Integrative and Comprehensive Pain Management Provide Only Small Benefits

By Pat Anson, PNN Editor

As concerns rose in recent years about opioid addiction and overdoses, it became trendy for healthcare providers to offer “comprehensive” or “integrative” pain management programs to patients – usually a combination of medication, physical and behavioral therapy, lifestyle changes and alternative treatments such as massage and acupuncture.

But a new study commissioned by the Agency for Healthcare Research and Quality (AHRQ) found that integrative and comprehensive pain management provide only small improvements in pain and function for people with chronic pain.   

Researchers at Oregon Health & Science University (OHSU) reviewed 57 “fair quality” clinical studies, most involving patients with moderate chronic pain caused by fibromyalgia, osteoarthritis and musculoskeletal conditions. Although the improvements in pain and function were small and the evidence limited, researchers concluded that integrative (IPMP) and comprehensive (CPMP) pain management programs worked about as well as individual treatments.

“Our review suggested that IPMPs and CPMPs may provide small to moderate improvements in function and small improvements in pain for patients with chronic pain compared with usual care and may be more effective than some medications alone. The average improvements in function and pain in our review were consistent with those reported for other therapies for pain, including opioids for chronic pain, nonpharmacologic treatments, and surgery,” researchers found.

One of the problems researchers encountered was the mish-mash of terms used to define integrative and comprehensive pain management – such as multimodal, multidisciplinary, interdisciplinary and biopsychosocial – the meaning of which often varies from provider to provider. Researchers said there was “no firm consensus on their definition or use,” which made it harder to evaluate their effectiveness. Only a few of the reviewed studies compared treatments head-to-head and many were of poor quality.

Although none of the trials specifically included Medicare patients, researchers concluded that IPMPs and CPMPs should be more widely used to address pain in the Medicare population.   

“To the extent that programs are tailored to patients’ needs, our findings are potentially applicable to the Medicare population. Programs that address a range of biopsychosocial aspects of pain, tailor components to patient need, and coordinate care may be of particular importance in this population,” they said. 

“Although use of selected individual treatments may serve some patients, a broader range of therapies that address the full scope of biopsychosocial concerns available in formal programs may benefit others. Research in the Medicare population and in patients with a broader range of pain conditions is needed as is research on the impact of program structures, coordination methods, and components on patient outcomes. Additional evidence from primary care-based programs is particularly needed.” 

One of the co-authors of the AHRQ study is Dr. Roger Chou, a primary care physician who heads the Pacific Northwest Evidence-based Practice Center at OHSU.  Chou, who co-authored the 2016 CDC opioid guideline, is a prolific researcher who has collaborated on several occasions with members of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid advocacy group.

PROP Vice President Gary Franklin, MD, “provided input” on the AHRQ study, as well as others.

In July, Chou declared a conflict of interest and recused himself from a meeting of the CDC’s Board of Scientific Counselors, which is evaluating a revision and possible expansion of the agency’s controversial guideline. Chou’s recusal apparently applied only to that meeting, as he is one of the co-authors of the revised opioid guideline — which has yet to be released publicly — and continues his involvement in federally funded pain research. 

OHSU researchers have conducted a series of reviews on a wide variety of pain therapies for the AHRQ. According to the website GovTribe, over the last five years OHSU has been awarded over $2 billion in federal grants for medical research. 

A group of patient advocates and researchers recently called for a congressional or DOJ investigation of the CDC opioid guideline, due to Chou’s significant role in writing it and his then-undeclared conflicts of interest.

OHSU Researchers Find ‘No Evidence’ to Support Use of Kratom

By Pat Anson, PNN Editor

A federally funded review of plant-based treatments for chronic pain has yet to find adequate clinical evidence on the benefits or harms of kratom, an herbal supplement used by millions of Americans to relieve pain, anxiety, depression and other medical conditions.

In an update released this week, researchers at Oregon Health & Science University (OHSU) reported that some cannabis products provide small to moderate pain relief, a finding based on a systematic review of two dozen clinical trials of cannabis.  But no similar studies were found to support the use of kratom or any other plant.   

“No evidence on other plant-based compounds, such as kratom, met criteria for this review,” researchers said.

OHSU was awarded a contract last year by the Agency for Healthcare Research and Quality (AHRQ) to review the evidence for cannabis, kratom and other plant based treatments for chronic pain.  

Kratom comes from the leaves of the mitragyna speciosa tree in southeast Asia. Although it has been used for centuries as a natural stimulant and pain reliever, few clinical trials have been conducted to test kratom’s efficacy or safety. The few studies that have been conducted were excluded by OHSU researchers due to their size, methodology or because they weren’t published in English.

For example, a 2020 Malaysian study that found kratom provided “a substantial and statistically significant increase in pain tolerance” was excluded because the young men who participated in the one-day trial were considered an “ineligible population.” OHSU researchers excluded all studies lasting less than 4 weeks.

“The conclusion that there is no evidence to support the effects of kratom on chronic pain is absurd.”

— Mac Haddow, American Kratom Association

“Setting aside the disappointment that AHRQ does not appear to be taking the purpose of the review of plant-based compounds very seriously, the conclusion that there is no evidence to support the effects of kratom on chronic pain is absurd,” said Mac Haddow, a lobbyist for the American Kratom Association.  “It’s like denying that Chicago is a windy city because the instrument that was selected for assessing wind speed was not used.”

Haddow said the AHRQ review should be expanded to include survey results from kratom users, animal studies and other types of research that don’t rise to the level of a clinical trial.

“The review appears to be excluding any research that is not a pharmaceutical development clinical trial model that would involve controlled kratom administration in a full-blown human clinical trial,” Haddow told PNN. “The deeply embedded bias against plant-based compounds that offer potential values for addressing the opioid crisis — or even providing a non-addictive and safer alternative for the management of acute and chronic pain should be a priority for the AHRQ.”

This isn’t the first time the quality of federal research into the safety and efficacy of kratom has been questioned. In 2018, the Department of Health & Human Services quietly withdrew an FDA request to classify kratom as a Schedule I controlled substance because of “lack of evidence” it can be abused or posed a public health threat. A former HHS official recently said the FDA’s recommendation was rejected because of “embarrassingly poor evidence & data.”

$2 Billion in Federal Grants

A final report on plant-based treatments for chronic pain is expected in August. As PNN has reported, OHSU researchers have recently conducted a series of reviews on a wide variety of pain therapies for the AHRQ, which are being used by the Centers for Disease Control and Prevention to revise and possible expand its controversial 2016 opioid guideline.   

Much of that research is being led by Dr. Roger Chou, a primary care physician who heads the Pacific Northwest Evidence-based Practice Center at OHSU.  Chou, who co-authored the CDC opioid guideline, is a prolific researcher who has collaborated on several occasions with members of Physicians for Responsible Opioid Prescribing (PROP), an advocacy group that seeks to reduce the use of opioid medication.

The contract on plant-based pain treatments is potentially worth up to $1.4 million for OHSU, a public research university that the federal government often turns to for medical research. According to the website GovTribe, in the last five years OHSU has been awarded nearly $2 billion in federal research grants to study everything from cancer and contraceptives to Alzheimer’s and Parkinson’s Disease.

OHSU paid $1.3 million back to the government to settle allegations that it misused grant money in its primate research center. Although the settlement was reached in 2018, it was not made public until recently in an Inspector General’s report, according the animal rights group Rise for Animals.

Contact Congress to Make Changes in Federal Pain Study

By Richard Lawhern, PNN Contributor

On January 20, I sent a letter by email to the Acting Director and senior staff of the Agency for Healthcare Research and Quality (AHRQ).  The letter requests the federal agency to immediately withdraw its recent review of prescription opioids and other treatments for short-term acute pain. 

Grounds for the request are clear evidence of unjustified anti-opioid bias by the authors and gross fatal errors of methodology – all of which invalidate the review as resource material for efforts to revise and expand the 2016 CDC opioid guideline.

The anti-opioid bias of Roger Chou and his co-authors is revealed by their selective cherry-picking of references that fail to explore the major effects of genetics in patient response to opioid therapy, as well as improperly generalized findings based on trials of weak opioids like tramadol, which were applied to all opioids.

The AHRQ authors also omit any exploration of serious side effects and mortality caused by non-opioid treatments such at acetaminophen.

But the most fundamental error in the methods of the AHRQ Review is improper use of “meta-analysis” to lump together data and outcomes from multiple small-scale studies of opioid therapy for acute pain. A major underlying assumption of meta-analysis is that patient response in each trial is distributed on a Normal (bell-shaped) curve. However, this assumption doesn’t work for patients treated with prescription opioids.

The distribution of patient outcomes is actually “bi-modal.” One group of patients may experience side effects from opioids, but very little short-term pain relief; while a second group may have substantial pain relief from just one dose of opioid medication. This reality invalidates the major findings of the AHRQ review.

A detailed critique of the AHRQ study is available on my website. Feel free to review and share this information with your personal physician.

AHRQ is fully aware of the errors noted above but has no intention of responding to demands for a correction of its malfeasance and fraud.  Thus, it may be necessary for the U.S. House Government Oversight and Reform Committee to direct AHRQ to withdraw or rewrite its review. 

Such an action has precedents.  In 2015, the Oversight Committee reviewed complaints from the Washington Legal Foundation and others concerning inadequate public hearings on the CDC’s proposed opioid guideline. The committee sent a letter to then-CDC Director Thomas Frieden asking him to explain why so much secrecy was involved in the drafting of guideline and why it wasn’t made publicly available.

Faced with a congressional inquiry, CDC reversed course by delaying the guideline’s release and publishing the draft in the Federal Register for a 30-day public comment period. A new advisory committee was also formed to review the guideline, which resulted in some changes to its final recommendations.

Urgent Action Request

A similar effort is urgently needed by pain sufferers and their advocates to bring the AHRQ review to the attention of Congress, specifically to the House Government Oversight and Reform Committee. Those who wish to involve the committee in corrective action should telephone any or all of the Congressional offices of committee members. 

It is very doubtful that the representatives will actually see anything you leave in their contact portals online. But short, focused telephone calls are harder to ignore. The telephone numbers for members of the House Committee can be found here. If you reach a staff member in their office, you might offer the following information:

1) Identify yourself and provide a call-back number. If you are a medical professional, state your qualifications (i.e. “I am a board certified physician” or “I am a former nursing professional now disabled by agonizing pain.”)

2) If you are a resident of the Representative’s district, say so. You don’t have to be a constituent to make your input.

3) Tell the staffer that you want to report fraud and abuse to the Representative and to the House Congressional Oversight and Reform Committee. 

“I want the Committee to demand corrective action from the Agency for Healthcare Research and Quality, in the same way it did in 2015 when it told the CDC to re-open its proposed opioid guideline to extended public review.”

“AHRQ published a review of treatments for acute pain in December 2020. The review is deliberately biased against the only therapies that work, deeply flawed by errors of scientific method, and outright fraudulent in its conclusions. This review must be withdrawn for independent review.”

4)  Thank the staffer for their time.  Ask “May I expect a callback from a member of the Representative’s staff?”

This is an opportunity to be heard, despite the lies being shouted by anti-opioid fringe groups like Physicians for Responsible Opioid Prescribing (PROP) and Shatterproof.

It is time for you to speak up!

Richard “Red” Lawhern, PhD, has for over 20 years volunteered as a patient advocate in online pain communities and a subject matter expert on public policy for medical opioids.  Red is co-founder of The Alliance for the Treatment of Intractable Pain.

Study Finds Limited Evidence to Support Use of Non-Opioid Drugs for Chronic Pain

By Pat Anson, PNN Editor

A new study by federal researchers has found limited evidence to support the use of non-opioid medications in treating chronic pain conditions such as fibromyalgia, neuropathy, rheumatoid arthritis and low back pain.

Only small improvements in pain and function were found in the use of anti-convulsants and non-steroidal anti-inflammatory drugs (NSAIDs), while moderate improvement was found in the use of some antidepressants.

Researchers noted that evidence was “too limited to draw conclusions” on long-term use of non-opioid drugs, and “no treatment achieved a large improvement in pain or function.” They also cautioned that “careful consideration of patient characteristics is needed in selecting nonopioid drug treatments” because of the risk of side effects.

The report was prepared for the Agency for Healthcare Research and Quality (AHRQ) by the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University. The EPC has recently finalized two other studies on the use of opioids and nonpharmacological treatments for chronic pain.

Unlike their report on opioids, EPC researchers did not consult with technical experts and peer reviewers associated with Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

The researchers analyzed nearly 200 clinical studies and systematic reviews of non-opioid medication. Only 25 of the studies were rated as good quality and only 8 lasted a year or more. The pharamceutical industry funded 82 percent of them.

The EPC report is more cautious than other federal studies on the use of non-opioids such as pregabalin (Lyrica) and gabapentin (Neurontin).  Side effects from those drugs were often so severe that some patients stopped taking them and dropped out of clinical studies.

“Large increases in risk of adverse events were seen with pregabalin (blurred vision, cognitive effects, dizziness, peripheral edema, sedation, and weight gain), gabapentin (blurred vision, cognitive effects, sedation, weight gain), and cannabis (nausea, dizziness),” EPC researchers found. “Dose reductions reduced the risk of some adverse events with SNRI antidepressants. In the short term small increases in risk of major coronary events and moderate increases in serious gastrointestinal events (both short and long term) were found with NSAIDs.”

The EPC study is in marked contrast to the 2016 CDC opioid guideline, which recommends pregabalin, gabapentin and NSAIDs as alternatives to opioids with little to no mention of their side effects.

Other researchers have also warned that the effectiveness of gabapentin and pregabalin, which belong to a class of anti-convulsant drugs known as gabapentinoids, is often exaggerated in prescribing guidelines.

“Gabapentinoids have become frequent first-line alternatives in patients with chronic pain from whom opioids are being withheld or withdrawn, as well as in patients with acute pain who traditionally received short courses of low-dose opioid,” researchers at the University of South Carolina School of Medicine warned in a 2019 study.

“The evidence to support off-label gabapentinoid use for most painful clinical conditions is limited. For some conditions, no well-performed controlled trials exist.”

The EPC’s trio of studies on opioids, non-opioid drugs and non-pharmacological treatments are expected to help guide the CDC as it prepares an update and expansion of its 2016 opioid guideline, which is expected in late 2021. The update is likely to include new guidelines for treating short term, acute pain.  

How will CDC interpret the EPC findings on opioids and non-opioids? One outcome is suggested in the opioid study.

“Findings support the recommendation in the 2016 CDC guideline that opioids are not first-line therapy and to preferentially use nonopioid alternatives,” researchers said.

PROP Linked to New Federal Opioid Study

By Pat Anson, PNN Editor

A small but influential group of anti-opioid activists continues to play an outsized role in guiding federal policy on the use of opioid pain medication.

The latest example is a new report by the Agency for Healthcare Research and Quality (AHRQ) on the effectiveness of opioids in treating chronic pain. In a lengthy review of over 150 clinical studies, AHRQ researchers concluded that opioids were no more effective in treating pain than nonopioid medication, and that long-term use of opioids increases the risk of abuse, addiction and overdose, especially at high doses.

The findings are essentially the same as those in a draft report released by the AHRQ last year. What’s different is that the agency finally disclosed the authors of the report and the outside advisors they consulted with. They include a cabal of academic researchers and physicians with biased views about opioids that federal agencies keep bringing in as consultants.   

The AHRQ’s report confirms what PNN reported in November. The study was led by Dr. Roger Chou, a primary care physician who heads the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University.

Most public health researchers keep a low profile to avoid accusations of bias, but Chou has been a vocal critic of opioid prescribing for years. In a 2019 podcast, for example, Chou said the benefits of opioids were “clinically insignificant” and the medications were often quite harmful.

“The impact of prescription opioids in terms of mortality and substance use disorder and all the other things that come along with it have really been quite staggering,” he said.

Chou also served on a state task force last year that supported a rigid opioid tapering policy. If adopted, the policy would have forced thousands of Oregon’s Medicaid patients off opioids.

DR. ROGER CHOU

“I don’t think there’s anything compassionate about leaving people on drugs that could potentially harm them,” Chou said.

Collaboration with PROP

Chou has collaborated on several occasions with members of Physicians for Responsible Opioid Prescribing (PROP), an advocacy group that seeks to reduce the use of opioid medication. PROP has never disclosed its donors or funding.

Last year Chou co-authored an op/ed with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to consider tapering “every patient receiving long term opioid therapy.”

In 2011, Chou co-authored another op/ed with PROP founder Dr. Andrew Kolodny and PROP vice-president Dr. Michael Von Korff. 

The article was prescient because it called for a major overhaul of opioid guidelines that were then primarily developed by pain management specialist organizations.

“Guidelines for long-term opioid therapy should not be developed by the field of pain medicine alone.”

— Kolodny, Chou, et al 2011

“Guidelines for long-term opioid therapy should not be developed by the field of pain medicine alone. Rather, experts from general medicine, addiction medicine, and pain medicine should jointly reconsider how to increase the margin of safety,” they said.

That major overhaul came in 2016, when the Centers for Disease Control and Prevention released its controversial opioid guideline, which soon displaced all of the other guidelines. Chou was one of the co-authors of the CDC guideline – so it’s not altogether surprising that the AHRQ study reaffirms many of the CDC’s conclusions.

“Findings support the recommendation in the 2016 CDC guideline that opioids are not first-line therapy and to preferentially use nonopioid alternatives,” Chou and his colleagues wrote.

In preparing the AHRQ study, researchers sought input from a dozen outside experts, who served as technical experts and peer reviewers. Three of the 12 are PROP board members: Drs. Mark Sullivan and David Tauben were technical experts, and PROP vice-president Dr. Gary Franklin was a peer reviewer. Sullivan, Tauben and Franklin are all professors at the University of Washington, and played prominent roles in the development of Washington state’s opioid prescribing regulations, which are some of the toughest in the nation.

Another peer reviewer was Dr. Erin Krebs, an associate professor at the University of Minnesota Medical School. Krebs was the lead author of a controversial 2018 study that found non-opioid pain relievers worked better than opioids in treating osteoarthritis pain. While some critics said the study was poorly designed and amounted to junk science, it drew praise from Chou.

"The fact that opioids did worse is really pretty astounding," Chou told the Chicago Tribune. "It calls into question our beliefs about the benefits of opioids." 

In addition to her work as a researcher, Krebs also appeared in a lecture series on opioid prescribing funded by the Steve Rummler Hope Foundation, which lobbies against the use of opioids. The non-profit foundation is the fiscal sponsor of PROP, and Kolodny and Ballantyne both serve on its medical advisory committee.

If these intertwining connections are making your head spin, there’s more.

Core Expert Group

Ballantyne, Franklin and Krebs served on the “Core Expert Group” that advised the CDC when it drafted its opioid guideline, and Tauben was on the CDC’s peer review panel. Kolodny and yet another PROP board member, Dr. David Juurlink, were part of a “Stakeholder Review Group” that provided input to the CDC.

When PNN filed a request under the Freedom of Information Act (FOIA) to see what kind of advice the Core Expert Group gave to the CDC, we were stiff-armed by the agency. The CDC sent us nearly 1,500 pages of documents, but most were so heavily redacted they were completely blank.    

Even financial conflict of interest statements were scrubbed of information, with the CDC citing “personal privacy” and “deliberative process privilege” as reasons not to provide them in full.

At least two unidentified members of the Core Expert Group worked for or consulted with organizations with an interest in opioids or other controlled substances. One of those individuals also provided “expert opinion or testimony,” which has become a lucrative sideline for some PROP members.

Critics wonder why federal health agencies keep bringing in consultants with obvious biases and conflicts of interest.

“The AHRQ review presents itself as an objective scientific analysis of the medical literature. In my opinion, the document is arguably contaminated with a political agenda,” says Dr. Dan Laird, a physician attorney in Las Vegas. “Some of those involved in the review could be perceived by the chronic pain community as having strong anti-opioid political views and biased ideas about the meaning and treatment of chronic pain.

“Most importantly, there is no input whatsoever from the chronic pain community in the review. There are certainly chronic pain patients with academic credentials that would qualify them to conduct a literature review. Several highly regarded academic physicians and scientists, known for opioid moderatism, are conspicuously absent as investigators, peer reviewers, or technical experts; these include pain medicine academicians such as Drs. Michael Schatman, Sean Mackey, Stefan Kertesz, and Vanila Singh.”

AHRQ Conflict Policy

If a peer reviewer or technical expert has a financial or professional conflict of interest, that does not automatically disqualify them in the eyes of the AHRQ, which will retain them “because of their unique clinical or content expertise.”  

It’s also been a long-standing AHRQ policy not to disclose the names of advisors or authors until its reports are finalized.

“This policy is aimed at helping the authors maintain their independence by not being subject to lobbying by industry reps or others with conflicts of interest, either financial or intellectual,” AHRQ spokesman Bruce Seeman explained in an email.

But others wonder if the policy damages the agency’s reputation and the credibility of its research, by not giving the public a chance to review and comment on possible biases before a final report is released. The American Medical Association urged the AHRQ to change its policy last year.

“We would suggest that AHRQ publish the list of all those involved in any aspect of the report during the comment period to help remove any perception of potential conflict,” Dr. James Madara, the AMA’s Executive Director and CEO, wrote in a letter to the agency last year.

CDC Guideline Update

It might be tempting to dismiss the work of an obscure federal agency that produces wonky reports that are mostly read by public health researchers and government bureaucrats. That would be a mistake. It was a 2014 AHRQ report on opioids – co-authored by Chou – that played a foundational role in the CDC guideline.

Although the CDC guideline is voluntary and only intended for primary care physicians treating chronic pain, it has become mandatory policy for doctors in all specialties, as well as other federal agencies, dozens of states, insurers, pharmacy chains and law enforcement agencies. In effect, the guideline has delivered on the goals sought by Kolodny, Von Korff and Chou in 2011. The standard of care in pain management is no longer determined by pain specialists.

Chou and his colleagues hope the new AHRQ report will have a similar impact, not just in government, but throughout the healthcare system.

“The information in this report is intended to help healthcare decision makers — patients and clinicians, health system leaders, and policymakers, among others — make well-informed decisions and thereby improve the quality of healthcare services,” they said.

In addition to its report on opioid treatments for chronic pain, AHRQ has also finalized studies on the effectiveness of Nonopioid Medications for Chronic Pain and Nonpharmacologic Treatments for Chronic Pain, such as acupuncture and meditation.

All three reports will be utilized by the CDC as it prepares an update and expansion of its opioid guideline, which is expected in late 2021.  That effort is being overseen by the Board of Scientific Counselors at the CDC’s Center for Injury Prevention & Control.  Roger Chou happens to be one of its members.  

CDC Considering ‘Update or Expansion’ of Opioid Guideline

By Pat Anson, PNN Editor

When the Centers for Disease Control and Prevention released its controversial opioid prescribing guideline in March 2016, it pledged to study the impact of the guideline on patients, doctors and pain treatment in the United States.

“CDC is committed to evaluating the guideline to identify the impact of the recommendations on clinician and patient outcomes, both intended and unintended, and revising the recommendations in future updates when warranted,” the agency said.

Three and a half years later, after widespread reports of patient suffering, abandonment and suicide, the CDC may finally be getting around to an update. But it may not be what patients and doctors were hoping for.

In a meeting next week of the Board of Scientific Counselors (BSC) for the CDC’s National Center for Injury Prevention and Control (NCIPC), guideline co-author Dr. Deborah Dowell is scheduled to give a 30-minute presentation entitled “Background for Updating the CDC Guideline for Prescribing Opioids.”

According to the agenda for the December 4 meeting in Atlanta, Dowell’s presentation will be preceded by an update from NCIPC Director Dr. Debra Houry, who oversaw development of the opioid guideline. Presentations are also planned on overdose prevention and the formation of an “Opioid Workgroup.”

“CDC is scheduled to give a background presentation for a potential update/expansion of the CDC Guideline,” Courtney Lenard, a CDC spokesperson, said in an email to PNN. “CDC will also request that NCIPC’s BSC establish an Opioid Workgroup to provide expert input and observations on a possible update or expansion of the guideline.”

Public pressure has been building on the CDC to clarify the guideline — but not to expand it. Although voluntary and only intended for primary care physicians treating chronic pain, the guideline’s recommended limits on opioid prescribing have been widely adopted as policy by federal agencies, state governments, insurers, pharmacy chains and many doctors.

The guideline has also been applied to short-term acute pain situations, such as patients being treated for post-surgical pain or emergency room trauma. Last year, CDC Director Dr. Robert Redfield said he wanted the agency to develop opioid prescribing guidelines for acute pain and to use a new enhanced data system to track overdoses in hospital emergency rooms.

“I hope this does not become CDC Prescribing Guideline 2.0. In the original CDC Guideline, the identity of the key expert group was unknown, there were concerns over conflict of interest and secrecy, and legislatures or regulatory agencies eventually adopted the guideline and treated it as gospel despite the limitations stated in the report,” said Stephen Ziegler, PhD, a Professor Emeritus at Purdue University.

Last year the American Medical Association took a stand against the “misapplication” and “inappropriate use” of the guideline -- and adopted a resolution stating that some patients “can benefit from taking opioids at greater dosages than recommended by the CDC.”   

In April, the Food and Drug Administration warned that many patients were being tapered off opioids inappropriately, putting them at risk of withdrawal, uncontrolled pain and suicide. That was followed days later by a pledge from Redfield to re-evaluate the guideline and “clarify its recommendations.”

A clarification is long overdue. In a PNN survey early this year of over 6,000 pain patients and healthcare providers, an overwhelming majority said the guideline was harmful to patients and should be revised.

“Cannot understand or know why the CDC will not speak out on the harm done to undertreated, denied and abandoned patients,” one patient told us.

“The guidelines were written in secret, and the carnage that we predicted has come to pass,” said an emergency medicine physician.

“They should be revoked. People are suffering and committing suicide due to inability to tolerate suffering. This is inhumane,” another provider wrote. “It blemishes CDC’s reputation.”

CDC Funding AHRQ Studies

Instead of getting input from doctors and patients on the impact of the guideline, the CDC appears to be focused on more research to help expand its use. PNN has learned that the CDC is funding three new studies on the effectiveness of opioid and non-opioid therapies — essentially doubling down on previous research that found little evidence that opioids are effective for chronic pain.    

“CDC is funding the Agency for Healthcare Research & Quality (AHRQ) through an interagency agreement to conduct systematic reviews of new scientific evidence that has been published since the Opioid Prescribing Guideline was released,” said CDC’s Lenard. “The reviews will evaluate the effectiveness and comparative effectiveness of opioids, non-opioid pharmacologic therapy, and nonpharmacologic therapy for chronic and acute pain.

“Results of these reviews will help CDC determine whether evidence gaps have been addressed and if the Opioid Prescribing Guideline should be updated or expanded. If a Guideline update or expansion occurs, the development process would include consideration of findings from the systematic reviews and an additional public comment period through the Federal Register once an update or expansion is drafted.”

All three AHRQ studies were awarded on the same day – at an estimated cost of $1.1 million – to the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, which is headed by Dr. Roger Chou, one of the co-authors of the CDC guideline.

As PNN has reported, Chou is a primary care physician and longtime researcher who has publicly aligned himself with Physicians for Responsible Opioid Prescribing (PROP), an influential anti-opioid activist group that seeks drastic reductions in the use of opioid medication.  

Chou recently co-authored an article with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to consider tapering “every patient receiving long term opioid therapy.”

Chou also consulted with PROP founder Dr. Andrew Kolodny and other PROP members for Oregon Pain Guidance, an advisory group that claims opioid tapering “will improve the quality of life for the majority of patients.”

DR. ROGER CHOU

It is not clear if PROP members are also involved in the three AHRQ studies, as they were in drafting the CDC guideline. But critics say Chou’s continuing association with PROP raises questions about his impartiality as a researcher.

“For years, we have called out a ‘False Narrative’ that prescription opioids drive the current overdose crisis; current data shows this is demonstrably false,” said Dr. Chad Kollas, a palliative care specialist in Florida. “We have not done as well calling out a “Hidden Narrative,” where PROP-affiliated physicians have wrongly influenced and encouraged the misapplication of federal policy in a way that has systematically harmed vulnerable patients in pain. We must call out their conflicts of interest loudly now.”

As a matter of policy, AHRQ does not release conflict of interest statements or disclose the names of its consultants, investigators and peer reviewers until after its reports are finalized. The AMA is recommending that the agency end that policy.

“We would suggest that AHRQ publish the list of all those involved in any aspect of the report… to help remove any perception of potential conflict,” Dr. James Madara, the AMA’s Executive Director and CEO, wrote in a letter to AHRQ. The letter also urges the agency to clearly state that the opioid epidemic was not fueled by prescription opioids and that its research should not be used to justify tapering.

Draft versions of the three AHRQ studies have been completed and were recently posted for 30 days on the agency’s website. They were removed after a public comment period ended, which is another AHRQ policy. Fortunately, PNN was able to obtain copies before the draft reports were withdrawn from public view.

• Opioid Treatments for Chronic Pain

• Nonopioid Pharmacologic Treatments for Chronic Pain

• Nonpharmacologic Treatment for Chronic Pain

What did Chou and his researchers conclude? The three draft reviews support many of the same conclusions as the CDC guideline — hardly a surprise since Chou helped write the guideline.

“For patients with chronic pain, opioids are associated with small beneficial effects versus placebo but are associated with increased risk of short-term harms and do not appear to be superior to nonopioid therapy. Evidence on intermediate-term and long-term benefits remains very limited and additional evidence confirms an association between opioids and increased risk of serious harms,” one draft says. 

“Findings of this review, with expansion of scope to include short-term trials, support the recommendation in the 2016 CDC guideline that opioids are not first-line therapy for chronic pain and to preferentially use nonopioid alternatives.”    

The AHRQ expects to release final versions of the three pain management reports in early 2020. A list of experts and informants will be released at that time, along with any conflicts of interest. 

Still unclear is what the CDC will do with the reports and what kind of “update or expansion” the agency is considering for its opioid guideline.

CDC Guideline Author Leading New Rx Opioid Study

By Pat Anson, PNN Editor

One of the co-authors of the CDC’s controversial 2016 opioid guideline is leading a new federal study about the effectiveness of opioid medication in treating chronic pain, Pain News Network has learned. 

Dr. Roger Chou is a primary care physician who heads the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University (OHSU), which was awarded a $500,000 contract to conduct the opioid study by the federal Agency for Healthcare Research and Quality (AHRQ).   

A draft version of the AHRQ report echoes many of the conclusions drawn by the CDC – that there is little evidence to support the use of opioids for chronic pain and that nonopioid pain relievers such as Tylenol are just as effective as Vicodin.

Even when used for short-term acute pain, the draft report found “no differences between opioids versus nonopioid medications in improvement in pain function, mental health status, sleep, or depression.”

The AHRQ has not publicly disclosed the authors of the draft report, and only acknowledged in a statement to PNN that “the OHSU team is comprised of several experts who draw upon diverse experience and expertise in pain management.” Their final report is expected in January 2020.

In addition to his work on the CDC guideline, Chou has authored numerous articles on pain management in peer-reviewed medical journals and has led research efforts for the U.S. Preventive Services Task Force, World Health Organization and the American Pain Society. But Chou’s involvement in the AHRQ study has caused some alarm among patient advocates, who believe he and the agency are biased against prescription opioids.

“The agency is operating under a political agenda that has little to do with medical evidence or truth,” said Richard “Red” Lawhern, PhD, a patient advocate with the Alliance for the Treatment of Intractable Pain. “The report is fatally flawed and must be immediately withdrawn without replacement. AHRQ owes the public and millions of people in pain a public apology for its malfeasance and misdirection.”

PROP Collaboration

Most health researchers keep a low profile and try to avoid controversy, but Chou has publicly collaborated with Physicians for Responsible Opioid Prescribing (PROP), an influential anti-opioid activist group that seeks drastic reductions in the use of opioid medication.

Chou recently co-authored an article with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to consider tapering “every patient receiving long term opioid therapy.”

Chou and his co-authors thanked PROP Executive Director Dr. Andrew Kolodny and other PROP board members for their help in drafting the article:

“Acknowledgment: The authors thank the Oregon Pain Guidance Working Group (Jane Ballantyne, Roger Chou, Paul Coelho, Ruben Halperin, Andrew Kolodny, Anna Lembke, Jim Shames, Mark Stephens, and David Tauben) for discussions about tapering and for reviewing a draft of this article.”

As PNN has reported, Kolodny, Ballantyne and Lembke have worked as paid consultants to law firms that stand to make billions of dollars from opioid litigation. Their legal work was only recently disclosed in revised conflict of interest statements.

It is not clear if PROP members are involved in the AHRQ study, as they were with the CDC guideline. As a matter of policy, AHRQ does not disclose the names of its consultants and investigators until after reports are completed.

“This policy is aimed at helping the authors maintain their independence by not being subject to lobbying by industry reps or others with conflicts of interest, either financial or intellectual,” AHRQ spokesman Bruce Seeman said in an email.

“AHRQ’s failure to disclose Chou as an author of its draft report is troubling, given his prior work with Ballantyne and Lembke, who have admittedly worked on behalf of PROP in the past.”

— Dr. Chad Kollas

“AHRQ’s failure to disclose Chou as an author of its draft report is troubling, given his prior work with Ballantyne and Lembke, who have admittedly worked on behalf of PROP in the past. PROP heavily influenced the creation and implementation of the 2016 CDC Guideline, which was systematically misapplied over the last three years by lawmakers, health insurers and pharmacies in a way that became harmful to many patients with chronic pain,” said Dr. Chad Kollas, a palliative care specialist in Florida.

“Failing to disclose authorship of the AHRQ report reduces the agency’s transparency in a way that raises alarms for those familiar with the misapplication of the CDC Guideline and seek to prevent recurrent harm to patients suffering from chronic pain.”

Chou did not respond to requests for comment for this story. He recently served on a state task force that recommended a rigid tapering policy that would have forced many Oregon Medicaid patients off opioids and into withdrawal. The policy was scaled back after a backlash from patients and pain management experts, who said the recommendations were not supported by evidence or compassionate.  

“Compassionate sounds good but it’s a loaded term,” was Chou’s response at the time. “I don’t think there’s anything compassionate about leaving people on drugs that could potentially harm them.”

On a recent podcast, Chou said there was little of evidence to support the use of opioid medication.

DR. ROGER CHOU

“The impact of prescription opioids in terms of mortality and substance use disorder and all the other things that come along with it have really been quite staggering.  We have more evidence that the benefits of opioids are really not as large as we’d like them to be. In most studies, they’re actually quite small and often clinically insignificant,” he said.

Chou also claimed in the May 2019 interview that the opioid hydrocodone was “the number one prescribed drug in the United States and has been for many years.” That statement is false. Since 2011, hydrocodone prescriptions have fallen dramatically – as they have for all opioids -- and it is now the fifth most widely prescribed drug in the U.S., ranking behind cholesterol, thyroid and blood pressure medications.

Public Comment Period Ends

On Tuesday, the AHRQ ended a 30-day public comment period on its draft report. Unlike other federal agencies that routinely seek public comments in the Federal Register, the AHRQ only accepted comments on its website. The agency did little to publicize the draft report outside of a mass email to 100,000 subscribers notifying them the report was available for comment. 

One critic who had a chance to see the AHRQ’s review of over 150 opioid studies said it was filled with errors, biases and cherrypicked research – much like the CDC guideline that Chou co-authored.

“In laymen’s terms, AHRQ and CDC have been caught with their fingers on the balance scales, in a deliberate and unconscionable effort to bias public policy against the use of opioid therapies regardless of the medical evidence,” Lawhern said in a written public comment.  “CDC violated its own research standards by failing to explicitly acknowledge that the medical evidence for alternatives to opioids is no stronger than for opioids. Now AHRQ proposes to compound that lack of public transparency by doubling down on a false narrative.”

Although voluntary, the CDC’s dose recommendations have been widely misapplied by insurers, pharmacies, doctors, and federal and state regulators – who have adopted the guideline as policy or even law — and used it as an excuse to abruptly cutoff or taper patients on opioids.

“We are concerned that the AHRQ review may have similar unintended consequences,” the American Medical Association said in a letter to the agency. The letter points out that most opioid overdose deaths are caused by illicit fentanyl and other street drugs, not prescription opioids.

“We would suggest that AHRQ publish the list of all those involved in any aspect of the report... to help remove any perception of potential conflict.”

— Dr. James Madara, AMA

“The AMA urges the AHRQ to clarify that the review does not support a conclusion that the epidemic of opioid-related overdose deaths is due to efforts to treat patients with chronic pain or cancer pain, or to manage pain for patients receiving hospice or palliative care,” said Dr. James Madara, the AMA’s Executive Director and CEO. “The AMA further urges the AHRQ to clarify that this review should not be used to justify or support reductions in opioid therapy for patients with acute, chronic, palliative, cancer-related or other pain when clinically indicated by the patient’s physician.”

The AMA’s letter also urged the AHRQ to publicly identity everyone the agency consulted with before its final report is released.

“We would suggest that AHRQ publish the list of all those involved in any aspect of the report during the comment period to help remove any perception of potential conflict,” Madara wrote.

Feds Using ‘Cone of Silence’ Again for Rx Opioid Review

By Pat Anson, PNN Editor

Federal health officials are at it once again, releasing a draft report on the risks and benefits of opioid pain medication without seeking substantive input from the public or medical community.

So far they’ve done it with no public hearings, feeble attempts at soliciting public comment, and without disclosing the identities of the experts they consulted with.

If that reminds you of the CDC’s botched rollout of its opioid guideline in a comically secretive webinar that one critic compared to Get Smart’s “Cone of Silence” – you’re not alone.

Or as agent Maxwell Smart said to his boss, “You know this thing doesn't work, why do you always insist on using it?”

This time it’s not the CDC, but a little-known research agency in the Department of Health and Human Services called the Agency for Healthcare Research and Quality (AHRQ).

Last month, AHRQ quietly released a 287-page draft report on the effectiveness of opioid medication in treating chronic pain.

Like the CDC, the AHRQ concluded that evidence on the long-term effectiveness of opioids is limited, but there was enough evidence to warn of “increased risk of serious harms” at high doses.  Even when used short-term for acute pain, the report found “no differences between opioids versus nonopioid medications in improvement in pain function, mental health status, sleep, or depression.” In other words, Tylenol is just as effective as Vicodin.

Who is the author of the AHRQ report? What experts were involved in drafting it? Who are the peer reviewers? We don’t know because the AHRQ won’t identify any of the participants until the final report is released.

According to the draft report, “Key Informants” and “Technical Experts” that consulted with AHRQ were required to disclose financial or professional conflicts of interest. But even if they had conflicts, they were not automatically disqualified by AHRQ because “individuals with potential conflicts may be retained” due to their “unique clinical or content expertise.”

‘Identifying Authors Not Essential’

An AHRQ spokesman told PNN that the agency does not identify the researchers and experts it consults with until after a final report is released.

“This policy is aimed at helping the authors maintain their independence by not being subject to lobbying by industry reps or others with conflicts of interest, either financial or intellectual,” Bruce Seeman said in an email. “AHRQ maintains that identifying the authors is not essential to the primary goal of receiving comments on the science of the reports.”

But critics of the policy say the refusal to identify participants only raises doubts and suspicion. It is also eerily similar to what the CDC did in 2015, when it released a draft of its controversial opioid guideline without identifying the “core expert group” it consulted with.

It turned out few of the CDC’s experts had any experience in clinical pain management and several had conflicts, such as being affiliated with Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group. Faced with allegations that it violated federal open meeting laws, the CDC created a new expert panel and delayed releasing the final guideline for several months.

“I would hope that they, the AHRQ, would be able to provide far more notice and transparency as it relates to both substance and process than what was provided by the CDC and its secret Core Expert Group in the development of their ‘Guideline’ for Prescribing Opioids,” said Stephen Ziegler, PhD, a Professor Emeritus at Purdue University. “Governments rarely evaluate their own policies to see if they work or cause unintended harms. That needs to change.”  

“This failure to identify authorship in the draft essentially disqualifies the document. Without knowing who wrote and reviewed this document, we cannot identify their biases or predispositions,” said Richard “Red” Lawhern, PhD, a patient advocate with the Alliance for the Treatment of Intractable Pain (ATIP).

“If anyone among these groups was also among the writers group that supported CDC in 2015-2016, then we have reason for concern that the AHRQ comparative review will be equally biased and unsupported by real research. It should be noted that no less an authority than the American Medical Association has publicly repudiated many of the assumptions and all of the core methodology incorporated into the Guidelines.” 

Lawhern emailed a “flash alert” to ATIP members this morning, urging them to comment on the AHRQ draft report while there is still time. Unlike other federal agencies that routinely seek public comments in the Federal Register, where they would get broader exposure, the AHRQ is seeking comments on its own website. Comments will be accepted until Tuesday, November 12 at noon EDT. 

“We need large numbers of knowledgeable medical professionals, patients and caregivers to file protest at the public gateway,” said Lawhern, who learned of the AHRQ report after being tipped off by a patient. 

The AHRQ sent out no press releases notifying the news media that it was soliciting comments on the draft report. In an online search, this reporter could find no news coverage of the report itself.  

“AHRQ doesn’t issue press releases, publish newsletter articles or pursue other high visibility promotion of draft reports. We normally save those efforts for final products,” said Seeman.

The AHRQ spokesman said the agency did send a mass email on October 17th to about 100,000 subscribers notifying them that the opioid report was available for comment. 

Lawhern says there was not enough transparency or public involvement in the draft process.

“This draft report should be withdrawn immediately and re-published on the regulations.gov website after announcement in the Federal Register.  When re-published, the names and qualifications of all ‘key experts’ and peer reviewers should be disclosed,” said Lawhern.

Limited Evidence

In drafting the report, the AHRQ’s experts reviewed over 150 clinical studies and reviews of pain patients prescribed opioids. Few of the studies were long-term, an evidence gap that exists not only for opioids but for all medications used to treat pain. Long-term studies are lacking because it would be unethical for researchers to knowingly treat someone’s severe pain with a placebo — which would essentially amount to torture.

The old saying that “absence of evidence is not evidence of absence” would seem to apply to the effectiveness of opioid medication, but not in the AHRQ’s draft report. “Limited evidence” is repeatedly cited as a reason not to use opioids, while similar low-quality evidence is cited as proof that opioids are risky. 

“Limited evidence indicated no differences between long- and short-acting opioids in effectiveness, but long-acting opioids were associated with increased risk of overdose,” the report concludes.

“For patients with chronic pain, opioids are associated with small beneficial effects versus placebo but are associated with increased risk of short-term harms and do not appear to be superior to nonopioid therapy. Evidence on intermediate-term and long-term benefits remains very limited and additional evidence confirms an association between opioids and increased risk of serious harms that appears to be dose-dependent.”

Lawhern says the AHRQ is cherry picking the evidence. 

“The draft top level summary reveals a deliberate and scientifically unsupported bias against opioid analgesic therapy that continues and expands on the cherry picked ‘research’ quoted in the 2016 CDC guidelines on prescription of opioids,” he said.

Lawhern is particularly concerned about references in the draft to the Krebs report, a controversial study that found opioids no more effective than acetaminophen in treating back or knee pain. Critics say the Krebs study was small, poorly designed and failed to prove anything.

“The profoundly flawed and biased Krebs report is among the references quoted in the draft report. This inclusion by itself would be grounds for deep alarm,” Lawhern said.