Opioids, Pain and the CDC’s Guideline: Needs Improvement

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Opioids, Pain and the CDC’s Guideline: Needs Improvement |
by Stefan Kertesz Physician, researcher

These arguments against the CDC’s guidelines are specific, logically argued, and carefully thought out, explaining some aspects that seemed muddled, but are clear to a practicing doctor.

The Centers for Disease Control report that 2014 saw a record of 18,893 deaths related to opioid overdose, including both medications and heroin. Given a rising tide of deaths, it is only sensible to look at how opioids come into distribution.

A major portion of the public health response has focused on doctors and their prescriptions (disclosure: I’m a primary care doctor trained in internal medicine and addictions). Many authorities and researchers believe the rising tide of overdoses has something to do with the opioid prescriptions we write.

I don’t believe that all the opioid pills available on the black market have been from prescriptions. Instead, I predict that the real sources of opioids deal in huge quantities, the kind you find in storage and distribution facilities.

With few of the stringent safeguards restricting patients, these facilities could be “leaking” thousands of uncounted pills. There could be foxes guarding those henhouses, like corrupt employees or gang members. Because those jobs don’t require background checks like patients do.

Barring a few so-called pill mills (which alone cannot account for the rise in prescriptions), most doctors writing prescriptions for opioid pills do so in response to a patient with severe chronic pain. There are an estimated 100 million Americans with chronic pain, and between 5 and 8 million take opioids for that pain.

It stands to reason that among the patients who have received opioid prescriptions, surely some (or many) should not have received them. Many doctors are prescribing less, starting in 2012, data show. Thus, great hopes are pinned on getting doctors to prescribe differently (and less) for their patients with pain.

Last year the Centers for Disease Control prepared a draft guideline for doctors on prescribing opioids to effect such change By deadline on Jan. 13, 2016,  over 4,300 comments were received.

There is a reason this document excites so much passion. Already in December, Congress made the future guideline’s recommendations mandatory for over 14,000 doctors who care for our nation’s veterans. Organizations such as the American Cancer Society’s Action Network project this guideline will not be voluntary, but will carry force of law.

The hope is to prevent development of addiction and overdose that devastates countless families. Yet, there are those 5 to 8 million patients who receive opioids, some of whom are at risk of losing access to a crucial medication that is helping manage their pain, improve their quality of life and overall function.

As medical boards, insurers and government agencies enforce this guideline, prescribing differently from the top line recommendations is likely to become onerous, leaving many patients in the lurch.

My practice lines up closely with what this guideline recommends. And despite that, I feel the guideline is not yet ready, not given the regulatory power it will have.

I believe it reaches beyond the available science in places, neglects it in others, and misconstrues how best to translate it in the care of patients.

Friends, some of them national leaders in primary care, addiction and pain medicine, have urged me to publish this concern broadly. I want to show that one can take a different stand without rejecting the science or the underlying public health commitment that I share with the drafters of the CDC’s guideline.

How can you reject science that doesn’t exist (there are NO long-term studies on harms/benefits of opioids) or that contradicts the latest research? The guideline is rejecting science.

Central to the guideline is a preference statement. It says that any and all treatments for pain that do not include opioids are “preferred” to any that do include opioids. That statement is so broad as to be untestable.

Other national evidence based guidelines do not include such broad, unscientific propositions.

Behind that statement is an evidence review that oddly tilts the scales. When looking at opioids, the guideline asserts that only studies documenting benefit for over a year were worthy of inclusion. Studies of that length have generally not been conducted.

Shorter opioid-focused studies, some reporting benefit, were excluded. For non-opioid alternatives, short-term studies were included. That seems unbalanced when human suffering hangs in the balance.

The draft guideline takes a strong stand on opioid doses. Higher doses are associated with more overdose risk, which is compelling enough that I keep doses low for most patients.

But in most guidelines, such as the one for cholesterol, decisions are never based on relative risk, because 20 years of scholarship have shown that they are misleading.

One has to consider absolute risk, and consider all other protective and exacerbating risk factors that apply to a patient. In one study, being over 60 years old (versus 18-29) reduced overdose risk by 82 percent, arguably wiping out any risk increase associated with a higher dose.

I find it outrageous that these federal rules are based on such shoddy studies and statistics. These numbers have clearly been gamed to get the outcome the researchers (and their money sources) desire.

No other guidelines and rules use relative risk because it can be meaningless.

This is like saying that because chemotherapy #1 is 2 times as dangerous as  chemotherapy #2, only chemotherapy #2 should ever be used, without taking into consideration that chemotherapy #1 is 4 times as effective.

That’s why scientists use absolute risk or benefit of a treatment, not just relative to other treatments.

The guideline’s top line recommendation focuses on dose in a way that pressures doctors to ignore this part of the science, and what they know about their patients.

What caregivers know about the lives of their patients is central to good health care decisions, as described a series of federally-sponsored studies, summarized in the recent book Listening for What Matters.

Patients are not dough, waiting to be stamped into conformity with whatever the cookie cutter requires. The guideline’s top line recommendations do not recognize the central importance of personalized decisions. It opens the door to harsh and restrictive misinterpretation, even if the authors themselves had no such intention.

Here are more of his arguments on medium.com:

Considering CDC’s Proposed 2016 Guideline for Prescribing Opioids for Chronic Pain: A Good Start… — Medium

 

It stands to reason that among the patients who have received opioid prescriptions, surely some (or many) should not have received them. Many doctors are prescribing less, starting in 2012, data show. Thus, great hopes are pinned on getting doctors to prescribe differently (and less) for their patients with pain.

If prescribing went down while overdoses went up these past few years, it’s fair to say that there is room for argument about precisely how doctor’s prescriptions relate to overdoses.

Prescribing has gone down and overdoses seem to keep climbing, which means that the two are probably not linked. Doctors and patients are NOT the cause.

The hope is to prevent development of addiction and overdose that devastates countless families. Yet, there are those 5 to 8 million patients who receive opioids, some of whom believe that they are at risk of losing access to a crucial medication that is helping manage their pain, improve their quality of life and overall function.

As medical boards, insurers and government agencies enforce this guideline, prescribing differently from the topline recommendations is likely to become onerous, leaving many patients in the lurch.

The experts convened by the CDC include many I know and respect. They have taken a fairly strong stand.

  • They conclude that the literature shows no evidence of enduring benefit from opioids, and that measurable harms are tied closely to dose.
  • They urge careful assessment of risk and benefit.
  • They urge aggressive use of urine drug testing to identify patients who take opioid medication differently from intended or use illicit drugs.

For reasons I shared with the CDC (shown below), I think it reaches a bit beyond the available science in some places, neglects it in others, and misconstrues how best to translate it in the care of our patients.

It risks making opioids less available to patients who are benefiting from them.

(Below follows the full text, as submitted to the Centers for Disease Control public docket on January 13, 2016. I have made minor edits and added a hyperlink, relative to the submitted document)

Use of the Federal Register for public comment is required only for rules, not guidelines. The option to use the rule-making apparatus reflects CDC’s own appreciation of the power that will attach to this document. As if to underscore the point, Congress gave this guideline force of law within the Department of Veterans Affairs,

Guideline authors could be forgiven, last summer, for assuming that a “guideline” implies a degree of clinical judgment about how and when to apply it. But in fact, Congress did not order “consideration” of a “guideline” by professionals. It required, explicitly, adoption of the practices.

So, they are making enforceable laws using “guidelines” (meant to be suggestions) that are preliminary, based on skewed data, which is wrongly interpreted. This is a sad state of affairs.

This throws all the legal and disciplinary weight to this document’s top-line recommendations, even when the underlying text works hard to soften them and acknowledge multiple evidentiary shortcomings.

Comment:

I am a physician certified in addiction medicine with a history of research support from the National Institute on Drug Abuse. I run a primary care clinic where I see pain patients for whom opioid prescription has arisen either as a therapeutic proposition or as a clinical problem

Our day-to-day practice aligns with nearly all principles laid out in the guideline.

If this “guideline” were merely written to reflect current clinical wisdom and did not carry the enormous public and regulatory import that it does in fact carry, I would sign on as supportive.

However, this guideline has enormous potential regulatory impact nationally. It has guaranteed legal impact on all clinicians practicing in the US Department of Veterans Affairs. And despite the enormous work that obviously went into it, there are serious flaws in how this Guideline considered research evidence and translated them into clinical guidance.

As a result, it fails to offer meaningful and direct support for primary care providers who must, of necessity, make decisions daily in the care of actual patients.

I will note four.

  1. Inappropriately broad conclusions are drawn from untestable propositions and a problematic literature review.

Recommendation 1’s topline recommendation offers a global assessment that “nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain.”

In medicine, the evidentiary standard for favoring one treatment over another requires comparative study. It would be extraordinary in any guideline to declare that every conceivable therapy not including a named pharmacologic agent (i.e. opioids) is generally superior to all therapies that do include that agent. Such a statement is not a scientific proposition, and it is by its nature not a testable proposition.

I would urge avoidance of broad, untestable conclusions in a guideline.

Beneath the overbroad conclusion offered by Recommendation 1 is a problematic literature review in which the Guideline applies unequal standards for assessing the potential benefits of opioids versus the potential benefits of all other therapies.

  1. In Recommendation 5 concerning opioid dosage, there is a lack of any effort to discuss or consider absolute (as opposed to relative) risks, and a failure to consider the importance of risk and protective factors that can mitigate or exacerbate risk related to dosage. These combined flaws results in an unduly narrow focus on dosage alone (“should generally avoid increasing dosage to >90 MME/day”).

This narrow dose-focused top-line recommendation should be amended to encourage acknowledgment of the other risk and protective factors that are documented in the literature and known to clinicians, and to incorporate consideration of absolute as opposed to relative risk.

The literature on opioid overdose risk routinely reports absolute risk, and thus it is a flaw that such data are ignored in this guideline. Knowing the underlying absolute risk completely changes the true impact of prescribing a lower or higher dose, and must be considered by doctors.

An excellent study of US veterans receiving opioids for non-chronic cancer pain, published in 2011, found that doses ranging from 50–100 mg Morphine Milligram Equivalents (MME) was associated with overdose rate of 0.24 per 1000 person-months

That absolute risk may or may not be acceptable for a certain patient given the overall level of pain-related dysfunction and the actual benefits they obtain from opioids.

Perhaps equally problematic, research data show that the risk related to opioid dose should not be considered in isolation from all the other information a clinician may know.

The aforementioned study of veterans also showed that other characteristics, including age and race, had very strong effects that could eliminate or greatly amplify the dose-related risk. Being black versus white, in this sample, reduced risk by 2/3. Being over 60 years old (versus 18–29) reduced risk by 82%. Clinicians often know even more about their patients than these factors.

Thus, the topline recommendation’s focus on dose alone truly obscures a great deal of scientific evidence that has already been published, and which should be central to well-informed prescribing.

  1. The top-line recommendations for opioid prescribing lack a sufficient, explicit top-line endorsement of clinical decision-making based on a clinical relationship and knowledge of the patient’s overall functioning and life context.

It has been shown that a key element of good decision-making for any chronic condition depends substantively on the capacity of caregivers to understand what is going on in the life of the patient

What’s lacking is a guidance that squarely urges clinicians (and more important, health care organizations) to solicit and listen for the information about life functioning, social functioning and daily activities that help one to determine if a prescription fits well or fits poorly in the life context of a given patient.

The same guidance should serve to caution health care enforcers (administrators, licensing boards, and federal Departments) against punishing prescribers based on dosage or duration alone.

  1. Recommendations endorsing urine drug testing and holding treatment for acute pain to 3 days’ duration are not strongly grounded in science. Given the regulatory and legal force applied to this guideline, they either should be jettisoned or significantly reconfigured.

As a practicing clinician, we use urine drug testing, although my fellow physicians and I spend a great deal of time trying to interpret the results, because they are often very complicated.

…and WRONG! Urine Drug Tests are notoriously difficult to interpret. Here are a few posts about problems with these tests:

The guideline itself reviews the weakness of the research data to support urine drug testing. The guideline does not sufficiently consider cost, which will in fact be a prohibitive barrier for many indigent patients. This was the case when I worked in a community health center.

To support drug testing as a precondition to opioid therapy (top-line recommendation 10), knowing full well that many patients can’t afford to pay for it, poses a very serious problem of equity and justice. It is inappropriate, especially when the supporting data are explicitly acknowledged to be weak, to endorse a precondition that will eliminate the poor from access to a treatment that they could otherwise afford.

The recommendation to limit opioid prescription for acute injuries to 3 days is offered tentatively, as it should be. I was unable to find a single citation of a scientific study to support this recommendation, however.

If this document presented itself as merely a statement of current expert opinion, and not a document having legal and regulatory force, I would basically agree with it, pending better data.

But given the projected use of this guideline for health regulations and review of professionals across multiple contexts, I believe the top-line recommendations should explicitly reference the optional or guarded nature of the clinical wisdom being offered.