Peer Reviewers of Medical Studies Have Conflicts of Interest

By Crystal Lindell

How much are medical studies impacted by financial conflicts of interest? New research shows the problem may run deeper than most people realize. 

The authors of peer-reviewed studies in medical journals usually have to disclose whether or not they received money from pharmaceutical companies or medical device manufacturers. But new research published in JAMA looks at the next layer: the peer reviewers themselves.

Due to the “traditionally opaque nature of peer review,” it’s difficult to investigate the issue, but an international team of researchers studied peer reviewers at high-impact medical journals like The BMJ, JAMA, The Lancet, and The New England Journal of Medicine.

They looked specifically at nearly 2,000 U.S-based physicians who served as peer reviewers. 

What they found is both unsurprising and alarming. Between 2020 and 2022, more than half (58.9%) of the peer reviewers analyzed had received at least one industry payment. In total, the peer reviewers received a staggering $1.06 billion in industry payments. 

It should be noted that companies don’t spend that kind of money out of some noble love of medicine. No, they are doing it because it helps increase their profits or advances their interests. 

Most of that money – $1 billion or 94 percent – was paid directly to individuals or to their institutions to help fund research programs. That’s why academics who churn out studies are highly prized at universities and research institutes.

The rest of the money – $64.18 million – was in the form of general payments, which includes everything from speaker fees and “honoraria” to food, drink, lodging and travel expenses. 

The median general payment to a peer reviewer was $7,614, while the median research payment was $153,173. 

Interestingly, the average male reviewer had a significantly higher total payment ($38,959) than the average female reviewer ($19,586). 

The authors also broke down differences between medical specialties. Doctors who specialize in cardiology, rheumatology, oncology, immunology or addiction treatment were the most likely to get payments (73.5%), followed by surgeons (72%), psychiatrists (65%), hospital-based specialists (47%) and primary care physicians (38%).

Those results shed light on which fields of medicine may be more susceptible to conflicts of interests.

The study’s authors came to the only conclusion that makes sense given all this data: "Additional research and transparency regarding industry payments in the peer review process are needed."

I agree that this is clearly an issue that needs to be addressed. But we shouldn’t have to wait for more research to start taking action. We need stronger policies at medical journals to help contain the potential harm it’s causing. 

At the very least, peer reviewers should have to disclose conflicts of interest. While that may conflict with the policy of some journals to keep peer reviewers anonymous, given the potential for bias and other negative consequences, it seems the financial disclosures should take precedence. 

Since peer reviewers also have the ability to reject research before it’s even published, they should have their names and potential conflicts listed in the publications. 

Beyond that, medical journals need to start having difficult conversations about whether peer reviewers should even be allowed to review studies that involve companies or industries that pay them. 

While it may not be entirely possible in our for-profit healthcare system, that doesn’t mean it shouldn’t be explored. After all, the study did not find that 100% of peer reviewers accepted payments. So clearly some peer reviewers found a way to do the work without an obvious conflict of interest.

It isn’t just medical journals that do a poor job flagging the conflicts of peer reviewers. When PNN made a Freedom of Information Act (FOIA) request to the CDC seeking more information about the “Core Expert Group” involved in the agency’s 2016 opioid guideline, most of the documents we received back were heavily edited or redacted.

The CDC’s FOIA office said the group was exempt from our request because of “deliberative process privilege” and that disclosing their conflicts would have been “a clearly unwarranted invasion of personal privacy.”  

Why Conflicts Matter

Why do conflicts of interest matter? The easiest way to understand it is that whenever money is involved, it can potentially lead to what is essentially a boss-employee power dynamic. And typically, people don’t like to upset their bosses. 

Intuitively, most people also understand that if a medical device company funds medical device research, the researchers are incentivized to manipulate both the research methods and results in hopes of providing the funder the results they seek. 

Sometimes it’s deliberate, but sometimes it just happens on a subconscious level. People naturally favor people who give them money. However, in this case, the result of that favoritism could harm the health of millions of patients. 

In one high-profile example from 2018, a top cancer researcher failed to disclose the millions of dollars in payments he received from drug and healthcare companies.

As ProPublica and The New York Times reported, Dr. José Baselga, then-chief medical officer at Memorial Sloan Kettering Cancer Center in New York, had a number of undisclosed conflicts of interests. 

One such conflict may have led Baselga to put a positive spin on the results of two Roche-sponsored clinical trials — trials that many others had considered disappointments. He did this without disclosing the more than $3 million in consulting fees he’d received from Roche. He also left out that he had a stake in a company Roche had acquired. 

Baselga resigned just days after the news investigation came out, but journalists just don’t have the resources to constantly investigate every single researcher for conflicts of interest. That’s why medical journals must regulate the issue themselves. 

Yes, most medical journals already have policies requiring study authors to disclose conflicts of interest, but as this new research makes clear, that’s not enough. It’s past time for peer reviewers to be required to do the same. 

After all, it’s not just because the public deserves to know. Our lives could depend on it. 

‘Misplaced and Dangerous’ Opioid Study Debunked by Critics

By Pat Anson, PNN Editor

Nearly a year after publishing a controversial study that questioned the effectiveness of opioid pain medication, The Lancet medical journal has published two rebuttal letters that challenge the study’s design and conclusions.

The blinded, placebo-controlled clinical trial – known as the OPAL study -- found that a 6-week course of low-dose oxycodone worked no better than a placebo in treating patients with recent mild-to-moderate back and neck pain. Based on that finding, Australian researchers recommended that opioids should not be used to treat acute back and neck pain, and that medical guidelines should be changed to reflect that view.

“Opioids should not be recommended for acute back and neck pain, full stop,” said lead investigator Christine Lin, PhD, a professor in the School of Public Health at University of Sydney.

“This recommendation is an extraordinary, misplaced, and dangerous conclusion, considering the authors studied the effects of only one type of slow-release opioid not indicated for acute pain and that guidelines should not be changed on the basis of a single randomized trial,” said Asaf Weisman, Dr. Youssef Masharawi and Dr. James Eubanks in their rebuttal letter. 

Weisman is a physiotherapist and spine researcher at Tel Aviv University, Masharawi is a professor of physical therapy at Tel Aviv University, and Eubanks is an assistant professor at the Medical University of South Carolina.    

“Relief of pain is one of the obligations of medical doctors. Despite the documented risks, which cannot be understated, opioids are indispensable for pain management, particularly in cases in which other forms of treatment are ineffective or inadequate,” they wrote. 

The second rebuttal letter noted that the OPAL study had an “extremely high” dropout rate and nearly a quarter of patients in the placebo group were taking opioids when the study began – two factors that confound and weaken the study’s findings. 

“We should be careful when drawing decisive conclusions based on this trial,” wrote Dr. Yu Toda, a palliative care specialist at Japan’s National Cancer Center Hospital. 

In reply to the letters, Lin and her co-authors defended the design of the OPAL study, but agreed the conclusions may have been too broad.

“We agree that we cannot generalize our results to all opioids. There are different opioid classes with different pharmacological profiles,” said Lin. “We agree that the OPAL results might not be generalizable to all patients with acute low back and neck pain, including those experiencing hyperacute pain requiring immediate pain relief in the emergency department.” 

Other critics found additional flaws in the OPAL study, pointing out that the daily dose of oxycodone was relatively low – ranging from 15 to 30 MME (morphine milligram equivalents) -- and that the oxycodone was combined with naloxone, a medication that blocks the effects of opioids. In clinical practice, a slow-release formulation of oxycodone is usually not prescribed for short-term pain and is never combined with naloxone,

Publishing rebuttal letters is a common practice for medical journals, but – until now -- The Lancet has not shared with its readers any counterpoints to the OPAL study

“The Lancet received submitted replies criticizing the OPAL Trial’s authors’ over-generalized conclusion within a month of the study’s online publication. Given evidence for patient harms from excessively rapid dose reductions or discontinuation of opioid therapy, waiting almost a year to publish these criticisms seems recklessly irresponsible,” said Dr. Chad Kollas, a palliative care physician and pain policy expert, whose rebuttal letter was rejected several months ago by The Lancet’s editors.

‘Many Patients Have Been Hurt’

The OPAL study received a fair amount of media attention when it came out and was even hailed as a “Landmark Trial” by some news outlets. But like many news stories dealing with opioids, they conveyed the simplistic message that all opioids are risky and ineffective, regardless of a patient’s condition, pain level or need.

“The Great Opioid Lie: Addictive painkillers do NOT reduce lower back or neck pain,” was the headline used by the Daily Mail. “Opioids might actually worsen pain in the long-run while increasing the odds of becoming addicted.”  

The OPAL study was even cited by U.S. Sens. Ed Markey (D-MA) and Joe Manchin (D-WV) in a letter to the FDA urging the agency not to conduct studies on the efficacy of opioids. Further studies are not needed, they claimed, and would only lead to the approval of new opioid medication.

“A recent randomized placebo-controlled study found that prolonged opioid use was ineffective for acute back and neck pain,” Sens. Markey and Manchin wrote. “For too long, drug manufacturers have been given the benefit of the doubt in developing and marketing a drug that unleashed a widespread, decades-long epidemic. Using a study model that risks continued bias in favor of approval is unacceptable.”

Weisman and his two colleagues say “opioid phobia” in the U.S. has led to pain patients around the world being denied appropriate treatment, causing unnecessary suffering.  

“Unfortunately, the opioid epidemic in the USA has led to many countries adopting strict umbrella policies and led to so-called opioid phobia among clinicians, and many patients worldwide have been hurt due to these processes,” they wrote.

U.S. Falls to 8th Globally in Per Capita Opioid Sales

By Pat Anson, PNN Editor

Concerns about opioid addiction and overdoses have caused opioid sales to plummet in the United States in recent years. Opioid consumption has fallen so sharply that Canada, Australia and several European countries have overtaken the U.S. and become the highest consumers of opioid analgesics, according to a new study.

But in many poor and middle-income countries, access to opioids remains very limited, causing unnecessary pain and suffering for millions of sick and dying people.

“There are still concerningly low rates of opioid use in large parts of the world, even in numerous middle-income countries,” said lead author Wallis Lau, PhD, a Lecturer at the School of Pharmacy, University College London.

“Opioids have been listed by the World Health Organization as an essential class of medicine for acute pain, cancer-related pain, and palliative care since 1977, so it is troubling that in many parts of the world, people are unable to access this medicine. There is an urgent need to tackle the global gap in opioid access.”

Lau and her colleagues analyzed global pharmaceutical sales in 66 countries from 2015 to 2019. They found that opioid use in some African and South American countries was less than one tenth of 1% of the rates in wealthier countries in North America, Europe and Australia, according to findings published in The Lancet Public Health.

The highest opioid rate was found in Canada, estimated at 988 milligram morphine equivalents (MME) per day for every 1,000 people. That was down from an average of 1,581 MME per day in Canada in 2015.

By comparison, the U.S. rate was 738 MME per 1,000/day, a 45% decline since 2015. Long touted as having the highest per capita opioid consumption in the world, the U.S. now ranks 8th globally in opioid sales.

At the other end of the scale, a group of 12 West African countries reported only 0.01 MME per 1,000/day. A few other countries, including three in South America, reported rates below 1 MME per 1,000/day.

Opioid Sales Per Capita (2019)

SOURCE: THE LANCET

Researchers say the disparities in opioid consumption go beyond factors such as a nation’s wealth, healthcare quality and disease prevalence. For example, wealthy countries such as the United Arab Emirates and Saudi Arabia reported very low rates of opioid use. Kazakhstan also reported low rates of opioid consumption, despite having high cancer prevalence and high cancer death rates.

“Some countries have low opioid analgesic consumption despite a high cancer prevalence, which could suggest inadequate access to opioid analgesics as much-needed pain control,” said Lau.

Overall, global opioid sales increased by 4% annually from 2015 to 2019. Opioid consumption rates increased in most areas that reported low use, including Eastern Europe, Asia, and South America, but not in Africa.

“These findings reinforce the need to recognise palliative care and pain relief as a global public health priority. In countries that already have good access to opioid analgesics, it is important to avoid opioid misuse and overprescribing, without leaving patients undertreated.” said co-senior author Professor Ian Wong of UCL School of Pharmacy and University of Hong Kong.

According to a 2017 international study commissioned by The Lancet, over 25 million people die annually in severe pain because they have little or no access to morphine and other painkillers. Another 35 million people live with chronic pain that is untreated. The Lancet commission said there were several barriers that stood in the way of effectively treating pain, including “opiophobia” – prejudice and misinformation about the medical value of opioids.

“Unbalanced laws and excessive regulation perpetuate a negative feedback loop of poor access that mainly affects poor people,” the commission said.

Report Warns of Million More Opioid Overdose Deaths

By Pat Anson, PNN Editor

A new report is warning that over a million more people will die of opioid overdoses in the U.S. and Canada by the end of the decade unless public health policies are prioritized to treat opioid addiction and marketing by pharmaceutical companies is prohibited.

“Unrestrained profit-seeking and regulatory failure instigated the opioid crisis 25 years ago, and since then, little has been done to stop it,” says Keith Humphreys, PhD, a Stanford psychiatry professor who chaired the Stanford-Lancet Commission on the North American Opioid Crisis. “Pharma companies are all being sued, and they deserve to be sued, but we have to remember they exploited weaknesses in our health care regulatory system that are still there.”

The commission’s report, published in The Lancet medical journal, projects that from 2020 to 2029, opioid deaths in the U.S. will reach 1.22 million if no action is taken.

The Stanford-Lancet commission lays most of the blame for the North American opioid crisis on the pharmaceutical industry, particularly Purdue Pharma’s heavy-handed promotion of OxyContin, as well as lax regulation by the Food and Drug Administration. The report calls for a ban on all direct-to-consumer drug advertising and for an end to pharmaceutical funding of continuing medical education programs.

The commission’s 50-page report was prepared by a panel of academics, clinicians and policymakers, including several longtime critics of opioid prescribing practices. They include Drs. Anna Lembke and David Juurlink, who are board members of the anti-opioid activist group Physicians for Responsible Opioid Prescribing (PROP), and Erin Krebs, MD, a researcher who hosted a lecture series on opioid prescribing for the Steve Rummler Hope Foundation, which lobbies against the use of opioids. The Rummler foundation is the fiscal sponsor of PROP.

Humphreys is also a frequent critic of opioid prescribing. In 2018, he co-authored a controversial article that dismissed concerns that cutbacks in prescribing would be harmful to patients, saying that reducing the supply of opioids “may increase heroin use and reduce quality of life in the short term, but in the long term could generate positive health benefits.”

Humphreys’ commission took a more even-handed approach to opioids, saying the drugs “are in some cases of great benefit and in others very harmful” and that regulators should avoid “overly lax or overly restrictive prescribing policies, both of which have substantial potential for harm.”

But there is little discussion in the report of how opioid prescribing has already declined significantly in the U.S. and Canada, how it has harmed pain patients, or that the overdose crisis is now largely fueled by illicit fentanyl and other street drugs, not prescription opioids.

"The Stanford/Lancet report on the so-called opioid crisis is not only one-sided. It is fundamentally wrong on facts and deliberately slanted on interpretation. This is unsurprising, given the participation of several long-time anti-opioid zealots on its commission,” said patient advocate Richard “Red” Lawhern, PhD. 

"It is now well established from multiple published sources that over-prescription of pain relievers by physicians treating pain patients is not now and never has been a significant source of addiction or overdose-related mortality in the US.  Deaths solely due to prescription opioids are in fact quite rare. Overdose deaths are dominated by deaths due to poly-pharmacy, alcohol, and illegal street fentanyl.” 

The commission’s work was funded by Stanford University’s School of Medicine.

Lancet Study Calls for Improvements in Pediatric Pain Care

By Pat Anson, PNN Editor

An international study by The Lancet has found that childhood pain often goes untreated, unrecognized and poorly managed, leading to chronic pain, disability and other negative consequences in adulthood.

The report by the Lancet Child and Adolescent Health Commission, led by the Centre for Pain Research at the University of Bath, found that too many children live with pain — even in developed countries — and calls for improvements in pediatric pain care, including diagnosis, pain management, social support and psychological treatment.

"Among health-care professionals, it is easy to agree that no child should experience pain if that pain can and should be prevented, avoided, or successfully treated,” said lead author Emma Fisher, PhD, a Versus Arthritis fellow at the University of Bath.

“In practice, however, we know there is ample evidence that children frequently experience preventable pain, and that in high-income settings, with advanced health-care systems and highly educated and regulated health professionals, children and young people experience pain that often goes unnoticed, unreported, or is not responded to, across healthcare including in the Emergency Department, post-surgical care, and in tertiary care.”

Childhood Pain ‘Swept Under the Carpet’

The report provides several examples of childhood pain not being recognized or treated adequately, such as what happened to Caitriona Roberts of Belfast, Northern Ireland. At age 12, she went to her doctor with pain and swelling in her ankle. Initially written-off as 'just a sprain' that would go away, she would spend the next six months living in almost constant pain, until she was referred to a specialist who diagnosed her with juvenile idiopathic arthritis, an autoimmune condition.

Now 28, Roberts has learned how to live and manage the disease. She helped researchers prepare The Lancet report.

"I think this issue has been swept under the carpet for too long. Still today, over 15 years on from my diagnosis with arthritis, I find people, including medical professionals, unaware of the condition or its effects on my day-to-day life. And when I speak to other young people, I find that sadly, very little seems to have changed in terms of how they experience pain or the support they receive,” Roberts said.

Researchers say up to 10% of young people experience chronic pain into early adulthood, with conditions such as arthritis, other types of musculoskeletal pain, recurring abdominal pain, and headaches.  

"This really matters, both for those experiencing pain and those around them but also across wider society. We know that chronic pain experienced in childhood is likely to feed through to adulthood and this has long-term health and economic costs associated,” said Fisher.

She called on providers and policymakers “to sit up and listen to the fact that too many of our young people are in pain and need help."

Myths About Opioids

One obstacle to getting that help is the stigma associated with opioid pain medication, particularly in the United States and Canada, where researchers say guidelines intended to control opioid use in adults are being “inappropriately applied to young people.”

“Substance use disorders and pain medication are both conflated in policy and in the media's portrayal of the North American opioid crisis,” the report found. “Through this media, public views have been influenced to consider opioids as drugs of addiction rather than pain medicine.  

“Health-care professionals, young people, and parents continue to hold misconceptions and believe myths about opioid use in pediatric patients, whereby the media depicts opioids as the villain and the underlying reason for substance misuse. Opioids have their place in pediatric pain medicine. In the context of the oversupply of opioids, childhood pain can usefully be considered a risk factor for long-term harmful exposure to opioids.”

More Than Growing Pains

The report found that improvements in pediatric pain care have come slowly. The last major intervention in the field came in the 1980’s, when it was recognized for the first time that babies experienced pain. Up until that point, a number of routine and major operations, including heart surgery, were carried out on babies without anesthetics.

"Parents tell us about the struggle they have convincing their GP that their child's illness is more than growing pains,” said Zoe Chivers, Head of Services at Versus Arthritis, which funded the report. “While the focus, attention, and dedication in providing quality services to children is consistently in place for conditions like cancer it's woefully absent for childhood arthritis and chronic pain.

"As a society we need to understand that dismissal of arthritis comes at high price and that adults and children living in pain with the condition should no longer be expected to pay it."

The study has four key goals: to make childhood pain matter, to make it understood, to make it visible, and to make it better. One recommendation is to make routine vaccinations less painful and stressful for children, such as allowing parents to be present during the injections and using topical analgesics.

"For many parents and children, a trip to the doctors for routine inoculations will be a stressful and painful experience. This does not have to be the case - we know how we can make the experience less painful for young people, but we're not doing it. This is just another example of how pain has been accepted as an everyday feature of growing up," said Fisher.

Study Critical of Hydroxychloroquine Withdrawn by Medical Journal

By Pat Anson, PNN Editor

One of the world’s most respected medical journals has issued a rare retraction, essentially disowning a controversial study published last month that claimed the use of hydroxychloroquine and chloroquine for treating COVID-19 had no benefit for hospitalized coronavirus patients.

The Lancet issued the retraction after receiving a letter from the study’s authors saying they were unable to complete an independent audit of the data underpinning their analysis. As a result, the authors concluded they “can no longer vouch for the veracity of the primary data sources.”

The study looked at data from nearly 15,000 patients with COVID-19 who received the antimalarial drugs hydroxychloroquine or chloroquine. They were compared to a control group of over 81,000 patients who did not take the drugs. The study included patients being treated at 671 hospitals in North America, Europe, Asia, Africa, South America and Australia.

The study concluded that chloroquine and hydroxychloroquine significantly increased the risk of death for COVID-19 patients, particularly when taken with an antibiotic.

However, soon after publication, critics began questioning the legitimacy of data used in the study, pointing to inconsistencies such as five Australian hospitals reporting more coronavirus deaths than had been found on the entire continent.

In a letter to The Lancet, study authors Mandeep Mehra, Frank Ruschitzka, and Amit Patel said they could not get full access to the data and could not conduct an independent peer-review of their own research:

“After publication of our Lancet Article, several concerns were raised with respect to the veracity of the data and analyses conducted by Surgisphere Corporation and its founder and our co-author, Sapan Desai, in our publication. We launched an independent third-party peer review of Surgisphere with the consent of Sapan Desai to evaluate the origination of the database elements, to confirm the completeness of the database, and to replicate the analyses presented in the paper.

Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process.

We always aspire to perform our research in accordance with the highest ethical and professional guidelines. We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologise to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

The Lancet’s retraction is likely to lead to more claims and conspiracy theories that the coronavirus has been “politicized” by mainstream medicine and left-leaning media to embarrass President Trump.

In recent months, the president and conservative media have touted hydroxychloquine as a possible "game changer" in the treatment of COVID-19. Trump took the drug as a preventative treatment last month after two White House staff members tested positive for coronavirus. A statement from the president’s doctor yesterday indicated he suffered no ill effects.

“I’m not going to get hurt by it. It’s been around for 40 years,” Trump said last month. “For malaria, for lupus, for other things. I take it. Front-line workers take it. A lot of doctors take it."

Hydroxychloroquine is only approved for the treatment of autoimmune diseases such as lupus and rheumatoid arthritis. The FDA has warned against using hydroxychloroquine as a treatment for COVID-19 outside of a hospital or clinical study because of “serious and potentially life-threatening heart rhythm problems.”

The FDA's Adverse Events Reporting System lists over 10,000 reported cases involving hydroxychloroquine in the past decade, many of them serious or resulting in hospitalizations. Nearly 600 people have died since 2010, including 48 deaths so far this year.

A study published yesterday in The New England Journal of Medicine, found that hydroxychloroquine was no better than a placebo in preventing COVID-19 infections.

Study Debunks Use of Hydroxychloroquine for COVID-19

By Pat Anson, PNN Editor

A large international study on the use of hydroxychloroquine and chloroquine for treating COVID-19 has found the antimalarial drugs offer no benefit for hospitalized coronavirus patients and appear to significantly raise the risk of death, particularly when taken with antibiotics.

The study, published in the peer-reviewed journal The Lancet, looked at data from nearly 15,000 patients with COVID-19 who received hydroxychloroquine or chloroquine, with or without the use of antibiotics. They were compared to a control group of over 81,000 patients who did not take the drugs. The study included patients being treated at 671 hospitals in North America, Europe, Asia, Africa, South America and Australia.

(Update: On June 4, The Lancet retracted this study after the authors said were unable to complete an independent audit of their research and concluded they “can no longer vouch for the veracity of the primary data sources.”)

“We found no evidence of benefit of hydroxychloroquine or chloroquine when used either alone or with a macrolide (antibiotic),” researchers said. “Our study included a large number of patients across multiple geographic regions and provides the most robust real-world evidence to date on the usefulness of these treatment regimens. Although observational studies cannot fully account for unmeasured confounding factors, our findings suggest not only an absence of therapeutic benefit but also potential harm.”

The study found that 9.3% of patients in the control group died in the hospital. Of those treated with chloroquine or hydroxychloroquine alone, 16.4% died. The outcomes were even worse for patients who used chloroquine with an antibiotic (22.2%) or hydroxychloroquine with an antibiotic (23.8%).

Researchers also found that serious cardiac arrhythmias, which cause the lower chamber of the heart to beat rapidly and irregularly, were more common in the groups that took hydroxychloroquine or chloroquine.

“This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19. Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death,” said lead author Mandeep Mehra, MD, Executive Director of the Brigham and Women’s Hospital Center for Advanced Heart Disease.

“Randomised clinical trials are essential to confirm any harms or benefits associated with these agents. In the meantime, we suggest these drugs should not be used as treatments for COVID-19 outside of clinical trials.”

President Trump disclosed this week that he has been taking hydroxychloroquine as a preventative treatment for COVID-19, even though there is only anecdotal evidence the drug may work against the virus. The president said he was prescribed the drug by his physician after two White House staff members were diagnosed with the virus. Trump said he would only take hydroxychloroquine for about two weeks.

The Food and Drug Administration has said hydroxychloroquine or chloroquine should not be used as frontline treatments for COVID-19 outside of hospitals and clinical trials.

The FDA has only approved chloroquine to treat malaria and hydroxychloquine as a treatment for lupus and rheumatoid arthritis. Both drugs have good safety profiles for those conditions.

Chloroquine and hydroxychloquine have been shown to have antiviral effects in laboratory tests, which has sparked interest in their use as potential treatments for COVID-19. Some countries have been stockpiling the drugs. In March, the FDA added hydroxychloquine and chloroquine to its list of drug shortages. Chloroquine was recently taken off the list.

“Several countries have advocated use of chloroquine and hydroxychloroquine, either alone or in combination, as potential treatments for COVID-19,” said co-author Frank Ruschitzka, MD, Director of the Heart Center at University Hospital Zurich.

“Justification for repurposing these medicines in this way is based on a small number of anecdotal experiences that suggest they may have beneficial effects for people infected with the SARS-CoV-2 virus. However, previous small-scale studies have failed to identify robust evidence of a benefit and larger, randomised controlled trials are not yet completed. However, we now know from our study that the chance that these medications improve outcomes in COVID-19 is quite low.”

In addition to their findings on chloroquine and hydroxychloroquine, researchers also noted that obesity, heart disease, diabetes and smoking raise the risk of death for hospitalized COVID-19 patients. Interestingly, patients being treated with statins or ACE inhibitors for high blood pressure had a lower risk of mortality, suggesting that medications that stabilize the cardiovascular system may be beneficial.

Australian Study Finds Cannabis Does Little for Pain

By Roger Chriss, PNN Columnist

A controversial study recently published in The Lancet Public Health followed over 1,500 Australian adults with chronic non-cancer pain for four years – one of the longest studies of its kind. All used prescription opioids and about half tried using cannabis for pain, some occasionally and others daily or near daily.

Advocates of medical marijuana as a treatment for pain may be surprised by the findings.

In the Pain and Opioids IN Treatment (POINT) study, Gabrielle Campbell, PhD, and colleagues at the University of New South Wales found "no evidence that cannabis use improved patient outcomes.”

"At each assessment, participants who were using cannabis reported greater pain and anxiety, were coping less well with their pain, and reported that pain was interfering more in their life, compared to those not using cannabis," said Campbell, who was lead author of the study. "There was no clear evidence that cannabis led to reduced pain severity or pain interference or led participants to reduce their opioid use or dose."

These findings are not unique. Campbell was co-author of a recent review in the journal Pain that found that “evidence for effectiveness of cannabinoids in chronic non-cancer pain is limited.”  Cochrane reviews came to similar conclusions about cannabis for treating fibromyalgia and neuropathic pain.

In short, cannabis helps, but maybe not that much.

The POINT study would seem to contradict the 2017 National Academies of Sciences (NAS) report, which found “substantial evidence” that cannabis is an effective treatment for chronic pain, but in only five good-to-fair quality studies. Overall, the NAS report found that “cannabinoids demonstrate a modest effect on pain.”

About a third of the cannabis users in the POINT study reported reduced opioid use, but the prescription data showed that there was actually no difference.

The study also found that most cannabis users believed they were benefiting from cannabis, but there was no objective improvement in their pain scores.

“It is really difficult to disentangle the reasons for this,” Campbell told Cosmos. “One hypothesis is that it may improve sleep and subjective well-being.”

This is consistent with other findings that cannabis doesn’t reduce pain, but helps people feel better. The book “A New Leaf: The End of Cannabis Prohibition” states that “patients often say that cannabis mostly disassociates them from the pain, like it’s placed in another room instead of eliminated.”

Similar results were obtained in an Oxford study, which found that “an oral tablet of THC, the psychoactive ingredient in cannabis, tended to make the experience of pain more bearable, rather than actually reduce the intensity of the pain.”

Masking pain may seem like a good thing. But as Grant Brenner, MD, points out in Psychology Today, believing that there is a benefit when there isn't one is problematic. Making pain more bearable may improve mood and sleep, but it could also lead patients to underestimate the significance of a serious health issue. This problem applies to many forms of pain management and requires further research.

“The illusion that a drug is helping with a condition when it is not can get in the way of seeking effective treatment and obtaining real relief,” said Brenner. “Rather than helping with actual pain, difficulty from pain, and need for opioid medication, cannabis consumption may lead people to believe they are improving when in reality they are not.”

The POINT study found what many other studies have been finding about cannabis and chronic pain: Some people experience some benefits some of the time. But the study also has limitations. Participants had chronic pain severe enough to merit opioid therapy, so they may not be representative of people with chronic conditions in general. They also only had access to illicit cannabis that was not part of structured pain management program.

Still, as an editorial in The Age points out: "The findings do not mean medical cannabis does not merit a place in the treatment of various other ailments."

Cannabis and cannabis-derived pharmaceuticals like Epidiolex are proving useful for managing seizures, reducing chemotherapy side effects, and treating multiple sclerosis. There may yet be other uses to be discovered. For instance, cannabis may be effective for more rare disorders. And cannabis may be a viable add-on therapy or alternative for people who cannot tolerate or do not do well with conventional therapies.

The POINT study shows that cannabis is not a panacea for pain. Instead, cannabis is a drug, and we have to treat it with the respect we give any drug if we're going to learn how to use it effectively.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

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.

Study Finds Many Treatments for Back Pain Ineffective

By Pat Anson, Editor

Lower back pain is the world’s leading cause of disability, affecting about 540 million people at any given time. With so many people suffering, you'd think there would be a consensus on the best way to treat or at least manage low back pain.

And you'd be wrong.

In a series of reviews appearing in The Lancet medical journal, an international team of researchers found that low back pain is usually treated with bad advice, inappropriate tests, risky surgeries and painkillers -- often against treatment guidelines.

“The majority of cases of low back pain respond to simple physical and psychological therapies that keep people active and enable them to stay at work,” says lead author Professor Rachelle Buchbinder of Monash University in Australia. “Often, however, it is more aggressive treatments of dubious benefit that are promoted and reimbursed.”

Buchbinder and her colleagues say low back pain is best managed in primary care, with the first line of treatment being education and advice to exercise, stay active and continue to work. Instead, a high number of low back pain patients are treated in emergency rooms, encouraged to rest and stop work, referred for scans or surgery, and prescribed painkillers.

“In many countries, painkillers that have limited positive effect are routinely prescribed for low back pain, with very little emphasis on interventions that are evidence based such as exercises," adds co-author Professor Nadine Foster of Keele University in the UK.

"As lower-income countries respond to this rapidly rising cause of disability, it is critical that they avoid the waste that these misguided practices entail."

Low back pain mostly affects adults of working age in lower socioeconomic groups. People with physically demanding jobs, physical and mental comorbidities, smokers, and obese individuals are at greatest risk of reporting low back pain. 

Most people with new episodes of low back pain recover quickly, but recurrences are common. It’s also important to rule out more serious causes of back pain, such as cancer, arthritis and spinal fractures. In a small proportion of people, low back pain can become chronic and disabling.

The Lancet authors say patients should avoid harmful and useless treatments, and doctors need to address widespread misconceptions about their effectiveness. For example, there is limited evidence to support the use of opioids for low back pain, and epidural steroid injections and acetaminophen (paracetamol) are not recommended at all.

The authors recommend counseling, exercise and cognitive behavioral therapy as first-line treatments for short-term low back pain, followed by spinal manipulation, massage, acupuncture, meditation and yoga as second line treatments.

“Millions of people across the world are getting the wrong care for low back pain. Protection of the public from unproven or harmful approaches to managing low back pain requires that governments and health-care leaders tackle entrenched and counterproductive reimbursement strategies, vested interests, and financial and professional incentives that maintain the status quo,” said co-author Professor Jan Hartvigsen of University of Southern Denmark.

“Funders should pay only for high-value care, stop funding ineffective or harmful tests and treatments, and importantly intensify research into prevention, better tests and better treatments.”

The findings in The Lancet series are similar to those reported in other medical journals. A 2016 study published in JAMA Internal Medicine found that regular exercise and education reduce the risk of developing lower back pain by as much as 45 percent.

Another study in JAMA found that opioid medication provides only modest short-term relief for low back pain. Previous studies published in the British Medical Journal and The Lancet also found little evidence that acetaminophen was effective in treating low back pain.