Pain management, Rx opioid mortality, and the CDC

Pain management, prescription opioid mortality, and the CDC: is the devil in the data? by Michael E Schatman & Stephen J Ziegler – Journal of Pain Research – Oct 2017

Though a year old, this article explains the flaws in the CDC opioid prescribing guideline.

Transparency, freedom from bias, and accountability are, in principle, hallmarks of taxpayer-funded institutions. Unfortunately, it seems that at least one institution, the Centers for Disease Control and Prevention (CDC), continues to struggle with all three.

What began with a prescribing guideline created in secrecy has now evolved to the use of statistical data and public statements that fail to capture not only the complexity of the problem but also the distinction between licit and illicit opioids and their relationship to the alarming increase in unintentional overdose.  For instance, when the CDC was in the process of drafting guidelines for the use of long-term prescription opioids to treat chronic pain, the identities of the project’s Core Expert Group members remained a secret until they were leaked.

When its members were eventually identified, many were concerned that the group’s composition was not balanced and had an inherent bias against the use of prescription opioids to treat pain.

The actual guideline itself was not publicly available and was not posted on the CDC website, and admission to the webinar was limited.

Those fortunate enough to gain entry were sometimes able to see the actual recommendation as it flashed on the screen, and while attendees were permitted to ask questions, the CDC stated that they would not provide any answers.

At the end of the webinar, attendees could then email their comments to the CDC, but they only had 25 hours to do so. …the CDC decided to repeat the webinar on the following day and allow an additional 24-hour comment period.

But the controversy did not end there. Following the webinar, allegations of unlawful behavior by the CDC in the creation of the guideline were made, specifically that the CDC had violated the Federal Advisory Committee Act.

The United States Congress eventually stepped in, and the CDC caved under pressure and permitted a 30-day open comment period during the Christmas holidays. Although the new open comment period yielded several thousand comments in the Federal Register, there was little change between the draft guideline and the final guideline

Remarkably, the actions of the CDC in the creation and publication of the prescribing guideline appears to violate every single standard that the Institute of Medicine recommended whenever clinical practice guidelines are created.

Consequently, the authors of this commentary fear that the CDC’s earlier lack of transparency, freedom from bias, and accountability in the creation of a prescribing guideline has now infected the way they characterize statistical data to the public regarding the relationship between opioids (licit and illicit) and unintentional overdose

Simplicity and data conflation is making the problem worse.

While we do not believe that all actors or variables contributed equally to the present crisis, nor do we believe that the unintended negative outcomes flowing from their actions were intended, there is understandably one universal contributor to the increase in unintentional overdose that continues to be singled out by policymakers and the CDC: opioids

But the more important question becomes: about what opioids are they speaking?

• All opioids in general,
• some opioids in particular,
• illicit opioids such as heroin and illicitly manufactured fentanyl, or
• prescription opioids?

These distinctions matter.

According to the CDC, the “majority of drug overdose deaths (more than six out of ten) involve an opioid,”12 and “as many as 1 in 4 people who receive prescription opioids long term for noncancer pain in primary care settings struggles with addiction.” Absent accompanying qualification of the statistics associated with these alarming statements, are they facially accurate or do they reflect a particular agenda – a campaign that fails to recognize the complexity of the issues, the factors, sources, and problems that once identified could help forge effective solutions? We believe it is the latter

The following commentary examines some of the recent statistical claims asserted by the CDC and argues that not only are these statements inaccurate, but they also impede the ability of the public and policymakers to understand the complexity of the problem and create solutions that are balanced and effective

In brief, while prescription opioids continue to play a part in the crisis, illicit opioids such as heroin and illicitly manufactured fentanyl, not prescription opioids and overprescribing, are currently the driving forces behind the increase in unintentional overdose deaths in the United States.

This critical distinction is often ignored or underappreciated by the press and policymakers, and is a distinction that needs to be emphasized by the CDC. The failure to do so has far-reaching consequences in terms of policy, pain treatment, substance abuse prevention, and reduction of unintentional overdose

Prescribing: is the problem under- or over-prescribing?

Pain is individualized, and so should be its treatment.

Opioids can be effective in treating pain, and while there may be a variety of alternatives to opioids, some may not be as effective or covered by insurance reimbursement

…there is scant evidence that the CDC considers chronic pain a serious public health problem.

For instance, the CDC maintains an A–Z index on their public website, an index of “topics with relevance to a broad cross-section of CDC.gov’s audiences” that “are representative of popular topics [. . .] or have critical importance to CDC’s public health mission.”

While undertreated pain does not seem to be of critical importance to the CDC, that has not prevented them from creating a prescribing guideline to treat pain, recommending against the use of prescription opioids, and asserting that nonpharmacologic therapy is preferred

But whether pain is treated with or without prescription opioids, one thing seems clear: it has been undertreated for decades.

So, what amount of prescribing is appropriate? This represents a difficult question since one size does not fit all.

A particular type or dose of one medication may be appropriate for one patient and condition and wholly inappropriate for someone else. Yet despite the medical necessity of tailoring treatments to the individual, the tendency today is for an across-the-board reduction in prescription opioid availability

According to the CDC and several states’ Departments of Health, less opioids are being prescribed, which in turn indicates that there may be something other than just prescription opioids that are contributing to the escalation in unintentional overdose.

Data from the CDC indicate that between 2010 and 2015, the amount of opioids prescribed in the United States actually decreased by more than 18%, with a 13.1% decrease reported between 2012 and 2015 alone.

Survey data also suggest that more than half of physicians in the United States have reduced their opioid prescribing, with nearly 10% having stopped prescribing opioids altogether

Consequently, there is little doubt that the amount of opioids being prescribed is decreasing dramatically, so it would be disingenuous to suggest otherwise.

Measuring and reporting prescription opioid mortality

What constitutes “a prescription opioid death?”

It appears that there is some disagreement and controversy regarding this issue, a disagreement that may be agenda-driven or subject to bias.

Although there is a need for more consistency between coroners and medical examiner offices across the United States when opioid-related deaths are involved, many states utilize death certificate data, which often do not include

• the source of a drug,
• the purpose for which the drug was used,
• the level of opioid tolerance in the decedent, and
• even the specific type or the name of the drug(s) that were involved

Extrapolating from the reported figures, only a mere 5% of all “fentanyl” overdose deaths were due to a legal, pharmaceutical product, with the remaining 14% due to “an unknown source of fentanyl.”

if only 5% of all “fentanyl overdose deaths” are due to pharmaceutical fentanyl, and fentanyl (defined broadly) is now responsible for approximately 79% of all “prescriptionopioid overdose” and “fentanyl” deaths (extrapolating from 2016 Maryland data), could the number of actual prescription opioid deaths be only a small percentage of the overall opioid overdose statistics?

This is not only a measurement problem; this becomes a policy and solution problem if the public and policymakers continue to fixate on prescription opioids as the problem and the primary factor involved in unintentional overdose.

In order to more accurately assess the actual number of prescription opioid analgesic deaths, it was necessary for the first author (MES) to go to individual states’ Departments of Health (DOH).

In speaking to one of DOH’s statisticians, he confirmed our suspicion:

This dramatic increase was almost completely driven by illicit fentanyl and its potent analogs, not by legitimate pharmaceutical opioids used to treat pain.

Furthermore, he noted that irrespective of the number of dangerous substances that are found in toxicology reports, the state’s death certificate data categorize any death in which even an iota of a prescription opioid (or a nonpharmaceutical fentanyl product) is found as a “prescription opioid death”.

The investigators determined that more than half of decedents with an opioid-positive toxicology had alcohol in their systems, and the average number of drugs identified in the toxicologies was six.

a deeper analysis of the existing data helps reveal the complexity of the issue and what is really behind the current opioid crisis.

Yet another cause of the unfortunate overestimation of opioid mortality in the United States (and its link to prescription pain medication) relates to difficulties in distinguishing between heroin and morphine in postmortem samples.

Heroin is twice as potent as morphine, has a half-life of only 6–25 minutes prior to its metabolism to morphine in the liver, resulting in studies suggesting that heroin deaths are also underestimated while morphine deaths are overestimated in their prevalence.

Compounding the problem is that heroin is frequently laced with illicit, nonpharmaceutical fentanyl products, resulting in coroners’ reports now often yielding inaccurate data suggesting that addicts are succumbing to the effects of not just one prescription opioid but two.

Nevertheless, despite the data and their shortcomings, the CDC continues to claim that we are in the midst of a prescription opioid crisis.

The concern is this:

for the CDC to suggest that more than 15,000 died in that year from “prescription opioids” when a closer examination of the data indicates that illicit opioids and/or polypharmacy were involved is not only inaccurate and disingenuous, it can

• negatively impact patients who are well-managed on long-term opioid therapies and have no effective safe alternatives that are covered by insurance,
• negatively impact health care providers who seek to relieve suffering, and
• negatively impact people who are suffering from substance use disorders

The necessity of balance

Prescription opioids can bring enormous benefits to those who are suffering from acute or chronic long-term pain.

Prescribed appropriately, prescription pain medication has provided relief to millions of Americans; it has

• increased their quality of life,
• improved their function,
• provided an option to those for which other analgesics are contraindicated due to certain medical conditions, and
• reduced their suffering.

At the same time, however, prescription opioids by their chemical nature are susceptible to abuse, misuse, and physical harm, particularly among certain subgroups of the population.

Despite decreases in the prescribing of prescription opioids, we continue to see an increase in the rates of unintentional overdose.

While there is clear evidence that this increase is driven by the use of illicit opioids such as heroin or illicitly manufactured fentanyl derivatives, this particular fact continues to get lost in the shuffle and results in knee-jerk reactions calling for the reduction of both the supply and use of prescription opioids.

Conclusion

It is easy to demonize and point fingers at industry, prescribers, or anyone who calls into question the newest battle in the never-ending war on drugs.

Prescription opioids are not the panacea, but they have medicinal benefits, unlike tobacco. For instance, according to the CDC, “cigarette smoking is responsible for more than 480,000 deaths per year in the United States, including more than 41,000 deaths resulting from secondhand smoke exposure.”

In contrast to appropriately prescribed and administered opioids, we are unaware of any legitimate medical treatments involving the use of cigarettes, a product that continues to be available to anyone over 18 years without a prescription.

First, we would suggest that the CDC refrain from making alarmist statements that cite statistics that are not supported by the evidence without qualification.

Second, the CDC should recognize that chronic pain impacts millions of people in the United States and should, at a minimum, create an entry for pain on their website’s A–Z index.

We are concerned that the absence of information about the millions of Americans who suffer from chronic pain sends the message that pain does not “have critical importance to CDC’s public health mission.”

Finally, we need to find ways to work together, instead of against each other, emphasizing civil discourse instead of finger pointing.