FDA Approves First Biosimilar for Multiple Sclerosis

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved Tyruko (natalizumab-sztn) as the first biosimilar for adults with relapsing forms of multiple sclerosis (MS), a move that could substantially reduce treatment costs for MS patients. Biosimilars are “highly similar” to brand-name biologic medicines, but about 30% cheaper.

"Approval of the first biosimilar product indicated to treat relapsing forms of multiple sclerosis furthers the FDA's longstanding commitment to support a competitive marketplace for biological products and ultimately empowers patients by helping to increase access to safe, effective and high-quality medications at potentially lower cost," said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars.

Like Tysabri (natalizumab), the biologic it is modeled after, Tyruko is administered by infusion every four weeks to patients with MS, a chronic disease that attacks the body’s central nervous system, causing numbness, paralysis, loss of vision, fatigue and pain. Many MS patients experience periods of remission, followed by relapses.  

The listed cash price for a single vial of Tysabri is over $17,000, although the discounted price for insured patients is about $8,500 or $102,000 a year. Sandoz, a pharmaceutical company that specializes in biosimilars and generics, has not revealed its pricing plans for Tyruko or said when it will become available. Sandoz is a division of Novartis.

“Of the nearly one million people in the US living with multiple sclerosis, hundreds of thousands experience disease relapse. Tyruko has the potential to extend the reach of natalizumab treatment for these patients, increase healthcare savings and fuel innovation through competition in the market,” Keren Haruvi, President North America, Sandoz Inc., said in a news release.

Like Tysabri, Tyruko may also be used to treat adults with moderate to severe symptoms from Crohn's disease who have not responded well to other treatments. Crohn’s causes chronic inflammation in the digestive tract.

The FDA says patients using natalizumab products (including Tyruko and Tysabri) are at higher risk of developing progressive multifocal leukoencephalopathy (PML), a viral infection of the brain that can lead to death or severe disability. Because of that risk, prescribers must evaluate patients three and six months after their first infusion, every six months thereafter, and even after they discontinue treatment.

Growing Market for Biosimilars

Patients have long complained about the high price of MS drugs in the US, which cost two to three times more than the same drugs in Canada, Australia or the UK. One reason biologics are so expensive is that they derived from living organisms such as animal cells or bacteria, making them costly to develop.

Drug patents also last a long time – usually five years – before a “copycat” version can be introduced. Patent holders often take their competitors to court to further delay the introduction of generics or biosimilars, as was the case with AbbVie’s Humira, a biologic widely used to treat rheumatoid arthritis and other chronic inflammatory diseases. At least 9 new Humira biosimilars are finally entering the U.S. market this year.

Last week, CVS Health announced that it was launching a wholly owned subsidiary called Cordavis, which will work with drug manufacturers to commercialize biosimilars. The first biosimilar CVS plans to market in early 2024 is Hyrimoz (adalimumab-adaz), a biosimilar for Humira produced by Sandoz. CVS says the list price of the Hyrimoz will be over 80% lower than the current list price of Humira.

"Biosimilars are crucial to creating competition and reducing costs for specialty pharmaceuticals where drug prices are rising the fastest," said Prem Shah, PharmD, Executive Vice President and Chief Pharmacy Officer for CVS. "Through our direct involvement, we will expand the supply chain and ensure biosimilar availability in the market.”

As more patents expire, the biosimilars market in the U.S. is projected to grow from $6.7 billion in 2021 to more than $100 billion in 2029, according to one market forecast..

Tramadol Banned by Anti-Doping Agency

By Pat Anson, PNN Editor

When it comes to treating pain, tramadol (Ultram) is widely seen as a weak synthetic opioid that provides little relief to patients with severe or chronic pain.

“I get a lot more relief from aspirin” and “this stuff does nothing but make you dizzy and sleep,” are some of the comments PNN readers have made about tramadol.  

But some professional athletes, particularly those in cycling, have a completely different take on tramadol. They use it as a performance enhancing drug that can help them run, skate or peddle faster, and for longer periods of time. That’s why the World Anti-Doping Agency (WADA) is adding tramadol to its list of prohibited drugs, starting in 2024.

“Tramadol has been on the WADA Monitoring Program for some years. Monitoring data has indicated significant use in sports including cycling, rugby and football,” WADA said in a statement. “Research studies funded by WADA have confirmed the potential for tramadol to enhance physical performance in sports.”

Results from one of those studies, recently published in the Journal of Applied Physiology, confirm many of WADA’s concerns. UK researchers enrolled 27 cyclists in a double-blind randomized study, in which they were given either 100mg tramadol or a placebo before engaging in 30 minutes of high intensity cycling, followed by a 25-mile time trial.

On average, the cyclists who took tramadol were 1.3% faster in the time trial (TT) than those given a placebo. That doesn’t sound like much, but in the highly competitive world of professional cycling, even a few seconds can be the difference between finishing first or second.

Interestingly, the researchers found there were “no differences in pain intensity” between the cyclists on tramadol and those who took the placebo.

“This study demonstrates that highly trained cyclists can maintain a significantly higher power output and complete a competitive TT in a significantly faster time following acute ingestion of 100 mg of fast-acting soluble tramadol. Tramadol reduced the perception of effort for a given power output but had no discernible impact on pain intensity whilst cycling,” wrote lead author Alexis Mauger, PhD, a professor in the School of Sport and Exercise Sciences at the University of Kent.

“The findings from this study suggest that tramadol elicits a significant performance-enhancing effect in highly trained cyclists, such that it can change the outcomes of a race. Given the evidence of the historical prevalence of use of tramadol in sport with the intention of improving performance, and the risks pertaining its use, this study provides strong evidence to justify its inclusion on the 2024 Prohibited Substance List.”

To be clear, no one is taking tramadol away from pain patients. But professional athletes who test positive for tramadol — without a medical reason for taking it — run the risk of suspension or disqualification if their sport follows the WADA guidelines..

Previous studies by Mauger found that acetaminophen (Tylenol) gave a 2% boost in performance for cyclists, suggesting that even a mild analgesic can be helpful in making endurance exercise seem easier. Conversely, it also lends weight to pain sufferers who say tramadol works no better than Tylenol or aspirin.      

“Now we have a conundrum. Tramadol, an opioid painkiller, appears to have had no effect whatsoever on the pain experienced during cycling. On the other hand, it significantly lowered the perception of effort, which in turn…  improved performance,” journalist Alex Hutchinson wrote in Outside. “I’m not sure what to make of this finding, but it reaffirms my sense that we still have a lot to learn about how pain and effort and other related constructs like mental fatigue influence our performance.”

The U.S. Food and Drug Administration classifies tramadol as a Schedule IV controlled substance, meaning it has less potential for abuse and addiction compared to opioids like oxycodone or hydrocodone, which are Schedule II drugs.

In recent years, prescriptions for tramadol have soared in the U.S. because it is considered “safer” than other opioids. In many third world countries, however, tramadol is widely misused. In 2019, Public Citizen filed an unsuccessful petition with the FDA to have tramadol reclassified as a Schedule II drug, saying there was “overwhelming evidence” that tramadol was a public health risk.

The Way Forward: California’s New Opioid Guidelines

By Dr. Forest Tennant and Kristen Ogden

The Medical Board of California recently published new guidelines for prescribing opioids and other controlled substances for pain, which emphasize “individualized care” that is customized for each patient. 

The guidelines are a remarkable, positive and practical way forward in pain care. All persons concerned about chronic pain treatment with opioids, benzodiazepines and other controlled drugs need to know the basic concepts embedded in them.    

As the medical board was updating its guidelines, we had great concern that they would bury California’s Pain Patient's Bill of Rights and Intractable Pain Treatment Act. When these laws were passed in the 1990’s, they were a godsend to patients with chronic intractable pain, who were given the right to “request or reject the use of any or all modalities in order to relieve his or her pain.”

That means patients, with the support of their doctors, could get opiate medication without first having to submit to surgery, medical devices and other forms of pain treatment.  

To our great pleasure, the medical board’s new guidelines recognize, define and support these worthy laws.  Importantly, the guidelines also state that they are “not in any way intended to limit treatment” of patients in hospice or palliative care. And they allow for doctors to prescribe high dose opioids, provided they keep good medical records that document a need for them.

Defining Intractable Pain

The California guidelines provide a classic definition of intractable pain as “a state in which the cause cannot be removed or otherwise treated and no relief or cure has been found after reasonable efforts.” 

The problem with this definition is that intractable pain may be mild or intermittent and not curable, but may still be treated with non-opioid modalities. To require and receive treatment with opioids and other controlled drugs, one really needs a specific causative diagnosis of the unremitting “high impact” pain that produces physiologic complications such as hypertension, tachycardia, and endocrine deficiencies. 

Put another way, is intractable pain an incurable but treatable problem? Or is it constant and incurable with potentially life-threatening complications? 

Physicians, as a group, are often mystified, confused and unaware of how to determine which patients have an incurable, but readily treatable problem, and which patients have the constant and incurable pain that causes complications and require opioid therapy.

Physicians need help to make sound, defensible treatment decisions in the face of this quandary.  Some patients with complex intractable pain are greatly impacted and require non-standard treatment, which may include high-dose opioids, benzodiazepines and stimulant drugs. 

Here are the recommended criteria to identify such patients and support non-standard treatment plans.

  1. A specific medical cause of intractable pain has been identified.

  2. Constant pain has impacted some physiological and/or mental functions such as sleep, eating, hygiene, reading, concentration, and mobility.

  3. Trials of standard medications and dosages with such agents as anti-depressants, muscle relaxants, anti-inflammatories, stimulants, anti-seizure medications, and low-dose opioids have not controlled pain or normalized functions.

  4. There is objective physical evidence of the causative disease or complications of the pain, such as hypertension, tachycardia, neurologic deficits, or anatomic structural abnormalities.

  5. There is an objective, diagnostic test result that documents an abnormality of the cause of pain or its complications, such as a magnetic resonance imaging (MRI), hormone deficiency, elevated autoimmune or inflammatory marker, or an abnormal electrodiagnostic test.

It is the lack of adequate treatment of complex intractable pain that is really the crux of the suffering and deaths that have emerged due to overzealous and misinformed opioid regulations and guidelines.  These legitimate, complex patients comprise about 3 to 5% of chronic pain patients.

The California medical board’s new guidelines provide clinicians the opportunity to implement individualized and effective treatments for these unfortunate and deserving intractable pain patients. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain. Dr. Tennant was the lead physician in crafting California’s Intractable Pain Law and Pain Patient Bill of Rights, and worked with the legislature to get them passed. 

Kristen Ogden is a patient advocate from Virginia. Kristen and her husband Louis travel regularly to California for his intractable pain treatment and prescriptions, which are not available in their home state. Kristen testified during public hearings on the California guidelines and closely followed their development. 

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

America’s Biggest Fear: Fentanyl and Opioid Addiction

By Pat Anson, PNN Editor

The fentanyl crisis is the biggest public health problem in the US, according to two new surveys that highlight Americans’ growing fears about opioid addiction and the toxicity of street drugs.

The first survey, conducted by Axios-Ipsos, found that opioids and fentanyl have surpassed Covid-19, firearms, obesity and cancer as the nation’s #1 public health threat. Over one in four Americans (26%) ranked opioids and fentanyl first, replacing gun violence as the top threat to public health.  

Top U.S. Public Health Threats

Fentanyl is a synthetic opioid that is 100 times more potent than morphine. It has been used safely for decades as an analgesic during surgery and to treat severe pain, but in recent years illicit versions of fentanyl have come to dominate the black market, where they are used in counterfeit medication or mixed with substances like heroin. Most fatal overdoses in the U.S. involve illicit fentanyl, not prescription opioids.

The Axios-Ipsos survey found that about four in ten adults (44%) are aware that U.S. overdose deaths reached a record high last year. Americans who live in rural areas, which have some of the highest overdose rates, are even more familiar (51%) with the rising number of drug deaths. 

Over half the respondents (51%) said they cared a lot about overdoses and think the government should be doing more to reduce drug deaths (79%). Most also believe that government does not make the health and well-being of citizens a priority (62%).  

While most Americans trust the health information they get from federal agencies like the CDC (64%) and FDA (62%), there is more trust placed in health information from personal doctors (89%) and family members/close friends (75%). 

Other key findings about respondents’ drug use in the last three months:

  • 26% used a pain medication for which they had a prescription or knew someone who did

  • 3% used a pain medication for which they did not have a prescription or knew someone who did

  • 20% used cannabis or knew someone who did

  • 2% used hallucinogenic drugs or new someone who did

  • 2% used “other illegal drugs” or knew someone who did

“Pain medication” was not defined in the survey questions, so the responses may include some non-opioid analgesics.

The recently updated Axios-Ipsos American Health Index is based on a nationally representative sample of 1,162 adults, who were surveyed on a wide array of health topics from August 11-14.

Most Families Impacted by Addiction

The second survey, conducted by the non-profit KFF, asked a representative sample of 1,327 adults online and over the phone in July about a variety of drug and substance use issues.

Two-thirds of respondents said either they or a family member were addicted to alcohol or drugs, experienced homelessness due to addiction, or had a drug overdose resulting in hospitalization or death.  

Nearly three in ten (29%) said they or someone in their family were addicted to opioids, either prescription opioids or illicit ones like fentanyl and heroin. Opioid addiction was most common among rural residents (42%) and White adults (33%). Among those who experienced addiction firsthand, most said it had a negative impact on their family’s relationships and finances. 

Only 5% felt they themselves might be addicted to opioid painkillers, far less than those who believe they might be addicted to alcohol (13%). 

Fear about addiction is common. Over half (51%) of adults are worried that someone in their family will experience a substance use disorder and one-third (32%) are worried that someone in their family will overdose on opioids.  

About four in ten adults (39%) are worried that someone in their family will unintentionally consume illicit fentanyl, a fear that looms largest in rural areas (48%). 

SOURCE: KFF

Nearly three in ten respondents (29%) said they had been prescribed opioid pain medication in the past five years. Of those, most said their doctors had warned them about the risks of opioid addiction and dependence (57%), side effects from opioids (69%), other ways to manage pain (60%), and about keeping their medications in a safe place (58%).  

While fears about addiction to opioid pain medication are common, it doesn’t happen nearly as often as many people believe. A recent study in Australia found that 92% of patients prescribed opioids for the first time never progressed to long-term use. Less than 3% became persistent users or needed higher doses — and they were mostly seniors with chronic health problems.

Neither the KFF or Axios-Ipsos polls asked respondents about growing shortages of opioid pain medication or how the reduced supply was impacting legitimate pain patients.   

‘Unintended Victims’

The patient side of the story was shared this week in an opinion video by The New York Times. Video producers Vishakha Darbha, Lucy King and Adam Westbrook spoke with chronic pain patients who are the “unintended victims” of the national crackdown on opioid prescribing.

“America’s doctors have been put in a difficult position. But it doesn’t need to be this way. It is possible to stop overprescribing yet ensure that pain sufferers get the relief they deserve. The patients in our video have one message: Listen to us,” the producers said.

Kaiser Permanente’s Expansion Faces Skepticism

By Harris Meyer, KFF Health News

As regulators review Kaiser Permanente’s proposed acquisition of a respected health system based in Pennsylvania, health care experts are still puzzling over how the surprise deal, announced in April, could fulfill the managed care giant’s promise of improving care and reducing costs for patients, including in its home state of California.

KP said it would acquire Danville, Pennsylvania-based Geisinger — which has 10 hospitals, 1,700 employed physicians, and a 600,000-member health plan in three states — as the first step in the creation of a new national health care organization called Risant Health. Oakland-based Kaiser Permanente said it expects to invest $5 billion in Risant over the next five years, and to add as many as six more nonprofit health systems during that period.

Industry experts believe KP’s aim is to build a big enough presence across the country to effectively compete with players like Amazon, Aetna CVS Health, Walmart Health, and UnitedHealth Group in providing health care for large corporate customers. Kaiser Permanente executives touted the potential for spreading the group’s vaunted brand of quality, lower-cost care around the country.

But it’s not clear how KP will be able to bring its model, in which facilities and doctors receive a monthly per-member fee for all care, to markets where it doesn’t own an integrated system of physicians, hospitals, and health plans, as it does in California. Critics note that KP’s efforts to expand failed in a number of states in the 1980s and 1990s.

In addition, the physician-led Permanente Medical Groups, which lead KP’s patient care, were not involved in the Risant deal, raising questions about how their expertise would be shared.

“I don’t know how Kaiser will bring its knowledge and best practices to improve health care delivery without the involvement of the medical group, which does all the care delivery,” said Robert Pearl, a former CEO of the Permanente Medical Group who’s now a lecturer at the Stanford Graduate School of Business.

Is Bigger Better?

There are also questions about how the expansion will benefit current KP customers. The tax-exempt, nonprofit organization has 39 hospitals, 24,000 physicians, and 12.7 million health plan members in eight states and Washington, D.C., though about three-quarters of its members are in California, where it controls nearly half of the private insurance market. KP reported $95 billion in revenue last year.

“We’ve asked Kaiser Permanente management questions about the deal’s advantages to employees and customers, but we haven’t heard back,” said Caroline Lucas, the executive director of the Coalition of Kaiser Permanente Unions, several of which are in contentious contract talks with the company. “Where is the money coming from? Are the citizens of California and other states subsidizing this expansion? How are they benefiting?”

Kaiser Permanente CEO Greg Adams declined to comment. A KP spokesperson, Steve Shivinsky, said the group’s physicians would be involved in developing a “platform” to offer other health systems its value-based care expertise, including in design of care models, pharmacy practices, consumer digital engagement, development of health insurance products, and best practices for supply chains. Shivinsky said work on the platform was just beginning.

“Risant Health’s success will firmly establish value-based care as a better model for health care in this country,” said Shivinsky, KP’s director of national media relations.

“If there is a commitment to truly delivering higher-quality and lower-cost care, it will take time and hard work,” said John Toussaint, chair of Catalysis, a nonprofit that trains executives in health care and other industries in quality improvement. “But frankly I’m skeptical that’s the reason for these types of mergers. Bigger may be better for increasing prices, but not necessarily for improving care.”

The deal may be a sign that KP, founded in 1945, is hearing the alluring call of lucrative fee-for-service medicine. “This gets Kaiser into the much bigger part of the market — commercial insurance — and expands beyond their traditional model of owning all the pieces and selling their own insurance,” said Glenn Melnick, a health economics professor at the University of Southern California.

The Geisinger acquisition is being reviewed by the Pennsylvania Insurance Department, with a 30-day public comment period ending Aug. 7, 2023. The Federal Trade Commission and the California attorney general’s office declined to say whether they were reviewing the deal. KP expects the deal to close sometime in 2024. There was no purchase price, but KP said Risant would make a minimum of $2 billion available to Geisinger through 2028, including income that Geisinger generates itself.

Federal and state antitrust regulators have expressed growing concern about consolidation of hospitals and physician groups into ever-larger organizations with the power to drive up prices. But antitrust experts say it’s unlikely regulators will challenge the deal since KP does not currently have a presence in Pennsylvania, Delaware, or Maine, where Geisinger operates.

Indeed, the deal could boost competition if KP’s investment enables Geisinger to expand beyond central and eastern Pennsylvania and take on the University of Pittsburgh Medical Center and Highmark, the state’s two dominant integrated health systems.

Around the country, Risant could be appealing to businesses that offer health plans to their employees.

“If Kaiser can become an effective player in more markets through Risant and that leads to greater price competition, that will be very attractive to large employers,” said Bill Kramer, senior adviser for health policy at the Purchaser Business Group on Health, which represents large employer health plans.

Smaller health systems and physician groups that are struggling financially may also see joining Risant as a more palatable option than being acquired by more profit-hungry entities, such as private equity firms, Melnick noted.

Through tight coordination between its physicians, hospitals, and health plans, KP has a strong track record of producing good health outcomes, particularly for plan members with chronic conditions such as high blood pressure and diabetes. In recent years, Kaiser doctors have also significantly reduced opioid prescribing.

KP hospitals and doctors are paid a monthly per-member fee for all care — called capitated payment. That gives KP a powerful financial incentive to keep members healthy and prevent costly hospital admissions and emergency room visits.

In contrast, Geisinger and most other health systems across the country generally are paid for each separate procedure — known as fee-for-service payment — giving them less incentive to keep patients healthy and reduce overall costs. Because of that, it’s not clear how KP’s value-based care model will work at Geisinger and other health systems acquired through Risant.

Adams has said Risant won’t try to fully replicate Kaiser Permanente’s model. Instead, Risant will help other health systems achieve the same kind of outcomes and cost savings while working with multiple insurers and providers.

KP also could potentially learn lessons from Geisinger and other health systems about producing better health outcomes at lower cost for members. Geisinger has won acclaim for its ProvenCare model, in which it accepts a fixed fee for providing an entire episode of care, such as heart bypass surgery, with no extra charge if the outcome isn’t satisfactory and the patient needs additional care.

But Kramer, a former KP executive, is skeptical. “It’s hard if not impossible to transform a medical group that’s reliant on fee-for-service payment into something like the Kaiser Permanente Medical Group,” he said.

Critics of the deal, citing KP’s failed expansion moves in the 1980s and 1990s, also worry that building Risant Health could distract KP executives from cost-control and quality improvement efforts in their home state and draw down the organization’s financial reserves, potentially leading to premium hikes.

In 1999, for example, KP sold a money-losing medical group it had established in North Carolina in the mid-’80s. It faced opposition from the local medical community and challenges with employer health plans, among other factors. Kramer also pointed to its withdrawal from other markets including Connecticut, Missouri, Ohio, and Texas.

Still, KP did succeed in establishing a significant presence in the mid-Atlantic states, Washington, D.C., and Georgia, though it doesn’t own hospitals in those markets. It also has long-standing operations in Hawaii, Colorado, and Oregon.

With Risant, KP will be up against very large, sophisticated managed care competitors including UnitedHealth’s Optum, which employs about 70,000 physicians across the country.

“Hopefully Kaiser’s senior leadership will be smarter this time around and avoid the kinds of problems they had when they expanded in the past,” Kramer said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues. It is not affiliated with Kaiser Permanente.

Expanded Insurance Coverage ‘Urgent Priority’ for Chronic Pain Patients

By Pat Anson, PNN Editor

A panel of experts convened by the University of Michigan is recommending expanded insurance coverage and better training of providers to address problems faced by millions of chronic pain patients on long-term opioid therapy. Although improving access to pain care is an “urgent priority,” it took nearly three years for the panel’s recommendations to be developed and released.

“Patients who take opioids for chronic pain face unique challenges in the present opioid policy landscape, including reduced access to care,” wrote lead author Adrianne Kehne, a former researcher at Michigan Medicine who is now a Research Project Manager at U.S. Department of Veterans Affairs.

“While there have been substantial efforts to improve access to care for OUD (opioid use disorder), the needs of this patient population have gone largely unrecognized and unaddressed.  Limited access to high-quality care has caused significant distress among both patients and providers, and increasing access is an urgent priority.”

In a paper recently published in the Journal of Pain Research, Kehne and her colleagues said recent efforts to improve access, such as a revised CDC guideline that takes a more flexible approach to opioid prescribing, may not be adequate.

“It remains to be seen how providers and policymakers respond to these new recommendations. The non-binding guideline may not be sufficient to reverse prescribing rules at the state and health system level or significantly change provider behaviors,” they wrote.

A Michigan-based panel of 24 experts, including providers, researchers, regulators, insurers and patients, first met online in September, 2020 to discuss ways to improve access to pain care. Their long-delayed recommendations -- which are only being made public now -- stop well short of reversing policies that discourage opioid prescribing.

Instead, they focus on changing insurance reimbursement policies, to allow providers to spend more time with patients and to offer multimodal, non-pharmacological treatments. Multimodal therapy includes acupuncture, chiropractic care, cognitive behavioral therapy, injected pain therapies and “collaborative care” techniques that are often not covered by insurance.

“In order to encourage more clinics to offer multimodal pain care and increase access for patients who currently don’t receive it, insurance companies and government health coverage programs such as Medicaid need to change how they pay for it,” said senior author Pooja Lagisetty, MD, an assistant professor of internal medicine at Michigan Medicine and the VA Ann Arbor Healthcare System.

“We are starting to see some change, most notably at the VA and in insurance coverage of physical therapy, but more is needed in order for patients and providers to have time to develop individualized approaches, overcome stigma around providing opioid-related care, and for clinics to begin offering non-medication services.”

Other key recommendations of the panel:

  • Make providers aware of how Michigan’s Prescription Drug Monitoring Program (PDMP) is “used in investigating and disciplining providers”

  • To reduce stigma, educate providers on the differences between addiction and dependency in patients on long-term opioid therapy

  • Improve provider education about chronic pain, as well as multimodal and non-pharmacological therapies

  • Train social workers in biopsychosocial factors involved in chronic pain treatment

  • Improve provider education and practices to address racial barriers and biases in pain care

  • Increase recruitment of providers from racial and ethnic minorities

The expert panel study was funded by the Michigan Health Endowment Fund, the National Institute on Drug Abuse and the National Institute on Aging.

Researchers say between 5 and 8 million U.S. patients currently take opioids long-term. That’s down from about 11 million a few years ago. Opioid prescribing in the U.S. has decline by 64% since its peak, and now stands at levels last seen in the year 2000. Despite that historic decline, fatal overdoses have climbed to record levels, fueled primarily by illicit fentanyl and other street drugs.

Large Study Debunks Myths About Rx Opioid Addiction

By Pat Anson, PNN Editor

A large new study in Australia is debunking myths about the addictive nature of opioid pain medication and how a single prescription can lead to long term use.

In an analysis of nearly 3.5 million Australians who were prescribed opioids for the first time, researchers found that 92% never progressed beyond low opioid use and only 3% became persistent users or needed higher doses. The “sustained use” of opioids occurred mostly in seniors (65 and older) suffering from cancer, depression, anxiety and other chronic health problems.

“Results of this cohort study suggest that most individuals commencing treatment with prescription opioids had relatively low and time-limited exposure to opioids over a 5-year period,” wrote lead author Natasa Gisev, PhD, a clinical pharmacist at National Drug and Alcohol Research Centre, UNSW Sydney.

“The small proportion of individuals with sustained or increasing use was older with more comorbidities and use of psychotropic and other analgesic drugs, likely reflecting a higher prevalence of pain and treatment needs in these individuals.”

Previous research estimated the risk of long-term opioid use as high as 57 percent, but Gisev and her colleagues say those studies are flawed because they excluded people with cancer and opioid use disorder, or used various definitions of long-term use. The Australian researchers took a different approach in tracking opioid prescriptions, developing five “trajectories of opioid use.”

The vast majority of patients had very low (75%) or low use (17%) of opioids. Others started with moderate opioid use and decreased to low use (3%), or began with low use and increased to moderate use (3%). Only 3% became sustained users or took higher doses.

Five-Year Trajectories of Opioid Use

JAMA NETWORK OPEN

“Overall, these findings suggest that most people who initiate an opioid prescription are likely to have low, time-limited exposure to opioids with little indication of ongoing use. This possibility is an important consideration for policymakers and stakeholders considering population-level prescribing of high-risk drugs,” researchers reported in JAMA Network Open.

“Opioids are essential drugs for acute and cancer pain, and many people with CNCP (chronic non-cancer pain) benefit from opioids. Continued focus and policy responses based on findings from a small group of people with increased risk of harms run the risk of limiting access to people who safely derive objective benefits from opioids.”  

That’s exactly what happened to millions of pain patients in the US, who lost access to opioids due to steep cuts in prescribing, chronic shortages of opioid medication, and a relentless drumbeat in the media about people becoming addicted or overdosing after one pill.  

“One prescription can be all it takes to lose everything,” the CDC said in a 2017 advertising campaign that emphasized the risks of prescription opioids, while ignoring the far more serious problem of illicit fentanyl and other street drugs.

Just how common is opioid addiction? Estimates are all over the map, ranging as low as 1% to as high as 40% for long-term opioid users.

“The problem with all of these studies is that they are retrospective in nature, limited to a particular patient population, and constrained by the diagnostic criteria in use at the time,” my late colleague Roger Chriss pointed out in a 2019 column on opioid addiction.  

Roger was prescient about the imprecision of diagnostic criteria. A little known 2021 study of U.S. veterans who were diagnosed with opioid use disorder (OUD) challenged how many actually had it. Researchers found that nearly 20% of veterans with OUD used prescription opioids without any signs of abuse and evidence was lacking in another 7% of cases. Less than 60% of the veterans had a “high likelihood” of being correctly diagnosed with OUD.

DEA Considering More Changes to Telehealth Prescribing Rules

By Pat Anson, PNN Editor

The U.S. Drug Enforcement Administration will hold two public hearings next month – what it calls “listening sessions” – to consider if providers should continue prescribing controlled substances through telehealth without first requiring patients to have an in-person medical evaluation.

Patients are currently allowed to get a controlled medications without visiting their doctor under emergency telehealth rules adopted three years ago at the start of the Covid-19 pandemic. Controlled substances include many opioids, stimulants, sedatives, steroids, and addiction treatment medications such as methadone and buprenorphine (Suboxone).

“DEA recognizes the importance of telemedicine in providing Americans with access to needed medications, and DEA has been, and remains, committed to expanding access to telemedicine in a way that puts patients — and their safety — first, is simple to understand and apply, reflects technological advancements, and is consistent with lessons learned during the COVID–19 PHE and the ongoing opioid epidemic,” the agency said in a statement.

Rules that are “simple to understand and apply” may be the key issue. In March, the DEA proposed changing the telehealth rules to reimpose “guardrails” on Schedule II opioids such as oxycodone and hydrocodone. For those medications, a patient would first be required to have an in-person meeting with a doctor, with refills then allowed via telehealth. Other drugs that are classified as Schedule III, IV or V substances could initially be prescribed for 30 days via telehealth, but any refills would require an in-person meeting.

The proposed rule changes are so confusing and drew so much opposition that the DEA delayed implementing them until this November. Next month’s public hearings are another sign the agency is still uncertain what to do.

In a notice published in the Federal Register, the DEA said it was open to creating a special registration process that would allow providers to continue prescribing “some controlled substances” without seeing patients in-person. The agency didn’t specific which controlled substances it is referring to.

“DEA is open to considering — for some controlled substances — implementation of a separate Special Registration for telemedicine prescribing for patients without requiring the patient to ever have had an in-person medical evaluation at all,” the DEA notice said.

“DEA also observes that making permanent some telemedicine flexibilities on a routine and large-scale basis would potentially create a new framework for medicine that fundamentally expands access to controlled substances in a way that warrants a new framework for accountability based, in part, on increased data collection and visibility into prescription practices in order to ensure patient safety and prevent diversion in near-real-time.”

Opioid Diversion Rare

Contrary to popular belief, opioid diversion is rare. Using data gathered from prescription drug monitoring programs (PDMPs), pharmacies, hospitals and others in the drug supply chain, the DEA’s most recent estimate is that less than one percent of oxycodone (0.3%) and hydrocodone (0.42%) is lost, stolen or diverted to someone they were not prescribed to.

Opioid prescriptions are also harder to obtain and there are chronic opioid shortages around the country, so few pain patients are willing to part with their legally prescribed medications. Counterfeit medications and other street drugs made with illicit fentanyl are the real problem, which the DEA “listening sessions” won’t address.

The public hearings will be held on September 12 and 13 at DEA headquarters in Arlington, Virginia. Medical practitioners, patients, pharmacists, drug makers, distributors, law enforcement, and other interested parties can express their views either in-person or by video teleconference. The public hearings will also be streamed live online.

The DEA is seeking input on these key questions:

  • Should telemedicine prescribing of Schedule II medications be permitted without an in-person medical evaluation?  If it is permitted, what safeguards would you recommend to ensure patient safety and prevent diversion?

  • If telemedicine prescribing of Schedule III–V medications is permitted without an in-person medical evaluation, what safeguards and data should be collected for those substances? 

To register as a speaker, click here. The deadline for registering is August 21.

My Story: A Bone Cancer Survivor’s Search for Pain Relief  

By Kristen Hernandez

The past three weeks have been the most challenging since my cancer diagnosis 20 years ago. Shortages of opioid pain medication have taken their toll, costing me weeks of productivity, mental and physical anguish, and a negative bank account.

When I was 25, I had a different life -- a career as a corporate travel consultant for RCA Records in New York City. I clawed my way out the ghettos of the Bronx and into corporate America, and purchased my first home in the suburbs of Long Island.

But everything changed when I was diagnosed with an insidious and rare form of bone cancer called Chordoma. It’s a literal one-in-a-million disease, with just one in every million individuals diagnosed with it each year.

The type of Chordoma that chose me is extremely rare, due to the tumor’s location: it was housed inside the L3 vertebra of my lumbar spine. And it was extraordinarily painful.

KRISTEN HERNANDEZ

Because Chordoma doesn't respond to chemotherapy or radiation, surgery is the only treatment. To save my life, surgeons reconstructed my spine, replacing a vertebra with a titanium cage and filling it with bone graft from my hip.

They also replaced a spinal disc with two more titanium cages, adding 16 rods and 20 screws for reinforcement.

My spine today resembles a nightmarish ladder that Tim Burton might have created.

After eight reconstructive spinal surgeries, I was given a miraculous drug called OxyContin. Doctors did not think I’d ever walk again because they needed to sever the nerves to my legs so that they could remove the cancer-infected bone.

Because of OxyContin, I was able to take my first step and eventually walk. This was in 2005, at the beginning of the so-called opioid crisis.

Once I relocated to Florida, pain management doctors refused to prescribe OxyContin to me, fearing lawsuits and scrutiny from law enforcement. Regardless of how much I protested, I was dismissed as if I was the problem, instead of having a problem.

At the time, pill mills were everywhere in Florida. They were places where if you had cash, you could get any medication. It’s also why there’s a such stigma today against chronic pain sufferers.

Eventually, I found a legitimate pain management doctor in Fort Lauderdale. Instead of OxyContin, he changed my regimen to a fentanyl patch, along with oxycodone/acetaminophen tablets (Percocet) for breakthrough pain, essentially replacing one opioid with two. That was my pain management routine for the past twelve years, until recently.

When I went to a Walgreens pharmacy this past June, I was shocked to hear, “Sorry, oxycodone is on back order, and we have no idea if or when it’s coming back.”

Opioid Shortages

Shortages of oxcodone, hydrocodone and other opioids are increasing around the country. And there is zero advance notice from pharmacies about when a prescribed medication will be available. Patients like me who suffer from severe pain are forced to go through withdrawal until the pharmacy restocks.

It’s a nightmare to deal with. Pain patients are usually not prepared for the sudden halt in medical care. Even the smallest disruption can have devastating effects, such as loss of productivity, reduced quality of life, and a diminished social life. Even smiling takes an effort.

Patients are always the last to know when there’s a problem with a prescription. Like thousands of others, I made frantic phone calls to my doctor, who scrambled to find an alternative medication. Without consulting me, he wrote a script for hydrocodone/acetaminophen (Vicodin), a medication I had never taken before. That’s when my three-week nightmare began. Because I wasn’t prepared to handle the ineffectiveness of hydrocodone for bone pain, my condition quickly began to decline.

Each morning, the first sensation I get feels like someone dug their elbow into my lower back all night long. It’s so fierce, it takes my breath away. Then, when I stand and all the titanium in my spine settles, the nerves hum in my legs and a crawling sensation shoots up and down, vibrating constantly.

As the morning coffee brews, I get the “poke” sensation. Due to a 200-pound weight loss, there’s a rod that sticks out of my thoracic spine area that rubs up against everything -- the bed, couch, office chair, car seat, everything. It’s miserable because it’s there forever.

Hydrocodone/acetaminophen tablets seem to exacerbate those symptoms, causing my body to swell and tighten into a ball of pressure, while the pain intensified. My productivity stopped and the bills began to pile up. Working while experiencing severe spinal and bone pain is nearly impossible.

After a recent candid discussion with my pain management doctor, we formed a “Plan B.” We’re trying oxycodone without acetaminophen to see if that works better. Having a backup plan with an alternate list of medications is essential with the shortages and fear-based drug culture we’ve found ourselves dumped into.

Government regulators and health policies have failed the people who suffer the most in this country, who often live with medical conditions they cannot control, like cancer. They’ve failed us time after time, filing lawsuits and adopting guidelines that make it harder for us to get prescription opioids – even though over 82% of opioid overdoses are caused by illicit fentanyl and other street drugs.

Patients who suffer from chronic pain all have one common goal: relief. When that relief is interrupted, and access to crucial therapies and drugs is denied, you leave us with few choices. We can either live our lives without pain relief or seek out riskier alternatives. Those are not good choices.

Kristen Hernandez is a freelance journalist and creative nonfiction writer living in South Florida. 

Do you have a “My Story” to share? Pain News Network invites other readers to share their experiences about living with pain and treating it.

Send your stories to editor@painnewsnetwork.org.

FDA and DEA Leaders Call for More ADHD Meds, But Ignore Rx Opioid Shortages

By Pat Anson, PNN Editor

Leaders of the Food and Drug Administration and the Drug Enforcement Administration say they’re working to end one of the worst drug shortages in decades.

“The lack of availability of certain medications in recent months has been understandably frustrating for patients and their families,” FDA commissioner Robert Califf, MD, and DEA Administrator Anne Milgram said in an unusual joint letter. “We are calling on key stakeholders, including manufacturers, distributors, pharmacies, and payors, to do all they can to ensure access for patients when a medication is appropriately prescribed.”

Those should be welcome words for pain patients across the U.S. who have trouble getting their prescriptions filled for opioid medication. Unfortunately, the letter has nothing to do with opioids. It’s only about shortages of Adderall and other prescription stimulants, which are used primarily to treat attention-deficit/hyperactivity disorder (ADHD).

The letter is the latest example of how the FDA and DEA have turned a blind eye to opioid shortages, which both agencies have played prominent roles in creating. Two widely used painkillers, oxycodone and hydrocodone, have been difficult to get for months, leaving thousands of patients in uncontrolled pain or going into withdrawal. Even big chain pharmacies like CVS are out of opioids or have a limited supply.   

“I had to once again follow up with CVS, just to be told they received absolutely nothing! Pain management provider in response sent another prescription to the outpatient pharmacy,” says Christine Kucera, a pain patient who recently wrote a column for PNN about her problems getting prescriptions filled for oxycodone.

“I'm currently sitting in the waiting area at the outpatient pharmacy, stressing, waiting for another bomb to drop.”

The American Society of Health-System Pharmacists (ASHP) first warned about a shortage of immediate release oxycodone in March. Over the next few months, hydrocodone/acetaminophen tablets (Vicodin) and oxycodone/acetaminophen tablets (Percocet) were added to the ASHP’s shortage list. Those shortages could soon grow even worse, because one of the largest generic drug makers in the world, Teva Pharmaceutical, is discontinuing production of immediate release oxycodone. 

Despite these warning signs, the FDA and DEA have yet to acknowledge shortages of either oxycodone or hydrocodone, and appear to be doing nothing about them. But they are moving to boost production of stimulants used to treat ADHD. The agencies say drug makers have sold only 70% of the stimulants they were authorized to produce.   

“We want to make sure those who need stimulant medications have access,” Califf and Milgram said in their letter. “We have called on manufacturers to confirm they are working to increase production to meet their allotted quota amount.” 

“What this latest notice shows is that the FDA and DEA could get involved with the opioid shortage if they wanted to,” says Rick Martin, a retired pharmacist disabled by back pain. Martin recently had to switch to a weaker opioid for pain relief because he can’t find a pharmacy with hydrocodone in stock.

“Teva said they were going to stop making oxycodone. The DEA/FDA could be proactive and ask Teva to relinquish their remaining 2023 quota allotment, then redistribute to other manufacturers,” Martin told PNN. 

Lower Production Quotas

The DEA sets annual production quotas for opioids, stimulants and other controlled substances, working closely with the FDA in assessing demand. Last year, the FDA advised the DEA that demand for hydrocodone, oxycodone and other Schedule II opioids would fall by 5.3% in 2023, which resulted in another year of cuts by the DEA in opioid production. Since 2013, the supply of oxycodone has fallen by 65 percent and hydrocodone by 73 percent. 

The FDA also advised the DEA that domestic medical use of stimulants would fall by 0.1% in 2023, even while warning that shortages were developing. The DEA’s response last December was that amphetamine and other stimulants were overprescribed to patients who didn’t really need them, and that its proposed production quotas (APQ) for the drugs in 2023 would be adequate.

“The majority of the manufacturers contacted by DEA and/or FDA have responded that they currently have sufficient quota to meet their contracted production quantities for legitimate patient medical needs,” the DEA said in the Federal Register. “Based on this trend, DEA has not implemented an increase to the APQ for amphetamine at this time.”

That kind of background detail is missing from Califf’s and Milgram’s letter, which disingenuously claims that there is little that the DEA and FDA can do to ensure that there are adequate supplies of medication. 

“This is not a problem that the FDA and DEA can solve on our own,” Califf and Milgram wrote. “The FDA and DEA do not manufacture drugs and cannot require a pharmaceutical company to make a drug, make more of a drug, or change the distribution of a drug.” 

Only briefly do Califf and Milgram acknowledge that their own production quotas are part of the problem, saying they were “committed to reviewing and improving our quota process.” 

“These (stimulant) shortages were caused by the DEA, which limited the manufacture of these medications,” says Andrea Anderson, a pain sufferer and patient advocate. “This exact problem has affected patients who require opioid analgesics to manage their severe pain. It has been affecting them for over six years, yet we see no mention of the extraordinary difficulties these patients are experiencing trying to find pain medication.  

“The DEA has no reason to be involved in deciding how many prescriptions should be written for any medical condition. This is the purview of trained medical clinicians and quantities should not be dictated by law enforcement agencies.” 

Drug manufacturers are required to report shortages and supply interruptions to the FDA. Doctors, hospitals, pharmacies and consumers can also report supply problems by sending an email to drugshortages@fda.hhs.gov.

That’s where Christine Kucera recently sent an email addressed to the FDA commissioner.

“Three different medications used in my treatment are continuously unavailable, sometimes for weeks and months. CVS IS OUT, the system is not working, and all you do is NOTHING!” Kucera wrote to Califf. 

“When will you address the unethical treatment and harms being inflicted upon millions of US citizens directly caused by government practicing medicine, limiting and denying access to essential medicines based on biased and manipulated facts, reduced quotas, faulty CDC prescription guidelines that should never have been created; and the DEA who are making up their own rules, practicing medicine, and deciding what they think appropriate medical care is?”  

Army Veteran Is Latest Casualty of DEA’s War on Drugs

By Pat Anson, PNN Editor

Becky Snyder and her husband Vance were soldiers when they first met in 1979 at Fort Lewis, Washington. Becky was a legal clerk for the Army, while Vance was a combat medic who later became an Army-trained physician assistant and chief warrant officer. They soon married and had a son.

After years spent defending their country, Vance and Becky could not have imagined they’d windup becoming unintended casualties of the DEA’s failed War on Drugs. Vance lost the love of his life when Becky died last month at the age of 70, after a lifetime of suffering from chronic pain.

“She had scoliosis her whole life, probably congenital. And that made it hard for her to do sit ups in the in the military and probably injured her spine trying to do that,” said Vance. “She could walk with difficulty. Usually when we went out, we used a wheelchair.”

Becky’s back pain progressively worsened and she became bedridden after developing intractable pain from two very serious complications: Complex Regional Pain Syndrome (CRPS) and arachnoiditis, a chronic inflammation of spinal nerves.

Both conditions are incurable and cause severe pain, but Becky found relief under the care of two Los Angeles-area doctors, Forest Tennant and David Bockoff. 

BECKY SNYDER AND SON

The careers of both physicians effectively ended after their offices were raided by DEA agents, Dr. Tennant in 2017 and Dr. Bockoff in 2022. They were targeted by the DEA for giving patients like Becky with complex medical conditions high doses of opioid pain medication — which, in the eyes of the DEA, has no legitimate medical use.

There is no evidence that any of Tennant’s patients were harmed or overdosed while under his care, but he retired in 2018 rather than face a costly legal battle with the DEA and Department of Justice.

Becky and other Tennant patients became “opioid refugees,” scouring the country for doctors because no one was willing to treat them locally. Several eventually found their way to Bockoff, with some traveling thousands of miles from out-of-state to see him and get their prescriptions filled in California. That made Bockoff a target for the DEA.

Last November, the DEA suspended Bockoff’s license to prescribe opioids and other controlled substances, even though he practiced medicine for over 50 years in California with no record of any disciplinary action or complaints filed with the state medical board. The DEA claimed five of Bockoff’s patients were in “imminent danger,” but then waited a year to suspend him.  

Patient Deaths

While Bockoff appeals his suspension, at least three of his former patients have died, including one who committed suicide with his wife and another who died after buying opioid medication in Mexico. Becky Snyder is the most recent death.        

“The last six years have been very difficult, because we couldn’t get the amount of medicine that Dr. Tennant gave. Dr. Bockoff, I mean to his credit he did the best he could, but he couldn’t give the amount that Forest Tennant was willing to give,” said Vance.

“But if there hadn’t been Dr. Bockoff, I think she would have died even sooner.”

Becky didn’t die from withdrawal, but from pancreatic cancer. She was diagnosed earlier this summer after complaining of stomach pain, and the cancer quickly metastasized. Becky didn’t drink, and Vance is convinced that poorly treated pain contributed to her death.

BECKY SNYDER

“I was in Army medicine. Clinically and diagnostically, pain can be an important indicator of what’s wrong with a patient. You have to take the suffering seriously,” Vance told PNN. “I believe pain kills people all the time because it just wears the person out. It leads to all kinds of conditions, whether it’s endocrine, whether it’s cancer, whether it’s depression and suicide. There’s all kind of things that pain causes.”

“Cancer follows intractable pain like night follows day,” says Tennant, who believe Becky’s death was preventable. “Because if you can’t get the pain relieved, you disturb your hormonal systems and your immune system. I can’t tell you how common cancer is in these people who can’t get care. It’s just one of the complications.

“I’m sure if I was still in practice or Dr. Bockoff was, she’d still be alive.“

Vance Snyder says intractable pain took a toll on Becky’s physical and mental health, and she aged considerably in her final years. He believes high dose opioids is what kept her alive.

“For the worst, worst cases of intractable pain, opioids have to be part of the package. The idea that nerve blocks, epidurals, aromatherapy, cognitive behavioral therapy and all those things are going to make a big difference with the worst kind of pain is ridiculous,” he said.

Snyder has joined with several other Bockoff patients in a lawsuit asking the U.S. Court of Appeals to give them legal standing as interested parties in the Bockoff case. 

In an open letter, Snyder urged the court to find a “proper balance” between appropriate pain care and the needs of law enforcement.

“Severe intractable pain does not exist in isolation, but is connected to every other aspect of the patient’s overall health,” he wrote. “Becky is gone now, but there are many thousands of agonized patients who are desperate and on the verge of suicide. Please think about them when you make your decisions.”     

Why Cheap Generic Drugs Are Harder to Find

By Dr. Geoffrey Joyce, University of Southern California

Past public ire over high drug prices has recently taken a back seat to a more insidious problem – no drugs at any price.

Patients and their providers increasingly face limited or nonexistent supplies of drugs, many of which treat essential conditions such as cancer, heart disease and bacterial infections. The American Society of Health System Pharmacists now lists over 300 active shortages, primarily of decades-old generic drugs no longer protected by patents.

While this is not a new problem, the number of drugs in short supply has increased in recent years, and the average shortage is lasting longer, with more than 15 critical drug products in short supply for over a decade. Current shortages include widely known drugs such as the antibiotic amoxicillin; the heart medicine digoxin; the anesthetic lidocaine; and the medicine albuterol, which is critical for treating asthma and other diseases affecting the lungs and airways.

What’s going on?

I’m a health economist who has studied the pharmaceutical industry for the past 15 years. I believe the drug shortage problem illustrates a major shortcoming of capitalism. While costly brand-name drugs often yield high profits to manufacturers, there’s relatively little money to be made in supplying the market with low-cost generics, no matter how vital they may be to patients’ health.

The shortage includes chemotherapy drugs, antibiotics, medications to treat ADHD and other critical drugs. Some patients are able to get their drugs, while others are not, and in some cases patients are getting ‘rationed care.’

Brand Name Drugs More Profitable

The problem boils down to the nature of the pharmaceutical industry and how differently the markets for brand and generic drugs operate. Perhaps the clearest indication of this is the fact that prices of brand drugs in the U.S. are among the highest in the developed world, while generic drug prices are among the lowest.

When a drugmaker develops a new pill, cream or solution, the government grants the company an exclusive patent for up to 20 years, although most patents are filed before clinical testing, and thus the effective patent life is closer to eight to 12 years. Nonetheless, patents allow the drugmakers to cover the cost of research and development and earn a profit without the threat of competition from a rival making an identical product.

But once the patent expires, the drug becomes generic and any company is allowed to manufacture it. Since generic manufacturers are essentially producing the same product, profits are determined by their ability to manufacture the drug at the lowest marginal cost. This often results in low profit margins and can lead to cost-cutting measures that can compromise quality and threaten supply.

Outsourced Production Creates Supply Risks

One of the consequences of generics’ meager margins is that drug companies outsource production to lower-cost countries.

As of mid-2019, 72% of the manufacturing facilities making active ingredients for drugs sold in the U.S. were located overseas, with India and China alone making up nearly half of that.

While overseas manufacturers often enjoy significant cost advantages over U.S. facilities, such as easy access to raw materials and lower labor costs, outsourcing production at such a scale raises a slew of issues that can hurt the supply. Foreign factories are more difficult for the Food and Drug Administration to inspect, tend to have more production problems and are far more likely than domestic factories to be shut down once a problem is discovered.

In testimony to a House subcommittee, Janet Woodcock, the FDA’s principal deputy commissioner, acknowledged that the agency has little information on which Chinese facilities are producing raw ingredients, how much they are producing, or where the ingredients they are producing are being distributed worldwide.

The COVID-19 pandemic underscored the country’s reliance on foreign suppliers – and the risks this poses to U.S. consumers.

India is the world’s largest producer of generic drugs but imports 70% of its raw materials from China. About one-third of factories in China shut down during the pandemic. To ensure domestic supplies, the Indian government restricted the export of medications, disrupting the global supply chain.

This led to shortages of drugs to treat COVID-19, such as for respiratory failure and sedation, as well as for a wide range of other conditions, like drugs to treat chemotherapy, heart disease and bacterial infections.

Low Profits Hurt Quality

Manufacturing drugs to consistently high-quality standards requires constant testing and evaluation. A company that sells a new, expensive, branded drug has a strong profit motive to keep quality and production high. That’s often not the case for generic drug manufacturers, and this can result in shortages.

In 2008, an adulterated version of the blood-thinning drug Heparin was recalled worldwide after being linked to 350 adverse events and 150 deaths in the U.S. alone.

In 2013, the Department of Justice fined the U.S. subsidiary of Ranbaxy Laboratories, India’s largest generic drug manufacturer, US$500 million after it pleaded guilty to civil and criminal charges related to drug safety and falsifying safety data. In response, the FDA banned products made at four of the company’s manufacturing facilities in India from entering the U.S., including generic versions of gabapentin, which treats epilepsy and nerve pain, and the antibiotic ciprofloxacin.

And while there may be multiple companies selling the same generic drug in the U.S., there may be only a single manufacturer supplying the basic ingredients. Thus, any hiccup in production or shutdown due to quality issues can affect the entire market.

A recent analysis found that approximately 40% of generic drugs sold in the U.S. have just one manufacturer, and the share of markets supplied by just one or two manufacturers has increased over time.

Repatriating the Drug Supply

It is hard to quantify the impact of drug shortages on population health. However, a recent survey of U.S. hospitals, pharmacists and other health care providers found that drug shortages led to increased medication errors, delayed administration of lifesaving therapies, inferior outcomes and patient deaths.

What can be done? One option is to simply find ways to produce more generic drugs in the U.S.

California passed a law in 2020 to do just that by allowing the state to contract with domestic manufactures to produce its own generic prescription drugs. In March 2023, California selected a Utah company to begin producing low-cost insulin for California patients.

Whether this approach is feasible on a broader scale is uncertain, but, in my view, it’s a good first attempt to repatriate America’s drug supply.

Geoffrey Joyce, PhD, is director of Health Policy at the USC Schaeffer Center, an associate professor and chair of the Department of Pharmaceutical and Health Economics at the USC School of Pharmacy, and research associate at the National Bureau of Economic Research.

Prior to his position at USC, Dr. Joyce was a Senior Economist at the RAND Corporation and currently co-directs UCLA's post-doctoral program in Health Services Research.

This article originally appeared in The Conversation and is republished with permission.

Pain Clinic Chain to Pay $11M to Settle Fraud Claims

By Don Thompson, KFF Health News

The owner of one of California’s largest chains of pain management clinics has agreed to pay nearly $11.4 million to California, Oregon, and the federal government to settle allegations of Medicare and Medicaid fraud.

The U.S. Department of Justice and the states’ attorneys general say Francis Lagattuta, a physician, and his Lags Medical Centers performed — and billed for — medically unnecessary tests and procedures on thousands of patients over more than five years.

It was “a brazen scheme to defraud Medicare and Medicaid of millions of dollars by inflicting unnecessary and painful procedures on patients whom they were supposed to be relieving of pain,” Phillip Talbert, U.S. attorney for the Eastern District of California, said in a statement this month.

The federal Medicare program suspended reimbursements to Lags Medical in June 2020, and Medi-Cal, California’s Medicaid program, followed in May 2021. Lags Medical shut down the same day the state suspended reimbursements. The company, based in Lompoc, California, had more than 30 pain clinics, most of them in the Central Valley and the Central Coast.

A KFF Health News review last year found the abrupt closure left more than 20,000 California patients — mostly working-class people on government-funded insurance — struggling to obtain their medical records or continue receiving pain prescriptions, which often included opioids.

Lagattuta and Lags Medical did not admit liability under the settlement. Lagattuta denied the governments’ claims, saying in a statement he was “pleased” to announce the settlement of a “long-standing billing dispute.” As part of the agreement, Lagattuta will be barred for at least five years from receiving Medicare and Medicaid reimbursements.

“Since the Centers have been closed for a couple of years, it made sense for Dr. Lagattuta to settle the dispute and continue to move forward with his other business interests and practice,” Malcolm Segal, an attorney for Lagattuta and the centers, said in the statement.

According to state officials, the federal government will receive the bulk of the money, about $8.5 million. California will receive about $2.7 million, and an additional $130,000 will go to Oregon. The settlement amount is based in part on Lagattuta’s and Lags Medical’s “ability to pay.” It does not cover the governments’ full losses, which the U.S. attorney’s office in Sacramento said are not public record.

Blanket Orders for Unnecessary Tests

A nearly four-year investigation by federal officials and the California Department of Justice found that from March 2016 through August 2021, Lagattuta and his company submitted reimbursement claims for unneeded skin biopsies, spinal cord stimulation procedures, urine drug tests, and other tests and procedures.

Lagattuta began requiring all his clinics to perform various medical procedures on every patient, the officials said, no matter if they were needed or requested by patients’ medical providers. Patients who refused were told they would have their pain medication reduced and could suffer adverse medical consequences.

U.S. and California investigators piggybacked on a federal claim filed in late 2018 by a whistleblower, Steven Capeder, Lags Medical’s former operations and marketing director, who will receive more than $2 million of the settlement.

As part of the settlement, Lagattuta and his company acknowledged that in mid-2016 he began requiring his providers to do at least two to three skin biopsies on Medicare patients each day and told providers to quit if they wouldn’t comply. Such biopsies are used to measure small-fiber neuropathy, which causes burning pain with numbness and tingling in the feet and lower extremities.

According to the settlement, a monthly report in early 2018 set a goal of performing 250 biopsies a week. Lagattuta created a separate team that was required to order at least 150 biopsies weekly, often overruling providers. And the company’s chief executive officer in late 2019 texted Lagattuta to report a particularly high number of biopsies, illustrating the text with emojis of a money bag and a smiley face.

Authorities said Lagattuta violated regulations requiring that skin biopsy results be interpreted by a trained pathologist or neurologist. Instead, they say, Lagattuta had the biopsies read by a family member who had no formal medical training and by a former clinic executive’s spouse, who was trained as a respiratory therapist.

Lags Medical clinics performed more than 22,000 biopsies on Medi-Cal patients from 2016 through 2019.

The settlement also alleges Lagattuta encouraged unsuitable patients to undergo spinal cord stimulation. It describes the procedure as “an invasive surgery of last resort,” in which implants placed near the spinal cord apply low-voltage electrical pulses to nerve fibers.

Lagattuta paid a psychiatrist $3,000 each month to falsely certify that every Lags Medical candidate for the procedure had no psychological or substance use disorders that would negatively affect the outcome, according to the settlement. For instance, the settlement says the psychiatrist overruled a Lags Medical social worker to OK the procedure for a young woman who had bipolar disorder with hallucinations that included hearing a man’s voice ordering her out of bed.

He also issued blanket orders for every patient to have urine drug testing, a policy the company’s CEO said “should be a big money maker.”

KFF Health News found that from 2017 through 2019 nearly 60,000 of the most extensive urine drug tests were billed to Medicare and Medi-Cal under Lagattuta’s provider number. Medicare reimbursed Lagattuta $5.4 million for those tests.

The clinics “carefully examined, tested, and treated” more than 60,000 patients during the time covered by the settlement, “when others might have been content to prescribe medication to mask pain,” said Lagattuta’s statement. 

KFF Health News is a national newsroom that produces in-depth journalism about health issues.

FDA and DEA Silent as Rx Opioid Shortages Worsen

By Pat Anson, PNN Editor

Shortages of opioid pain medication in the U.S. appear to be worsening, with no apparent action from the FDA or DEA to ease the suffering of patients left in uncontrolled pain or going into withdrawal.

Last week the American Society of Health-System Pharmacists (ASHP) added another widely used painkiller to its drug shortage list: oxycodone/acetaminophen tablets, which are more widely known under the brand names Percocet and Endocet. The medication is typically prescribed for moderate to severe pain.   

The ASHP reports that five drug makers are either running low or have exhausted their supply of oxycodone/acetaminophen in 2.5, 5, 7.5 and 10mg tablets.  Amneal, Major and Rhodes did not provide ASHP with a reason for the shortage, while Camber and KVK-Tech said they were “awaiting DEA quota approval for active ingredient.”

Amneal, Camber and KVK-Tech said the tablets were on back order with no estimated resupply date. Major and Rhodes said additional supplies were expected in mid-September or early August, respectively. Limited supplies and doses of oxycodone/acetaminophen tablets are still available from other drug manufacturers.

There are already shortages of two other widely used painkillers. The AHSP put immediate release oxycodone on its list of drug shortages in March and added hydrocodone/acetaminophen tablets to the list in May.  

But those shortages have yet to be acknowledged by the FDA. Asked why oxycodone and hydrocodone were missing from the FDA’s drug shortage list, a spokesperson referred PNN to an FDA website for “Frequently Asked Questions about Drug Shortages.”

One possible explanation, according to the website, is that the FDA “focuses on shortages that have the greatest impact on public health.” Shortages are also not reported if they are expected to be resolved quickly, if other substitutes are available, or if there are only local supply issues.

Manufacturers are required to report shortages and supply interruptions to the FDA, while providers, hospitals, pharmacies and consumers can report them by email to drugshortages@fda.hhs.gov.  

‘No One Seemed to Care’

At PNN, we hear from readers almost daily about opioid shortages.

“I am now past my usual fill date,” said Rick Martin, a retired pharmacist in Las Vegas who lives with chronic back pain. “My CVS pharmacist manager told me that she was told by their wholesaler that hydrocodone won't be available until the middle of August.” 

Martin said pharmacists at Walgreens, Smith’s and Sav-on have also told him they were out of oxycodone and hydrocodone tablets.  

“It's been spotty for 6 months but now seems entrenched. I got switched to tramadol. Not as effective, but I can just barely get by. I've heard that's what doctors are doing. Tramadol or Tylenol with codeine,” he told PNN.

Steve Keating, another Las Vegas resident, has been taking oxycodone for chronic neck pain after his vehicle was rear-ended by another driver. He had no problems getting his prescription refilled at either Walgreens or CVS, until last month. Now he is out of pain medication. 

“I began having withdrawal symptoms. No one seemed to care,” said Keating, who turns 73 this month. “The pharmacy recommendations were to obtain tramadol, which I've tried in the past and found ineffective.  I cannot take opiates with acetaminophen as it upsets my stomach.   

“It seems that there is a huge gap between prescribers, pharmacies and whatever governmental agencies are involved.  Do these governmental idiots not realize how important the medication we've been prescribed for months or years is to give us some degree of a better quality of life?” 

There are several reasons behind the opioid shortages. It started with misleading information that demonized prescription opioids and the false portrayal of patients and doctors as the primary cause of the “opioid epidemic.” That was followed by medical guidelines that discourage opioid prescribing and a tsunami of opioid litigation that cost drug makers, wholesalers and pharmacies tens of billions of dollars. 

Egged on by politicians, the Drug Enforcement Administration also aggressively cut production quotas for opioids and other controlled substances, reducing the supply of oxycodone by 65% and hydrocodone by 73% since 2013.  

DEA PRODUCTION QUOTAS FOR OXYCODONE (KILOGRAMS)

SOURCE: DEA

The DEA quotas are rigidly enforced, making it difficult for a drug maker to boost production of opioids when another manufacturer has shortages or discontinues production, like Teva Pharmaceutical recently announced.

It’s not just opioids in short supply. Drugs used to treat cancer and attention deficit disorder (ADHD) are also hard to get. These problems have been building in plain sight for years, yet the FDA’s commissioner says there is little his agency can do to correct them.

“We wish that we could fix all these things, but we don't make the medicines and we can't tell someone that they must make medicines. There are some things that are out of our control,” FDA Commissioner Robert Califf, MD, said in a May interview. 

That’s not exactly true. The DEA sets annual production quotas for drug makers only after consulting with the FDA. The 2023 DEA quotas for hydrocodone, oxycodone and several other opioids were cut — for the 7th year in a row — based on the advice of the FDA.

“FDA predicts that levels of medical need for schedule II opioids in the United States in calendar year 2023 will decline on average 5.3 percent from calendar year 2022 levels,” the DEA said in a notice published last year in the Federal Register.   

DEA administrator Anne Milgram, meanwhile, has not made any public comments about shortages of opioid medication. In a recent appearance on Meet the Press, she said illicit fentanyl was being used to make counterfeit versions of prescription opioids — the same legal drugs that are now in short supply due to DEA actions.

“They're pressing it into these fake pills made to look exactly like oxycodone or Percocet or or Adderall, when it's just fentanyl and filler. So tens of thousands of Americans are dying without having any idea that they're taking fentanyl,” Milgram said.

(Update: On August 1, Milgram and Califf released a joint letter saying the FDA and DEA were working “as quickly as possible” to resolve the drug shortages, but took no responsibility for causing them. The letter only addressed shortages of prescription stimulants used to treat ADHD, binge eating and narcolepsy. It makes no mention of opioid shortages.)

JAMA: Patients on Long-Term Opioids Often ‘Irrational’

By Pat Anson, PNN Editor

Do pain patients on long-term opioid therapy make irrational decisions? Is their mental capacity so diminished by opioids that they shouldn’t be involved in treatment decisions with their doctors?

The answer to both questions is often yes, according to a controversial new op/ed published in JAMA Internal Medicine. At issue is a recent update to the CDC’s opioid prescribing guideline, which calls for shared decision-making (SDM) when a prescriber considers tapering a patient or abruptly discontinuing their opioid treatment. The guideline was revised last year after reports of “serious harm” to patients caused by forced tapering.

“In situations where benefits and risks of continuing opioids are considered to be close, shared decision-making with patients is particularly important,” the 2022 guideline states.

But that advice about consulting with patients goes too far, according to the lead author of the JAMA op/ed, Mark Sullivan, MD, a professor of psychiatry at the University of Washington and a longtime board member of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

“The value of SDM has been recognized for many years but also has its limitations, including where patients make irrational or short-sighted decisions,” Sullivan wrote. “Long-term opioid therapy induces a state of opioid dependence that compromises patients’ decisional capacity, specifically altering their perception of the value and necessity of the therapy; and although patients with chronic pain are not usually at imminent risk of death, they often can see no possibility of a satisfying life without a significant and immediate reduction in their pain.”

Sullivan and his two co-authors, Jeffrey Linder, MD, and Jason Doctor, PhD, have long been critical of opioid prescribing practices in the U.S. In their conflict of interest statements, Sullivan and Doctor disclose that they have worked for law firms involved in opioid litigation, a lucrative sideline for several PROP members.

Sullivan, Linder and Doctor call for more “structured” decision-making that includes the patient’s family and friends, “motivational interviewing” of patients about opioid risks and treatment goals, and education about non-drug alternatives such as yoga and meditation.

“We believe that a fully individualized, unstructured decision-making process will not be adequate to protect patients receiving long-term opioid therapy,” they wrote.

In the case of opioid prescribing, and especially opioid tapering, working to persuade the patient is almost always the best clinical strategy. But there are circumstances where tapering should occur even if the patient objects.
— Dr. Mark Sullivan

And what happens if a patient refuses to have their dose reduced? The op/ed doesn’t explicitly state it, but in an email to PNN, Sullivan said forced tapering would be acceptable in some situations.

“In the case of opioid prescribing, and especially opioid tapering, working to persuade the patient is almost always the best clinical strategy. But there are circumstances (opioid use disorder, diversion, serious medical risks) where tapering should occur even if the patient objects,” Sullivan wrote.

Opioid diversion by patients is actually rare. The DEA estimates that less than one percent of oxycodone (0.3%) and hydrocodone (0.42%) will be used by someone they were not intended for.

As for patients on opioids behaving “irrational,” Sullivan and his co-authors cite an op/ed published 33 years ago in The New England Journal of Medicine (NEJM). But that article doesn’t even discuss opioids or tapering, it’s about whether patients and doctors should collaborate in making decisions about end-of-life medical care.  It also makes an important disclaimer that “even the irrational choices of a competent patient must be respected if the patient cannot be persuaded to change them."

Sullivan rejects that approach to opioid treatment.

“We cite (the NEJM article) to demonstrate that SDM does not exclude or prevent irrational decisions,” he wrote in his email.  “You are right that we do not endorse the conclusion you cite, that patient’s irrational decisions must be respected.”

In a rebuttal to Sullivan’s op/ed also published in JAMA Internal Medicine, Mitchell Katz, MD, and Deborah Grady, MD, dispute the notion that a patient’s choices shouldn’t be respected.

“Primary care professionals generally highly value the inclusion of the patient’s perspective in decision-making, consistent with the principles of patient autonomy and self-determination, and are loathe to go against a patient’s wishes,” they wrote.

“As primary care professionals, we have found it helpful to tell patients that it is not recommended to take more than a specific threshold of opioids and that we do not want to prescribe something that is not recommended. However, that does not mean sticking to rigid cut points for dose and duration of opioid use, abandoning patients, or having them undergo too rapid a taper.”

Others questioned JAMA’s decision to publish Sullivan’s op/ed.

“While I recognize the editors’ legitimate intellectual interest in providing a forum for open discussion on the opioid policy space, I question their decision to publish an editorial that represents an ongoing call for broad, ill-defined reductions in opioid prescribing,” said Chad Kollas, MD, a palliative care specialist who rejects the idea that patients shouldn’t be involved in their healthcare choices.

“Errantly embracing a lower evidentiary standard for medical decision-making capacity creates an unacceptable risk for harm to patients with pain by violating their rights of medical autonomy and self-determination.”

Opioids were once commonly prescribed in the U.S. for both acute and chronic pain, but those days are long over. Opioid prescribing has been cut in half, to levels not seen since the 1990’s. And many patients today have trouble just getting their prescriptions filled at pharmacies due to opioid shortages.

Despite that, fatal overdoses have climbed to record levels, with illicit fentanyl and other street drugs involved in the vast majority of drug deaths, not prescription opioids.