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.