Woman Files Civil Rights Lawsuit Over Denial of Pain Treatment

By Madora Pennington, PNN Columnist

In September of 2022, millions watched Tara Rule’s emotional video on TikTok, about a doctor who refused to give her a non-narcotic pain medication because it might cause birth defects. The doctor would not even name the drug, even though Rule told him she has no intention of having children because she has Ehler's Danlos syndrome (EDS), a genetic disorder that causes severe health issues.

The 32-year old Rule recently filed a civil rights lawsuit to better establish the illegality of refusing medical treatment to women simply because they are of childbearing age.

Rule’s fight began when neurologist Jonathan Braiman, MD, steered her away from an effective treatment for her agonizing cluster migraines, a common symptom of EDS. According to Yale Medical School, cluster headaches can hurt more than childbirth.

When Rule realized she was being discriminated against by her doctor, she surreptitiously switched on her cell phone to record their discussion, which is legal in New York state. 

Brainman can be heard in the recording asking Rule intrusive questions about her sex life, while ignoring her answers. Rule explained that she was already on a medication that can cause birth defects -- known as teratogenic drug -- and wasn't well enough to have children anyway.

Brainman patronizingly told her she might change her mind if she were to become pregnant. He recommended that she bring in her boyfriend to consent to any treatment that might cause birth defects. Rule left without getting the pain relief she needed for her migraines.

In the parking lot of Albany Medical Center, where the appointment took place, a distraught and tearful Rule made the video and posted it online. Her raw emotion and disturbing story quickly went viral, not only on social media, but in news stories.

In her lawsuit against Braiman and Albany Medical, Rule alleges she was retaliated against by the hospital system. Rule says she was ejected from an unaffiliated urgent care center because Albany Medical had told other hospitals not to treat her. She believes this was a violation of her medical privacy.  

Rule suspects she was blacklisted by other providers in her area. She tried to make an appointment with another neurologist, but was told she was “not an appropriate patient.” Her primary care provider sent a back-dated letter to Rule and her mother saying he was dismissing them as patients. That doctor gave no valid reason for the patient abandonment.

TARA RULE (TIKTOK)

Rule is on disability and lives on less than $1,000 per month. Being banned as a patient is a real hardship.

“Now I have to go to Connecticut to see physicians in a different hospital system. Or travel three and a half hours to New York City. With hotels and gas, it’s very hard. Some of these specialists outside the state are not fully covered by my insurance,” Rule said.

Traveling is made more complicated because Rule can’t stay just anywhere — she needs accessible hotel rooms. And she is accumulating thousands of dollars in debt.

After posting her video, Rule heard from many other patients who have also been discriminated against by their doctors. She felt motivated to find out what legal remedies existed.

With legal guidance, Rule wrote the civil rights complaint herself in what is known as a “federal question” lawsuit, an action that seeks to clarify a constitutional issue in US federal court. Rule has been advised that the medical care she sought does not fall under “conscience protections,” which allow doctors to refuse treatment on religious or moral grounds.  

In preparation for her lawsuit, Rule obtained her medical and insurance records, to help prove that privacy violations occurred. She discovered she had been billed for services not received, and believes her medical records were forged.

Albany Medical did not respond to a request for comment.

Rule’s lawsuit is potentially precedent-setting. It marks the first federal question case against a medical provider for refusing to provide teratogenic drugs because a woman is of “childbearing age.” Refusing to give routine medical care because a patient might get pregnant is discrimination. Patients cannot be forced into unnecessary restraints on their care.

"I am prepared for whatever happens,” says Rule, who is hopeful her lawsuit will help prevent other patients from being discriminated against by their doctors. 

Madora Pennington is the author of the blog LessFlexible.com about her life with Ehlers-Danlos Syndrome. She graduated from UC Berkeley with minors in Journalism and Disability Studies. 

Lawsuits Accuse DEA of ‘Incompetence’ in Regulating Drug Supply

By Pat Anson, PNN Editor

Two federal lawsuits accuse the Drug Enforcement Administration of incompetence and heavy-handed regulation of the nation’s drug supply, which could worsen shortages of ADHD medication and drive a drug manufacturer and specialty pharmacy out of business.

At issue is the DEA’s enforcement of the Controlled Substances Act (CSA), a federal law that gives the agency broad authority to limit the production and sale of opioids, ADHD drugs and other controlled medications that have the potential for abuse. Under the CSA, the DEA decides who can write and dispense prescriptions for hundreds of controlled substances and the amount that drug makers can produce.   

“They shouldn't be playing God with people's medications. And really, that's what's happening here,” says attorney Jim Walden, who recently filed a lawsuit in the Second Circuit Court of Appeals on behalf of Ascent Pharmaceuticals, a leading producer of generic drugs used to treat attention deficit hyperactive disorder (ADHD), a condition that primarily affects children.

By its own estimate, Ascent produces about 20% of the nation’s supply of generic ADHD medication. In its 12-year history, Ascent had never been accused of a regulatory violation or faced any sanctions, so it was surprised to learn on September 29 that DEA would not renew its production quota for ADHD drugs because it has doubts about the company’s record keeping.

“After reviewing these records, DEA lacks confidence in the data provided by Ascent in its quota requests,” the agency said in its denial.

Ascent’s lawsuit disputes that claim, saying DEA investigators spent 18 months “bumbling about” its business records, without ever making clear what they were concerned about or why the quota was denied.

“The Quota Denial nowhere explains the basis for DEA’s alleged confidence gap. If that detail resides in the administrative complaint served alongside the Quota Denial, DEA should be embarrassed: the errors in it reveal a fundamental inaptitude with DEA’s own recordkeeping requirements,” the lawsuit alleges.

“This case highlights the perils of a hapless administrative agency, which (ironically) acknowledged the scarcity of ADHD medications on the very day it effectively sought to shutter Ascent, a company with a time-proven capability of quickly getting medicine to children in need. Ascent and patients have been victimized by DEA’s incompetence, having rendered an arbitrary, capricious, and unsubstantiated quota denial based on erroneous conclusions.”

Before going into private practice, Walden spent 10 years as a federal prosecutor, often handling DEA cases. He’s asking the federal appeals court to issue an emergency injunction that forces DEA to approve Ascent’s quota application.

“We're in the middle of a national scarcity crisis that is really putting children at risk. So it's very, very hard to understand what could possibly be motivating DEA, because they're obviously not alleging that there are quality control problems with the drugs or that there's a threat of diversion,” Walden told PNN. “So, by definition, their decision is arbitrary and it should be reversed.”

The DEA’s actions do seem puzzling. Shortages of ADHD drugs began in the early stages of the pandemic and have steadily worsened, as more children and adults sought mental health treatment. Yet in December of last year, when the DEA issued its quotas for 2023, the agency said there was no need to increase production because the supply of Adderall and other stimulants was sufficient to meet demand.

“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.”

A few months later, DEA and FDA officials changed their tune. In an unusual joint letter,  FDA commissioner Dr. Robert Califf and DEA Administrator Anne Milgram admitted there was an ADHD shortage, blamed drug makers for not making enough medication, and washed their hands of the problem.

“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.” 

DEA production quotas may also be partially responsible for shortages of opioid pain medication. In recent years, the agency has aggressively cut the supply of many opioids, leading to current shortages of hydrocodone and oxycodone.     

Judge, Jury and Executioner

The second lawsuit against DEA involves Simfa Rose Pharmacy, a Pembroke Pines, Florida pharmacy that specializes in making drugs for seniors, palliative care, and cancer patients.

Simfa Rose came under scrutiny nearly three years ago when investigators saw it was filling an unusual number of high-dose, immediate release opioid prescriptions, often in combination with stimulants and muscle relaxants. Some of the prescriptions were paid for in cash.

As far the DEA is concerned, these were signs of “multiple red flags of abuse or diversion” that posed “an imminent danger” to public health. On May 2 of this year, DEA suspended the pharmacy’s license to dispense controlled substances, a move that severely impacts its ability to continue operating.

“It’s affected them greatly. It’s a miracle they are still open at this point,” says Vittorio Penza, a lawyer for Simfa Rose.

Under DEA rules, there is only one recourse for a pharmacy or doctor to challenge a license suspension – an appeal to a DEA Administrative Law Judge. Such appeals are not only time consuming; they are rarely granted. The few that are granted are referred back the DEA Administrator, who then has the final say on whether the license is restored or permanently revoked.

The Simfa Rose lawsuit alleges this is an “unconstitutional administrative process” that denies the pharmacy due process.

“It’s totally nuts what they are doing. You have a judge, jury and executioner system. It’s all in secret. They don’t publish anything until it’s a decision that’s favorable to them. You’re kept in the dark by it,” Penza told PNN. “All you have to do is take someone's license, whether they need it or not. You're still screwed and you're going to go down. Because once your reputation is tainted, you lose your customers and you lose the patients.”

Penza says the expert witness hired by DEA to review the pharmacy’s practices made outrageous claims.

“Their expert says you can't fill immediate release opioids more than two times. If you are a cancer patient or someone on their deathbed, it doesn't matter. It's an unresolvable red flag if you give someone an immediate release opioid,” he said. “And the kicker is he doesn't even look at what the patient's diagnosis is. One of the patients was shot was shot in the back, the bullet is still lodged in there. The other one was wounded overseas in the Gulf War.”

Perhaps the biggest challenge faced by someone seeking to reverse a DEA decision is that federal agencies have sovereign immunity – they can’t be sued for monetary damages. All they can do is challenge the DEA’s statutory authority under the Controlled Substances Act and its use of an in-house “kangaroo court” to keep pharmacies, doctors and drug makers in line.        

“I've come to realize that this is a nationwide issue. I've been getting calls ever since we filed from around the country. It pains me to hear some of these stories of doctors and nurses and pharmacists that have just been stripped of their livelihoods because of what the DEA is doing,” Penza said.  

Lack of Education Is Fueling Overdose Crisis

By Pat Anson, PNN Editor

Anti-opioid activists have long claimed that excessive prescribing of opioids over a decade ago created an “epidemic of addiction” that lingers to this day. Once hooked on prescription opioids, patients turned to stronger and more lethal drugs — like heroin and illicit fentanyl — sending the overdose rate to record levels.

A large new study debunks that theory, showing that socioeconomic factors – particularly lack of education -- play a hidden but central role in the overdose crisis.

"The analysis shows that the opioid crisis increasingly has become a crisis involving Americans without any college education," said lead author David Powell, PhD, a senior economist at RAND, a nonprofit research organization. "The study suggests large and growing education disparities within all racial and ethnic groups --- disparities that have accelerated since the beginning of the COVID-19 pandemic."

Powell looked at data from the National Vital Statistics System from 2000 to 2021, and identified over 912,000 fatal overdoses for which there was education information on the people who died.

His findings, published in JAMA Health Forum, show that overdose deaths increased sharply among Americans without a college education and nearly doubled in recent years for those who don’t have a high school diploma. The findings are notable because they came during a period when per capita consumption of prescription opioids plummeted, sinking to levels last seen in 2000.

For people with no college education, the overdose death rate increased from 12 deaths per 100,000 individuals in 2000 to 82 deaths per 100,000 in 2021. That rate is sharply higher than Americans who have some college education. In 2000, their overdose rate was 4.6 deaths per 100,000 people, which rose to 18.6 deaths per 100,000 in 2021.

Trends in Overdose Deaths by Educational Attainment

JAMA HEALTH FORUM

Powell is not the first researcher to link socioeconomic factors to overdose deaths. The so-called “deaths of despair” were first reported in 2015 by Princeton researchers Angus Deaton and Anne Case, who found that economic, social and emotional stress were major factors in the reduced life expectancy of middle-aged white Americans, who increasingly turned to substance abuse to dull their physical and emotional pain.

Education plays a significant role in socioeconomic status. People without college degrees are more likely to have blue-collar jobs requiring manual labor, which raise the risk of work-related injuries and conditions such as arthritis. One recent study found that people who did not finish high school in West Virginia, Arkansas and Alabama were three times more likely to have joint pain compared to those with bachelor degrees in California, Nevada and Utah.

“Overall, the analysis suggests that the opioid crisis has increasingly become a crisis disproportionately impacting those without any college education. Research is needed to understand the driving forces behind this gradient, such as isolating the independent roles of differences in income, employment, family composition, health care access, and other factors,” said Powell.

“Overdose death rates grew during the COVID-19 pandemic, and the education gradient increased further, although it is unclear what role the pandemic had relative to changes in fentanyl penetration in illicit drug markets and other factors.”

Powell says education merits further attention in understanding how and why the opioid crisis continues to intensify and lower U.S. life-expectancy.

Sens. Manchin and Markey Want Opioid Research Stopped

By Pat Anson, PNN Editor

Seven years ago, Sens. Ed Markey (D-MA) and Joe Manchin (D-WV) wrote a letter to the acting administrator of the Drug Enforcement Administration, asking for stricter limits on the production of opioid pain medication. They joined with over a dozen of their colleagues with another letter in 2017, asking for the same thing.

The letters said too many Americans were becoming addicted to opioids and that there was “insufficient research body about the effectiveness of opioids when used long term.”

The letters and a personal meeting with the DEA administrator had an impact. The agency embarked on a years-long campaign to slash production quotas for opioid manufacturers, which now stand at their lowest levels in two decades. Since their peak, DEA production quotas have fallen by 65% for oxycodone and 73% for hydrocodone. And the U.S. now has chronic shortages of opioid medication.    

Flash forward to 2023, and Sens. Markey and Manchin are at it again, but in a different way.  

In a new letter --- this time to the Food and Drug Administration – the senators called on the agency to scrap plans for a new clinical trial that could help prove whether opioids are effective long term – the very thing the senators said there was “insufficient research” on just a few years ago.

“Other studies have already evaluated prolonged opioid use,” Markey and Manchin wrote in their letter, which was first reported by STAT.

SENS. JOE MANCHIN AND ED MARKEY

At issue is an FDA plan to use a research design known as enriched enrollment randomized withdrawal (EERW) to study the use of opioids by patients with chronic pain – persistent pain that lasts for over three months.  Such a study would require patients on extended-release morphine to either continue taking the medication or be unwittingly switched to a placebo – which would essentially amount to a rapid taper with no pain relief.  

Markey and Manchin say such a study is biased in favor of opioids and would “needlessly expose” patients on morphine to the risk of addiction. They also make the dubious claim that long-term clinical studies of opioids are no longer needed, citing a controversial Australian study – known as the OPAL study -- that found low dose opioids gave little relief to patients with back and neck pain.

“A recent randomized placebo-controlled study found that prolonged opioid use was ineffective for acute back and neck pain. The study found that after six weeks, there was no significant difference in pain scores for the patients taking opioids compared to those who took a placebo,” the senators wrote.

Critics were quick to note the OPAL study has a number of flaws, the most obvious one being that the treatment period only lasted six weeks. OPAL was a short-term study of opioids for acute pain – not “prolonged opioid use” as Manchin and Markey claimed.   

“The letter by Markey and Manchin is a phenomenon of misinformation and lack of understanding of the opioid crises,” said Stephen Nadeau, MD, a Professor of Neurology at the University of Florida College of Medicine.

“The OPAL study indisputably examined only ACUTE neck and back pain; it is completely inappropriate to apply its results to chronic pain,” said Chad Kollas, MD, a palliative care physician and pain policy expert.

Kollas posted a long thread on Twitter (now known as X) debunking other aspects of the OPAL study, saying its findings were “overstated & oversimplified to support the policy agenda of opioid reductionists.”

“I believe Manchin and Markey are being influenced to shut down any public funding of research that would demonstrate positive benefits for the long-term use of opioids -- of which, enriched enrollment trials are a prime example. By whom, I do not know,” says patient advocate Richard “Red” Lawhern.   

The “whom” in this case appears to be Dr. Andrew Kolodny, the president and founder of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group that is funded by dark money. Several PROP members, including Kolodny, have repeatedly failed to disclose their conflicts of interest and enriched themselves by testifying as paid expert witnesses in opioid litigation cases.  

Kolodny has worked previously with Manchin on anti-opioid legislation and is apparently doing so again. Manchin is co-sponsoring a bill that would require the FDA to review the use of EERW studies on opioids. Kolodny is quoted in a recent Manchin press release promoting the senator’s bill. 

“The FDA has been putting new painkillers on the market based on improper studies that skew results in favor of approval. The methodology they're using was cooked up in private meetings with drug makers. The time for outside experts to examine the use of enriched enrollment randomized withdrawal is long overdue,” said Kolodny, who is Medical Director of Opioid Policy Research at Brandeis University.  

Coincidentally, when the OPAL study was published in The Lancet medical journal, it was accompanied by an invited commentary from two other PROP members, Drs. Jane Ballantyne and Mark Sullivan, who said the study “raises serious questions about the use of opioid therapy for acute low back and neck pain.”

More Opioid Studies Needed

Although opioids have been used for thousands of years for pain relief, there are surprisingly few placebo-controlled clinical studies of their long-term effectiveness. That is mainly due to the ethical issues involved in giving a placebo to someone in pain. Few pain patients would want to participate in a long-term study in which there’s a good chance they don’t get any pain relief. And few studies duplicate the real world experiences of pain sufferers.

“Depriving patients of benefits they might gain from receiving LTOT (long term opioid therapy) ethically precludes using randomized controlled studies (RCTs) as a research method in studying LTOT. This necessitates using other types of research, including the type of research that the senators seek to eliminate,” Kollas told PNN.

“The reason that RCTs of opioids for chronic pain have failed is very simple:  the trial design is fundamentally flawed. It is simply not adequate to address the scientific question at hand,” says Nadeau. “EERW trials have shown promise, and certainly more evidence of efficacy then the conventionally designed trials, but they have their problems.” 

Nadeau and other have proposed that EERW studies be modified so that patients on opioids are gradually tapered, not just suddenly switched to a placebo. 

“What is glaringly evident is that the gold standard of randomized double-blind trials cannot be applied with opioids because of very high failure rates in the placebo arm, due to breakthrough pain,” said Lawhern. “Moreover, even short-term trials are invalidated by protocols that do not remotely resemble actual clinical use of these medications.”  

As flawed as they might be, EERW studies may be a way to fill in some of the missing gaps in opioid research. Do opioids work long-term? Do they inevitably lead to addiction?  Are chronic pain patients helped or harmed by using opioids? Those are simple questions we still don’t have definitive answers to – and may never know if politicians dictate health policy and try to block much needed pain research. 

“We ask the FDA not to permit the use of EERW to determine the long-term efficacy and tolerability of opioids in chronic pain patients. We also urge you to reject EERW study designs for any future new drug applications for opioids and reconsider past opioid approval decisions using EERW,” Manchin and Markey wrote.

‘A Devil’s Bargain’: Why Pharmacy Benefit Managers Are Sticking with Humira

By Arthur Allen, KFF Health News

Tennessee last year spent $48 million on a single drug, Humira — about $62,000 for each of the 775 patients who were covered by its employee health insurance program and receiving the treatment. So when nine Humira knockoffs, known as biosimilars, hit the market for as little as $995 a month, the opportunity for savings appeared ample and immediate.

But it isn’t here yet. Makers of biosimilars must still work within a health care system in which basic economics rarely seems to hold sway.

For real competition to take hold, the big pharmacy benefit managers, or PBMs, the companies that negotiate prices and set the prescription drug menu for 80% of insured patients in the United States, would have to position the new drugs favorably in health plans.

They haven’t, though the logic for doing so seems plain.

Humira has enjoyed high-priced U.S. exclusivity for 20 years. Its challengers could save the health care system $9 billion and herald savings from the whole class of drugs called biosimilars — a windfall akin to the hundreds of billions saved each year through the purchase of generic drugs.

The biosimilars work the same way as Humira, an injectable treatment for rheumatoid arthritis and other autoimmune diseases. And countries such as the United Kingdom, Denmark, and Poland have moved more than 90% of their Humira patients to the rival drugs since they launched in Europe in 2018.

Kaiser Permanente, which oversees medical care for 12 million people in eight U.S. states, switched most of its patients to a biosimilar in February and expects to save $300 million this year alone.

Biosimilars Are Cheaper

Biologics — both the brand-name drugs and their imitators, or biosimilars — are made with living cells, such as yeast or bacteria. With dozens of biologics nearing the end of their patent protection in the next two decades, biosimilars could generate much higher savings than generics, said Paul Holmes, a partner at Williams Barber Morel who works with self-insured health plans. That’s because biologics are much more expensive than pills and other formulations made through simpler chemical processes.

For example, after the first generics for the blockbuster anti-reflux drug Nexium hit the market in 2015, they cost around $10 a month, compared with Nexium’s $100 price tag. Coherus BioSciences launched its Humira biosimilar, Yusimry, in July at $995 per two-syringe carton, compared with Humira’s $6,600 list price for a nearly identical product.

“The percentage savings might be similar, but the total dollar savings are much bigger,” Holmes said, “as long as the plan sponsors, the employers, realize the opportunity.”

That’s a big if.

While a manufacturer may need to spend a few million dollars to get a generic pill ready to market, makers of biosimilars say their development can require up to eight years and $200 million. The business won’t work unless they gain significant market share, they say.

The biggest hitch seems to be the PBMs. Express Scripts and Optum Rx, two of the three giant PBMs, have put biosimilars on their formularies, but at the same price as Humira. That gives doctors and patients little incentive to switch. So Humira remains dominant for now.

“We’re not seeing a lot of takeup of the biosimilar,” said Keith Athow, pharmacy director for Tennessee’s group insurance program, which covers 292,000 state and local employees and their dependents.

The ongoing saga of Humira — its peculiar appeal to drug middlemen and insurers, the patients who’ve benefited, the patients who’ve suffered as its list price jumped sixfold since 2003 — exemplifies the convoluted U.S. health care system, whose prescription drug coverage can be spotty and expenditures far more unequal than in other advanced economies.

Biologics like Humira occupy a growing share of U.S. health care spending, with their costs increasing 12.5% annually over the past five years. The drugs are increasingly important in treating cancers and autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease, that afflict about 1 in 10 Americans.

Humira’s $200 billion in global sales make it the best-selling drug in history. Its manufacturer, AbbVie, has aggressively defended the drug, filing more than 240 patents and deploying legal threats and tweaks to the product to keep patent protections and competitors at bay.

The company’s fight for Humira didn’t stop when the biosimilars finally appeared. The drugmaker has told investors it doesn’t expect to lose much market share through 2024. “We are competing very effectively with the various biosimilar offerings,” AbbVie CEO Richard Gonzalez said during an earnings call.

How AbbVie Maintains Market Share

One of AbbVie’s strategies was to warn health plans that if they recommended biosimilars over Humira they would lose rebates on purchases of Skyrizi and Rinvoq, two drugs with no generic imitators that are each listed at about $120,000 a year, according to PBM officials. In other words, dropping one AbbVie drug would lead to higher costs for others.

Industry sources also say the PBMs persuaded AbbVie to increase its Humira rebates — the end-of-the-year payments, based on total use of the drug, which are mostly passed along by the PBMs to the health plan sponsors. Although rebate numbers are kept secret and vary widely, some reportedly jumped this year by 40% to 60% of the drug’s list price.

The leading PBMs — Express Scripts, Optum, and CVS Caremark — are powerful players, each part of a giant health conglomerate that includes a leading insurer, specialty pharmacies, doctors’ offices, and other businesses, some of them based overseas for tax advantages.

Yet challenges to PBM practices are mounting. The Federal Trade Commission began a major probe of the companies last year. Kroger canceled its pharmacy contract with Express Scripts last fall, saying it had no bargaining power in the arrangement, and, on Aug. 17, the insurer Blue Shield of California announced it was severing most of its business with CVS Caremark for similar reasons.

Critics of the top PBMs see the Humira biosimilars as a potential turning point for the secretive business processes that have contributed to stunningly high drug prices.

Although list prices for Humira are many times higher than those of the new biosimilars, discounts and rebates offered by AbbVie make its drug more competitive. But even if health plans were paying only, say, half of the net amount they pay for Humira now — and if several biosimilar makers charged as little as a sixth of the gross price — the costs could fall by around $30,000 a year per patient, said Greg Baker, CEO of AffirmedRx, a smaller PBM that is challenging the big companies.

Multiplied by the 313,000 patients currently prescribed Humira, that comes to about $9 billion in annual savings — a not inconsequential 1.4% of total national spending on pharmaceuticals in 2022.

The launch of the biosimilar Yusimry, which is being sold through Mark Cuban’s Cost Plus Drugs pharmacy and elsewhere, “should send off alarms to the employers,” said Juliana Reed, executive director of the Biosimilars Forum, an industry group. “They are going to ask, ‘Time out, why are you charging me 85% more, Mr. PBM, than what Mark Cuban is offering? What is going on in this system?’”

Cheaper drugs could make it easier for patients to pay for their drugs and presumably make them healthier. A KFF survey in 2022 found that nearly a fifth of adults reported not filling a prescription because of the cost. Reports of Humira patients quitting the drug for its cost are rife.

Inflated Sticker Prices

When Sue Lee of suburban Louisville, Kentucky, retired as an insurance claims reviewer and went on Medicare in 2017, she learned that her monthly copay for Humira, which she took to treat painful plaque psoriasis, was rising from $60 to $8,000 a year.

It was a particularly bitter experience for Lee, now 81, because AbbVie had paid her for the previous three years to proselytize for the drug by chatting up dermatology nurses at fancy AbbVie-sponsored dinners. Casting about for a way to stay on the drug, Lee asked the company for help, but her income at the time was too high to qualify her for its assistance program.

“They were done with me,” she said. Lee went off the drug, and within a few weeks the psoriasis came back with a vengeance. Sores covered her calves, torso, and even the tips of her ears. Months later she got relief by entering a clinical trial for another drug.

Health plans are motivated to keep Humira as a preferred choice out of convenience, inertia, and fear. While such data is secret, one Midwestern firm with 2,500 employees told KFF Health News that AbbVie had effectively lowered Humira’s net cost to the company by 40% after July 1, the day most of the biosimilars launched.

One of the top three PBMs, CVS Caremark, announced in August that it was creating a partnership with drugmaker Sandoz to market its own cut-rate version of Humira, called Hyrimoz, in 2024. But Caremark didn’t appear to be fully embracing even its own biosimilar. Officials from the PBM notified customers that Hyrimoz will be on the same tier as Humira to “maximize rebates” from AbbVie, Tennessee’s Athow said.

Most of the rebates are passed along to health plans, the PBMs say. But if the state of Tennessee received a check for, say, $20 million at the end of last year, it was merely getting back some of the $48 million it already spent.

“It’s a devil’s bargain,” said Michael Thompson, president and CEO of the National Alliance of Healthcare Purchaser Coalitions. “The happiest day of a benefit executive’s year is walking into the CFO’s office with a several-million-dollar check and saying, ‘Look what I got you!’”

Executives from the leading PBMs have said their clients prefer high-priced, high-rebate drugs, but that’s not the whole story. Some of the fees and other payments that PBMs, distributors, consultants, and wholesalers earn are calculated based on a drug’s price, which gives them equally misplaced incentives, said Antonio Ciaccia, CEO of 46Brooklyn, a nonprofit that researches the drug supply chain.

“The large intermediaries are wedded to inflated sticker prices,” said Ciaccia.

AbbVie has warned some PBMs that if Humira isn’t offered on the same tier as biosimilars it will stop paying rebates for the drug, according to Alex Jung, a forensic accountant who consults with the Midwest Business Group on Health.

AbbVie did not respond to requests for comment.

One of the low-cost Humira biosimilars, Organon’s Hadlima, has made it onto several formularies, the ranked lists of drugs that health plans offer patients, since launching in February, but “access alone does not guarantee success” and doesn’t mean patients will get the product, Kevin Ali, Organon’s CEO, said in an earnings call in August.

If the biosimilars are priced no lower than Humira on health plan formularies, rheumatologists will lack an incentive to prescribe them. When PBMs put drugs on the same “tier” on a formulary, the patient’s copay is generally the same.

In an emailed statement, Optum Rx said that by adding several biosimilars to its formularies at the same price as Humira, “we are fostering competition while ensuring the broadest possible choice and access for those we serve.”

Switching a patient involves administrative costs for the patient, health plan, pharmacy, and doctor, said Marcus Snow, chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

Doctors Reluctant to Switch

Doctors seem reluctant to move patients off Humira. After years of struggling with insurance, the biggest concern of the patient and the rheumatologist, Snow said, is “forced switching by the insurer. If the patient is doing well, any change is concerning to them.” Still, the American College of Rheumatology recently distributed a video informing patients of the availability of biosimilars, and “the data is there that there’s virtually no difference,” Snow said. “We know the cost of health care is exploding. But at the same time, my job is to make my patient better. That trumps everything.”

“All things being equal, I like to keep the patient on the same drug,” said Madelaine Feldman, a New Orleans rheumatologist.

Gastrointestinal specialists, who often prescribe Humira for inflammatory bowel disease, seem similarly conflicted. American Gastroenterological Association spokesperson Rachel Shubert said the group’s policy guidance “opposes nonmedical switching” by an insurer, unless the decision is shared by provider and patient. But Siddharth Singh, chair of the group’s clinical guidelines committee, said he would not hesitate to switch a new patient to a biosimilar, although “these decisions are largely insurance-driven.”

HealthTrust, a company that procures drugs for about 2 million people, has had only five patients switch from Humira this year, said Cora Opsahl, director of the Service Employees International Union’s 32BJ Health Fund, a New York state plan that procures drugs through HealthTrust.

But the biosimilar companies hope to slowly gain market footholds. Companies like Coherus will have a niche and “they might be on the front end of a wave,” said Ciaccia, given employers’ growing demands for change in the system.

The $2,000 out-of-pocket cap on Medicare drug spending that goes into effect in 2025 under the Inflation Reduction Act could spur more interest in biosimilars. With insurers on the hook for more of a drug’s cost, they should be looking for cheaper options.

For Kaiser Permanente, the move to biosimilars was obvious once the company determined they were safe and effective, said Mary Beth Lang, KP’s chief pharmacy officer. The first Humira biosimilar, Amjevita, was 55% cheaper than the original drug, and she indicated that KP was paying even less since more drastically discounted biosimilars launched. Switched patients pay less for their medication than before, she said, and very few have tried to get back on Humira.

Prescryptive, a small PBM that promises transparent policies, switched 100% of its patients after most of the other biosimilars entered the market July 1 “with absolutely no interruption of therapy, no complaints, and no changes,” said Rich Lieblich, the company’s vice president for clinical services and industry relations.

AbbVie declined to respond to him with a competitive price, he said.

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

Moderation – Not Prohibition – Is Key to Treating ER Patients With Opioids

By Pat Anson, PNN Editor

Over the years many people living with pain have told us that they avoid going emergency rooms because they fear their pain will be ignored and that they’ll be treated as an addict if they ask for opioids.  

“Going to the ER terrifies me and I am an RN,” one patient said. “I was recently there on 2 separate episodes for kidney stones. Over a three-day period they gave me absolutely nothing for pain!” 

“I can't and won't return to an ER even if I am dying because I won't accept being treated like an addict ever again,” said a 60-year-old disabled woman.  

“It took me 12 hours and a staged public fit to get any pain relief at my local ER when I went in with a pinched nerve,” another patient told us. 

“Called suicide hotline and was told to go to ER,” said a woman suffering from a severe flare from rheumatoid arthritis. “Well, that was a waste. Told I was drug seeking and received a hefty bill to pile on top of all the others.”

A new study suggests that moderation – not prohibition -- is the key to treating pain in the ER with opioids. Researchers in Canada found that half of patients discharged from an emergency department needed only a handful of opioid tablets to control their pain.

“Patients are often prescribed too many opioid tablets and that means unused tablets are available for misuse,” Raoul Daoust, MD, a professor of Family and Emergency at University of Montreal, said in a press release. “On the other hand, since the opioid crisis, the tendency in the USA is to not prescribe opioids at all, leaving some patient in agonising pain.

“With this research I wanted to provide a tailored approach to prescribing opioids so that patients have enough to manage their pain but almost no unused tablets available for misuse.”

Daoust and his colleagues surveyed 2,240 adult patients who were treated for acute pain at one of six hospital emergency departments in Canada. All were discharged with an opioid prescription and were asked to complete a pain diary for two weeks.

Their findings, presented over the weekend at the European Emergency Medicine Congress in Spain, showed five or fewer morphine tablets (5mg) were adequate for about half the patients. The rest needed more tablets, depending on their condition. For example, patients suffering from renal colic or abdominal pain needed eight tablets, while a patient with broken bones needed 24 tablets. 

Daoust says emergency room physicians need to recognize that morphine can be “very beneficial” for patients. The key is to individualize treatment and prescribe the right amount to minimize the risk of addiction.

“Our findings make it possible to adapt the quantity of opioids we prescribe according to patient need. We could ask the pharmacist to also provide opioids in small portions, such as five tablets initially, because for half of patients that would be enough to last them for two weeks,” said Daoust.

The researchers plan to apply their findings in a clinical setting to evaluate whether they can reduce the long-term use and misuse of opioids. 

“This study shows how opioid prescriptions could be adapted to specific acute pain conditions, and how they could be dispensed in relatively small numbers at the pharmacy to lower the chance of misuse. This research could provide a safer way to prescribe opioids that could be applied in emergency departments anywhere in the world,” said Youri Yordanov, MD, an emergency physician at Saint-Antoine Hospital in Paris, who was not involved in the research.

A large 2017 study found that the risk of long-term opioid use is lower for ER patients than it is for patients treated in other medical settings. Researchers found that only 1.1% percent of ER patients taking opioids for the first time progressed to long term use. That compares to 2% of patients in non-emergency settings.

Stimulants Involved in Growing Number of Fentanyl Overdoses

By Pat Anson, PNN Editor

The number of drug deaths involving both fentanyl and stimulants has soared in recent years, according to a new UCLA study that highlights the complex and changing nature of the U.S. overdose crisis.

Stimulants such as cocaine and methamphetamine are now involved in nearly a third of fentanyl-related overdoses, the most of any other drug class. Fentanyl is a synthetic opioid up to 100 times more potent than morphine and 50 times as potent as heroin.

In 2010, researchers say there were only 235 fatal overdoses in the U.S. involving illicit fentanyl and stimulants. In 2021, there were 34,429 drug deaths linked to fentanyl and stimulants, a 14,550% increase in a little over a decade.

"We're now seeing that the use of fentanyl together with stimulants is rapidly becoming the dominant force in the US overdose crisis," said lead author Joseph Friedman, PhD, an addiction researcher at the David Geffen School of Medicine at UCLA. "Fentanyl has ushered in a polysubstance overdose crisis, meaning that people are mixing fentanyl with other drugs, like stimulants, but also countless other synthetic substances. This poses many health risks and new challenges for health care providers.

“We have data and medical expertise about treating opioid use disorders, but comparatively little experience with the combination of opioids and stimulants together, or opioids mixed with other drugs. This makes it hard to stabilize people medically who are withdrawing from polysubstance use."

People who overdose on stimulants and other non-opioid substances mixed with fentanyl may not be as responsive to naloxone, which only works as an antidote to opioids.

The study findings, published in the journal Addiction, highlight the four “waves” of the overdose crisis, which began with an increase in deaths from prescription opioids (Wave 1) in the early 2000s, followed by a rise in heroin deaths (Wave 2) in 2010, and fentanyl-related overdoses in 2013 (Wave 3). The fourth wave — overdoses from fentanyl and stimulants — began in 2015 and continues to escalate.

The Four Waves of Overdose Crisis

SOURCE: ADDICTION

Since cocaine, methamphetamine and other stimulants are not opioids, the findings undercut the long-held theory that the overdose crisis started with prescription opioids and is still being fueled by people addicted to them. Deaths involving prescription opioids and heroin have been in decline for several years.

Researchers found that fentanyl/stimulant deaths disproportionately affect African Americans and Native Americans. There are also geographical patterns to fentanyl/stimulant use. In the northeast US, fentanyl is usually combined with cocaine, while in the south and western US, fentanyl is most commonly found with methamphetamine.

"We suspect this pattern reflects the rising availability of, and preference for, low-cost, high-purity methamphetamine throughout the US, and the fact that the Northeast has a well-entrenched pattern of illicit cocaine use that has so far resisted the complete takeover by methamphetamine seen elsewhere in the country," Friedman said.

In addition to its low cost, drug users say methamphetamine helps prolong fentanyl’s “high” and delays the onset of withdrawal symptoms.  

Counterfeit pills laced with fentanyl – which are frequently made to look like oxycodone or alprazolam (Xanax) – represent about a quarter of all illicit fentanyl seizures. Researchers say it is difficult to track deaths involving counterfeit pills because they are often mistaken for legitimate medication, so the data is not completely reliable.

In its most recent update on the overdose crisis, the CDC estimates there were a record 111,355 drug deaths in the 12-month period ending April 2023 -- about a thousand more deaths than the year before. Fentanyl and its analogues were involved in nearly 70% of the overdoses, stimulants were linked to about a third of them, and cocaine was involved in about a quarter of the drug deaths.

The National Opioid Settlement Is Causing Drug Shortages

By Pat Irving, Guest Columnist

I am a retired nurse with over 40 years of healthcare experience. The principal focus of my career was on healthcare regulations, risk management and patient safety.  My most recent position was as National Leader for Risk and Patient Safety for Kaiser Permanente. 

As a pain patient myself and the victim of a mandatory opioid taper, I was motivated to understand the reasons behind the many difficulties patients have getting opioids, anti-anxiety medications and other controlled substances. 

The goal of my research over the last several months is to help patients and their families understand the drastic changes in pain management that have occurred in recent years. While much of it is due to the CDC opioid guideline and the law enforcement crackdown on prescribers, the fallout from opioid litigation now plays a major role in our inability to get prescriptions filled.

As early as 2017, acting on the incorrect premise that prescription opioids were the primary cause for the opioid crisis, the National Association of Attorneys General began a legal assault on entities they believed were responsible for the “opioid crisis.”  This included opioid manufacturers, big chain pharmacies, and the three biggest wholesale distributors -- AmerisourceBergen, Cardinal Health, and McKesson.

On July 21, 2021, the Attorneys General announced that they had reached a $26 billion settlement with the three distributors and Johnson & Johnson, who agreed to make major changes in how they do business.  The intent was to improve the safety and oversight of prescription opioids, but the unintended consequences of the settlement have caused incalculable harm to patients with chronic pain and mental health disorders.

In addition to the monetary settlement, the three distributors agreed to substantially increase measures to identity suspicious orders from pharmacies for ten years.  The distributors, collectively known as “Injunctive Relief Distributors,” also established an independent clearinghouse to keep track of every shipment of opioids and other controlled substances to pharmacies.

Red Flags and Suspicious Orders

For reference, the 571-page settlement can be found at this link.  The most important section (Exhibit “P”) begins on page 478.  Among other things, it requires the distributors to collect from each pharmacy a list of their top prescribers for opioids and other “Highly Diverted Controlled Substances,” the number of prescriptions and doses they wrote, their DEA registration number, address and medical specialty.

You may notice several other things.  Many of the restrictions came directly out of DEA regulations.  For example, there is language about “Red Flags” and “Suspicious Orders,” the latter being “orders of unusual size, orders deviating substantially from a normal pattern, and orders of unusual frequency.”

Other potential red flags include patients paying for a prescription in cash and “out-of-area” patients with prescribing doctors from a zip code that’s 50 miles or more from the pharmacy. 

If a pharmacy customer has an excessive number of suspicious orders or “unresolved Red Flag activity,” it risks being “terminated” from receiving further controlled substances – which would effectively put the pharmacy out of business: 

“In the event that an Injunctive Relief Distributor identifies one or more unresolved Red Flags or other information indicative of potential diversion of Controlled Substances through the onboarding process or otherwise, the Injunctive Relief Distributor shall refrain from selling Controlled Substances to the potential Customer pending additional due diligence.”

It is easy to see why the settlement has made pharmacists more hesitant, even fearful, about filling orders that might be suspicious. 

Under federal law, pharmacists already had a “corresponding authority” to decide whether a prescription is suspicious and if it should be filled. Whereas before a pharmacist might call a prescriber to double check on a prescription and the reasons for it, under the settlement a pharmacist may err on the side of caution and not fill the prescription at all.

To make the situation worse, the definitions of “suspicious orders” are purposely vague, and may be interpreted in the strictest way possible.  For example, since the CDC guideline recommends that physicians “should carefully evaluate” increasing doses above 50 morphine milligram equivalents (MME), the distributor or pharmacy may see that as hard limit, not a suggestion.  

And because the CDC guideline urges caution when prescribing opioids and benzodiazepines together, that may be another hard stop on a prescription, regardless of how long or how safely a patient was managed on these medications. There may be serious consequences for the prescribing physician as well, who could be reported to state authorities and the DEA if they have too many suspicious prescriptions.

Medication Thresholds 

The injunction also brought with it medication “thresholds.”  Unlike the annual DEA production quotas which are imposed on drug makers nationwide, the settlement thresholds are very specific to each pharmacy or pharmacy chain. It limits the total volume of a controlled substance that a pharmacy may receive in any given month, quarter and year.  These threshold limits, are developed by the distributor using a statistical algorithm of their own design. 

Once a pharmacy has exceeded its particular threshold, it is unable to obtain additional medication in that drug category. Physicians and patients have no way of knowing if they are the unlucky ones to have exceeded a pharmacy’s threshold.  For many patients, this means being cutoff cold turkey, waiting another month, or having a prescription only partially filled – essentially a forced taper.

Many health plans talk about their concern for patient safety, but there is often a lack of information given to patients about the known risks of tapering, especially for “legacy” patients who have been on prescribed opioids for an extended period, and who were stable and doing well. There is often no discussion with the tapered patient on the possibility of withdrawal, suicidal thoughts, anxiety, depression, and unmanaged pain. 

The patient population most affected by the distributors’ settlement are either disabled, seniors or both.  This is the very population that has difficulty accessing alternative pain therapies such as acupuncture or injections, and in many cases are alone and homebound. It has been almost impossible to get attention for this segment of the population that needs the most support. 

There has been no strong response to the settlement and resulting drug shortages from the Health and Human Services Administration, DEA, CDC, or FDA.  There has also been a lack of a coordinated response from Medicare/CMS to patients being forcibly tapered. 

It is likewise unclear what position state medical and pharmacy boards are taking on the ruptured drug supply chain. Many patients with legitimate prescriptions now have to wait weeks for their medications to become available or are forced to travel to other pharmacies to get their prescriptions filled. Worst of all, the suffering imposed on these patients has done nothing to reduce the number of drug overdose deaths.

Our government must wake up to the fact that the injunction portion of the settlement must be modified.  There are sections of the settlement that allow for “potential adjustments” and “modifications” in the event of a national or state emergency “to meet the critical needs of the supply chain.” Such an emergency now exists.

Future efforts by stakeholders must focus attention on these sections and the need for changes. It is possible to have a safe and well monitored drug supply chain that also allows legitimate patients to have the medical treatment they deserve. As it stands now, patients are needlessly suffering due to the unreasonable restrictions imposed by the national opioid settlement.

Pat Irving, RN, lives with Complex Regional Pain Syndrome (now in remission) and piriformis syndrome, a type of sciatica. Pat wishes to thank Monty Goddard, a patient advocate, for his contributions to her research.

Rx Opioid Shortages Persist With No Federal Action

By Pat Anson, PNN Editor

There is no end in sight to shortages of opioid pain medication in the US, with the federal government taking no apparent action to increase opioid production and several drug makers unable to estimate when full supplies will be restored.

In a recent update, the American Society of Health-System Pharmacists (ASHP) said five generic drug makers were running low or have exhausted their supply of oxycodone/acetaminophen tablets, which are better known as the brand names Percocet and Endocet. The medication is usually prescribed for moderate to severe pain.   

ASHP asked drug makers about their current supplies and received these responses:

• Camber has no doses of oxycodone/acetaminophen available. The tablets are on back order and “the company cannot estimate a release date.” Camber said it was still awaiting DEA approval for additional supplies.

• Amneal and KVK-Tech said they had limited supplies of 5 and 7.5 mg oxycodone/acetaminophen tablets, and that 10 mg tablets were on back order with no estimated resupply date.

• Major anticipates getting 7.5 mg tablets in late September and 10 mg tablets in late October.

• Rhodes said it had 7.5 and 5 mg tablets on “intermittent back order” and would only be releasing supplies as they become available.

Percocet and Endocet tablets in various doses are still available from Endo and Par Pharmaceuticals, according to the ASHP.

Shortages of oxycodone/acetaminophen tablets, as well as immediate release oxycodone and hydrocodone/acetaminophen tablets, were first reported by ASHP several months ago. But they have yet to appear on the FDA’s drug shortage list or even be publicly acknowledged by the agency.

In a recent joint letter, FDA Commissioner Robert Califf, MD, and DEA administrator Anne Milgram said they were working “as quickly as possible” to resolve persistent drug shortages. But the letter only addressed shortages of prescription stimulants used to treat ADHD, and makes no mention of opioids.

When asked by PNN, one federal health official did acknowledge shortages of opioid medication, but was vague about possible solutions.

“This is an important issue that CDC and other federal partners are aware of and working to find solutions to,” said Stephanie Rubel, who heads the CDC’s Overdose Preparedness and Response Team (ORRP). Rubel’s office works with other federal and state agencies to reduce the serious risks posed to patients who suddenly lose access to prescription opioids. 

“As part of ORRP’s work, we strongly encourage state health officials to proactively partner with pharmacists and pharmacies to ensure that impacted patients are able to continue receiving appropriate pain management care after a disruption,” said Rubel in a statement to PNN. “Because ORRP cannot provide medical care or make referrals to healthcare providers, advanced preparation and partnerships with pharmacists is essential to ensure continuity of care.” 

But many pharmacists have their hands tied due to opioid litigation. Last year, three large drug wholesalers reached a $21 billion settlement with 46 states, requiring them to impose strict limits on the pharmacies they do business with. Most pharmacies are capped on the amount of opioids they can dispense in any given month, regardless of patient needs. An unusually large order for opioids could get a pharmacy red-flagged by its wholesale supplier and the order cancelled.  

Another reason for the shortages are persistent problems in the drug supply chain and the heavy US reliance on foreign suppliers for many drugs, especially low-cost generic ones.  A third factor is aggressive cuts in the opioid supply by the DEA, which sets annual production quotas for controlled substances that drug manufacturers must follow.

Whatever the cause, it’s leaving many patients with uncontrolled pain and little faith in their government.

“I've been on hydrocodone for 10 years. With the shortage that is going on in Las Vegas, I've been out for 4 weeks,” one patient told PNN. “Unfortunately, the pain has made it too difficult to take care of myself. I cannot clean, cook or sleep without my pain levels increasing. I've been living on frozen foods and Alka Seltzer.”

“I live with 200 other seniors in a low-income complex.  I’ve seen three older veteran residents commit suicide because they couldn’t get pain medication.  I know several other seniors who live with horrible pain and are not able to get medication,” another patient told us.

“The US Government is just screwing us over by limiting what the pharmacies can get and what their suppliers can make. This is driving people to buy pain meds off the street and that's like playing Russian roulette,” said another patient who has trouble getting Norco prescriptions filled by his pharmacy. “Our government is supposed to help us, not hurt us.”

Drug makers are required to report shortages and supply interruptions to the FDA, but prescribers, pharmacies and consumers can also report them by email to drugshortages@fda.hhs.gov.  

To report a drug shortage to the ASHP, click here.

CDC Report ‘Likely Underestimated’ Deaths Linked to Counterfeit Drugs

By Pat Anson, PNN Editor

A new report from the Centers for Disease Control and Prevention found that fatal overdoses in the U.S. from counterfeit medication more than doubled in recent years, with 93% of those deaths involving illicit fentanyl.

Deaths from counterfeit pills rose from 2% of all overdoses in the third quarter of 2019 to 4.7% of drug deaths in the last quarter of 2021, according to the CDC’s Morbidity and Mortality Weekly Report (MMWR). The overdose rate from fake medication was three times higher in western U.S. states (14.7%). 

However, due the unreliability of death certificates, witnesses and coroner investigations, as well as other flaws in the study’s methodology, the MMWR report acknowledges that the number of deaths involving counterfeit medication is “likely underestimated.”

CDC researchers only looked at overdose data from 34 states and the District of Columbia, identifying 2,437 deaths linked to counterfeit pills during the 30-month study period.

Nearly 106,700 people in the U.S. died from drug overdoses in 2021, so if the 4.7% death rate was applied to that year alone, that would suggest there were over 5,000 deaths nationwide involving counterfeit medication.

Even that estimate is probably on the low end, because CDC researchers focused on counterfeit pills made to look like oxycodone and the anti-anxiety drug alprazolam (Xanax).

While “Mexican Oxy” – blue tablets that look like 30mg oxycodone – are favored by counterfeiters, fake pills are also designed to look like Vicodin, Norco, Adderall, and many other medications. Deaths from those pills were not counted.  

Importantly, whether a death was even linked to fake medication “depended largely on scene or witness evidence of pill use” and other anecdotal evidence, rather than toxicology tests on the pills or the actual people who died.

And while pills are obviously designed to be taken orally, the MMWR report only includes “noningestion routes of drug use,” such as smoking, snorting or injection, which require the pills to be ground into powder or liquefied. CDC researchers considered data on the oral ingestion of counterfeit pills so unreliable, “that information is not presented” in the report.

Many of these details on the study’s strange methodology are buried in the footnotes of the MMWR report, which a casual reader could easily miss. 

Not surprisingly, given the limitations on data, smoking was found to have an outsized role in overdose deaths. According to the MMWR, nearly 40% of the deaths linked to counterfeit medication involved smoking – a misleading statistic, given the study’s flaws. But that didn’t stop researchers from drawing conclusions or recommending “safer smoking practices.”

“The higher percentage of deaths with evidence of drug use by smoking might reflect recent general shifts from injecting drugs to smoking them in western states or could be specific to counterfeit pill use methods,” wrote lead author Julie O’Donnell, PhD, an epidemiologist at the CDC’s National Center for Injury Prevention and Control.

“Harm reduction services that expand outreach to persons using drugs by methods other than injection, such as smoking, and provide education about safer smoking practices and risks related to smoking, might be most successful at addressing diverse drug use patterns.”

There’s a safer way to smoke illicit fentanyl?

This is the CDC’s first MMWR report to look exclusively at deaths caused by fake pills, a public health crisis that the agency has been slow to acknowledge. The DEA started warning about a “fentanyl crisis” as far back as 2016, a time when the CDC was preoccupied with its guideline to reduce opioid prescribing.

There were major flaws in CDC research even back then. The agency eventually admitted that thousands of overdose deaths linked to illicit fentanyl and other street drugs were misclassified as deaths caused by prescription opioids. Some deaths that involved more than one drug were counted multiple times.

Artificial Intelligence May Decide Whether You Get Rx Opioids

By Andy Miller and Sam Whitehead, KFF Health News

Elizabeth Amirault never heard of NarxCare until last year, when she learned its software was tracking her medication use. During a visit to a hospital in Fort Wayne, Indiana, Amirault told a nurse practitioner she was in severe pain and received a puzzling response.

“Your Narx Score is so high, I can’t give you any narcotics,” she recalled the man saying, as she waited for an MRI before a hip replacement.

Tools like NarxCare are used to help medical providers review controlled substance prescriptions. They influence, and can limit, the prescribing of painkillers, similar to a credit score influencing the terms of a loan. NarxCare’s overdose risk ratings – known Narx Scores -- are produced by health care technology company Bamboo Health (formerly Appriss Health).

NarxCare’s software uses artificial intelligence to analyze data about prescriptions for controlled substances to identify patterns of potential problems involving patients and physicians. State and federal health agencies, law enforcement officials, and health care providers have enlisted these tools, but the mechanics behind their algorithm formulas are generally not shared with the public.

Artificial intelligence is working its way into more parts of American life. As AI spreads within the health care landscape, it brings familiar concerns of bias and accuracy and whether government regulation can keep up with rapidly advancing technology.

The use of systems to analyze opioid-prescribing data has sparked questions over whether they have undergone enough independent testing outside of the companies that developed them, making it hard to know how they work. Lacking the ability to see inside these systems leaves only clues to their potential impact.

Some patients say they have been cut off from needed care. Some doctors say their ability to practice medicine has been unfairly threatened.

Researchers warn that such technology — despite its benefits — can have unforeseen consequences if it improperly flags patients or doctors.

“We’re concerned that it’s not working as intended, and it’s harming patients.”

— Jason Gibbons, Health Economist

“We need to see what’s going on to make sure we’re not doing more harm than good,” said Jason Gibbons, a health economist at the Colorado School of Public Health at the University of Colorado’s Anschutz Medical Campus. “We’re concerned that it’s not working as intended, and it’s harming patients.”

Amirault, 34, said she has dealt for years with chronic pain from health conditions such as sciatica, degenerative disc disease, and avascular necrosis, which results from restricted blood supply to the bones.

The opioid Percocet offers her some relief. Amirault had been denied the medication before, but never had been told anything about a Narx Score, she said.

In a chronic pain support group on Facebook, she found others posting about NarxCare, which scores patients based on their supposed risk of prescription drug misuse. She’s convinced her ratings negatively influenced her care.

“Apparently being sick and having a bunch of surgeries and different doctors, all of that goes against me,” Amirault said.

Database-driven tracking has been linked to a decline in opioid prescriptions, but evidence is mixed on its impact on curbing the epidemic. Overdose deaths continue to plague the country, and patients like Amirault have said the monitoring systems leave them feeling stigmatized as well as cut off from pain relief.

The Centers for Disease Control and Prevention estimated that in 2021 about 52 million American adults suffered from chronic pain, and about 17 million people lived with pain so severe it limited their daily activities. To manage the pain, many use prescription opioids, which are tracked in nearly every state through electronic databases known as prescription drug monitoring programs (PDMPs).

The last state to adopt a program, Missouri, is still getting it up and running.

More than 40 states and territories use the technology from Bamboo Health to run PDMPs. That data can be fed into NarxCare, a separate suite of tools to help medical professionals make decisions. Hundreds of health care facilities and five of the top six major pharmacy retailers also use NarxCare, the company said.

The platform generates three Narx Scores based on a patient’s prescription activity involving narcotics, sedatives, and stimulants. A peer-reviewed study showed the “Narx Score metric could serve as a useful initial universal prescription opioid-risk screener.”

NarxCare’s algorithm-generated “Overdose Risk Score” draws on a patient’s medication information from PDMPs — such as the number of doctors writing prescriptions, the number of pharmacies used, and drug dosage — to help medical providers assess a patient’s risk of opioid overdose.

Bamboo Health did not share the specific formula behind the algorithm or address questions about the accuracy of its Overdose Risk Score but said it continues to review and validate the algorithm behind it, based on current overdose trends.

Guidance from the CDC advised clinicians to consult PDMP data before prescribing pain medications. But the agency warned that “special attention should be paid to ensure that PDMP information is not used in a way that is harmful to patients.”

This prescription-drug data has led patients to be dismissed from clinician practices, the CDC said, which could leave patients at risk of being untreated or undertreated for pain. The agency further warned that risk scores may be generated by “proprietary algorithms that are not publicly available” and could lead to biased results.

(Editor’s note: A citizen’s petition filed with FDA earlier this year alleged that NarxCare software “altered the practice of medicine in the U.S. to the detriment of patients,” and sought to have the software declared a misbranded medical device and recalled. The petition by the Center for U.S. Policy was rejected by FDA on technical grounds because it was “not within the scope” of the agency’s petition process.)

Impact on Patients

Bamboo Health says NarxCare’s rating system should never replace decisions made by physicians. But some patients say the risk scores have had an outsize impact on their treatment.

Bev Schechtman, 47, who lives in North Carolina, said she has occasionally used opioids to manage pain flare-ups from Crohn’s disease. As vice president of the Doctor Patient Forum, a chronic pain patient advocacy group, she said she has heard from others reporting medication access problems, many of which she worries are caused by red flags from databases.

“There’s a lot of patients cut off without medication,” according to Schechtman, who said some have turned to illicit sources when they can’t get their prescriptions. “Some patients say to us, ‘It’s either suicide or the streets.’”

The stakes are high for pain patients. Research shows rapid dose changes can increase the risk of withdrawal, depression, anxiety, and even suicide.

Some doctors who treat chronic pain patients say they, too, have been flagged by data systems and then lost their license to practice and were prosecuted.

Lesly Pompy, a pain medicine and addiction specialist in Monroe, Michigan, believes such systems were involved in a legal case against him.

His medical office was raided by a mix of local and federal law enforcement agencies in 2016 because of his patterns in prescribing pain medicine. A year after the raid, Pompy’s medical license was suspended. In 2018, he was indicted on charges of illegally distributing opioid pain medication and health care fraud.

“I knew I was taking care of patients in good faith,” he said. A federal jury in January acquitted him of all charges. He said he’s working to have his license restored.

One firm, Qlarant, a Maryland-based technology company, said it has developed algorithms “to identify questionable behavior patterns and interactions for controlled substances, and for opioids in particular,” involving medical providers.

The company, in an online brochure, said its “extensive government work” includes partnerships with state and federal enforcement entities such as the Department of Health and Human Services’ Office of Inspector General, the FBI, and the Drug Enforcement Administration.

In a promotional video, the company said its algorithms can “analyze a wide variety of data sources,” including court records, insurance claims, drug monitoring data, property records, and incarceration data to flag providers.

William Mapp, the company’s chief technology officer, stressed the final decision about what to do with that information is left up to people — not the algorithms.

Mapp said that “Qlarant’s algorithms are considered proprietary and our intellectual property” and that they have not been independently peer-reviewed.

“We do know that there’s going to be some percentage of error, and we try to let our customers know,” Mapp said. “It sucks when we get it wrong. But we’re constantly trying to get to that point where there are fewer things that are wrong.”

Prosecutions against doctors through the use of prescribing data have attracted the attention of the American Medical Association.

“These unknown and unreviewed algorithms have resulted in physicians having their prescribing privileges immediately suspended without due process or review by a state licensing board — often harming patients in pain because of delays and denials of care,” said Bobby Mukkamala, chair of the AMA’s Substance Use and Pain Care Task Force.

Even critics of drug-tracking systems and algorithms say there is a place for data and artificial intelligence systems in reducing the harms of the opioid crisis.

“It’s just a matter of making sure that the technology is working as intended,” said health economist Gibbons.

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

New DEA Rule Allows Pharmacies to Transfer Opioid Prescriptions

By Pat Anson, PNN Editor

The U.S. Drug Enforcement Administration has adopted a new rule that allows patients, doctors and pharmacists to transfer initial prescriptions for opioids and other controlled substances from one pharmacy to another.  

The rule became effective August 28, but has been in the works for several years. It revises DEA regulations to allow prescribers, hospitals and pharmacists the ability to write, dispense and transfer electronic prescriptions for controlled substances “upon request of the patient.” Under the old rule, prescriptions could not be transferred if a pharmacy is unwilling or unable to fill them – forcing doctors to write a second prescription for another pharmacy and creating delays for patients in need of treatment.

“The final rule amends DEA regulations to explicitly state that an electronic prescription for a controlled substance in schedule II–V may be transferred between retail pharmacies for initial filling on a one-time basis only, upon request from the patient, and clarifies that any authorized refills included on a prescription for a schedule III, IV, or V controlled substance are transferred with the original prescription,” DEA said in a lengthy notice published in the Federal Register.

In recent years, many patients have experienced delays or outright refusals getting prescriptions filled for opioids, stimulants, sedatives, steroids and other medications classified as controlled substances.  The problem has grown worse in recent months, due to chronic shortages of oxycodone, hydrocodone and stimulants.

It would be nice to say the DEA changed the rule to make it easier for patients to get their prescriptions filled, but the agency’s primary goal is to reduce drug diversion. Having doctors write duplicate prescriptions for the same patient is not only a waste of time, in the eyes of the DEA it raises the risk of the original prescription being misused.

“DEA realizes that this scenario creates the potential for duplication of prescriptions, if the practitioner transmits a new prescription to a different pharmacy and does not cancel or void the original prescription that was sent to the first pharmacy. It also recognizes that this scenario creates additional burden for patients, who have to get back in touch with the prescribing practitioner to request a new prescription,” the agency said.

“DEA believes that allowing the electronic transfer of controlled substance prescriptions will decrease the potential for duplicate prescriptions and thus reduce the opportunity for diversion or misuse.”

The diversion of prescription opioids is actually rare. According to the DEA, less than one percent of oxycodone (0.3%) and hydrocodone (0.42%) is lost, stolen or diverted to someone they were not prescribed to.

The DEA estimates the new prescription transfer rule will cost pharmacies over $91 million annually due to additional record-keeping and time spent transferring prescriptions, but will reduce overall costs to the healthcare system by $22 million a year.  

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.