CDC 2016 guidelines and all the studies and using the “MME system” that has no basis in medical science and the CDC, DEA, VA and other entities that knew or should have known that the CDC 2016 guidelines would create a covert genocide on a portion of our society that is a protected class under the Americans with Disabilities Law and Civil Rights Act from discrimination.
https://www.acsh.org/news/2022/03/01/true-story-morphine-milligram-equivalents-mme-16154
By Chuck Dinerstein, MD, MBA — March 1, 2022
They are the foundation of the CDC’s 2016 opioid guidelines, resulting in legislation that limits opioid prescribing in 36 states. Morphine milligram equivalents, or MMEs, are used to set arbitrary prescribing limits for opioids by physicians, since many state legislators fail to understand – and translate into policy and law – the ‘16 guidelines. If we had all known the history of MMEs, perhaps we would not have been so eager to embrace them.
What exactly is a Morphine Milligram Equivalent (MME)? The CDC defines it as
“The amount of milligrams of morphine an opioid dose is equal to when prescribed. Calculating MME accounts for differences in opioid drug type and strength.” [emphasis added]
MMEs are used in pain management. Clinically, to help transition patients from an ineffective treatment choice to a more effective dosage, form, or medication. Researchers have also used MMEs in attempting to standardize data on medications and prescribing habits when using varying datasets.
The Source of MMEs – Not at all what you’d think
The origin of MMEs seems to be shrouded in the mists of history. The earliest reference to comparing one opioid to another was in a 1974 JAMA article treating the acute pain of myocardial infarction, “Meperidine hydrochloride in parenterally administered doses of 75 mg provides effective analgesia of the same duration as does 10 mg of morphine sulfate.” Two months later, that view of equivalence was rebutted as
“… counter to that of standard texts and journals of pharmacology and is not consistent with our own experience. While it is accepted that the meperidine dose equivalent to 10 mg of morphine is 75 to 100 mg, duration of analgesia by meperidine may be as little as 50% that of morphine. …in chronic or sustained pain, such as occurs in malignant invasion of bones or in sickle cell crisis, the difference is readily apparent to the alert physician and nurse. It has been suggested that physicians are undertreating patients in pain.” [emphasis added]
All the hallmarks of today’s concerns were there.
- Clinical experience
- Equianalgesic dosage (the amount to provide the same level and duration of pain relief)
- The distinction between acute and chronic pain
- Undertreatment of patients in pain
The next reference I found was published in 1984, coming from a study of 38 patients receiving opioids for chronic, non-malignant pain at Memorial Sloan Kettering’s pain clinic.
“A 25-year-old man developed severe left calf pain associated with swelling and tenderness. He was admitted to hospital in June 1975, taking approximately 28 morphine equivalent mg/24 h for pain.” [emphasis added]
There was no citation. The authors relied on their expertise or some unreferenced work to draw that equivalence.
A paper in the journal Pain from 1996 begins to unravel the underlying scientific studies performed in 1936.
“The morphine dose equivalents for hydromorphone and other opioids derive from single dose studies, all of which involved intramuscular or oral administration and measured pain reduction as the therapeutic endpoint.”
But the authors settle for an even more unsettling definition, based on a 1975 paper in the journal Anaesthesiology. The use of this paper to define MMEs is nothing short of astounding:
“Subjective responses to nurse-observer questions were used to quantitate analgesia for postoperative pain. Hydromorphone is more potent than commonly believed: approximately 0.9 to 1.2 mg is equianalgesic with 10 mg of morphine, with a similar incidence of side effects.” [emphasis added]
It is scientifically illiterate to use this subjective casual observation to form the basis of policy. Yet, this paper is used as a reference by the CDC in its 2016 Opioid Prescribing Guide.
The CDC’s MMEs – Lost in Translation
The CDC explanation of their MME conversions references this paper, Defacto Long-term Opioid Therapy for Non-Cancer Pain, so let’s take a brief look at this study.
It looked at opioid use of adults in two healthcare plans, between 1997 to 2005, reflective of their regional demographics. There is exactly one sentence in the paper that you need to pay attention to:
“The conversion factors were based on information from multiple sources. After reviewing published conversion factors, consensus was reached among two physicians with clinical experience in pain management and a pharmacist pharmacoepidemiologist.” [emphasis added]
The basis of the CDC recommendations comes down to two physicians and a pharmacoepidemiologist. Not overwhelmingly “established” science. Let’s leave those subjective MME conversions to the side for a moment and consider the researchers’ quest to identify a “threshold” to long-term opioid therapy.
In their study, the overwhelming majority of patients took them for less than a month; 80% used opioids for less than a week, 14% took opioids, on average, for only a month. Only 5.5% of the patients receiving opioids took them for longer than a year; they became the focus. In searching for even longer-term use, a possible marker of “addiction,” the researchers found that half of those patients continued therapy into the next year – they were those most likely “to continue frequent use of opioids in future years.” [1] They identified a boundary or signal that an individual’s opioid use might be problematic.
“By setting a clear boundary between acute and episodic use on the one hand, and long-term use on the other, it may be possible for physicians and health plans to establish a check point ….”
There is no mention of MMEs. The variation in the amount of MMEs prescribed or taken among that 6% was too variable [2] to be a threshold; not surprising, given the subjective nature of their calculation. The researcher’s boundary line was the duration of prescribing – a year, the point that would identify that half of the 5.5% they felt to be “at risk.” Most importantly, their boundary was a call to reconsider therapy, not a limit on MME.
Other researchers with similar studies sought their bright line defining those at risk. But quietly, the risk changed from a concern over addiction, as a threshold based on length of treatment would suggest, to a concern over the risk of “overdose.” See the difference in the focus of a 2016 review which concluded
“A clear cut-point in opioid dosage to distinguish between overdose cases and controls was not found. However, lowering the recommended dosage threshold below the 100 MME used in many recent guidelines would affect proportionately few patients not at risk for overdose while potentially benefitting many of those at risk for overdose.”
Somewhere along the way, lost in translation, the concern of addiction morphed to concern over overdose. Despite a lack of “a clear cut-point in opioid dosage,” MMEs replaced fuzziness with pseudo-certainty.
If the ambiguity of what a threshold MME means is insufficient, MME suffers from two additional problems: its calculation and what is being measured. Topics we will address another day.
[1] This does not answer the question of whether their chronic pain had been adequately managed or whether some form of “addiction” or misuse was present.
[2] Among that 6%, there was a greater than 2-fold difference in prescribed amounts and a nearly 4-fold difference in amounts consumed.
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Currently in a dispute with my district manager (who is a licensed pharmacist) at a chain because they called me in the middle of my shift and told me I wasn’t filling scripts fast enough. I responded by stating that I was doing my best, that I felt this was inappropriate behavior from one licensed pharmacist with managerial authority over another, hung up the phone, blocked their phone number, and continued my shift. Thoughts?
