Cost of MS Drugs Soars Despite Competition

By Pat Anson, PNN Editor

The cost of multiple sclerosis drugs has soared over the past decade for Medicare patients to nearly $76,000 per patient annually, according to a new study published in JAMA Neurology.

"We're not talking about patients without health insurance here," said senior author Inmaculada Hernandez, PharmD, assistant professor of pharmacy at the University of Pittsburgh. "We're talking about insured patients, under Medicare. Still, they are paying much more for multiple sclerosis drugs than they were 10 years ago."

Hernandez and her colleagues looked at Medicare Part D claims data from 2006 to 2016 for disease modifying therapies (DMTs) that reduce the frequency and severity of multiple sclerosis (MS) flare-ups. MS is a chronic and progressive disease that attacks the body’s central nervous system, causing pain, numbness, difficulty walking, paralysis, loss of vision, and fatigue.

Some of the most widely used DMTs for treating MS are Copaxone, Tecfidera and Avonex. Although there’s a fair amount of competition between the drugs -- the FDA has approved 19 DMTs for MS – prices have risen in tandem for nearly all of them.

The annual list prices of the drugs more than quadrupled over the 2006-2016 study period, far outpacing inflation.

Not only did the researchers find steep increases in list prices -- the starting point before rebates, coupons or insurance kicks in -- but also in the ultimate costs to both Medicare and its beneficiaries.

"We wanted to see how increases in list prices translated to increases in out-of-pocket spending, and we discovered that actual price increases do get passed down to patients, and that can negatively affect access," said Hernandez.

Alvaro San-Juan-Rodriguez

When it was first introduced by Biogen in 1996, Avonex had an annual list price of about $8,700. Two decades later, Avonex costs nearly $76,000 per patient per year.

“The pharmaceutical and biotechnology industries claim that the high prices reflect the expense of research and development and need to incentivize continued innovation. These claims are never backed up with transparent data,” said Daniel Hartung, PharmD, and Dennis Bourdette, MD, in an editorial in JAMA Neurology. “These drugs have long since recouped any cost of drug development, yet their prices have continued to rise.

“What is driving this increase is uncertain. However, the simplest explanation is that pharmaceutical and biotechnology companies increase prices because they can, they do it to increase their profit margins, and there are few limits on what they can charge.”

Hartung and Bourdette say neurologists who prescribe DMTs should be more aware of their cost. A generic DMT made by Mylan, for example, sells for about $2,000 a month, compared to a branded version that sells for about $6,000.  

Is Ketamine an Opioid?

By Pat Anson, PNN Editor

A drug used to treat depression and pain is being touted as possible solution to the opioid crisis.

This week a South Carolina drug maker said it would partner with a medical device company to sell ketamine in take home medication bags that can be administered by an ambulatory pain pump. The idea is to give patients recovering from surgery a safer alternative to opioids.

“We are proud to partner with InfuTronix Solutions to deliver opioid-free pain medication to patients across the country,” Nephron Pharmaceuticals CEO Lou Kennedy said in a statement. “The overuse of opioids is a crisis in America. Non-narcotic pain management is a cost-saving way that companies like ours can help save lives.”

Non-narcotic? Opioid-free?

That’s not what a team of researchers at Stanford University concluded last year after studying how ketamine works in the brain. In a small clinical study, they gave a dozen patients diagnosed with depression a combination of ketamine and naltrexone – an opioid-receptor blocker. To their surprise, naltrexone stopped ketamine from working as an antidepressant.

In effect, the researchers discovered that ketamine works just like oxycodone, hydrocodone and other painkillers – by activating opioid receptors in the brain. 

“Everything that I was taught, and everything that I’ve always taught my students — all of the evidence supports the fact that ketamine is not an opioid,” said lead author Boris Heifets, MD, a clinical assistant professor of anesthesiology, perioperative and pain medicine. “I was really surprised at the results.”

“And the results were so clear that we ended the study early to avoid exposing additional patients to the ineffective combination treatment,” said co-lead author Nolan Williams, MD, a clinical assistant professor of psychiatry and behavioral science.

The Stanford research, published in The American Journal of Psychiatry, caught psychiatrists and pain management experts by surprise. Some urged caution about the long-term use of ketamine until more can be learned about potential side effects such as addiction. Some depressed patients taken off ketamine have shown signs of withdrawal and became suicidal.

“Given the rapid relapse and potential suicide risk, it is hard to know what to recommend to clinicians. Should they really continue to use the agent beyond an acute course? For how long? In whom?” Alan Schatzberg, MD, a Stanford professor of psychiatry and behavioral sciences, warned in a commentary. “The drug’s opioid properties need to be considered when considering how best to use it.”

‘A Black Eye to Ketamine’

Talk like that has given ketamine a bad rap, according to experts at Johns Hopkins University School of Medicine. They’ve published a commentary of their own, defending the use of ketamine as a necessary treatment for depression that doesn’t respond to typical antidepressants.

“A (Stanford) study done late last year delivered a black eye to ketamine, and as a result of the coverage, there was a wholesale acceptance by both potential patients and physicians that ketamine is an opioid,” says Adam Kaplin, MD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins.

“This is most worrisome if people continue to think this way, particularly in the wake of the opioid epidemic; clinicians won’t refer patients for a treatment, despite that it has been shown to be incredibly effective for many patients with treatment-resistant depression.”

Kaplin says there is ample evidence that ketamine sticks to NMDA receptors in the brain that are involved in learning and memory. Because these NMDA receptors are found together with opioid receptors, Kaplin says it’s no surprise that the can meddle with one another, like interference picked up on a phone call or static on the radio.

“This interference and cross-talk does not mean that ketamine is an opioid, and to wrongly label it as such could eventually keep patients from essential antidepressant medications that could make a huge difference in their quality of life,” said Kaplin, who plans on opening a ketamine clinic.

The debate over whether ketamine is an opioid comes at a time when its use is expanding.  Ketamine was approved by the FDA in 1970 solely as a surgical anesthetic to be taken intravenously or by injection. But a growing number of clinics now offer off-label infusions of ketamine to treat depression, post-traumatic stress disorder and difficult chronic pain conditions such as Complex Regional Pain Syndrome (CRPS).

Demand has grown so much there are reports of ketamine shortages. Although ketamine itself is inexpensive, the infusions can cost several hundred dollars and are not covered by insurance.

Ketamine Nasal Spray

Not until this year did the Food and Drug Administration approve the use of ketamine to treat depression, when it okayed a nasal spray (Spravato) made by Janssen Pharmaceuticals that contains a ketamine compound.

The FDA approved Spravato even though 2 out of 3 short term trials failed to prove its effectiveness. The spray was effective in a longer trial, but only when taken with a conventional antidepressant.

Because of the risk of abuse and side effects, Spravato can only be administered in a doctor’s office, where patients can be observed for two hours after taking a dose. A single dose will cost about $900.

The FDA has called the herbal supplement kratom an opioid because it acts on opioid receptors, but the agency has not taken that step with ketamine. Given current attitudes about opioids, it’s fair to say the FDA would have never approved Spravato if it was considered an opiate.

In addition to its medical uses, ketamine is used as a recreational party drug – known as “Special K” -- because it can cause hallucinations and intense dream-like states.

Whether taken to get high or to treat pain and depression, it’s clear that ketamine is a potent drug that has both harms and benefits. And experts say it needs to be viewed with caution until we know with more certainty how it works.

“Unfortunately, when one approaches ketamine as another antidepressant rather than a drug of abuse, this type of trap is easy to fall into, and in the end, such mistakes can be catastrophic,” Schatzberg said in his commentary. “We have witnessed four decades of supposedly new and safer opioids that have turned out often to be, if anything, even more abusable and lethal."

Surgeons Reduce Rx Opioids Without Increasing Pain

By Pat Anson, PNN Editor

Surgeons in Michigan have reduced the amount of opioid medication prescribed to patients recovering from common operations by nearly a third -- without causing patients to feel more postoperative pain.

In a new research letter published in the New England Journal of Medicine, a team from the Michigan Opioid Prescribing Engagement Network (OPEN) reported on the results of a statewide effort to get surgical teams to follow prescribing guidelines for postoperative pain.

In just one year, surgeons at 43 Michigan hospitals reduced the number of opioid pills prescribed to patients after nine common operations, from an average of 26 pills per patient to an average of 18.

The surgeries included minor hernia repair, appendix and gallbladder removal, and hysterectomies. Most were minimally invasive laparoscopic surgeries.

The ratings patients gave for their post-surgical pain and satisfaction didn't change from the ratings given by patients treated in the six months before opioids were reduced.

Researchers say patients only took about half the opioids prescribed to them, even as the prescription sizes shrank. They attribute this to improved counseling about pain expectations and non-opioid pain control options.

"The success of the statewide effort suggests an opportunity for other states to build on Michigan's experience, and room for even further reductions in prescription size," said Michael Englesbe, MD, a University of Michigan surgery professor. "At the same time, we need to make sure that patients also know how to safely dispose of any leftover opioids they don't take."

The study involved over 11,700 patients who had operations at hospitals participating in the Michigan Surgical Quality Collaborative. About half of the patients also filled out surveys sent to their homes after their operations, asking about their pain, satisfaction and opioid use after surgery.

The Michigan-OPEN team has been working since 2016 to reduce opioid prescribing and quantify the appropriate number of pills patients should take. Their research led to the the development of new guidelines that were first tested on gallbladder surgery patients before being expanded to other types of surgery.

Some hospitals have stopped giving opioids to surgical patients. Patients at Cleveland Clinic Akron General Hospital get acetaminophen, gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs) to manage their pain before and after colorectal operations – and their surgeons say the treatment results in better patient outcomes

It’s a common misconception that many patients become addicted to opioids after surgery. A 2016 Canadian study, for example, found that long term opioid use after surgery is rare, with less than one percent of older adults still taking opioid pain medication a year after major elective surgery.

Another large study in the British Medical Journal found similar results. Only 0.2% of patients who were prescribed opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or a non-fatal overdose.

Another fallacy is that leftover pain medication is often stolen, sold or given away. The DEA says less than one percent of legally prescribed opioids are diverted.

Panel Recommends All Adults Be Screened for Illicit Drug Use

By Pat Anson, PNN Editor

The next time you visit a doctor, he or she may want to know more than what medications you take or if you consume alcohol.

An influential national panel of health experts is recommending for the first time that U.S. doctors screen all adult patients for illicit drug use, including the nonmedical use of opioids and other prescription drugs. “Nonmedical” means the use of a friend’s or relative’s prescription or buying medications off the street. It can also mean using a legal medication more frequently or in higher doses than prescribed.

The U.S. Preventive Services Task Force concluded with “moderate certainty” that screening for illicit drug use would be beneficial because it would lead to a more accurate diagnosis and treatment for substance abuse.

Screening typically involves questions about drug use and frequency. This can include questions on routine intake forms or asking patients directly when they visit with a healthcare provider. Screening does not include drug testing, although nothing would stop a doctor from ordering such tests.

“Illicit drug use can have a devastating impact on individuals and families,” said task force co-vice chair Karina Davidson, PhD, a professor of behavioral medicine at the Zucker School of Medicine at Hofstra University. “Clinicians can help by screening their adult patients and connecting people who use illicit drugs to the care they need to get better.”

About 11.5% of Americans age 18 years or older reported using cannabis or illicit drugs in a national survey. Illicit drug use is more common in young adults ages 18 to 25 years (24.2%) than in older adults (9.5%).  About one in five illicit drug users reported the nonmedical use of psychotherapeutic drugs, including opioids, pain relievers, or other medications. Less than 8% reported using cocaine, hallucinogens, or inhalants.

Although illicit drug use is relatively common among adolescents (7.9%) aged 12 to 17, the task force said there was not enough evidence to support screening for Americans under the age of 18.

“We want to help prevent illicit drug use in teens, so we’re calling for more research on the benefits of screening,” said task force member Carol Mangione, MD, chief of general internal medicine at the David Geffen School of Medicine at UCLA. “Clinicians should continue to use their professional judgement to determine what’s best for their teen patients.”

The task force’s draft report is available for public comment through September 9. After the task force reviews the comments, it will issue a final report. The panel’s recommendations are not mandatory for healthcare providers, but like many federal guidelines – such as the 2016 CDC opioid guideline -- they could be adopted as a “standard of care” by medical associations and healthcare systems.  Some already recommend that providers routinely screen their patients about illicit drug use.

AG’s Call for Weakening of HIPAA Laws

Federal laws that have long protected the privacy of patients undergoing addiction treatment may also be changing. The National Association of Attorneys General wants Congress to end regulations that prevent doctors from sharing information about their patients’ addiction treatment histories.

In a letter recently sent to congressional leaders, 39 state attorneys general called on Congress to “replace the cumbersome, out-of-date, privacy rules” contained in the Health Insurance Portability and Accountability Act (HIPAA). One section of the law – known as 42 CFR Part 2 – sets strict rules about disclosing patient records for substance abuse treatment.

“These privacy rules were created more than 40 years ago in a time of intense stigma surrounding substance use disorder treatment. They were created to assure patients that they would not face adverse legal or civil consequences when seeking treatment by protecting confidentiality of substance use disorder patient records,” the AG’s said.

“Unfortunately, they now serve to perpetuate that stigma, as the principle underlying these rules is that substance use disorder treatment is shameful and records of it should be withheld from other treatment providers in ways that we do not withhold records of treatment of other chronic diseases. While maintaining confidentiality is imperative to encouraging individuals to seek and obtain treatment, the inability to share records among providers can burden coordination of care, potentially resulting in harm to the patient.”

Two bills under consideration in Congress, the Overdose Prevention and Patient Safety Act and the Protecting Jessica Grubb’s Legacy Act would amend 42 CFR Part 2 to allow for addiction treatment records to be shared. The bills have been endorsed by over 40 national healthcare organizations, including the American Hospital Association, the American Psychiatric Association, and the American Society of Addiction Medicine.

Study: Prescription Drug Databases Overestimate Opioid Misuse

By Pat Anson, PNN Editor

Prescription drug monitoring has long been seen as the gold standard for tracking the opioid crisis. Patients who fill an opioid prescription for more than three months are considered long-term users with a higher risk of misuse, addiction and overdose. Many pharmacy chains assign a “risk score” to these patients and their doctors could even get a warning letter from the government.

But in a small study of emergency room patients, Canadian researchers found the risk of opioid misuse by long-term users is small and one out of five patients who fill opioid prescriptions don’t even use them. Their findings suggest that prescription databases alone are a poor way to measure opioid misuse.

“The rate of long‐term opioid use reported by filled prescription database studies should not be used as a surrogate for opioid misuse,” said lead author Raoul Daoust, MD, a professor and researcher in the Department of Family Medicine and Emergency Medicine at the University of Montreal.

Daoust and his colleagues surveyed 524 patients who were discharged from a hospital emergency department (ED) with an opioid prescription for acute pain. Instead of just relying on a database to track their prescriptions, the researchers asked the patients about their opioid use.

Three months after discharge, only 47 patients – about 9 percent – said they were still using opioids. Of those, 72% said they used opioids to treat their initial pain and 19% were using the drugs to treat a new pain condition.

The remaining four patients said they used opioids for another reason, suggesting possible misuse. That’s less than one percent (0.8%) of the original 524 patients.

“Within the limit of our study, our results suggest that the risk of long‐term opioid use for reasons other than pain is low for ED discharged patients with an opioid prescription treating an acute pain condition,” Daoust reported in the journal Academic Emergency Medicine.

Daoust’s findings are controversial because they throw into question the widely accepted theory that all opioid prescribing is risky, whether it’s for chronic or acute pain. The methodology used in his study was questioned by one critic.

"Emergency physicians should not be reassured by the authors' findings. The lack of a denominator, poor response rate (56%), and applied definition of misuse are significant limitations,” said Gail D'Onofrio, MD, a professor of emergency medicine and chair in the department of emergency medicine at Yale University.

D'Onofrio cites a 2017 CDC study, which found that the probability of long-term opioid use increases sharply after the first few days of treatment.

“Transitions from acute to long-term therapy can begin to occur quickly: the chances of chronic use begin to increase after the third day supplied and rise rapidly thereafter,” CDC researchers warned.

But that analysis is based solely on the number of opioid prescriptions – not actual opioid use. And Daoust found that studies like that are a poor way to measure risk.

“These studies used filled prescriptions databases that could overestimate opioid use since not all patients filling an opioid prescription consumed them. As a case in point, in this study, 21% of patients who filled their opioid prescription after the initial ED visit did not consume them,” Daoust reported.

What is the risk of long-term opioid use after an emergency room visit? In a large 2017 study by the Mayo Clinic, only about 1 percent of ER patients given an opioid prescription progressed to long term use – similar to what Daoust found.

"Our paper lays to rest the notion that emergency physicians are handing out opioids like candy," said lead author Molly Moore Jeffery, PhD, scientific director of the Mayo Clinic Division of Emergency Medicine Research. “Most opioid prescriptions written in the emergency department are for shorter duration, written for lower daily doses and less likely to be for long-acting formulations."

A 2018 study also questioned the value of prescription drug monitoring programs (PDMPs) which have long been promoted as critical tools in the fight against opioid abuse. The study found little evidence that PDMPs are reducing overdoses and that they may lead to unintended consequences such as patients turning to street drugs for pain relief.

Are Rx Opioids Scapegoats for the Opioid Crisis?

By Dr. Lynn Webster, PNN Columnist

The Washington Post recently published a series of stories about the volume of opioid medication distributed over the past several years in the United States. Over 76 billion pills were distributed from 2002 through 2012.

That sounds like a huge amount, but it is difficult to know what the number means. What is clear is that the stories are meant to suggest the number of pills is excessive and responsible for the rise in opioid overdose deaths. 

This presumed correlation is one reason for the recent lawsuits that have been filed against opioid manufacturers and distributors. It has also spawned policies that appear to have worsened, not prevented, overdoses.

Though the situation has been framed largely as a prescribing problem, the reasons for the drug crisis are many. While overprescribing has certainly been a factor, it is probably less important than other factors, such as joblessness, homelessness and despair, which are more challenging to address.

Let’s look at the data about the relationship between opioid prescriptions and overdose death rates. The number of opioid prescriptions in the United States peaked in 2012 and began a steady decline. By 2017, they reached a 15-year low.

Despite the decline in the number of opioids prescribed, overdoses from all opioids – both legal and illegal -- continued to increase. Overdoses involving prescription opioids represent only about 25% of the total number of drug overdoses.  

Obviously, something more than the supply of prescription opioids is driving overdoses higher.

No Correlation Between Opioid Prescriptions and Overdoses

After winning a year-long court battle with the Justice Department, the Post and HD Media, publisher of the Charleston Gazette-Mail in West Virginia, were able to access data from the DEA’s Automation of Reports and Consolidated Orders System (ARCOS).

The information in the database shows that, between 2006 and 2012, West Virginia received the largest per capita amount of prescription opioids. The state also experienced the highest opioid-related death rate during that period. Is there a correlation?

Kentucky also had a high number of pills and a high death rate, but as Jacob Sullum recently reported in Reason, Kentucky’s death rate in 2017 was actually lower than Maryland’s and Utah’s, where prescription rates are substantially lower. He also pointed out that although Oregon’s prescription rate was among the highest in the country, the rate of deaths involving pain pills in Oregon was just 3.5 per 100,000, lower than the rates in most states. 

Sullum further showed that Kentucky, Nevada, Oklahoma, Oregon, South Carolina and Tennessee were among the 10 states with the highest per capita prescribed pills during the 2006-2012 period. But they were not the states with the highest overdose rates. 

In a separate analysis, the CDC and Agency for Healthcare Research Quality found no correlation -- not even a weak one -- between opioid prescribing rates and overdoses when comparing data from each state. 

In addition, the rate of opioid prescribing is highest nationally for people 55 years and older, but that age group has the lowest rate.  

This lack of correlation between opioid overdoses and the volume of prescribed opioids is consistent internationally. In 2016, England prescribed the most opioids and saw the most overdose deaths in its history. However, the drug responsible for many of those deaths was heroin, not prescription opioids. 

There is a raging opioid crisis in West Africa where, despite a low prescription rate, the number of overdoses has surged. 

In 2018, Scotland's drug overdose rate exceeded that of the United States -- largely because of heroin. There is no evidence of an overall increase in opioid prescribing in Scotland. 

No Simple Answers to the Opioid Crisis

It is clear that the data does not support a simple answer to the opioid crisis. Focusing all of our efforts on decreasing the supply of prescriptions will not solve the problem and is already creating unintended consequences.

In fact, cocaine and methamphetamine were involved in more overdose deaths in the U.S. in 2018 than prescription opioids. As the supply of prescription opioids has decreased due to the policies of the last few years, people have moved from prescription opioids to other illicit drugs.

The solution to the opioid crisis must be multi-pronged. Overprescribing played a role in causing the crisis, but sociological factors appear to have driven the demand. We must consider what prompts people to turn to drugs in despair. A recent study published in SSM-Population shows job loss bears a significant correlation to opioid-caused deaths.

In addition, in the Proceedings of the National Academy of Sciences, Princeton University economists Anne Case and Angus Deaton (recipient of the 2015 Nobel prize in economics) showed mortality from substance use was linked to declining economic opportunity and financial insecurity.

Solving the drug crisis will not be easy. However, the disenfranchised members of our most impoverished communities deserve viable solutions to their problems. It is crucial to understand the degree to which job loss and hopelessness contribute to the drug problem.

Reputable data proves that the volume of opioids prescribed is not solely, or even primarily, responsible for the opioid crisis. Let’s focus on what is responsible.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, “The Painful Truth” and co-producer of the documentary, “It Hurts Until You Die.”

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Use of NSAIDs Risky for Osteoarthritis Patients

By Pat Anson, PNN Editor

It’s long been known that nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen can raise the risk of cardiovascular problems. A large new study in Canada has documented how NSAIDs can significantly raise the risk of heart disease, congestive heart failure and stroke in people with osteoarthritis.

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. NSAIDs are frequently used to treat the pain and inflammation caused by OA.

The Canadian study, published in the journal Arthritis & Rheumatology, looked at nearly 7,750 osteoarthritis patients in British Columbia and compared them with a control group of over 23,000 patients without OA. The average age of the participants was 65 and a little over half were women.

The risk of developing cardiovascular disease was found to be about 23% higher among people with OA than the control group. Researchers attributed about 41% of that increased risk to the use of NSAIDs.

NSAIDs appeared to play a significant role in several cardiovascular problems. The risk of congestive heart failure was 42% higher among people with OA, followed by a 17% greater risk of heart disease and a 14% greater risk of stroke.

"To the best of our knowledge, this is the first longitudinal study to evaluate the mediating role of NSAID use in the relationship between osteoarthritis and cardiovascular disease in a large population-based sample," said senior author Aslam Anis, PhD, of the School of Population and Public Health at the University of British Columbia.

"Our results indicate that osteoarthritis is an independent risk factor for cardiovascular disease and suggest a substantial proportion of the increased risk is due to the use of NSAIDs. This is highly relevant because NSAIDs are some of the most commonly used drugs to manage pain in patients with osteoarthritis."

The association of cardiovascular disease with NSAIDs is consistent with previous research.  A large international study in 2017, for example, found that prescription strength NSAIDs raises the risk of a heart attack as soon as the first week of use.

NSAIDs are used to alleviate pain and reduce inflammation, and are found in a wide variety of over-the-counter products, including cold and flu remedies. They are found in so many products -- such as Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Canada adopted guidelines in 2017 that recommend NSAIDs as an alternative to opioid pain medication. The guideline makes no mention of the health risks associated with NSAIDs, but focuses on their cost effectiveness.

“NSAID-based treatment may have lower mean costs and higher effectiveness relative to opioids,” the guideline states. “Naproxen-based regimens in particular may be more cost effective compared to opioids and other NSAIDs, such as ibuprofen and celecoxib.”

Opioid guidelines released in 2016 by the U.S. Centers for Disease Control and Prevention also recommend NSAIDs as an alternative to opioids, but acknowledge the medications “do have risks, including gastrointestinal bleeding or perforation as well as renal and cardiovascular risks.”

In 2015, the Food and Drug Administration ordered warning labels for all NSAIDs to indicate they increase the risk of a fatal heart attack or stroke. The FDA warning does not apply to aspirin.

The European Society of Cardiology recommends limited use of NSAIDs by patients who are at risk of heart failure. People already diagnosed with heart failure should refrain from using NSAIDs altogether.

CDC: Still Not Enough Naloxone

By Pat Anson, PNN Editor

The Trump Administration is stepping up efforts to increase prescribing of naloxone, an overdose recovery drug credited with saving thousands of lives.

Although naloxone prescriptions have increased dramatically, a new CDC Vital Signs report estimates that nearly 9 million additional prescriptions could have been dispensed last year if every patient with a high-dose opioid prescription was offered naloxone.  Patients are considered “high risk” if they take an opioid dose of 50 morphine milligram equivalent (MME) or more per day.

Naloxone has been used for years by first responders and emergency medical providers to revive overdose victims. Current efforts are focused on expanding access to the drug by prescribing it directly to patients considered at risk of an overdose.

In 2018, CDC researchers say only one naloxone prescription was dispensed for every 70 high-dose opioid prescriptions nationwide. Naloxone “under-prescribing” was even more acute in rural counties, which are nearly three times more likely to be ranked low in naloxone dispensing than metropolitan counties.

“It is clear from the data that there is still much needed education around the important role naloxone plays in reducing overdose deaths. The time is now to ensure all individuals who are prescribed high-dose opioids also receive naloxone as a potential life-saving intervention,” CDC Director Robert Redfield, MD, said in a statement.

Ironically, federal policies contribute to the under-prescribing. In 2018, most (71%) Medicare prescriptions for naloxone required a copay, compared to 42% for commercial insurance.

In January, the Food and Drug Administration encouraged drug makers to make naloxone available over-the-counter without a prescription. The FDA even developed an OTC label for Narcan, a naloxone nasal spray that sells for about $135. Seven months later, the FDA could not confirm to PNN that any company had submitted an application for an OTC version of naloxone.

Last year the Department of Health and Human Services released guidance urging doctors to “strongly consider” prescribing naloxone to patients on any dose of opioids when they also have respiratory conditions or obstructive sleep apnea, are co-prescribed benzodiazepines, have a mental health or substance abuse disorder, or a history of illegal drug use or prescription opioid misuse.

Many states are also taking steps to increase naloxone prescribing. California now requires doctors to “offer” naloxone prescriptions to pain patients deemed at high risk of an overdose. State law does not make the prescriptions mandatory, yet some patients say they were “blackmailed” by pharmacists who refused to fill their opioid scripts unless naloxone was also purchased. Patients around the country report similar experiences.   

Unintended Consequences

The drumbeat for naloxone comes at a time when sales are already booming. There were 556,000 naloxone prescriptions in 2018, twice as many as in 2017.

There’s no doubt naloxone saves lives, but some researchers say the drug has had little effect on the overdose crisis and may in fact be making it worse. In a recent study published by SSRN, two economics professors warned of “unintended consequences” if naloxone becomes more widely available.

“We expect these unintended consequences to occur through two channels. First, the reduced risk of death makes opioid abuse more appealing, leading some to increase their opioid use — or use more potent forms of the drug — when they have naloxone as a safety net. Some of those abusers may become criminally active to fund their increased drug use,” wrote Jennifer Doleac, PhD, Texas A&M University, and co-author Anita Mukherjee, PhD, University of Wisconsin.

“Furthermore, expanding naloxone access might not in fact reduce mortality. Though the risk of death per opioid use falls, an increase in the number or potency of uses means the expected effect on mortality is ambiguous.”

The researchers said there were anecdotal reports of “naloxone parties” where attendees used heroin and prescription opioids to get high knowing they could be revived. News reports have also quoted first responders who are frustrated that the same opioid abusers “are saved again and again by naloxone without getting treatment.”

Co-Pay Assistance Programs Fail to Help Uninsured Patients

By Pat Anson, PNN Editor

Co-pay assistance programs – also known as co-pay charities – are ostensibly designed to help needy patients pay for prescription drugs. But a new study by researchers at the Johns Hopkins Bloomberg School of Public Health found that nearly all co-pay programs fail to cover uninsured patients who need financial help the most.

The researchers also found that co-pay programs were more likely to cover high-cost, brand-name prescription drugs, despite the availability of lower-priced generic medications. The findings are published online in JAMA.

“Independent patient assistance programs favor higher-priced drugs, and the higher the drug price, the higher the likelihood of it being covered,” says co-author Gerard Anderson, PhD, professor in the Bloomberg School’s Department of Health Policy and Management. “Unfortunately patients with the greatest financial needs -- people without health insurance -- do not qualify for these programs.”

Anderson and his colleagues looked at the six largest charity organizations, which ran 274 different patient assistance programs in 2018.

Most of the programs only covered drugs for cancer-related conditions or genetic and rare diseases. None offered free drugs and typically they only covered the most expensive medications.

“Only covering insured patients may help these programs cover more patients with their limited funds,” said lead author So-Yeon Kang, MPH, a research assistant in the Bloomberg School’s Department of Health Policy and Management. “But leaving out the uninsured diminishes the charitable aspects of these organizations supported by tax-exempted donations.”

Misconduct Widespread

Patient assistance programs run by independent charities are usually funded by pharmaceutical companies. Federal investigations into several co-pay assistance programs led to multimillion-dollar settlements with drug companies for allegedly steering patients to their higher-priced drugs.

Over the past year, Pfizer, Amgen, Jazz Pharmaceuticals, Astellas Pharma, Lundbeck and Alexion have all paid heavy fines to settle allegations that they used co-pay programs to defraud Medicare. Federal anti-kickback laws prohibit pharmaceutical companies from making any kind of payment to induce Medicare patients to purchase their drugs. The prohibition includes co-pays.

“We are committed to ensuring that pharmaceutical companies do not use third-party foundations to pay kickbacks masking the high prices those companies charge for their drugs,”  U.S. Attorney Andrew Lelling said in a statement. “This misconduct is widespread, and enforcement will continue until pharmaceutical companies stop circumventing the anti-kickback laws to artificially bolster high drug prices, all at the expense of American taxpayers.”

Similar allegations were made against Insys Therapeutics and the “Gain Against Pain” co-pay program run by the U.S. Pain Foundation. Insys donated over $3.1 million to U.S. Pain, with most of the money going to its co-pay program to help patients pay for Subsys, an expensive fentanyl spray made by Insys. A four-day supply of Subsys can cost nearly $24,000.

The founder of Insys and four former executives were recently found guilty of racketeering charges unrelated to the co-pay program. The company also agreed to pay $225 million in fines and penalties to settle criminal and civil investigations. U.S. Pain ended the “Gain Against Pain” program in 2018 and said it would no longer accept funding from Insys.

In an editorial, Katherine Kraschel, a lecturer at Yale Law School, and Gregory Curfman, MD, deputy editor of JAMA, called for more oversight of co-pay programs to make sure they help patients who truly need it.

“Although patient assistance programs may provide important financial relief for patients, the current patient assistance program structure largely neglects uninsured individuals,” they wrote.  “Absent other regulatory interventions, the Department of Justice needs to continue to scrutinize patient assistance program practices, and the Internal Revenue Service and state attorneys general should examine the tax-exempt status of patient assistance programs.”

Would Decriminalization Solve the Overdose Crisis?

By Pat Anson, PNN Editor

Vancouver, British Columbia was the first major North American city to be hit by the overdose crisis. In 2016, after a wave of overdose deaths involving illicit fentanyl and even more deadly synthetic opioids like carfentanil, the western Canadian province declared a public health emergency.

Despite efforts to decrease the supply of prescription opioids in BC, over 3,600 more people have overdosed since the emergency was declared, with fentanyl detected in 87% of the deaths last year.

So when BC’s largest healthcare system recommends some radical solutions to the overdose crisis, it’s worth noting. Vancouver Coastal Health (VCH) released a report last month recommending that illegal drugs be decriminalized and that drug users be given access to prescription opioids as an alternative to the black market.

"Legalization and regulation of all psychoactive substances would reduce people's dependence on the toxic illegal supply, criminal drug trafficking and illegal activities that people with addictions must engage in to finance their drug use," said Dr. Patricia Daly, VCH’s chief medical health officer.  

Some Canadian drug policy experts think the idea makes sense.

"The illegal market is an absolute toxic mess right now," Donald MacPherson, executive director of the Canadian Drug Policy Coalition, told the CBC. "It's really in line with consumer protection strategy ... just like we do with every other substance that we ingest, whether it be food or drugs."

Also notable about the VCH report is that – unlike most regulators and politicians in Canada and the U.S. – prescription opioids are not singled out as the root cause of the overdose crisis. Instead, opioid medication is seen as part of the solution.

The report recommends pilot programs to see if prescription fentanyl and other opioid medications made available at supervised consumption sites could help high-risk illicit drug users “transition” to legal opioids.

“Piloting legal access to opioids is different from OAT (opioid agonist therapy) as treatment and would be low-barrier and flexible. Initial pilots would include observation of consumption, followed by pilots allowing distribution of opioids for people to take away for later consumption,” the report recommends.

The idea is controversial, but some doctors are warming up to it. A pilot program recently began at a Vancouver clinic, where hydromorphone tablets are given to about 50 patients who ingest them on site under staff supervision. In Ontario, over 400 healthcare providers and researchers recently signed an open letter asking that high dose injectable hydromorphone be made widely available to illicit drug users.

Substance Abuse and Socioeconomic Problems

The primary cause of the opioid crisis, according to the VCH report, is a “complex interaction” of socioeconomic problems, such as unemployment and homelessness, combined with substance abuse and an increasingly dangerous black market supply.

VCH analyzed the deaths of 424 overdose victims from 2017 and found that less than half (45%) even sought treatment for acute or chronic pain. They were far more likely to be unemployed (72%) and have a substance abuse problem (84%). About four out of ten overdose victims used opioids, alcohol or stimulants daily.

“Most of those who died used multiple substances including opioids, alcohol and stimulants such as cocaine and crystal meth. A significant percentage of those who died of opioid overdoses had primary alcohol use disorder and/or stimulant use disorder,” the report found.

Importantly, most of those who died were no strangers to the healthcare system. The vast majority (77%) had seen a healthcare provider in the year before they overdosed and one out of five (21%) had seen a provider a week before their death. Six out of ten (59%) had received Suboxone or methadone to treat opioid addiction, but the medications were either not effective or they dropped out of treatment.

In addition to decriminalization, the VCH report recommends improving access to addiction treatment, better substance abuse training of healthcare providers, and increased access to the overdose reversal drug naloxone.

Lessons from the Opioid Database

By Roger Chriss, PNN Columnist

Last month The Washington Post made public for the first time a DEA database of opioid prescribing that shows “the path of every single pain pill” sold in the United States from 2006 to 2012.

The Post’s analysis showed that 76 billion pills flowed through the country and nearly 100,000 fatal overdoses occurred over a seven-year period.

Biospace explained that opioid manufacturers, distributors and retailers “allowed the drugs to reach the streets of communities large and small, despite persistent red flags that those pills were being sold in apparent violation of federal law and diverted to the black market.”

The first lesson from the database seems obvious. Too many pills were prescribed, with opioid manufacturers, distributors and retailers failing to report suspicious orders and government agencies failing to oversee the prescription opioid supply.

“If you don’t start millions of opioid-naive people on opioids they don’t need, it translates … in the longer term into fewer overdoses,” Stanford psychiatry professor Keith Humphreys told the Post.

But this misses a key lesson. Although no drug should ever be used when it is not needed, this leaves open the obvious and essential question: How do we reduce risks in people who do need opioids?

We cannot ban opioids completely without returning to pre-Civil War medicine. But each year we have millions of car crashes, severe battlefield and workplace injuries, new cases of cancer, major surgeries and devastating long-term illness.

In the many commentaries on the opioid database, little has been said about improving prescribing safety. We need better ways to use opioids safely because sometimes we just don’t have any other option.

If it is true, as Julie Croft, an Oklahoma addiction treatment provider wrote, “We are all just one accident away from becoming addicted to painkillers” -- then we had better rapidly improve how we use opioids or come up with better alternatives since we have millions of accidents annually.

To this end, Yale and the Mayo Clinic were recently awarded a $5.3 million FDA grant to study patients with acute pain and their use of opioids.

Reduced Prescribing May Not Be Enough

The next lesson in the database is vulnerability to substance abuse. Dennis Scanlon, PhD, and Christopher S. Hollenbeak, PhD, note in the American Journal of Managed Care, that “although using government or regulatory mechanisms to prevent or significantly curb the supply of addictive narcotics is certainly valuable, there is also value in preventing or reducing addiction at its core.”

In other words, policies that reduce opioid prescribing may be helpful, but they may also not be enough. We need better tools and greater understanding of opioid prescribing. The National Institute of Drug Abuse currently estimates that 8% of people on long-term opioid therapy develop some form of opioid use disorder, while The BMJ estimates that less than 1% of surgical patients receiving opioids face a similar fate. These numbers may seem low, but every effort should be made to reduce them.

As bioethicist Travis Reider states in his book “In Pain” about his personal struggle with opioids: “The bottom line is that we are not, by and large, acting decisively in an evidence-based way to tackle the myriad problems raised by opioids. Although we don’t know everything about how to turn the corner on this crisis, we know a lot, and we’re simply not doing it.”

The last essential lesson from the opioid database is that opioid abuse and addiction came long before the crisis. The clichéd response that we “cannot arrest our way” out of the crisis needs to be extended to we “cannot simply restrict our way out” either. We need better prevention and early intervention for opioid use disorder, and improved management of the opioid supply chain so as to prevent theft and diversion.

The crisis is a fast-moving target, with prescription opioid levels having dropped significantly since 2012. Overdoses involving prescription opioids have also fallen, while deaths linked to illicit opioids like fentanyl, cocaine and methamphetamine are rising sharply. We will need far more than a prescribing database to guide policy moving forward.

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

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Marijuana Use May Affect Patient Anesthesia

By Kata Ruder, Kaiser Health News

When Colorado legalized marijuana, it became a pioneer in creating new policies to deal with the drug.

Now the state’s surgeons, nurses and anesthesiologists are becoming pioneers of a different sort in understanding what weed may do to patients who go under the knife.

Their observations and initial research show that marijuana use may affect patients’ responses to anesthesia on the operating table — and, depending on the patient’s history of using the drug, either help or hinder their symptoms afterward in the recovery room.

Colorado makes for an interesting laboratory. Since the state legalized marijuana for medicine in 2000 and allowed for its recreational sale in 2014, more Coloradans are using it — and they may also be more willing to tell their doctors about it.

Roughly 17% of Coloradans said they used marijuana in the previous 30 days in 2017, according to the National Survey on Drug Use and Health, more than double the 8% who reported doing so in 2006. By comparison, just 9% of U.S. residents said they used marijuana in 2017.

“It has been destigmatized here in Colorado,” said Dr. Andrew Monte, an associate professor of emergency medicine and medical toxicology at the University of Colorado School of Medicine and UCHealth. “We’re ahead of the game in terms of our ability to talk to patients about it. We’re also ahead of the game in identifying complications associated with use.”

One small study of Colorado patients published in May found marijuana users required more than triple the amount of one common sedation medicine, propofol, as did nonusers.

Those findings and anecdotal reports are prompting additional questions from the study’s author, Dr. Mark Twardowski, and others in the state’s medical field: If pot users indeed need more anesthesia, are there increased risks for breathing problems during minor procedures?

Are there higher costs with the use of more medication, if a second or third bottle of anesthesia must be routinely opened? And what does regular cannabis use mean for recovery post-surgery?

But much is still unknown about marijuana’s impact on patients because it remains illegal on the federal level, making studies difficult to fund or undertake.

It’s even difficult to quantify how many of the estimated 800,000 to 1 million anesthesia procedures that are performed in Colorado each year involve marijuana users, according to Dr. Joy Hawkins, a professor of anesthesiology at the University of Colorado School of Medicine and president of the Colorado Society of Anesthesiologists. The Colorado Hospital Association said it doesn’t track anesthesia needs or costs specific to marijuana users.

As more states legalize cannabis to varying degrees, discussions about the drug are happening elsewhere, too. On a national level, the American Association of Nurse Anesthetists recently updated its clinical guidelines to highlight potential risks for and needs of marijuana users. American Society of Anesthesiologists spokeswoman Theresa Hill said that the use of marijuana in managing pain is a topic under discussion but that more research is needed. This year, it endorsed a federal bill calling for fewer regulatory barriers on marijuana research.

Should Patients Disclose Marijuana Use? 

No matter where patients live, though, many nurses and doctors from around the country agree: Patients should disclose marijuana use before any surgery or procedure. Linda Stone, a certified registered nurse anesthetist in Raleigh, N.C., acknowledged that patients in states where marijuana is illegal might be more hesitant.

“We really don’t want patients to feel like there’s stigma. They really do need to divulge that information,” Stone said. “We are just trying to make sure that we provide the safest care.”

In Colorado, Hawkins said, anesthesiologists have noticed that patients who use marijuana are more tolerant of some common anesthesia drugs, such as propofol, which helps people fall asleep during general anesthesia or stay relaxed during conscious “twilight” sedation. But higher doses can increase potentially serious side effects such as low blood pressure and depressed heart function.

Limited airway flow is another issue for people who smoke marijuana. “It acts very much like cigarettes, so it makes your airway irritated,” she said.

To be sure, anesthesia must be adjusted to accommodate patients of all sorts, apart from cannabis use. Anesthesiologists are prepared to adapt and make procedures safe for all patients, Hawkins said. And in some emergency surgeries, patients might not be in a position to disclose their cannabis use ahead of time.

Even when they do, a big challenge for medical professionals is gauging the amounts of marijuana consumed, as the potency varies widely from one joint to the next or when ingested through marijuana edibles. And levels of THC, the chemical with psychoactive effects in marijuana, have been increasing in the past few decades.

“For marijuana, it’s a bit of the Wild West,” Hawkins said. “We just don’t know what’s in these products that they’re using.”

Marijuana’s Effects On Pain After Surgery

Colorado health providers are also observing how marijuana changes patients’ symptoms after they leave the operating suite — particularly relevant amid the ongoing opioid epidemic.

“We’ve been hearing reports about patients using cannabis, instead of opioids, to treat their postoperative pain,” said Dr. Mark Steven Wallace, chair of the pain medicine division in the anesthesiology department at the University of California-San Diego, in a state that also has legalized marijuana. “I have a lot of patients who say they prefer it.”

Matthew Sheahan, 25, of Denver, said he used marijuana to relieve pain after the removal of his wisdom teeth four years ago. After surgery, he smoked marijuana rather than using the ibuprofen prescribed but didn’t disclose this to his doctor because pot was illegal in Ohio, where he had the procedure. He said his doctor told him his swelling was greatly reduced. “I didn’t experience the pain that I thought I would,” Sheahan said.

In a study underway, Wallace is working with patients who’ve recently had surgery for joint replacement to see whether marijuana can be used to treat pain and reduce the need for opioids.

But this may be a Catch-22 for regular marijuana users. They reported feeling greater pain and consumed more opioids in the hospital after vehicle crash injuries compared with nonusers, according to a study published last year in the journal Patient Safety in Surgery.

“The hypothesis is that chronic marijuana users develop a tolerance to pain medications, and since they do not receive marijuana while in the hospital, they require a higher replacement dose of opioids,” said Dr. David Bar-Or, who directs trauma research at Swedish Medical Center in Englewood, Colo., and several other hospitals in Colorado, Texas, Missouri and Kansas. He is studying a synthetic form of THC called dronabinol as a potential substitute for opioids in the hospital.

Again, much more research is needed.

“We know very little about marijuana because we’ve not been allowed to study it in the way we study any other drug,” Hawkins said. “We’re all wishing we had a little more data to rely on.”

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

Feds Warn of Counterfeit Oxycodone Deaths

By Pat Anson, PNN Editor

In the wake of four fentanyl overdoses in southern California, federal authorities have issued a public safety alert warning drug users about a lethal strain of counterfeit medication designed to look like 30mg oxycodone tablets.

The blue bills have the letter “M” in a box on one side and the number “30” with a line down the center on the other. On the street they are referred to as blues, M-30s or Mexican Oxy.

The pills were found at the scene of four fatal overdoses in San Diego County last week. The deaths in Poway, Santee, Lakeside and Valley Center were all reported within 24 hours.

Although tests on the pills are ongoing, authorities suspect they are laced with illicit fentanyl or carfentanil, which can be fatal in tiny doses.

SAN DIEGO SHERIFF’S DEPT. IMAGE

“That heroin, that meth, that coke, that oxy you think you are taking? Well, it just might have fentanyl in it, and it just might be the last thing you ever do,” U.S. Attorney Robert Brewer said in a statement. “I cannot be more clear than this: Fentanyl may be the costliest drug you ever do, because you may pay with your life, and you won’t even know you took it.”

Brewer said border seizures, prosecutions and overdoses are on pace to hit all-time highs in San Diego County by the end of 2019. The Medical Examiner’s Office has confirmed 50 fentanyl-related overdose deaths so far this year, plus another 28 suspected but yet-to-be confirmed cases.

If the trend continues, the death toll could potentially reach 130, which would amount to a 47 percent increase over last year’s total of 90 deaths. The victims are overwhelmingly male, with the average age about 36.

“Just when we think it can’t get any worse, the latest numbers prove us wrong,” Brewer said.  “I am alarmed by the dramatic surge in trafficking activity and deaths, particularly of young people. San Diego is the fentanyl gateway to the rest of the country, and we are working hard to close that gate with interdiction, prosecution and education.”

Federal authorities have confiscated 1,175 pounds of illicit fentanyl – more than half a ton -- at or near the international border so far this year. In addition, there has been a record number of seizures involving counterfeit blue pills labeled M-30 that contain fentanyl. The pills sell on the street for $9 to $30 each and are appearing around the country.

Ports of entry near San Diego are major transit points for illicit fentanyl smuggled in from Mexico. The fentanyl is usually transported in vehicles, often by legal U.S. residents acting as couriers.

A recent report from the Wilson Center found that Mexican cartels are playing an increased role in the fentanyl trade.

“San Diego is the fentanyl gateway to the rest of the country.”

— U.S. Attorney Robert Brewer

“Chinese companies produce the vast majority of fentanyl, fentanyl analogues, and fentanyl precursors, but Mexico is becoming a major transit and production point for the drug and its analogues as well, and Mexican traffickers appear to be playing a role in its distribution in the United States,” the report found.

“Both large and small organizations appear to be taking advantage of the surge in popularity of the drug, which is increasingly laced into other substances such as cocaine, methamphetamine, and marijuana—very often without the end-user knowing it. To be sure, rising seizures of counterfeit oxycodone pills laced with fentanyl illustrate that the market is maturing in other ways as well.”

Last week a former Mexican police officer was indicted for fentanyl trafficking by a federal grand jury in Texas. Assmir Contreras-Martinez, 30, was pulled over by a Texas trooper on Interstate 40 in Amarillo in May. About 73 pounds of illicit fentanyl powder was found inside his 2007 Ford Explorer, enough to kill 10 million people, according to DEA experts. 

Contreras-Martinez admitted he was paid $6,000 to transport the fentanyl from California to Florida and that it was his second such trip. Before his unlawful immigration to the United States nine months ago, Contreras-Martinez had been employed for eight years as a municipal police officer in Cananea, Sonora, Mexico.

‘Opioid of the Future’ Postponed

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration is tapping the brakes on NKTR-181, an experimental opioid pain medication that has less abuse potential than traditional opioids like oxycodone or hydrocodone.

In an SEC filing, Nektar Therapeutics said it received a letter from the FDA on July 23 saying the agency was postponing all advisory committee meetings for opioid analgesics, including one scheduled for August 21 to discus Nektar’s new drug application for NKTR-181.

The FDA was due to make a final decision on NKTR-181 eight days later, but that too is apparently being postponed while the agency considers “a number of scientific and policy issues relating to this class of drugs.”

Nektar called NKTR-181 the “opioid of the future” because it is the first full mu-opioid agonist that can provide pain relief without the euphoria or “high” that can lead to abuse and addiction.

The molecular structure of NKTR-181 is designed to have low permeability across the blood-brain barrier, which slows its rate of entry into the brain.

In a Phase III clinical study, patients with chronic back pain reported that their pain scores dropped an average of 65% when taking NKTR-181 twice daily. Safety studies also found that recreational drug users had significantly less “drug liking” of NKTR-181 when compared to oxycodone.

NEKTAR IMAGE

The research was so promising the FDA gave NKTR-181 “fast track” designation to speed its development. Nektar executives told PNN two years ago they were hopeful the drug would be approved in late 2018, with a commercial launch early this year.

Obviously that didn’t happen. And the FDA’s fast track has turned into a slow walk.

Two FDA advisory committees met last month and decided “much better-quality data” was needed before approving any new opioids — even ones with low risk of abuse.  

The agency has been under growing public and political pressure to tighten its regulation of opioids. In February, a 60 Minutes report claimed the FDA “opened the floodgates” to the opioid epidemic by approving the use of OxyContin for chronic pain. The following month, the agency received a petition from Public Citizen calling for a moratorium on new opioid approvals because the agency “can no longer be trusted” due to its “poor record” of regulating opioids.

On July 25, Howard Robin, Nektar’s President and CEO, sold 100,000 shares of Nektar for $3.1 million. A spokesman said the sale was previously scheduled due to expiring options. The company’s chief financial officer and a director also sold shares this month. Nektar shares (NASDAQ: NKTR) lost about 10% of their value after the SEC filing was made public.

Lawyer Calls for DOJ to End ‘Indiscriminate Raids’ on Doctors

By Pat Anson, PNN Editor

In recent years, hundreds of physicians, pharmacists and addiction treatment doctors have had their offices raided and searched by DEA agents.

Many of the raids were orchestrated by the Justice Department’s Opioid Fraud and Abuse Detection Unit, a special team of investigators created in 2017 to mine opioid prescribing data to identify suspicious orders and practices. The investigations have resulted in the high-profile arrests of healthcare providers for fraud and risky opioid prescribing.

"If you're a doctor and you want to act like a drug dealer, we're going to treat you like one. And sometimes the only difference between a doctor and a drug dealer is a white coat," U.S. Attorney Jay Town said about a federal takedown in April that resulted in charges against 60 practitioners in seven states.

Rarely publicized are the cases where criminal charges are never filed because the evidence against doctors is weak or non-existent.

“It’s quite frustrating to see how their careers were ruined even though they never faced criminal charges. That’s because the government was incapable of bringing credible charges against them,” says attorney Michael Barnes, who is managing partner at DCBA Law & Policy, a law firm that advises healthcare providers. “When I read a criminal complaint, what I would see as ‘best practices’ is construed as criminal exploitative behavior on the part of the prosecutors.

“There’s a heavy bias against medications to treat pain and opioid use disorder that is driving some of the aggressive enforcement actions. Also, an overzealousness combined with a lack of understanding of the practice of medicine.”

Barnes recently wrote an op/ed, published online by American University’s Washington College of Law, calling for an end to the DOJ’s “indiscriminate raids” on doctors.

“DOJ raids and searches of professionals’ homes and medical clinics interrupt the delivery of health care, put patients’ lives at risk, and unjustly destroy careers and livelihoods. They also create confusion and fear,” wrote Barnes. “Not all health care professionals subject to the DOJ’s searches and seizures are ‘dirty docs.’ In fact, some of them are nationally recognized leaders not just in pain management, but also in addiction medicine.” 

Barnes cites the case of Dr. Stuart Gitlow, an addiction psychiatrist whose Rhode Island home and office were raided by FBI agents in March 2018. Sixteen months later, the reasons for the raid remain unclear and Gitlow, the former president of the American Society of Addiction Medicine, has not been charged with a crime.  

MICHAEL BARNES

Neither has Dr. Forest Tennant. In November 2017, DEA agents raided the office and home of Tennant, a prominent California pain physician who was flagged for “very suspicious prescribing patterns.” In a search warrant, the 76-year old Tennant was depicted as the kingpin of a drug trafficking organization that spanned several states.

“I know based on my training and experience that patients traveling long distances to obtain controlled substance prescriptions is another ‘red flag’ of drug abuse and addiction,” wrote DEA investigator Stephanie Kolb, who led a two-year investigation of Tennant.

But Kolb, who was self-employed as a dog walker and pet groomer before she started working for the DEA in 2012, failed to note that Tennant only treated intractable pain patients, many from out-of-state, and often prescribed high doses of opioids because of their chronically poor health. Some patients were in palliative care and near death, and one committed suicide after learning of the raid, fearing she would lose access to opioid medication.

Tennant denies any wrongdoing and was never formally charged, but retired from clinical practice a few months after the raid.

“It’s hard to continue operating when they never closed my case, and so I’m going to retire and move on,” Tennant told PNN at the time. “That’s on the advice of both my lawyers and my doctors."

(Dr. Tennant and the Tennant Foundation have given financial support to Pain News Network and are currently sponsoring PNN’s Patient Resources section.)  

Biased Investigations

Barnes says the biases of some prosecutors extends to the expert witnesses they hire to help build their cases. The role of these witnesses is important because they help DOJ persuade judges to sign off on search warrants that are key to gathering evidence. It’s a lucrative sideline for some paid witnesses, who charge the government hundreds of dollars an hour for their time and expertise.

“Expert witnesses are eager to give DOJ business to get the expert witness fees, and they of course will help to spin the facts in a way that is prejudicial to the defendant,” Barnes said. “What we’re seeing here is people who are really not qualified to be making assessments of other practices serving as experts for the government.” 

Dr. Timothy Munzing, a Kaiser Permanente family practice physician in California, has worked as a medical consultant for the DEA, FBI and DOJ on over 100 investigations, most of which involve prescriptions for opioids and other controlled substances.

According to GovTribe.com, which tracks payments to federal contractors, Munzing has been awarded nearly $1 million in DOJ contracts since 2017 and is currently working on nearly two dozen DEA investigations, mostly reviewing patient files and data from prescription drug monitoring programs.

It would be unusual for a family practice physician to treat an intractable pain patient without making a referral to a pain or palliative care specialist. But Munzing was one of the expert witnesses hired by the DEA to analyze Tennant’s prescribing.

“I find to a high level of certainty that after review of the medical records… that Dr. Tennant failed to meet the requirements in prescribing these dangerous medications,” Munzing wrote in an affidavit. “These prescribing patterns are highly suspicious for medication abuse/and or diversion. If the patients are actually using all the medications prescribed, they are at high risk for addiction, overdose, and death.”  

Munzing’s affidavit and the DEA search warrant identified no patients who were actually harmed while under Tennant’s care. As PNN reported, some patients found the allegation that they were selling their medication and funneling the profits back to Tennant laughable.      

“It’s like everything else they do. They don’t talk to any patients. They don’t talk to any doctors. They just go and throw all this stuff out there and making all these incriminations against people. They don’t have any evidence that I’ve sold anything. It’s just ludicrous,” said Ryle Holder, a Tennant patient who lives in Georgia.  

Barnes says the bias against opioid prescribing “is inherent in the work of many of the investigators and prosecutors.”

“Then there is the incompetence as it relates to many of the law enforcement officers not having the medical expertise to make judgements of a medical nature. And then, when they do consult with the experts, those experts are typically trying to please their clients and getting repeat business as a result,” he told PNN. 

State Medical Boards

To bring more expertise into investigations of healthcare providers, Barnes is proposing that state medical boards play a more prominent role. He wants Congress to amend federal law to require DOJ investigators and prosecutors to get a referral from a state licensing board before investigating a practitioner for misconduct. Similar laws at the state level would also need to be changed to require state and local law enforcement to get a referral from a medical licensing board.

To make sure complaints are handled in a timely manner, Barnes says federal funds should be used to bolster the budgets of state licensing boards so they can investigate allegations of misconduct.  

“There are some detractors who say medical boards didn’t do an adequate job leading up to the overdose crisis. But the reality is neither did law enforcement,” Barnes says. “The medical boards could get up to speed and make these assessments on medical needs and patient care to make sure that healthcare providers can be assessed with medical expertise, rather than law enforcement trying to guess about standard of care and best practices.”

“Making it more difficult for law enforcement to investigate potential diversion of dangerous and addictive controlled substances, including powerful painkillers, is probably not going to happen right now,” says DEA spokesman Rusty Payne.

“This idea that people need to worry about the DEA hiding in the bushes if they write an oxycodone prescription is ridiculous.”

— Rusty Payne, DEA spokesman

Payne points out the DEA is both a law enforcement and regulatory agency, one that oversees 1.3 million practitioners licensed to prescribe controlled substances. He says enforcement actions are relatively rare and not “indiscriminate” as Barnes suggests.

“The numbers are incredibly low. It is a very, very, very small number.  So this idea that people need to worry about the DEA hiding in the bushes if they write an oxycodone prescription is ridiculous,” he told PNN. “We don’t have the resources. We don’t track individual prescriptions. We look for patterns and large-scale significant diversion.”  

Getting state medical boards involved, according to Payne, is not a good idea.

“I don’t think making it harder for us to scrutinize those that are acting outside the law is in anyone’s best interest,” he said.

But Barnes’ proposal makes sense, according to Dr. Lynn Webster, a PNN columnist and former president of the American Academy of Pain Medicine. 

“Barnes makes a sensible recommendation. If the law enforcement suspects a provider is not complying with the law, then the first step should be a referral to the medical board where the provider can be evaluated by their peers,” Webster said. “If a doctor goes to trial, they will not be evaluated by their peers. That is not the way the justice system is supposed to work.” 

Webster was once the target of a federal investigation of his opioid prescribing practices and DEA agents raided his Utah pain clinic in 2010. Four years later, the DOJ said it would not prosecute Webster, who said his “reputation was tarnished forever.”  

“DEA investigations are often designed to entrap a provider on technicalities.  Even if an investigation never leads to any charges the doctor's reputation is damaged.  In the court of public opinion an investigation must mean something was wrong,” Webster said.