Tag: Opioids

Politics, Confirmation Bias, and Opioids

This post co-authored with Rafael Fonseca, MD, Chairman of the Department of Medicine, Mayo Clinic, Phoenix, AZ

Much has been written about how politics and ideology influence research funding, suppress research in certain areas, and lead to the cherry-picking and misrepresentation of evidence in support of a narrative or agenda. Science journalist John Tierney explored “The Real War on Science” in an excellent essay in City Journal in 2016. Reflecting on this phenomenon in 2011, Patrick J. Michaels stated:

The process is synergistic and self-fulfilling. Periodicals like Science are what academia uses to define the current truth. But the monolithic leftward inclination of the reviewing   community clearly permits one interpretation (even if not supported by the results) and not another. This type of blatant politicized science is becoming the norm in the environmental arena, and probably has infiltrated most every other discipline, too.

It certainly has infiltrated research into the emotionally charged opioid overdose problem afflicting the US and many other western nations. Policy decisions have been rooted in a narrative seemingly immune to the facts: that the problem is largely the result of greedy pharmaceutical companies manipulating careless and poorly-trained doctors into “hooking” patients on highly addictive opioids and condemning them to a nightmarish life of drug addiction.

Tierney writes of confirmation bias—the tendency of people to seek out and accept information that confirms their beliefs and prejudices. He bemoans the “groupthink” that allows confirmation bias to infiltrate the peer review process. He cites a well-known study that demonstrated reviewers were more likely to find problems with a study’s methodology if the findings were contrary to their prejudices yet overlook methodological shortcomings if the findings were confirmatory.

Sometimes investigators try to “spin” their findings to make them comport to the narrative and appear confirmatory, increasing the likelihood that their research gets published. 

Both of us are practicing physicians, and each of us recently experienced reminders that research into the opioid overdose issue is not exempt from politicization and confirmation bias. We would like to present two recent examples where this confirmation bias became self-evident. 

Topics:

Civilian Casualties Continue to Mount in Governments’ War on Opioids

I have written here and here about how patients have become the civilian casualties of the misguided policies addressing the opioid (now predominantly fentanyl and heroin) crisis. The policies have dramatically reduced opioid prescribing by health care practitioners and have pressured them into rapidly tapering or cutting off their chronic pain patients from the opioids that have allowed them to function. More and more reports appear in the press about patients becoming desperate because their doctors, often fearing they may lose their livelihoods if they are seen as “outliers” by surveillance agencies, under-treat their pain or abruptly cut them off of their pain treatment regimen.

story in the July 23, Louisville (KY) Courier Journal illustrates the harm this is causing in Kentucky. “Doctors say the federal raids on medical clinics lead to unintended consequences — patients thrust into painful withdrawals and left vulnerable to suicide or dangerous street drugs,” states the article.  Dr. Wayne Tuckerson, President of the Greater Louisville Medical Society, said, “[When investigators] go in with a sledgehammer and shut down a practice without consulting community physicians, suddenly we have patients thrown loose.” He went on to say, “Docs are very much afraid when it comes to writing pain medications…We don’t want patients to become addicted. And we don’t want to have our licenses — and therefore our livelihoods — at stake.” And if pharmacists in the area learn of a police raid or investigation of a medical practice—regardless of the outcome of that investigation—many of them refuse to fill legal prescriptions presented by patients of those practitioners.

Last week Oregon regulators announced plans for a “forced taper” of chronic pain patients in its Medicaid system. This contradicts and is much more draconian than the recommendations of the 2016 guidelines issued by the Centers for Disease Control and Prevention, which in turn have been criticized as not evidence-based. The Oregon Health Evidence Review Commission announced: 

 

The changes include a forced taper for all chronic pain patients on opioids (within a year), no exceptions. Opioids will be replaced with alternative treatments (cognitive behavior therapy (CBT), acupuncture, mindfulness, pain acceptance, aqua therapy, chiropractic adjustments, and treatment with non-opioid medications, such as NSAIDS, Acetaminophen).

 

This proposal has sparked an outcry from patients and patient advocacy groups in Oregon. While this policy proposal only applies to Medicaid patients, they fear it will soon become the standard adopted by all third-party payers in the state.

University of Alabama Medical School Associate Professor Stefan Kertesz, an addiction medicine specialist at the Birmingham VA Medical Center, tweeted in reaction to this proposal:

 

I cannot imagine a more violent rejection of the CDC Guideline on Prescribing Opioids of 2016 than the plan current before Oregon Medicaid : forced taper to 0 mg of all opioid receiving pain patients.

 

Methadone and Mixed Messages

As a physician licensed to prescribe narcotics, I am legally  permitted to prescribe the powerful opioid methadone (also known by the brand name Dolophine ) to my patients suffering from severe, intractable pain that hasn’t been adequately controlled by other, less powerful pain killers. Most patients I encounter who might fall into that category are likely to be terminal cancer patients. I’ve often wondered why I am approved to prescribe methadone to my patients as a treatment for pain, but I am not allowed to prescribe methadone to taper my patients off of a physical dependence they may have developed from long-term opioid use, so as to help them avoid the horrible acute withdrawal syndrome. I am also not permitted to prescribe methadone as a medication-assisted treatment for addiction. These last two uses of the drug require special licensing and permits and must comply with strict federal guidelines. 

The synthetic opioid methadone was invented in Germany in 1937. By the 1960s, methadone was found to be effective as medication-assisted treatment for heroin addiction, and by the 1970s methadone treatment centers were established throughout the US, providing specialized and highly structured care for patients suffering from Substance Abuse Disorder. The Narcotic Addict Treatment Act of 1974 codified the methadone clinic structure. Today, methadone clinics are strictly regulated by the Drug Enforcement Administration, the National Institute on Drug Abuse, the Substance and Mental Health Services Administration, and the Food and Drug Administration. These regulations establish guidelines for the establishment, structure, and operation of methadone clinics, in most cases requiring patients to obtain their methadone in person at one fixed site. After a period of time, some of these patients are allowed to take methadone home from the facility to self-administer while they remain closely monitored. This onerous regulatory system has led to an undersupply in methadone treatment facilities for patients in need. Furthermore, the need for patients to travel, often long distances, each day to the clinic to receive their daily dose has been an obstacle to their obtaining and complying with the treatment program.

Earlier this month addiction specialists from the Boston University School of Medicine and Public Health and the Massachusetts Department of Public Health argued in the New England Journal of Medicine that community physicians interested in the treatment of Substance Abuse Disorder should be allowed to prescribe methadone to their patients seeing them in their offices and clinics. Doctors have been allowed to prescribe the opioid buprenorphine for medication-assisted treatment of addiction for years, and in recent years nurse practitioners and physicians’ assistants have been able to obtain waivers that allow them to engage in medication-assisted treatment as well.

The authors noted that methadone has been legally prescribed by primary care providers to treat opioid addiction in other countries for many years— in Canada since 1963, in the UK since 1968, and in Australia since 1970, for example. They state, 

Methadone prescribing in primary care is standard practice and not controversial in these places because it benefits the patient, the care team, and the community and is viewed as a way of expanding the delivery of an effective medication to an at-risk population.

Policymakers serious about addressing the ever-increasing overdose rate from (mostly) heroin and fentanyl afflicting our population should take a serious look at reforming the antiquated regulations that hamstring the use of methadone to treat addiction.

 

FDA Commissioner Gottlieb’s Sunday “Tweetorial” Is Both Encouraging and Frustrating

A fair reading of Food and Drug Administration Commissioner Scott Gottlieb’s “Sunday Tweetorial” on the opioid overdose crisis leaves one simultaneously encouraged and frustrated. 

First the encouraging news. The Commissioner admits that the so-called epidemic of opioid overdoses has “evolved” from one “mostly involving [diverted] prescription drugs to one that’s increasingly fueled by illicit substances being purchased online or off the street.” Most encouraging was this passage:

Even as lawful prescribing of opioids is declining, we’re seeing large increases in deaths from accidental drug overdoses as people turn to dangerous street drugs like heroin and synthetic opioids like fentanyl. Illegal online pharmacies, drug dealers and other bad actors are increasingly using the Internet to further their illicit distribution of opioids, where their risk of detection and the likelihood of repercussions are seen by criminals as significantly reduced.

As I have written here and here, the overdose crisis has always been primarily caused by non-medical users accessing drugs in a dangerous black market fueled by drug prohibition. As government interventions have made it more expensive and difficult to obtain diverted prescription opioids for non-medical use, the black market responds efficiently by filling the void with heroin, illicit fentanyl (there is a difference) and fentanyl analogs. So policies aimed at curtailing doctors’ prescriptions of opioids to patients only serve to drive up deaths from these more dangerous substitutes, while causing patients to suffer needlessly, sometimes desperately, in pain. Gottlieb validates my argument in his “tweetorial,” providing data from the Centers for Disease Control and Prevention and the Drug Enforcement Administration.

Now for the frustrating news. Gottlieb next reminds us, “No controlled substances, including opioids, can be lawfully sold or offered to be sold online. There is no gray area here.” He provides evidence of rampant illegal internet marketing of prescription opioids, with 95 percent of internet pharmacy websites selling opioids without a prescription, often conducting transactions with cryptocurrencies, and shipping these orders “virtually anywhere in the US.” This is also the way illicit fentanyl is flooding the market.

No, Babies Are NOT Born Addicted to Opioids

“A crisis is a terrible thing to waste,” is a phrase coined by Stanford economist Paul Romer. Politicians are always in search of new crises to address—new fires to put out—with rapid and decisive action. In their passion to appear heroic to their constituents they often act in haste, not taking the time to develop a deep and nuanced understanding of the issue at hand, insensitive to the notion that their actions might actually exacerbate the crisis.

An example of that lack of understanding was made apparent in a press release by the office of House Majority Whip Steve Scalise (R-LA) on June 22 supporting legislation that packages together over 70 bills (H.R.6) aimed at addressing the opioid (now mostly heroin and fentanyl) overdose crisis. The bills mostly double down on the same feckless—often deleterious—policies that government is already using to address the crisis. The release stated, “Whip Scalise highlighted a Slidell, Louisiana family whose son was born addicted to opioids, a syndrome called NAS, as a result of his mother’s battle with addiction.” 

The press release quoted Representative Scalise:

I highlight Kemper, a young boy from my district in Slidell, Louisiana. He was born addicted to opioids because his mother, while she was pregnant, was addicted to opioids herself…this example highlights something the Centers for Disease Control has noted. That is once every 25 minutes in America a baby is born addicted to opioids. Once every 25 minutes. That’s how widespread it is, just for babies that are born.

Before crowing that the “House Takes Action to Combat the Opioid Crisis,” as the press release was titled, Representative Scalise should get his science right. No baby is ever born addicted to opioids. As medical science has known for years, there is a difference between addiction and physical dependence—on a molecular level. Drs. Nora Volkow and Thomas McLellan of the National Institute on Drug Abuse pointed out in a 2016 article in the New England Journal of Medicine that addiction is a disease, and “genetic vulnerability accounts for at least 35 to 40% of the risk associated with addiction.” Addiction features compulsive drug use in spite of harmful, self-destructive consequences.

Physical dependence, on the other hand, is very different. As with many other classes of drugs, including antidepressants like Prozac or Lexapro, long-term use of opioids is associated with the development of a physical dependence on the drug. Abruptly stopping the drug can lead to severe withdrawal symptoms. A physically dependent patient needs the drug in order to function while avoiding withdrawal. Dependence is addressed by gradually reducing the dosage of the drug over a safe time frame. Once the dependence is overcome, such a patient will not have a compulsion to resume the drug.

Why Is the OECD Trying to Connect Labor Market Conditions and Opioids?

story in today’s Wall Street Journal discusses the latest report from the Organization for Economic Cooperation and Development on ”prime age” (25-54) labor-force participation rates among its 35 member countries through the last quarter of 2017. While the US rate has improved, it remains below the average OECD rate, lagging behind such developed countries as Japan and the UK. What’s puzzling is why the authors of the report decided to weigh in on the opioid overdose issue.

Noting that per capita opioid prescriptions in the US are “significantly higher” than in other OECD countries, the report finds that participation rates for all adults (not limited to prime age) vary from state to state. The rate was lowest in West Virginia at 53 percent, and highest in North Dakota at 71 percent. It mentioned that opioid prescription rates are “generally higher” in those states with lower labor participation rates, leading it to declare that the use of opioid drugs “appears to be connected” to labor market conditions.

The number of opioid prescriptions has been dropping steadily in the US since it peaked in 2010. In fact, high-dose opioid prescriptions are down over 41 percent. An April 2018 report from the American Medical Association trumpeted a 22 percent decrease in opioid prescriptions between 2013 and 2017. 

The false narrative dominating the media and driving opioid policy blames opioid abuse and overdoses on doctors addicting their patients to pain pills. The near quadrupling of the sales of prescription opioids between 1999 and 2014 is often used to help make the case. 

Yet correlation does not imply causation. The AMA made note of this in its April report on the dramatic drop in prescriptions when it stated:

It is notable that every state has experienced a decrease, but this is tempered by the fact that deaths related to heroin and illicit fentanyl are increasing at a staggering rate, and deaths related to prescription opioids also continue to rise. These statistics again prove that simply decreasing prescription opioid supplies will not end the epidemic.

Data from the Centers for Disease Control and Prevention show that overdoses—especially from fentanyl and heroin—continue to soar as prescription rates decline on the state level as well. 

The principle that correlation does not imply causation also applies to the observations in the OECD report.

The OECD report mentions that the overall labor-force participation rate tends to be lower in states where disability rates are higher. And West Virginia is a leader among states with respect to the percentage of its population on Social Security Disability benefits at 3.9 percent. It therefore points to a “possible connection between drug use and disability,” adding “addiction ultimately impairs participation.” It is certainly reasonable to expect that patients disabled by chronic severe pain conditions will be prescribed opioids. But there is no evidence that opioid use increases disability rates. In fact, Cochrane systematic studies in 2010 and 2012 found an addiction rate of approximately 1 percent in chronic non-cancer pain patients on long-term opioids. And many chronic pain patients are gainfully employed but have to stop working when they are cut-off from their opioids and their pain becomes debilitating. 

As I have written here and here, the overdose crisis was never about doctors and patients. It has always been primarily the result of non-medical users accessing drugs in the dangerous black market that results from drug prohibition.

Because correlation does not imply causation the OECD report carefully avoids drawing conclusions by using phrases like “appears to be connected” and “generally higher.” But its allusion to a connection between opioid prescribing and the labor participation rate is intellectually irresponsible and seems a gratuitous attempt to patronize the opioid policy establishment.

The AMA Gets it Right by Defending Evidence-Based Medicine and Patient, Physician Autonomy

Gun control advocates like to accuse legislators of being “afraid of the NRA,” implying that reason and principle have nothing to do with their legislative decisions. In the same way, Jackie Kucinich, in a column in The Daily Beast, suggests that the failure of Congress to pass CARA 2.0 (Comprehensive Addiction and Recovery Act) is due primarily to the lobbying clout of the American Medical Association, pointing to its status as the “seventh highest lobbying spender in 2017.”  

The article quotes opioid reform advocate Gary Mendell as saying “the AMA will resist anything that regulates healthcare”—an interesting opinion about an organization that supported passage of the Affordable Care Act, one of the deepest regulatory intrusions into American health care in half a century. Over the years, the AMA’s seeming reluctance to mount a principled defense of patient autonomy and freedom of choice in healthcare—perhaps fearing it may jeopardize the cartel it lobbied so hard to establish over the past century and a half—has led to an exodus of many disillusioned members. It is estimated that less than 17 percent of the country’s doctors belong to the special interest group today.

But on this one, the AMA gets it right. It opposes the “one-size-fits-all” imposition of the 2016 opioid prescribing guidelines issued by the Centers for Disease Control and Prevention; guidelines that many noted addiction medicine specialists have criticized as not-evidence based. The AMA maintains the CDC expressly meant for its guidelines to be suggestive “rather than prescriptive.” Other scholars have pointed out that the CDC’s suggestions were based upon “Type 4 evidence,” defined as evidence in which “one has very little confidence in the effect estimate, and the true effect is likely to be substantially different from the estimate of the effect.”  The AMA emphasizes the guideline’s statement, “Clinical decision making should be based on a relationship between the clinician and patient, and an understanding of the patient’s clinical situation, functioning and life context.”

When health care providers read and interpret these guidelines, they understand them to be informational, nonbinding, and inconclusive. But that’s not how politicians “do science.”

There is no evidence that prescription limits reduce overdose deaths. In fact, as the prescription rate has dropped dramatically since its peak in 2010, overdose rates are in turn rising

Kucinich seems to agree with the politicians who interpret the CDC guidelines as implying that a more than 3-day supply of prescription opioids is a major force behind addiction. But that is not a precise and critical reading of the guidelines. In fact, as Dr. Nora Volkow, Director of the National Institute on Drug Abuse pointed out in a 2016 New England Journal of Medicine article, “Addiction occurs in only a small percentage of persons who are exposed to opioids — even among those with preexisting vulnerabilities.” Cochrane systematic studies in 2010 and 2012 show a roughly 1 percent incidence of addiction in chronic non-cancer pain patients, and a January 2018 study of 568,000 “opioid naïve” patients given prescriptions for acute post-surgical pain found a “total misuse” rate of 0.6 percent. 

The AMA is actually a little late to the party. Numerous other specialists in the management of pain and addiction have criticized for months the tendency of politicians to codify the recommendations of the CDC. Even the Food and Drug Administration Commissioner, Scott Gottlieb, has expressed concerns. Announcing plans to hold a public meeting on July 9 on “Patient-Focused Drug Development for Chronic Pain,” Dr. Gottlieb set forth “the goal of providing standards that could inform the development of evidence based guidelines.”  

The article quotes Sen. Joe Manchin (D-WV) accusing his colleagues of being “too scared to take on the AMA.” My hope is that they may be finally responding to evidence and accounts from health care practitioners and patients who have spent months appealing to reason over dogma.