NIH Spent $1 Billion on Long Covid Research, With Little to Show for It

By Betsy Ladyzhets and Rachel Cohrs

The federal government has burned through more than $1 billion to study long Covid, an effort to help the millions of Americans who experience brain fog, fatigue, and other symptoms after recovering from a coronavirus infection.

There’s basically nothing to show for it.

The National Institutes of Health hasn’t signed up a single patient to test any potential treatments — despite a clear mandate from Congress to study them. And the few trials it is planning have already drawn a firestorm of criticism, especially one intervention that experts and advocates say may actually make some patients’ long Covid symptoms worse.

Instead, the NIH spent the majority of its money on broader, observational research that won’t directly bring relief to patients. But it still hasn’t published any findings from the patients who joined that study, almost two years after it started.

There’s no sense of urgency to do more or to speed things up, either. The agency isn’t asking Congress for any more funding for long Covid research, and STAT and MuckRock obtained documents showing the NIH refuses to use its own money to change course.

“So far, I don’t think we’ve gotten anything for a billion dollars,” said Ezekiel Emanuel, a physician, vice provost for global initiatives, and co-director of the Healthcare Transformation Institute at the University of Pennsylvania. “That is just unacceptable, and it’s a serious dysfunction.”

Eric Topol, the founder and director of the Scripps Research Translational Institute, said he expected the NIH would have launched many large-scale trials by now, and that testing treatments should have been an urgent priority when Congress first gave the agency money in late 2020.

“I don’t know that they’ve contributed anything except more confusion,” Topol said.

‘Pointless’ Study

Patients and researchers have already raised alarms about the glacial pace of the NIH’s early long Covid efforts. But a new investigation from STAT and MuckRock, based on interviews with nearly two dozen government officials, experts, patients, and advocates, and internal NIH correspondence, letters, and public documents, underscores that the NIH hasn’t picked up the pace — instead, the delays have compounded.

It’s difficult to pinpoint exactly why progress is so stalled, experts and patients involved in the project emphasized, because the NIH has obscured both who is in charge of the long Covid efforts and how it spent the money. The broader Biden administration has also missed opportunities for oversight and accountability of the effort — despite the president’s lofty promises to focus on the disease.

The NIH’s blunders have massive ramifications for the more than 16 million Americans suffering from long Covid, in addition to those with other, similar chronic diseases. As the biggest government-funded study on this topic, the NIH initiative, dubbed RECOVER, sets precedents for future research and clinical guidelines. It will dictate how doctors across the country treat their patients — and, in turn, impact people’s ability to access work accommodations, disability benefits, and more.

“The NIH RECOVER study is pointless,” said Jenn Cole, a long Covid patient based in Brooklyn, N.Y., who wanted to enroll in the study but found the process inaccessible. The research is “a waste of time and resources,” she said, and fails to use patients’ tax dollars for their benefit.

In response to STAT and MuckRock’s questions, the NIH and an institute at Duke University managing the clinical trials defended the initiative, without providing a clear explanation for the delays.

The NIH said it chose to fund a large-scale research program instead of small-scale studies to make sure data and processes could be shared across different groups of patients, adding that clinical trials will be launching soon. In these trials, standardized study designs will allow the agency to test multiple treatments across multiple sites. If there are signals a drug works, the agency said it can pivot to devote more resources there.

A Department of Health and Human Services spokesperson said the agency has made progress over the last year in responding to long Covid, and that there are research efforts underway in addition to the RECOVER program.

“The Administration remains committed to addressing the longer-term impacts of the worst public health crisis in a century,” HHS said.

Five Clinical Trials Delayed

In 2020, Congress made an investment of $1.2 billion to learn more about the mysterious ongoing symptoms that were afflicting some people infected with Covid-19. That sort of money to fund research into a chronic condition like long Covid was virtually unheard of.

The money was explicitly earmarked to fund both research to understand the disease and clinical trials to test treatments that could bring patients relief. But more than two years in, the agency hasn’t started testing a single treatment. Nor is it planning to test many in the future. Instead, it’s focused on observational research — and that, too, has produced few insights.

The NIH is planning five clinical trials, each of which will test treatments that may help with a major category of long Covid symptoms. Some of these treatments will be drugs, while others will be behavioral therapies, such as cognitive retraining. Each trial will include 300 to 900 patients, selected based on their symptoms, according to details shared during a webinar in mid-April.

The only trial to be formally announced so far will focus on Paxlovid, testing whether the drug alleviates symptoms by mitigating any ongoing viral infection in patients’ bodies. The study was supposed to start recruiting in January.

But as of April, RECOVER hasn’t signed up a single patient for any of those clinical trials. And the timeline has slipped over and over again.

Initially, in a letter to members of Congress prompted by STAT’s March 2022 reporting on the initiative’s slow start, the NIH told lawmakers that the agency expected to launch clinical trials by that fall. But by August, the estimated launch had slipped to “by the end of 2022.” Then, another delay became public in December, when one of the NIH officials leading RECOVER told advisers that clinical trials would begin by the first quarter of 2023. Now, Duke University, which is overseeing the clinical trial infrastructure, told STAT and MuckRock it expects the first patients to sign up for trials this summer.

Emanuel said the pace of trials shows little urgency on the part of NIH.

“If you don’t have the pathobiology figured out, you try things. You don’t just slow, slow, slow, walk it,” he said.

All five clinical trial protocols are going through safety reviews, and the Food and Drug Administration is reviewing the trials that will test Paxlovid and other drugs, the Duke Clinical Research Institute said. The institute plans to share these protocols publicly when reviews are complete, but did not provide an estimate for when that will happen.

Faster progress is possible. A similar study at Stanford, which received funding directly from Pfizer, was also announced in October 2022 but has already begun recruiting patients. This trial was “able to be more flexible and get the study started faster” in comparison to RECOVER because it’s smaller, said Upinder Singh, the study’s principal investigator. Singh and her colleagues are only testing Paxlovid and doing so at only one location, rather than comparing different treatments.

Duke was also supposed to create a patient registry to collect information about long Covid patients, but that initiative hasn’t been launched, either.

“A patient registry is still planned, but the scope is being reassessed to most effectively meet the needs of the Initiative,” Duke said.

Tracking Long Covid

Rather than prioritizing treatments from the start, the NIH used much of its long Covid funding on a large-scale study to track long Covid symptoms and learn how the disease works. This choice has frustrated patients because thousands of other studies have already answered many major questions about the condition.

“We didn’t need to recreate” existing studies that already answered these questions, said Cole, the long Covid patient. Researchers have been compiling lists of common symptoms since summer 2020, she said. For Cole, fatigue and brain fog are the most debilitating aspects of the condition.

And even the symptom study is moving slowly, in part because the initiative has failed to bring in healthy people who could be compared against long Covid patients. RECOVER quickly filled its slots for people who had Covid more than 30 days prior to their recruitment, but is still looking for people who were infected recently, study lead Leora Horwitz said in a statement. Most study sites closed enrollment for long Covid patients at the end of August 2022.

The majority of the scientific findings to emerge from RECOVER so far have been based on small groups of patients or on electronic health records, rather than on the thousands of people who signed up to participate.

The crawling pace of the government’s long Covid efforts stand in stark contrast with the government’s wildly successful partnership with the pharmaceutical industry to get Covid-19 vaccines to market in less than 12 months. There are no ongoing efforts to support independent private-sector companies or researchers trying to study treatments for long Covid through the NIH, even though some have proved promising. Just this month, the White House left long Covid out of a $5 billion effort to research next-generation Covid-19 treatments and vaccines.

Long Covid researchers feel there needs to be greater urgency. Singh compared the pressure that she’s currently under to the pressure many scientists faced earlier in the pandemic when studying vaccines and treatments. “We as a scientific community need to focus on long Covid and find solutions for long Covid,” she said.

Topol echoed this sentiment, citing a recent opinion piece in Scientific American that called for an Operation Warp Speed for long Covid treatments. “That’s what should have happened,” he said.

Where Did Money Go?

It’s almost impossible to tell where the NIH’s $1.2 billion pot of long Covid money has gone.

There is no single NIH official responsible for leading RECOVER, and the initiative has failed to share basic information that would typically be available for a government research project of this scale.

Unlike Operation Warp Speed and other Covid efforts, the NIH has outsourced much of the work of running RECOVER to outside organizations. New York University, RTI International, Mayo Clinic, Massachusetts General Hospital, and Duke University are responsible for various parts of the initiative.

Many of the research projects associated with RECOVER have been funded through these organizations rather than directly from the NIH. This process makes it hard to track how decisions are made or how money is spent through public databases, said Michael Sieverts, a member of the long Covid Patient-Led Research Collaborative who has a background in federal budgeting for scientific research.

Public records requests that MuckRock filed to the agency in late 2022, intended to answer questions about RECOVER’s funding, are still incomplete as of mid-April. Sieverts has similarly asked questions to NIH officials and received no responses.

The organization of RECOVER itself is convoluted, and difficult to figure out even for patient advocates who are directly involved, they said. It’s advised by a complex series of committees, some of which aren’t even posted on the initiative’s website. There’s no one person ultimately responsible for coordinating among the different institutes — and requests for information about the leadership hierarchy have been ignored.

“They don’t have an org chart for the entire thing that exists, after two-plus years,” said Diana Güthe, the founder of Survivor Corps and a RECOVER adviser who has asked at nearly every meeting she’s attended.

Lauren Stiles, a patient advocate and president and CEO of Dysautonomia International who serves on several RECOVER committees, shared similar concerns.

“There’s a complete lack of transparency. When we ask who made this decision … they won’t tell us,” Stiles said.

Budget Squeeze

As a result, when RECOVER says it’s running out of funds, it’s hard to identify who is responsible for major decisions.

In response to questions about the initiative’s budget, the NIH said it has no money available for additional programming. The agency said $811 million has been legally committed to various activities, and the rest is earmarked to support future research activities.

The budget restrictions are having practical impacts already.

A RECOVER advisory committee responsible for ranking and evaluating potential treatment options was put on hiatus “due to a lack of funds,” the committee’s leader told members in late January, per an email exchange shared with STAT and MuckRock that has not been previously reported.

The NIH told STAT and MuckRock that the committee was paused because the clinical trial medicines, devices, and treatment programs have been chosen. However, the agency said that the RECOVER clinical trials are “adaptive platform trials,” which means they are designed with the intention of removing and adding treatments as new information becomes available.

This current budget squeeze didn’t come without warning: The NIH was well-aware last summer that the agency wouldn’t have enough money to run clinical trials that matched the initiative’s goals of reaching patients with diverse symptoms.

One of RECOVER’s co-chairs wrote to Congress in June that “additional resources are necessary” to test the full range of treatments needed.

But the Biden administration isn’t taking any action to get more funding within the agency, or from lawmakers.

NIH acting Director Lawrence Tabak told patient advocates that the agency isn’t planning on directing any further funding for RECOVER within the agency. The agency said that such a request would potentially undercut a failed request for supplemental funding that Congress ignored last year.

The Biden administration didn’t request any new funds for RECOVER in its 2024 budget, a largely aspirational document that reflects the administration’s financial priorities.

The budget did include $130 million in long Covid-related asks for other agencies, including for the Health Resources and Services Administration to support care for long Covid patients with complex needs and to educate primary care providers, and for the Agency for Healthcare Research and Quality to research the delivery of long Covid care and to establish long Covid care hubs.

There’s also little accountability for NIH leaders to disclose how funds are spent or respond to other concerns with RECOVER because an entity intended to oversee long Covid research across the federal government hasn’t been created.

In April 2022, President Biden issued a presidential memorandum calling on federal agencies to “harness the full potential” of the government, in partnership with private sector partners, to respond to long Covid.

The follow-through has been lacking on the initiative’s highest-profile goal.

In August, in a congressionally mandated national long Covid research plan, the Biden administration said it would create an Office of Long Covid Research and Practice at HHS. This month, HHS put out a fact sheet touting the administration’s progress in reaching its goals — and omitted any mention of the office.

An HHS spokesperson said that the department is working to develop the office, and requested funding in next year’s White House’s budget for the Office of the Assistant Secretary for Health to coordinate response efforts to long Covid.

“It seems to have been like, well, if we don’t do anything, maybe no one will notice,” said Güthe. “It’s so important to do an evaluation of what was promised. What’s been accomplished, and what hasn’t?”

Exercise as Treatment

A huge chunk of funding to study a chronic illness like long Covid is rare, so any clinical trials that the NIH chooses to run are crucial choices — and some doctors and advocacy groups have voiced serious concerns about the selection of one clinical trial in particular.

That trial would test exercise as a potential long Covid treatment, despite years of research suggesting that exercise could harm patients and set back further study.

Many people with long Covid have similar symptoms to people with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), a debilitating condition that often follows viral infection. The defining feature of ME/CFS is intense fatigue and worsening of other health issues after physical or mental activity. This symptom, known as post-exertional malaise, often occurs with a lag, which can make it tough for doctors to diagnose — and even for patients to recognize themselves.

“What often happens is, people will go for a walk, they may not feel it for a day or two, and then suddenly, they feel ill on the third day,” said Adam Lowe, a ME/CFS patient and co-founder of advocacy group U.K. branch of the Myalgic Encephalomyelitis Action Network, or MEAction. Patients might suddenly become bed-bound and have trouble focusing, he said.

This worsening of symptoms happens because a patient isn’t producing and using energy in the same way as a healthy person, said Todd Davenport, a professor at University of the Pacific who has studied exercise and this condition. It’s an internal change similar to the whole-body exhaustion that a marathon runner might experience at the finish line of their race.

A number of past studies and surveys of patients have demonstrated how dangerous exercise can be for people with ME/CFS. Many patients told to exercise by their doctors later dropped out of studies or treatment regimens, citing worsening symptoms. One infamous trial that pointed to exercise as a potential treatment was later discredited as deeply flawed.

Studying exercise as a treatment could “frame long Covid as something that can be overcome with grit and hard work,” said Jaime Seltzer, the director of scientific and medical outreach at MEAction, arguing that such framing is “unsound and ethically troubling.”

Not all patients with long Covid experience post-exertional malaise, and those who don’t could find exercise helpful, Davenport said. In those cases, slow and careful exercise through a rehabilitation or physical therapy program might help repair energy systems that have fallen out of shape.

But it may be difficult to distinguish between these different groups of patients, unless a clinical trial is set up with the utmost caution. “Ideally, what you would want is a very coherent, very specific set of inclusion and exclusion criteria,” Davenport said. Otherwise, the study would risk producing results that oversimplify long Covid, he added, leading doctors to widely prescribe a treatment that doesn’t work for some or many.

Scientists and patient advocates responsible for advising RECOVER have warned that an exercise trial could harm patients, but received mixed responses. Patients involved in the study sent emails and social media posts demanding that RECOVER stop the planned trial, while MEAction sent a public letter to NIH leaders.

Scientists and clinicians on an NIH advisory committee focused on rehabilitation similarly suggested that post-exertional malaise could be a dangerous result of the trial, according to internal emails shared with STAT and MuckRock. In response, NIH program officer Antonello Punturieri pushed back on the concerns. Punturieri cited clinical guidelines from the World Health Organization and a U.K. agency, even though both recommend against exercise for people with ME/CFS.

In response to these concerns, RECOVER set up internal meetings including researchers in charge of the exercise study, patient representatives, and the initiative’s top advisory committee. “Work is now underway to further revise that protocol” based on these meetings, the Duke Clinical Research Institute said.

The study’s planned revisions will address concerns about patient safety, such as monitoring for post-exertional malaise after exercise. But it’s unclear how the researchers will do this screening, or whether ME/CFS doctors will be involved.

Even with revision, experts and patient advocates remain concerned that the exercise study takes resources away from other research and could lead to harmful recommendations from doctors. If RECOVER finds exercise is helpful for some patients, asked JD Davids, author of a petition asking the NIH to stop this trial, “What are the chances that doctors would correctly understand how limited this recommendation is? I think it’s very low.”

‘No Profit Margin for Anyone’

It’s not like there aren’t plenty of potential treatment options worth studying.

Topol and other researchers compiled a full table of other treatment candidates for a review paper published in Nature in January. Experts on one of RECOVER’s advisory committees compiled a similar list, for a paper published in March.

Given “the number of other candidate treatments out there, I can’t imagine why you would choose graded exercise therapy,” said Julia Moore Vogel, a researcher at the Scripps Translational Institute living with long Covid, and co-author of the Nature review paper. Vogel is leading a study of wearable devices for long Covid, which will start with about 500 participants despite planning for up to 100,000.

One study has even reported results already, via a preprint shared by The Lancet in early March. The trial found that metformin, a common treatment for diabetes that also has antiviral properties, lowered Covid patients’ risk of developing long-term symptoms by about 42%.

This research group actually didn’t set out to study long Covid, said David Boulware, one of the scientists and an infectious disease physician at the University of Minnesota Medical School. The initial goal was to evaluate potential treatments for acute Covid-19, but the team added long Covid tracking partway through the trial.

And it’s unlikely to get further study without some kind of government assistance. The initial study relied on philanthropic funding, and additional grants would be needed to keep studying this generic drug.

“It’s a great drug, it’s cheap, it’s available worldwide,” Boulware said, “but there’s no profit margin for anyone to study it.”

There may be similar concerns for research into low-dose naltrexone, an off-label use of the addiction drug that has become common for long Covid and other chronic diseases. In low doses, naltrexone can help reduce inflammation in the immune and neurological systems, potentially alleviating long Covid symptoms.

But because the drug has been widely available for decades, pharmaceutical companies aren’t motivated to fund large trials. A few small clinical trials are underway, according to reporting by Rolling Stone.

The lack of help from NIH has left biotech executives frustrated.

“You have to understand what you’re trying to tackle, so we support that, of course. But as patients will tell you, we want intervention, not observation,” said Axcella CEO Bill Hinshaw. His Massachusetts-based company has gone all in on testing a drug candidate to treat long Covid symptoms, without any help from NIH.

Tonix Pharmaceuticals, which is developing a fibromyalgia medication that the company is hoping could be an effective treatment for long Covid symptoms, didn’t receive any funding from NIH either, despite putting in an application.

“I hope there are more therapeutics trials. And I think that the therapeutics trials can go hand in hand with the natural history kind of studies like RECOVER,” Tonix CEO Seth Lederman said.

Patients and experts fear that if RECOVER is the extent of federal effort to study long Covid, the condition could fall into the longstanding pattern of apathy and lack of urgency that has made breakthroughs in chronic illness treatment challenging.

“It’s clear that there are a lot of people at the NIH who are dedicated and determined, trying to figure this out,” said Charlie McCone, a patient representative at RECOVER. As a result, “patients are confused” why only a handful of clinical trials have been planned and none of those have launched yet, he said.

As the NIH initiative drags its feet, patients are left largely on their own to research potential treatments, said Cole, the Brooklyn-based patient, who has been struggling with symptoms since April 2020. “Because we’re not funding these promising treatments, and we’re not disseminating them through the medical system, it’s left to me to figure out how to make that happen for myself,” she said.

Cole, like many others in the long Covid community, feels abandoned by the federal government and health care system at large. If her symptoms worsen to the point that she can no longer work, she said, “the system’s not going to be there to pick me up.”

This story was originally published by MuckRock and STAT News. It is republished under a Creative Commons (BY-ND 4.0) license. Funding came from Boston Globe Media and Columbia University’s Brown Institute for Media Innovation.

Lobbying for Better Access to Migraine Care

By Mia Maysack, PNN Columnist

Last week the Alliance for Headache Disorders Advocacy held its 15th annual Headache on the Hill, with over 200 patients and advocates from 48 states visiting close to 300 congressional offices to lobby and raise awareness about migraine and headache disorders. Like last year, most of the participants attended virtually online due to the pandemic. 

As a person living with never-ending head pain from a traumatic brain injury for over two decades, it has been an honor to participate in this event for multiple years. During that time, we've continued to make progress, such as more funding for migraine research, expanding options for symptom management, obtaining access to oxygen therapy, and helping to launch the VA’s Headache Centers of Excellence — which are all meaningful strides towards healthcare reform.

However, I have never been prouder to be a part of this year’s Headache on the Hill (HOH), which had two major “Asks” for our congressional representatives:

Ask #1

Support investment in Headache Centers of Excellence for Indigenous Communities, with $5 million per year in additional appropriations. The goal is to have the Health & Human Services Secretary designate 6 new headache centers in mostly rural reservations, with an emphasis on expanding options for telehealth, so that Native Americans and Alaskan Natives living in isolated areas will be able to connect with and consult with medical professionals online.

Ask #2

Have the General Accountability Office (GAO) issue a report on funding priorities for the National Institutes of Health (NIH), specifically as it relates to headache disorders. Although migraine impacts roughly 40 million Americans and is the main cause of disability for women under 50, migraine research still receives some of the least funding from NIH, even though it has a strategic plan to consider the "burden of individual diseases” when making funding decisions.   

There is a pressing need for more migraine research if we are to find new treatments, invest in viable solutions and alleviate the need for more providers who specialize in treating head pain. Headache and migraine disorders need to be prioritized at NIH -- not above or before any other health condition, but alongside them. 

Government accountability is a part of public service. We need to know in what ways are we moving forward and how our money is being spent.   

Navigating the healthcare system can be challenging. I cannot begin to keep track of the countless hours I've devoted to sitting in waiting rooms at clinics, fighting for insurance coverage, begging for referrals, convincing providers that my ailments are real, and attempting many treatments in desperation for relief.

But as horrendous as my experiences have been at times, nothing compares to the malpractice and neglect that is experienced by patients in marginalized communities. 

It has been documented that Native Americans and Alaskan Natives have the highest rates of disabling headache disorders. They are 40% higher than other races, with a particularly high impact on men. Despite this, Indigenous communities on average have only one neurologist for every 125,000 people!   

Health resources that are caring, regardless of cause or condition, are investments in people. We have huge disparities in equitable care. Why is it that communities with the biggest needs have the fewest resources?

Mia Maysack lives with chronic migraine, cluster headache and fibromyalgia. Mia is the founder of Keepin’ Our Heads Up, a Facebook advocacy and support group, and Peace & Love, a wellness and life coaching practice for the chronically ill. 

Does Cannabis Increase Risk of Suicide?

By Roger Chriss, PNN Columnist

A new National Institute of Health study confirms a long-standing association between cannabis use and suicidality in younger adults.

NIH researchers looked at data from over 280,000 people aged 18 to 34 who participated in the National Survey of Drug Use and Health from 2008 to 2019. Their findings, published in JAMA Open Network, concluded that cannabis increased the risk of suicidal thoughts (ideation), planning and attempts by young adults.

“While we cannot establish that cannabis use caused the increased suicidality we observed in this study, these associations warrant further research, especially given the great burden of suicide on young adults,” Nora Volkow, MD, director of the National Institute on Drug Abuse, said in a statement.

Cannabis use is rising fast in the United States. Use more than doubled from 22 million people in 2008 to 45 million in 2019, and regular use tripled to nearly 10 million people by the end of the study. The increased use of cannabis coincided with a spike in suicides among young adults, which rose by 52% for women and 45% for men from 2008 to 2019.

NIH researchers found that daily cannabis use and a history of a major depressive episode (MDE) increased the risk of suicide, particularly for women. The prevalence of a suicide plan in the past year was 52% higher for women with MDE than for men with MDE.

But even when a young adult was not depressed, suicide ideation rose in tandem with the frequency of their cannabis use. Seven percent of those who used cannabis occasionally had suicidal thoughts, a number that rose to 9% for people who use cannabis daily and to 14% for people with cannabis use disorder.

The NIH study supports prior findings. Stanford researchers recently reported that in states that legalized recreational marijuana there was a 46% increase in self-harm injuries among 21- to 39-year-old men.

A 2020 study in the Journal of Addiction Nursing and a 2019 study in JAMA Psychiatry also found a strong association between cannabis and suicidality.

But the relationship is complex. The 2020 study looked at recreational cannabis use, while the 2019 study examined adolescent use. The new NIH study looked at national survey data over a period that started well before adult-use legalization in Colorado and Washington. It makes no distinction between medical and recreational cannabis, a distinction that could be important.

Explanations for the suicide association also vary, such as the higher potency of cannabis and increased availability of cannabis products. But these trends vary by state and over time, so more granular analysis is needed in order to tease out relationships among these factors.

More important, it is not clear at this point if cannabis use is simply associated with an underlying trend, exacerbating a growing problem, or is itself an independent risk factor. Sorting this out will be extremely difficult, because cannabis use does not occur in a vacuum and cannabis itself is a delivery system for a slew of cannabinoids whose effects and interactions are not fully understood.

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. 

Prevalence of Chronic Pain Increasing

By Lynn Webster, MD, PNN Columnist

According to the Centers for Disease Control and Prevention, opioid prescribing quadrupled from 1999 to 2010. Some policymakers suggest that the amount prescribed in 1999 was appropriate and should remain static, and that any prescribing above the 1999 level exceeds the amount required to meet the needs of people in pain.

Perhaps, but it is important to understand that pain was vastly undertreated in the 1990s and there was a clear need to find effective treatment for pain patients. At least some of the increase in opioid prescribing would also seem logical, based on the greater number of people in pain.

According to the National Institutes of Health (NIH), the number of American adults suffering from at least one painful condition increased substantially from 120.2 million in 1997 to 178 million in 2014 – about 41 percent of the adult population. These numbers are from a comprehensive analysis of 18-year trends in the rates of noncancer pain, recently published in the Journal of Pain. 

 Aging Population

The NIH report may make you wonder why there are more people in pain now than there were in 1999. Here are some possible explanations.

Our aging population includes an ever-increasing number of elderly people. Baby boomers, who make up the largest demographic of society, recently began to enter their 70s. That is the decade during which we begin to experience a much greater prevalence of arthritis, spinal pain, obesity, surgical operations and cancer.

Mortality rates for cancer continue to decline, thanks to better treatments. More than 40% of cancer survivors now live longer than 10 years. That is good, of course, but many cancer survivors experience treatment-related chronic pain. 

Aging increases the likelihood that people will experience chronic pain. More than half of all adults older than 65 experience arthritic pain of the spine and other joints. For more age-related statistics regarding arthritis, click on this U.S. government PubMed abstract, the CDC's arthritis information page or the Arthritis Foundation’s website.  

In all age groups, the U.S. has an obesity epidemic (according to the CDC and the Journal of the American Medical Association) which can lead to diabetes. Obesity causes increased load on the back and joints, causing chronic pain. In addition, more people have peripheral neuropathy caused by diabetes. 

Finally, there is the problem of chronic post-surgical pain, which we began to recognize around the turn of the century. The incidence of chronic pain after major surgery is estimated to lie between 20% and 50%. Relatively minor operations, such as inguinal hernia repair or a C-section, seem to lead to this problem in approximately 10% of patients. This is an annuity that will keep growing as more operations occur every year.  

The increased prevalence of chronic pain has probably contributed to a greater number of opioid prescriptions. In addition, we have historically failed to recognize that pain deserves to be treated.

Alternative therapies like massage and acupuncture have not been widely available due to lack of insurance coverage. Thus, many people in chronic pain have not had access to any therapy except opioids. This can partially explain why there was an increase in the amount of opioids prescribed from 2001 to 2014.  

Undertreated Pain

Quadrupling the amount of opioids prescribed over several decades may sound excessive, unless we consider the growing number of people who were undertreated and in severe pain, year after year.  

Additionally, we must recognize opioids have not been distributed equally. It is possible that more opioids have been prescribed than appropriate for some patient populations, while other patients have been denied access to any pain treatment. 

A major shift in opioid prescribing began several years ago and by all accounts is accelerating. Between 2013 and 2017, the amount of opioids prescribed declined by 22%. The people most affected by the decrease appear to be those who reported benefit from opioid therapy.  

The amount of opioids that should be prescribed will remain open to debate. But millions of Americans have been -- and continue to be -- denied access to pain treatment, and there should be no debate about the fact that failure to treat severe pain is unacceptable.   

Everyone in the health care system and policymakers should be concerned about the NIH report on the prevalence of chronic pain. The dramatic increase in the number of people with chronic pain warrants our examination of all polices and resources to ensure that this population is receiving the care they need and deserve.  

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is a former president of the American Academy of Pain Medicine and the author of “The Painful Truth.”

You can find Lynn on Twitter: @LynnRWebsterMD. 

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.

CDC: 50 Million Americans Have Chronic Pain

By Pat Anson, PNN Editor

The Centers for Disease Control and Prevention and other federal agencies have faced a fair amount of criticism over the years for adopting insensitive policies and guidelines that are often harmful to the pain community. But there are growing signs the CDC and other agencies are starting to listen to or at least better understand pain patients.

Today the CDC released a new report estimating that 50 million Americans – just over 20 percent of the adult population – have chronic pain. About 20 million of them have “high-impact chronic pain” -- pain severe enough that it frequently limits life or work activities. The estimates are based on the 2016 National Health Interview Survey of over 33,000 adults.

“Pain is a component of many chronic conditions, and chronic pain is emerging as a health concern on its own, with negative consequences to individual persons, their families, and society as a whole,” reported James Dahlhamer, PhD, of the CDC's Division of Health Interview Statistics.

Dahlhamer and his colleagues found that women, unemployed older adults, adults living in poverty, rural residents and people without public health insurance are significantly more likely to have chronic pain, while the risk of pain is lower for people with a bachelor’s degree.

“Socioeconomic status appears to be a common factor in many of the subgroup differences in high-impact chronic pain prevalence,” they found. “Education, poverty, and health insurance coverage have been determined to be associated with both general health status and the presence of specific health conditions as well as with patients’ success in navigating the health care system. Identifying populations at risk is necessary to inform efforts for developing and targeting quality pain services.”

Different Estimates

Last week the National Institutes of Health (NIH) released its own research on high impact chronic pain (HICP), estimating that 11 million American adults have it -- about half the CDC’s estimate.

Both the NIH and CDC are part of the Department of Health and Human Services (HHS). It was not immediately clear why the two estimates are so far apart – or why two government agencies in the same department were studying the same thing at the same time.  

It’s certainly not the first time researchers have disagreed on the number of people in pain. In 2011, the Institute of Medicine released a landmark report claiming at least 100 million Americans have chronic pain, an estimate that one critic said was a “ridiculous number.” Other estimates range from 39 to 70 million.

“The multidimensional nature of chronic pain is not reflected in commonly used operational definitions… resulting in inordinately high prevalence estimates that limit our ability to effectively address chronic pain on a national level,” said Mark Pitcher, PhD, a visiting fellow at the National Center for Complementary and Integrative Health (NCCIH).

Like their counterparts at the CDC, NIH researchers found that socioeconomic factors play a significant role in high impact chronic pain. HICP sufferers not only have more severe pain, they are more likely to have mental and cognitive health issues, as well as substantially higher healthcare costs. About 83 percent of people with HICP are unable to work and one-third have difficulty with simple activities such as bathing and getting dressed.

“By differentiating those with HICP, a condition that is associated with higher levels of anxiety, depression, fatigue, and cognitive difficulty, we hope to improve clinical research and practice,” said co-author M. Catherine Bushnell, PhD, scientific director at NCCIH.

The concept of HICP was first proposed by the National Pain Strategy to better identify patients with pain severe enough to interfere with work and life activities. It also helps distinguish HICP from other types of chronic pain that are less impactful and more easily treated.

“It is crucial that we fully understand how people’s lives are affected by chronic pain. It will help improve care for individuals living with chronic pain and strategically guide our research programs that aim to reduce the burden of pain at the population level,” said Linda Porter, PhD, director of the Office of Pain Policy at the National Institute of Neurological Disorders and Stroke. 

The Food and Drug Administration has also recently taken steps to better understand the chronic pain population. In July, the FDA held a day-long public hearing and heard from dozens of pain patients and advocates. Some fought back tears as they testified about the lack of access to opioid medication and the deteriorating quality of pain care in the U.S.

Rats, Depression and Chronic Pain

By Pat Anson, Editor

An unusual study involving rats, depression and chronic pain is making headlines – the latest in a long line of flawed research studies being used to debunk the effectiveness of opioid pain medication.

“NIH study suggests opioid therapy not effective against chronic pain,” is the headline in UPI.

“Pain-induced changes in the brain explain the limited effectiveness of opioid therapy,” is how the Tech Explorist put it.

At issue is a small study by the National Institutes of Health (NIH) and McGill University in Montreal on pain-induced changes in 17 laboratory rats. That's right, 17 rats. The study findings, published in the journal Pain, concluded that chronic pain reduced the number of opioid receptors – the molecules that opioids bind to -- in the rats’ brains. In theory at least, that would make the rats less responsive to opioid pain medication.

Note that the research did not include any people, the rats were not given any opioids, and the effectiveness of opioids wasn't even measured in the rats. But that didn’t stop the NIH from drawing some sweeping conclusions.

“These results provide insights into why we see limited effectiveness of opioid therapy in chronic pain and the mechanism of the depression that may accompany it,” said David Shurtleff, PhD, acting director at the National Center for Complementary and Integrative Health (NCCIH).

“These basic research findings support NIH’s efforts to better understand chronic pain and comorbid symptoms and to develop better ways to help chronic pain patients effectively manage their pain.”

McGill University was more cautious, saying further studies were needed in humans to confirm the study findings.

“Although the study… was conducted in rats, and the results of animal studies may not be directly applicable to people, the findings provide new insights into how the brain may respond to pain and opioids,” a McGill press release states. “These findings, if confirmed in people, will enhance the understanding of the impact of chronic pain on the brain, its relation to depression, and the effects of opioids.”

Researchers have many theories about the origins and treatment of chronic pain, but conducting tests on humans to prove them is problematic. Laboratory animals are often used as an imperfect substitute.

In the NIH/McGill study, 17 rats had brain surgeries to produce a nerve injury that causes chronic pain, while another group of rats had sham surgeries (a similar procedure that did not cause chronic pain). Three months later, PET scan imaging showed opioid receptors had decreased in multiple regions of the brain in the nerve-injured rats, but no changes occurred in the sham-surgery rats.

These results suggest that pain itself, not treatment or pre-existing trauma, altered the brain’s opioid system. Other tests showed a weaker link between chronic pain and depression in the nerve-injured rats.

How did researchers determine the rats were depressed? 

When given a choice, healthy rats will normally drink water sweetened with sugar rather than plain water. But animals with a decreased ability to experience pleasure, a recognized symptom of depression, may not. The rats in the study with chronic pain showed a decreased preference for sugar water over plain water, while rats in the sham group still showed a preference for sweetened water. This, the researchers believe, was enough evidence to conclude the nerve-injured rates were depressed.

“It’s well known that there’s a link between chronic pain and depression,” explained co-author M. Catherine Bushnell, PhD, scientific director of NCCIH’s Division of Intramural Research.  “The results of this study indicate that pain-induced changes in the brain’s opioid system may play a role in this association. Animals with the greatest decrease in opioid receptor availability showed the greatest increase in depression-like symptoms after experiencing chronic pain.”

While intriguing, the results of this rat study are far from definitive and do not prove that opioids are an ineffective treatment for chronic pain in people. What they do show is that we need more and better research about opioids and chronic pain, not more misleading headlines and statements from the NIH.

Trump Budget Cuts Would Further Limit Pain Research

By Pat Anson, Editor

The Trump administration has proposed another $1.2 billion in budget cuts for the National Institutes of Health (NIH), which experts say could hamper already anemic efforts at developing new treatments for chronic pain.  Most of the reductions at NIH would come from research grant funding.

Only about 1 percent of the NIH budget is designated for pain research, even though more Americans suffer from pain than heart disease, diabetes and cancer combined.

The proposed $1.2 billion reduction in this year’s NIH budget is in addition to the $5.8 billion cut the Trump Administration has already proposed for the agency in 2018.

The $7 billion in savings will be used to help pay for an enhanced border wall with Mexico and increased military spending.

The White House Office of Management and Budget says the NIH budget for 2018 “eliminates programs that are duplicative or have limited impact on public health” and would “help focus resources on the highest priority research and training activities.”

"I will be the first one down lobbying against this," said Ann Romney, who suffers from multiple sclerosis and is the wife of former GOP presidential nominee Mitt Romney.

"Nothing comes from nothing. If you don't have that funding, there will be nothing," she told Yahoo News. "There will be no new treatments, there will be no new drug therapies. Progress in medicine will come to a halt."

Pain Research Already Limited

The lack of spending on pain research -- by both the government and the healthcare industry – was a problem long before the Trump administration came out with its budget plans.

In 2012, researchers at Johns Hopkins University estimated that chronic pain costs the U.S. economy up to $635 billion a year in healthcare costs and lost productivity. Yet the NIH spent only $358 million on pain research that year, according to journalist Judy Foreman in her book, “A Nation in Pain.”

“It is a huge burden with very little actual research going into it. And still a lot of unmet medical need,” said Gabriel Baertschi, CEO of Grünenthal, a German pharmaceutical company. “The odds of succeeding in pain research are lower than in other areas. It’s much more complex than other diseases in a sense that if you hit one target you are not necessarily resolving pain. Pain is multi-dimensional. That explains why from a research point of view you don’t always succeed.”

Grünenthal is a research-oriented company that focuses on finding new treatments for conditions such as bladder pain and Complex Regional Pain Syndrome (CRPS). Recently the FDA designated an experimental drug being developed by Grünenthal as a potential breakthrough therapy for CRPS. The company is now in advanced stages of clinical trials.

Because it’s smaller and privately owned, Baertschi says Grünenthal can afford to explore new treatments for rare diseases that “Big Pharma” companies are not interested in developing.

“Most of the companies that were active in pain have closed their pain research centers,” he told PNN in an interview last month. “I think a lot of companies are pulling out because the cost of developing pain drugs has been immense. If you look at the latest generation of pain drugs, it has cost billions of dollars.

“That has scared off companies and I think companies are more focused on areas where the returns are better from a pricing point of view. Because quite frankly, if you look at oncology you can get (drug) prices that are far better than for pain.”

Insurers Refuse to Pay for New Treatments

Another problem is insurance coverage. A few years ago the U.S. Food and Drug Administration pressured drug makers to develop abuse deterrent technology for opioids to reduce the risk of abuse and addiction. Some companies spent hundreds of millions of dollars developing abuse deterrent opioids that insurers now refuse to pay for because they are more expensive.

“Payers are a huge barrier to innovative therapies because they block coverage. Without insurance coverage there is little incentive to invest,” said Lynn Webster, MD, a leading expert and researcher in pain management, who is vice president of Scientific Affairs at PRA Health Sciences. 

“In the past 30 years there haven't been more than 3 new chemical entities approved by the FDA. One reason is that we don't understand enough about the different mechanisms generating pain,” Webster explained. “I see our current approach is similar to how cancer research was conducted 60 years ago.  Back then most cancers were treated with the same monotherapies.  Once research delved into the multi-mechanistic contributions to cancer, therapeutic advances were possible. We need to do the same for pain. And insurance has to pay for the innovations.”

“Pain is unfortunately penalized by society. People feel there is enough treatment available,” said Grünenthal’s Baertschi. “There are a lot of very good pain therapies out there. But there are quite a few areas, especially niche areas and specific pain types, that are not being treated adequately and that’s where we focus our research.”

One analyst said it is unlikely Congress will go along with the proposed cuts in the NIH budget because it funds politically popular programs.

"At worst, we believe NIH (funding) will remain flat in a continuing resolution if there is a government spending standoff," wrote Cowen analyst Doug Schenkel in a note to investors. "Although NIH funding hasn't kept up with inflation, the only time there were cuts to the agency in the past decade was when Congress' hand was forced by sequestration."

A Coalition to Save NIH Funding has also been formed to lobby against the budget cuts.

"We were dismayed to learn that the NIH is vulnerable to deep funding cuts," said Carrie Jones of JPA Health Communications, which is managing the coalition. "Each day America benefits from the innovation and scientific discoveries made at the NIH. We won't sit idly by and watch critical research be stifled."