Do Rx Opioids Really Increase Risk of Fatal Accidents?

By Pat Anson, PNN Editor

A recent study published in JAMA Network Open made headlines when it claimed that use of prescription opioids more than doubled the risk of causing a fatal car accident.  

Researchers at Columbia University Mailman School of Public Health looked at death certificates and toxicology tests on drivers involved in over 18,000 fatal two-vehicle accidents from 1993 to 2016. They found that 1,467 of the “crash initiators” tested positive for hydrocodone, morphine, oxycodone or other prescription opioids.    

The researchers reported their findings as “compelling evidence that use of prescription opioids by drivers is a significant contributing factor” in fatal crashes, which was a dog whistle for media outlets like CNN to warn, “Opioid epidemic spilling over onto roads.”

It turns out the evidence was not so compelling after all.

Like many states, Maryland faces growing rates of opioid abuse and addiction. But when researchers looked at opioid-related crashes in Maryland from 2006 to 2017, they found no significant increase in fatal accidents.

“The fact that opioid crashes in Maryland over the last 10 years have been more or less steady was a surprise,” Johnathon Ehsani, PhD, a professor at the Johns Hopkins Bloomberg School of Public Health told The Washington Post.

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That is striking, because Maryland is one of those states that has been quite severely affected by the overall opioid epidemic.”

Ehsani and his colleagues took another look at the toxicology data and realized it was misleading. The reason was simple: Because hospitals and first responders often give opioid medication to patients injured in accidents, autopsies will detect those opioids in patients who later die from their injuries. In other words, the drivers may not have been under the influence of opioids before the crash.

When researchers only looked at a sub-sample of drivers who died at the scene, they found that the use of prescription opioids was “considerably lower than those who died hours or days following the crash.”

“We applied a stricter definition than our other colleagues did,” said Ehsani, who published his findings in the less prominent journal Accident Analysis & Prevention. “We were more conservative in our case definition.”

The JAMA study apparently over-counted the number of opioid-related crashes by not differentiating between drivers who died at the scene and those who died after getting medical treatment with opioids.

"When determining the prevalence of opioid use in a population, it can be tricky to untangle the two circumstances," says Ehsani. "Thinking differently about the way in which researchers count cases has implications that can offer policymakers and public health professionals more meaningful results."

No one is suggesting that it’s okay to drive a vehicle while impaired by opioids. But it’s also not okay for researchers and prominent medical journals to use flawed data to suggest that patients using prescription opioids are more likely to cause fatal accidents.

In Maryland, they found just the opposite may be true.

“It could be that a number of people who are impaired by opioids choose not to drive,” Ehsani said. “It could be that there is some self-selection going on in that population or it could be that some of those who are most seriously impaired are unable to or don’t have access to a vehicle to drive.”

Study Finds Rx Opioids Provide Limited Pain Relief

By Pat Anson, PNN Editor

Prescription opioids relieve pain, improve physical functioning and help people with chronic pain sleep. But the improvements are small and come with side effects such as vomiting.

Those are the findings from a new meta-analysis (a study of studies) published in the Journal of the American Medical Association (JAMA). Researchers at McMaster University in Canada reviewed 96 clinical trials involving over 26,000 participants who received either prescription opioids or a placebo.

The findings do little to resolve the debate over the safety and effectiveness of opioids.

"Despite widespread use, there is not enough known about the benefits and harms of opioids for chronic non-cancer pain," said lead author Jason Busse, DC, a researcher with the DeGroote Institute for Pain Research and Care at McMaster University.

"We found that, compared to a placebo, 12 per cent more patients treated with opioids will experience pain relief, 8 per cent more will notice an improvement in their physical functioning, and about 6 per cent more will find improvement in their sleep quality.”

One expert questioned the designs of the studies used in Busse’s analysis. Because most participants received a relatively low dose of opioids, it’s not surprising such a small number experienced pain relief, according to Stephen Nadeau, MD, a research advisor for the Alliance for the Treatment of Intractable Pain (ATIP).      

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“With few exceptions, doses of opioids achieved were low (median dose 45 MME), trials were short, and opioids were rapidly titrated,” said Nadeau, a neurologist at the VA Medical Center in Gainesville, Florida.

“Because the study designs in all but a handful of studies did not remotely emulate clinical practice, it cannot be inferred that the results of this analysis are applicable to management of the general population of patients requiring opioid management of moderate to severe chronic nonmalignant pain.”

None of the opioid studies reviewed by Busse and his colleagues lasted longer than six months and many were considered low-to-moderate quality evidence. But the same thing could be said about virtually every pain reliever on the market. There is no good quality evidence proving that acetaminophen, pregabalin, ibuprofen, gabapentin or any other non-opioid pain medication is safe or effective long-term.

But opioid critics were quick to focus on the Busse study as proof that opioids should rarely be prescribed for pain.

“The findings reported by Busse et al illustrate that most patients who are prescribed opioids for the treatment of chronic noncancer pain will not benefit from those drugs,” wrote Michael Ashburn, MD, and Lee Fleisher, MD, in a JAMA editorial. “Given the clear risk of serious harm, opioids should not be continued without clear evidence of a clinically important benefit.”

But the only significant side effect the Busse study found was a 6% risk of vomiting. The study drew no conclusions about opioids increasing the risk of addiction, overdose and death – although Busse says those risks should not be overlooked.

“Given their risks, modest benefits, and the comparable effectiveness of alternatives, our results support that opioids should not be first line therapy for chronic non-cancer pain," said Busse, a chiropractor who was the lead author of Canada’s opioid prescribing guideline.

The study was funded by the Canadian Institutes of Health Research and Health Canada.

Is JAMA Opioid Study Based on Junk Science?

By Pat Anson, Editor

You may have read about a research study published this week in the Journal of the American Medical Association (JAMA), which compared the effectiveness of opioid and non-opioid medications in treating chronic pain. 

The yearlong study of 240 patients found that opioids were not superior to pain relievers like acetaminophen and ibuprofen in treating chronic back pain or hip and knee pain caused by osteoarthritis.  Pain improved for 41% of the patients who took opioids, compared to 54% in the non-opioid group.  

It’s an interesting study – one of the few to look at the effectiveness of any pain relievers long term – but some critics are questioning the study’s methodology and the alleged anti-opioid bias of its lead author, Erin Krebs, MD, a researcher for the Department of Veterans Affairs.

First let’s look at some of the news coverage the study is getting.

“Opioids Don’t Treat Chronic Pain Any Better Than Ibuprofen” reads the headline in Newsweek, an article that never mentions the JAMA study was limited to patients with back pain or osteoarthritis.

“Opioids Don’t Beat Other Medications for Chronic Pain” was the headline in NPR.com, while the Chicago Tribune went with “Opioids no better than common painkillers for treating chronic pain.”

The Tribune article included a quote from one of the co-authors of the CDC opioid guidelines. "The fact that opioids did worse is really pretty astounding," said Roger Chou, MD. "It calls into question our beliefs about the benefits of opioids."

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Notice the news coverage strongly suggests that opioids are ineffective for all types of chronic pain – not just back pain and osteoarthritis.  Patients living with chronic pain from arachnoiditis, trigeminal neuralgia or some other intractable pain condition would probably disagree about that. And they'd find the idea of taking ibuprofen laughable, if not infuriating. But no one asked for their opinion.

Also unmentioned is that opioids are usually not prescribed for osteoarthritis or simple back pain, which are often treated with NSAIDs and over-the-counter pain relievers.

So, what JAMA has published is a government funded study designed to look at a treatment (opioids) that most people with back pain and arthritis never actually get.

“You've been had by anti-opioid advocates disguising their advocacy as science.  Krebs is well known in professional circles for this kind of distorted advocacy junk science,” wrote patient advocate Red Lawhern, PhD, in a comment submitted to the Philadelphia Inquirer after it published a misleading headline of its own, “Prescription opioids fail rigorous new test for chronic pain.”

“I suggest that you retract your article.  In its present form, it is propaganda not fact,” said Lawhern, a co-founder of the Alliance for the Treatment of Intractable Pain (ATIP). “Opioids have never been the first-line medical treatment of choice in lower back pain or arthritis. That role is served by anti-inflammatory meds, some of them in the prescription cortico-steroid family.  NSAIDs have a role to play, recognizing that they are actively dangerous in many patients if taken at high doses for long periods.  Hundreds of people die every year of cardiac arrest or liver toxicity due to high-dose acetaminophen or ibuprofen.” 

Who is Erin Krebs?  

Dr. Krebs is an associate professor at the University of Minnesota Medical School and a prolific researcher at the VA Medical Center in Minneapolis.

She was also an original member of the “Core Expert Group” – an advisory panel that secretly drafted the CDC’s controversial opioid guidelines while getting a good deal of input from the anti-opioid activist group Physicians for Responsible Opioid Prescribing (PROP). The guidelines recommend that opioids not be prescribed for chronic pain.

Krebs also appeared in a lecture series on opioid prescribing that was funded by the Steve Rummler Hope Foundation, which coincidentally is the fiscal sponsor of PROP. 

Some of her previous opioid research has been controversial. In a study published last year in the Annals of Internal Medicine, Krebs reviewed 67 studies on the safety and effectiveness of opioid tapering. Most of the studies were of poor quality, but nevertheless Krebs came to the conclusion that pain levels and the quality of life of patients “may improve during and after opioid dose reduction.”

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“This review found insufficient evidence on adverse events related to opioid tapering, such as accidental overdose if patients resume use of high-dose opioids or switch to illicit opioid sources or onset of suicidality or other mental health symptoms,” wrote Krebs.

PROP founder Andrew Kolodny, MD, read the review and liked it, tweeting that “dangerously high doses should be reduced even if patient refuses.”

But forced opioid tapering is never a good idea, according to a top CDC official.

“Neither (Kreb’s) review nor CDC's guideline provides support for involuntary or precipitous tapering. Such practice could be associated with withdrawal symptoms, damage to the clinician–patient relationship, and patients obtaining opioids from other sources,” wrote Deborah Dowell, MD, a CDC Senior Medical Advisor, in an editorial also published in the Annals of Internal Medicine. 

As for Krebs’ contention that there is “insufficient evidence” of adverse events associated with opioid tapering, that notion may be put to rest next month when the VA releases a new study showing that tapering has led to a growing number of suicides by veterans.

In a summary of the findings, which will be presented at the Rx Drug Abuse & Heroin Summit, VA researchers report that “opioid discontinuation was not associated with overdose mortality, but was associated with increased suicide mortality.”  

Who and what should we believe in the neverending debate about opioids? PNN columnist Roger Chriss wrote about Krebs’ opioids vs. non-opioids study last year, when the initial reports of its findings came out. Roger said prescribing decisions are best left to physicians who know their patients’ medical conditions – not researchers, regulators or the news media.

“In reality, there is no ‘versus’ here. Opioids and NSAIDs are both valuable tools for chronic pain management. To pretend that one is inherently better than the other is to miss the essential point: Both work and should be available for use as medically appropriate,” Roger wrote. 

CDC Releases More Faulty Research About Opioids

By Pat Anson, Editor

A new study by researchers at the Centers for Disease Control and Prevention estimates that opioid overdoses have shaved two and a half months off the average life span of Americans – a somewhat misleading claim because the study does not distinguish between legally obtained prescription opioids and illegal opioids like heroin and illicit fentanyl.

The research letter, published in the medical journal JAMA, looked at the leading causes of death in the U.S. from 2000 to 2015. Overall life expectancy rose during that period, from 76.8 years in 2000 to 78.8 years in 2015, largely due a decline in deaths from heart disease, cancer, stroke, diabetes and other chronic health conditions.

But deaths due to Alzheimer’s disease, suicide, liver disease, drug poisoning and opioid overdoses rose, collectively causing a loss of 0.33 years in life expectancy – most of it due to opioids.

“This loss, mostly related to opioids, was similar in magnitude to losses from all the leading causes of death with increasing death rates,” wrote lead author Deborah Dowell, MD, of the CDC’s National Center for Injury Prevention and Control.

“U.S. life expectancy decreased from 2014 to 2015 and is now lower than in most high-income countries, with this gap projected to increase. These findings suggest that preventing opioid related poisoning deaths will be important to achieving more robust increases in life expectancy once again.”

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Dowell was also one of the lead authors of the CDC’s 2016 opioid prescribing guidelines, which discourage physicians from prescribing opioids for chronic pain. She and her two co-authors in the JAMA study --  both of them CDC statisticians -- do not explain why they failed to distinguish between black market opioids and legal prescription opioids, a dubious use of statistics akin to lumping arsonists in the same category as smokers or Boy Scouts learning to build campfires.  

They also fail to even mention the scourge of heroin and illicit fentanyl sweeping the country, which now accounts for the majority of opioid overdoses in several states.  

But Dowell and her co-authors don't stop there. The say the actual number of deaths caused by opioids is “likely an underestimate” because information on death certificates is often incomplete and fails to note the specific drug involved in as many as 25% of overdose deaths. This is another disingenuous claim, because it fails to explain why the data on the other 75% of overdoses is faulty too. 

Epidemic of Despair

Other researchers have also tried to explain the disturbing decline in American life expectancy – which began over adecade ago for middle-aged white Americans. Princeton researchers Anne Case and Angus Deaton were the first to document that trend,  when they estimated that nearly half a million white Americans may have died early because of depression, chronic pain, suicide, alcohol and drug abuse, and other health problems – an epidemic of despair linked to unemployment, poor finances, lack of education, divorce and loss of social connections.

The evidence was right there for Deborah Dowell and her co-authors had they looked for it. The JAMA study found that over 44,000 Americans committed suicide in 2015, a 66% increase from 2000, and over 40,000 died from chronic liver disease or cirrhosis, another 66% increase. Opioid overdoses during that same period rose to 33,000 deaths. 

Which is the bigger epidemic?

As PNN has reported, the CDC ignored early warnings from its own consultant that the agency’s opioid guidelines were being viewed as “strict law rather than a recommendation,” causing many doctors to stop prescribing opioid pain medication. Chronic pain patients also feel “slighted and shamed” by the guidelines, and are increasingly suicidal or turning to street drugs. We’ve also reported that the CDC has apparently done nothing to study the harms or even the possible benefits the guidelines have caused since they were released 18 months ago.

Instead of going back in time and selectively mining databases to fit preconceived notions about opioids, perhaps it is time for the CDC to take a giant step forward and see what its opioid guidelines have actually done.

Researchers Warn Against Opioid Backlash

By Pat Anson, Editor

The backlash against opioid medication has gone too far and is depriving chronic pain patients of a treatment many have used successfully for years, according to a commentary published in a prominent medical journal. The article also questions the use of the term “opioid epidemic” in describing the nation’s festering drug problem.

“The movement to virtually eliminate opioids as an option for chronic pain refractory to other treatments is an overreaction,” wrote Kurt Kroenke, MD, and co-author Andrea Cheville, MD, in JAMA.Many patients currently receiving long-term opioids were started when opioids were still considered a viable treatment option and if satisfied with their pain control and using their medications appropriately should not be unilaterally compelled to wean off opioids.”

Kroenke is a research scientist at the Regenstrief Institute and a professor at the Indiana University School of Medicine. Cheville is a professor and chair of research in the Department of Physical Medicine and Rehabilitation at the Mayo Clinic. She was recently elected to the National Academy of Medicine.

Kroenke and Cheville say many of the medications recommended as safer alternatives to opioids, such as acetaminophen and NSAIDs, provide little pain relief and have risky side effects. Others, such as pregabalin, gabapentin and antidepressants, may work for some pain disorders but have little benefit for others.

“Many patients respond better to one analgesic than another, just as patients with other medical conditions have differential medication responses,” they wrote. “Given the small analgesic effect on average of most pain drugs, the few classes of analgesic options, and the frequent need for combination therapy, eliminating any class of analgesics from the current menu is undesirable.”

Kroenke and Cheville say only a small minority of pain patients who start using opioids go on to use them long-term, yet medical literature and the mass media are filled with references to the so-called “opioid epidemic.”

“Excessive use of phrases like opioid epidemic should be avoided. An epidemic generally suggests a disease that is widespread and usually highly contagious rather than limited to a minority of those exposed,” they said. “Most patients receiving an initial opioid prescription do not proceed to chronic use and among the subset that do use long-term opioids, the majority neither misuse nor experience an overdose.

“An unintended consequence of excessive concerns raised about opioids could be an increasing reluctance among clinicians to prescribe even small amounts of opioids for a limited time for acute pain, including for patients discharged from the emergency department, those who are recuperating from surgical procedures, or persons with severe dental pain.”

A bill recently introduced in Congress would strictly limit opioids to just 7 days for acute pain, a prescription that could not be renewed. Maine, New Jersey, Ohio and several other states are adopting similar measures to limit opioid prescribing.

Kroenke and Cheville say few long-term studies have been conducted on the safety and effectiveness of any pain medications, and more research is needed on alternative therapies like cognitive behavioral therapy and medical marijuana before opioids are abandoned as a treatment option.

“Clinicians must be careful of replacing the opioid epidemic with a marijuana epidemic,” they warned. “Imperfect treatments do not justify therapeutic nihilism. A broad menu of partially effective treatment options maximizes the chances of achieving at least partial amelioration of chronic pain.”

CDC Guidelines Study: The Devil Is in the Details

By Stephen Ziegler, PhD, Guest Columnist

JAMA Internal Medicine has published a research letter that purports to be an examination of the relationship between funding from opioid manufacturers and opposition to the prescribing guidelines issued by the Centers for Disease Control and Prevention (CDC) in March of 2016.

The authors examined the written comments made to the CDC during the open comment period, asserted that those who had received funding were more likely to oppose the CDC guidelines, and concluded that their “findings demonstrate that greater transparency is required about the financial relationship between opioid manufacturers and patient and professional groups.”

The following commentary, while critical of information contained in the article written by Caleb Alexander, Andrew Kolodny and others, nevertheless concludes with some positive suggestions for the future.

Illicit Opioids: The Harms Associated With Conflation of Data

The research letter, like many articles authored by those who are rightly concerned about addiction and overdose, begins by asserting that an association exists between increases in opioid prescribing and “large increases in addiction and overdose deaths in the United States.”

However, there are several problems with such a statement. First, association is not causation. For example, while a positive association exists between the size of a fire and the number of fire engines on the scene, fire engines for the most part do not cause fires -- they are only associated with it. Further, it is misleading and harmful to lump all opioids, prescription and illicit, together.

While conflating the two may help create better headlines and fuel the hysteria, such conflation is misleading because studies continue to indicate that two opioids, illicit fentanyl and heroin, are major drivers in the alarming increase in addiction and overdose, not prescription opioids.

Moreover, lumping all opioids together can be harmful because it ignores the size and complexity of the problems associated with the use and abuse of illicit and licit drugs. Because drug abuse remains a moving target, it is important to draw distinctions between a variety of factors and sources so that solutions can be tailored and refined. One size does not fit all.

Unclear Methodology Used to Classify Comments

Another problem with the JAMA article was the lack of measurement clarity regarding content analysis and how the authors categorized (coded) the comments that were submitted to the CDC during the open comment period.

According to the authors, the comments were classified as belonging in one of four mutually exclusive categories: “supportive, generally supportive with recommendations, generally not supported with recommendations, and not supportive.”

While it is unclear whether the coding occurred before or after the comments were reviewed, one section of the paper the authors pointed out that about 6% of the comments “were coded as supportive by 1 reviewer and not supportive by the other; a third reviewer adjudicated these cases.”

The first question that comes to mind is: who was the reviewer? Since it is likely that the authors were not randomly selected, it remains unclear what criteria was used to adjudicate disputes related to coding, especially when we know that two reviewers were at opposite ends of the spectrum and the coding scheme was central to the study.

Along these same lines, what constitutes opposition to the CDC guidelines? Was opposition binary (yes/no), was it mixed (and if so, where was the line), or did opposition exist along a range (strong or weak)?

When dealing with qualitative data (words as opposed to numbers), there are tendencies in terms of direction, but the devil is in the details. This is notable because there were likely many different reasons commentators and organizations were not supportive of the CDC prescribing guidelines, such as, but not limited to:

  1. The secretive nature of the entire process
  2. The short time frame the CDC allotted for public comments (initially less than 24 hours)
  3. Allegations that the process violated the Federal Advisory Committee Act
  4. Strong recommendations based on weak evidence
  5. Committee membership that lacked balance and broad stakeholder involvement
  6. An anti-prescription opioid agenda or bias by some committee members
  7. The fixation on dosing limits ignored the problems associated with converting dosage from one opioid to another, the differences in patients, and the potential for unintentional overdose at any dosage level
  8. The lack of balance and selective nature of the literature cited in the guidelines
  9. The failure to recognize that non-pharmacologic therapy and alternatives to opioids may not be effective or covered by insurance
  10. An ironic lack of transparency and full disclosure concerning potential conflicts of interest among those involved in the guidelines at various levels from start to finish

Conclusion

While the reduction of harms associated with the use of prescription drugs and illicit opioids such as heroin remains essential to improving the public health, it serves no laudable purpose to continually lump all opioids together.

Drug abuse is a highly complex bio-psycho-social phenomenon that requires recognition that not all people, nor problems, are the same. We must also not lose sight of the fact that millions of Americans are suffering from chronic pain, alternatives to opioids may not be as effective or covered by insurance, and the overwhelming majority who take prescription opioids use them responsibly.

In regards to the conflicts of interest issue, while the authors eventually admitted that the “CDC did not prompt or require organizations to disclose their financial associations as part of their comments,” I agree that disclosing real or potential conflicts of interest in the future is good for all involved. However, such disclosure should not be limited to just the pharmaceutical industry. It should also include government agencies and those in the substance abuse community.

I have and continue to provide consultation to government and the pharmaceutical industry about the need for balanced solutions that help ensure appropriate access, while at the same time prevent abuse. I care about the under-treatment of pain, as I am sure that those in the substance abuse community care about those suffering from addiction.

Consequently, what both the pain community and the substance abuse community need to focus on is finding common ground and forging balanced solutions, since finger pointing, bullying or taking a zero-sum game approach only impedes progress.

Stephen J. Ziegler, PhD, is a Professor Emeritus of Public Policy at Indiana University-Purdue University in Fort Wayne, Indiana.

Dr. Ziegler conducts research, provides continuing medical education, and consults on the topics of opioid risk management and the impact of drug regulation and enforcement on the treatment of pain. He has been published in several peer reviewed journals and serves as a reviewer for several journals such as the Journal of Opioid Management, Pain Medicine, Cancer, and the Journal of Medical Ethics. Prior to obtaining his law degree, Dr. Ziegler worked as a police detective and as a Task Force Officer for the U.S. Drug Enforcement Administration.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Bias and Conflict of Interest in Opioid Guidelines Study

By Pat Anson, Editor

A new study published in JAMA Internal Medicine is claiming that some patient advocacy groups and medical organizations that opposed the Centers for Disease Control and Prevention’s opioid prescribing guidelines had a conflict of interest.

Ironically, the two main authors of the study appear to have a conflict of interest themselves, as well as a bias against opioid pain medication.

In their review of 158 organizations that made public comments on the CDC guidelines – which discourage doctors from prescribing opioids from chronic pain – researchers found that about one third (38%) of those that accepted funding from opioid manufacturers opposed the guidelines. This alleged conflict of interest should have been disclosed, they say.

“A major concern is that opposition to regulatory, payment, or clinical policies to reduce opioid use may originate from groups that stand to lose financially if sales of opioids decline,” wrote senior author G. Caleb Alexander, MD, an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health.

“Our findings demonstrate that greater transparency is required about the financial relationships between opioid manufacturers and patient and professional groups.”

One of the co-authors who designed the study is Andrew Kolodny, MD, the founder and Executive Director of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid group that helped draft the CDC guidelines and was itself accused of numerous conflicts of interest. Kolodny is the former chief medical officer of Phoenix House, which runs a chain of addiction treatment centers and was PROP’s chief source of financial support until recently.

Alexander, who is a widely published researcher who has collaborated several times with Kolodny on other opioid-related studies, failed to disclose in the JAMA study that he has accepted funding from Otsuka Pharmaceuticals. The Japanese drug company makes Abilify, an anti-psychotic medication prescribed off-label to treat chronic pain. The amount paid to Alexander in 2015 was relatively small, a $668 fee for consulting, but according to the criteria used in his own study, it represents a conflict of interest.

Any amount of money accepted from an opioid manufacturer was considered a conflict of interest in Alexander and Kolodny’s study, whether it was a grant, gift, advertising or some other material support. No evidence was required to prove the money swayed an organization one way or another. In fact, nearly two-thirds (62%) of the organizations that accepted funding from opioid makers supported the CDC guidelines, disproving their own theory.   

“I’ll be the first to say that our method of assessing financial relationships is somewhat imprecise,” Alexander told Pain News Network. “This study was not designed for causal inference. This study doesn’t permit us to say what the effect of these funding relationships has been. But one has to wonder, when this amount of money is being spent, what the effects are.”

PROP and the “Opioid Lobby”

The claim that many medical organizations and patient advocacy groups have come under the influence of the “opioid lobby” has long been used by Kolodny.

“CDC’s plan was effectively blocked by intense pressure from the opioid lobby, which sees more cautious opioid use as a financial threat,” wrote Kolodny in a newsletter sent to PROP supporters in December 2015, after the CDC guidelines were temporarily delayed after a public outcry and threats of a lawsuit.

Kolodny’s smear campaign was widely covered uncritically by the news media, even though there was no evidence cited to support it.

“This is a big win for the opioid lobby,” Koldony told the Associated Press.

“The story here is how the opioid lobby is using the Cancer Action Network to discredit a public health effort to limit opioid prescribing,” Kolodny told The Hill.

“Here’s background on shady organization now attacking CDC’s draft opioid guideline,” Kolodny posted on Twitter.

Kolodny did not respond to a request for comment for this story.

Like his co-author, Alexander also is convinced there is a quid-pro quo between opioid manufacturers and groups that they fund.   

“The biggest myth out there is that there’s a conflict between reducing our dependence on opioids and improving care for patients in pain,” Alexander told the AP last year. “It’s an artificial conflict, but there are lots of vested interests behind it.”

Does the opioid lobby even exist? Are patient advocacy groups so easily swayed by their funding sources? Kolodny and Alexander’s study presented little evidence of either, yet they still managed to get it published in an influential journal published by the American Medical Association.

“No one in the pharmaceutical industry has ever asked me or anyone that is on our voting board to publicly state a specific stance on any issue regarding treatment options. Not one pharmaceutical representative has ever asked anyone from iPain to comment on the CDC guidelines,” said Barby Ingle, a PNN columnist who is President of the International Pain Foundation (iPain), a patient advocacy group.

Ingle, who did submit her own personal comments on the CDC guidelines, says it is very difficult to get funding from drug makers.

“We have gotten to the point of not even applying for funding unless we are contacted,” said Ingle. “Even when notified of funds available, iPain did not receive the funding requested and it turned out to be a waste of time on our part.”

What is a Conflict of Interest?

“These people perhaps don’t quite understand what is the definition of a conflict of interest,” said Richard Samp, chief counsel of the Washington Legal Foundation, which threatened to sue the CDC for violating federal law when it drafted the opioid guidelines.

“As I understand conflict of interest under federal law, that generally means that somebody has been appointed to serve in one position, but they have some other financial or ideological interest that conflicts with the interests that they’re supposed to have,” Samp told PNN.

“That was the focus of our criticism of the process that CDC went through in adopting its draft guidelines, which were written with the assistance of an advisory group that included people who had very severe conflicts of interest. For example, one particular member of the group, Jane Ballantyne, was a paid consultant for a plaintiffs’ law firm that had a vested interest in suing opioid manufacturers.”

Dr. Ballantyne is the President of PROP, the organization founded by Kolodny. At least four other board members of PROP, including Kolodny himself, served on various CDC panels that advised the agency during the drafting of the guidelines, a matter that the agency refused to disclose for several months.   

“What they are talking about (in the JAMA study) is not a conflict of interest. They’re just talking about the fact that some people who file comments with federal agencies have a particular point of view,” said Samp. “Every citizen regardless of his or her point of view and regardless of his or her background has a right to comment on what our government is doing.”

Another way to look at whether there is a conflict of interest is offered by Stephen Ziegler, PhD, in a commentary for Pain News Network (see "CDC Guidelines Study: The Devil Is in the Details").

“Association is not causation. For example, while a positive association exists between the size of a fire and the number of fire engines on the scene, fire engines for the most part do not cause fires -- they are only associated with it,” Ziegler wrote.

Ziegler says it’s time for the pain community and the addiction treatment community to end the finger pointing and bullying over opioids, and start finding common ground.

“It is misleading and harmful to lump all opioids, prescription and illicit, together. While conflating the two may help create better headlines and fuel the hysteria, such conflation is misleading because studies continue to indicate that two opioids, illicit fentanyl and heroin, are major drivers in the alarming increase in addiction and overdose, not prescription opioids,” Ziegler wrote.

The American Academy of Pain Medicine (AAPM), an association of pain management physicians, also released a statement about the JAMA study, saying it agreed that “disclosure is one means of managing conflicts of interest.” 

While the AAPM cautiously supported the CDC guidelines, it also warned that their widespread implementation could lead to problems.

“It is incumbent upon us all to monitor the deployment of the guideline to ensure that it does not inadvertently encourage under-treatment, marginalization, and stigmatization of the many patients with chronic pain that are using opioids appropriately,” the AAPM said.

Since the guidelines were released in March 2016, many pain patients have complained to PNN that their opioid doses have been reduced or eliminated, and that it’s become difficult to find a doctor willing to treat chronic pain. Others have said they are contemplating suicide because their pain is going untreated.