Tag Archives: pseudobulbar affect

11/19/19

A Shot Across the Bow of Pharma

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Ending a four year-long federal investigation, Avanir Pharmaceuticals agreed to pay an estimated $116 million in criminal penalties and civil damages in a settlement reached with the Department of Justice (DOJ) on September 26, 2019. According to FiercePharma, the company also agreed to assist in the prosecution against former employees and a top prescriber of its bestselling drug, Nuedexta. As a part of the deal, Avanir agreed to a five-year Corporate Integrity Agreement with the Department of Health and Human Services (HHS). Avanir CEO Wa’el Hashad said the “company takes its responsibilities to patients, their families and caregivers, and healthcare providers very seriously. . . . Avanir is deeply committed to regulatory and legal compliance, integrity and ethical behavior, and the health and safety of patients.”

The DOJ reported Avanir agreed to pay over $95 million to resolve civil False Claims Act allegations that the company paid kickbacks to a physician to prescribe Nuedexta, and that it made false and misleading marketing claims about Nuedexta to long-term care facilities. Allegedly the false claims were targeted to influence providers to prescribe Nuedexta as an alternative to antipsychotic drugs. The federal government was trying to limit the use of antipsychotics as “chemical restraints” used to manage behaviors commonly associated with dementia patients.

Avanir has agreed to pay $95,972,017 to the United States to resolve allegations under the False Claims Act related to its marketing of Nuedexta. The government alleged that between October 29, 2010, and December 31, 2016, Avanir provided remuneration in the form of money, honoraria, travel, and food to certain physicians and other health care professionals to induce them to write prescriptions for Nuedexta. One form of remuneration included Avanir’s payment to certain health care professionals to give talks (commonly known as “speaker’s programs”) about Nuedexta based on their willingness to prescribe Nuedexta. These events were primarily social, with no educational value.

Nuedexta is only approved as a treatment for a rare condition called pseudobulbar affect (PBA) that causes uncontrollable laughing or crying that is not connected to a person’s mood. PBA is extremely rare in dementia patients, affecting less than 5%. It is most commonly associated with people who have multiple sclerosis (MS) or Lou Gehrig’s disease, ALS. Doctors were found to be inappropriately diagnosing PBA to justify using Nuedexta to treat difficult to manage elderly patients. There was a CNN investigation in 2017 that  indicated between 2012 and 2016 Nuedexta sales jumped 400%; more than half of which had gone to long-term care facilities. For more on this, see: “Conjuring Diagnoses For the Elderly.”

According to a recent CNN report, whistleblowers alleged that from the drug’s early years Avanir illegally directed salespeople to market Nuedexta in nursing homes as an alternative to antipsychotic drugs specifically for “use in controlling the behavior of patients prone to disruptive outbursts.” They also claimed salespeople coached doctors on how to describe patients’ conditions in order to guarantee approval, and even forged physician signatures on paperwork for insurers. One lawsuit stated, “At least one Avanir (salesperson) went so far as to dress in scrubs, review patients’ files at the nurses’ station in nursing homes, and write the diagnosis for PBA in the medical files of patients.” These tactics were allegedly praised by an executive on a national sales call. Government data indicated Medicare Part D spent around $225 million on Nuedexta in 2017, a 700% increase since 2012.

Assistant Attorney Jody Hunt of the DOJ said kickbacks can corrupt a provider’s medical judgment. “And it is particularly concerning when a pharmaceutical company uses kickbacks to drive up sales in connection with a vulnerable population, such as elderly patients in nursing care facilities.” The government alleged Avanir sought to take advantage of efforts by the Centers for Medicare and Medicaid Services to reduce the use of antipsychotics with dementia patients. Avanir instructed its sales force to initiate discussions in long-term care (LTC) facilities about antipsychotic use and how Nuedexta could be used to reduce their reliance on antipsychotics.

Avanir’s own studies demonstrated that the actual population of patients with PBA is limited. In order to counter the objection by certain physicians that they had few, if any, patients that exhibited signs of PBA in their facilities, Avanir instructed sales representatives to provide false and misleading information that PBA patients could be exhibiting a wide variety of “behaviors” such as crying without tears, moaning, or making other inarticulate sounds, when, in fact, those symptoms are commonly observed in patients who have dementia but do not have a diagnosis of PBA. This strategy worked, and Nuedexta utilization in LTC facilities increased.

The DOJ reported the civil settlement resolved lawsuits by three whistleblowers, who were all former employees of Avanir. Under the whistleblower provisions of the False Claims Act, private citizens are permitted to sue on behalf of the government for false claims and to share in any recovery.

The Employment Law Group® law firm reported Kevin Manieri was the first person to report the company’s activities to authorities. A biopharmaceuticals executive with decades of experience, he was fired only months after joining Avanir in 2014 when he complained to an Avanir vice president about the company using “speaker fees” to reward doctors for writing unnecessary prescriptions for Nuedexta. Many of Avanir’s speaking engagements were small, sparsely attended gatherings at local restaurants. The speakers tended to be individuals willing to diagnose PBA “based upon a bare minimum of symptoms,” according to Kevin Manieri’s complaint. A press release issued by the U.S. Attorney’s Office for the northern District of Ohio said many of the Nuedexta speaking engagements had “little to no educational value.”

According to the complaint filed by Mr. Manieri, whom the drug company hired to oversee Nuedexta sales to physicians in the northern U.S., Avanir pushed its reps to focus on a few high-volume prescribers who were willing to recommend Nuedexta to patients who likely didn’t need the drug. He cited a vivid example in the complaint: A Cleveland-area neurologist who wrote twice as many Nuedexta prescriptions as any other doctor in the U.S. — and who also was Avanir’s highest-paid speaker, with 42 engagements in 12 months yielding more than $56,000 in payments.

Sadly, Avanir’s marketing strategy is not unusual in the world of pharmaceutical companies. According to Dr. Marcia Angell in The Truth About Drug Companies, Parke-Davis paid academic experts to put their names on flimsy research papers that supposedly showed Neurontin (gabapentin) was effective for certain off-label conditions. The result was Neurontin becoming a blockbuster drug, with over 2 billion in sales for 2003. “About 80 percent of prescriptions that year were for unapproved uses—conditions like bipolar disorder, post-traumatic stress disorder, insomnia, restless legs syndrome, hot flashes, migraines, and tension headaches.” In fact, Neurontin became an all-purpose restorative for chronic discomfort. An internal company e-mail described Neurontin as “the ‘snake oil’ of the twentieth century.”

In May of 2004, Warner-Lambert, of which Parke-Davis was then a division, agreed to pay $430 million to resolve criminal charges and civil liabilities related to its “illegal and fraudulent promotion of unapproved uses” for Neurontin. See the Department of Justice announcement here. Also see “Twentieth Century Snake Oil” for more on this.

The larger issue is that we can no longer trust much of the clinical research that is published. Among the concerns are reportedly selective publication of clinical trials, rigging the outcomes of those trials, publication bias and industry payments to medical journals and their editors. Richard Horton, and editor in chief of The Lancet said: “The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue.” Marcia Angell, a former editor in chief of the New England Medical Journal (NEJM) said: “It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor.” See “Corrupted Clinical Trials” for more on this.

So, the actions of whistle blowers like Kevin Manieri are not simply the acts of disgruntled ex-pharmaceutical employees in the long run. What happened to a relatively small pharmaceutical company, Avanir, and its attempts to expand the marketing reach of its featured drug, Nuedexta, are hopefully a warning shot across the bow of Pharma. Marketing rhetoric disguised as “treatment” or “evidence-based medicine” will not be tolerated. And there will be individuals and firms like The Employment Law Group® ready to hold you accountable for your actions. For more on Avanir and Nuedexta, also see “A Reason to Cry Uncontrollably.”

12/11/18

A Reason to Cry Uncontrollably

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Danny Glover did a “public awareness” ad for pseudobulbar affect (PBA) in 2015. In the ad, he said if you have PBA, choosing to laugh or cry may not be your decision. The ad went on to note PBA is a neurological, not psychological condition that is treatable; by Avanir’s Nuedexta. You were given information to “get the facts” about PBA. But one of the facts you wouldn’t get is that almost half of Nuedexta claims filed with Medicare in 2015 “were filed by doctors who had received perks (financial or otherwise) from Avanir.”

The above quote was from an article on Nuedexta from the website Nursing Home Abuse Center that highlighted a CNN investigation into Avanir and Nuedexta. While experts say that PBA effects less than 5 % of elderly patients, CNN found that “more than half of all Nuedexta pills manufactured since 2012 have gone to nursing homes.” While Avanir claims in its ads that PBS can occur with patients having Alzheimer’s or dementia, it admits Nuedexta has not been extensively studied among elderly patients.

One study among Alzheimer’s patients found those taking Nuedexta were twice as likely to suffer a fall, not something you want to see with the elderly. “Fall risk has been a huge concern among Nuedexta users since 2013 when nursing home inspectors first started questioning use of the drug in dozens of nursing homes across the United States.”  The CNN investigation found over 80 cases through 19 states where nursing homes were cited for inappropriate use and monitoring of Nuedexta. Sometimes it was given to patients without a formal prescription or doctor approval. “Many of the cases were based on the fact that patients exhibited no signs of PBA.”

The original CNN investigation reported in October of 2017 stirred up concerns and significant interest in Avanir and its marketing tactics with Nuedexta. The same two reporters have written a series of articles on CNN since then noting how Los Angeles opened an investigation into Avanir following the CNN report; how a leading advocacy group for Alzheimer’s stopped accepting contributions from Avanir after the report; and that the US government warned insurance companies to look for suspicious prescriptions of Nuedexta. And there were several doctors with problem records, at least three had criminal convictions for illegal prescribing, promoting Nuedexta.

The Los Angeles City Attorney confirmed his office was seeking information and tips from the public to help assess whether state or federal laws were violated in the sale, marketing or prescribing of Nuedexta. The people receiving Nuedexta are vulnerable and rely on others to make decisions for them. “If there is a possibility they are being administered a medication not because it is in their best interest, but because it is in the financial interest of, say, the drug manufacturer, then it is important for us to intervene.” He said he would look for potential illegal activity including kickbacks to doctors and off-label marketing of Nuedexta, that is suggesting it as a treatment for any purpose not approved by the federal government.

This would include using it as a “chemical restraint” to sedate or control behavior problems. “State regulators … have found cases of doctors inappropriately diagnosing nursing home residents with PBA to justify using Nuedexta to treat patients whose confusion, agitation and unruly behavior make them difficult to manage.” In one LA nursing home, regulators found that 28% of its residents (46 of 162) had been placed on Nuedexta. A facility psychiatrist, a paid speaker for Avanir, had given a talk about the drug to employees.

At another facility, also in Southern California, an employee admitted to inspectors that a resident had been given a diagnosis of PBA to “somehow justify the use” of Nuedexta, even though its intended purpose was to control the resident’s “mood disturbances” and yelling out.

In order to line up prescriptions, sales people identified doctors, nurses and pharmacists who could be advocates for the drug. Then they worked closely with these advocates to identify potential patients. One salesperson worked with a doctor’s office manager to pull patient’s charts and identify those who should be screened for PBA. “CNN’s investigation also found that the sales force coached doctors and facility employees on how to fight for Medicare coverage of the drug if it was initially refused.”

Another CNN article noted that after the original CNN article on Avanir and Nuedexta, the Alzheimer’s Association said it would not accept any further funding from Avanir, pending the results of the LA City Attorney. Avanir gave the group almost $200,000 in 2017. In a statement, the association said: “We are committed to people living with the disease, and we encourage vigorous review and oversight of companies and prescribers to ensure best practices are followed for those impacted by Alzheimer’s disease.” It added the contribution by Avanir was only .056% of its annual revenue.

Another nonprofit, the Alzheimer’s Foundation of America, said it received $60,000 from Avanir in 2016-2017. The organization declined to comment on the findings of CNN’s report, adding that it stood by its educational programs and that Nuedexta is not mentioned in Avanir presentations. Nuedexta is the only FDA approved treatment for PBA. One of its medical advisory board members said the AFA’s Educational Conferences provide caregivers an opportunity to understand and recognize PBA, “which afflicts a certain percentage of those with dementia.”

“Between 2013 and 2016, he received nearly $50,000 from Avanir, in the form of consulting and royalty or licensing fees, as well as travel and meals, according to government data.” He was also the lead author on the Avanir-funded study on Nuedexta that found patients on Nuedexta were more than twice as likely to fall (8.6% versus 3.9%) than those on a placebo. A research professor who studies the marketing tactics of pharmaceutical companies said Avanir’s ties with nonprofit dementia advocacy groups was “deeply troubling” and a conflict of interest. This was a particular concern for him “because Nuedexta has not been approved specifically for Alzheimer’s or dementia.

Between 2013 and 2016 Avanir Pharmaceuticals paid almost 500 doctors to speak or consult on Nuedexta. After reviewing the top prescribers of Nuedexta, CNN noted 12 who had been disciplined by state medical boards. Former Avanir employees said the company’s speaker program sought out doctors and pharmacists to present the drug to medical colleagues and nursing home employees. “Avanir and its parent company, Otsuka, paid doctors nearly $14 million for Nuedexta-related consulting, promotional speaking and other services.” In effect, these doctors are being used as a sales force, according to Michel Santoro, an expert in pharmaceutical industry ethics at Santa Clara University.

Many of the doctors with medical board issues identified by CNN involved other medications such as opioids. But one case centered on the use of Nuedexta. An Oregon doctor had already been banned by the state board from providing mental health treatment to inmates. Then he was summoned for his treatment of four nursing home patients. For one of his patients he attempted to prescribe Nuedexta “when there was no support for a PBA diagnosis.” The others were cases of inappropriately prescribing medications, changing doses or discontinuing drugs without explanation. Despite all these allegations, he was being paid by Avanir to speak publically about Nuedexta.

Then in June of 2018 CNN reported they had received documents through a public records request that indicated there have been complaints filed with the FDA about Avanir’s marketing and advertising dating back to 2012. BlueCross BlueShield of Arizona said Avanir was misrepresenting Nuedexta as “safe and effective” in populations it had not been approved for or adequately studied. “We believe that the manufacturer appears to be marketing Nuedexta far beyond the scope of the clinical evidence.” An individual complaint in 2016 said they had overheard a salesperson promote the drug for unapproved uses. “Specifically they are targeting [sic] residents with Dementia with Behavioral Disturbances.”

In March of 2018 CMS (Centers for Medicare & Medicaid Services) issued a memo asking Medicare insurance providers to monitor prescriptions for Nuedexta in order to ensure it was being appropriately given to patients. The memo reminded plan sponsors that Nuedexta was only approved to treat PBA and that insurers were legally required to ensure it was only being used for medically accepted uses. The agency said the memo was provided to “inform plan sponsors about increases in utilization that may not be readily discerned or may relate to potential fraud.”

Sadly, Avanir seems to have placed profits ahead of ethical medical care with the elderly. They have encouraged the use of Nuedexta in nursing facilities as a kind of chemical restraint. This seems to have partly occurred in response to the FDA tightening regulations on the use of antipsychotics for the same reason. There is a reason to cry uncontrollably, but it’s for how Neudexta has been mis-marketed and mis-prescribed. For more on Nuedexta and the use of antipsychotics in nursing homes, see “Conjuring Diagnoses for the Elderly” and “Nursing Homes Want Docile.”

02/16/18

Conjuring Diagnoses for the Elderly

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In 2005, the FDA required atypical antipsychotics to carry a boxed warning that they had a higher risk of death related to use among individuals with dementia. In 2008, the FDA required the same warning with the older, typical antipsychotics. Antipsychotic use in nursing homes is now closely watched by government regulators, “who penalize and lower the ratings of facilities that overuse them.” This created an opportunity for the manufacturer of a little-used medication known as Nuedexta. Since 2012, there has been an increase of nearly 400% in the number of Nuedexta pills dispensed to long-term care facilities.

A CNN investigation reported on how “The maker of a little red pill intended to treat a rare condition is raking in hundreds of millions of dollars a year as it aggressively targets frail and elderly nursing home residents.” Nuedexta is approved to treat a disorder known as pseudobulbar affect or PBA. The disorder is a condition that causes sudden, uncontrollable crying and/or laughing. PBA afflicts less than 1% of all Americans and is most commonly found in people with multiple sclerosis (MS) or Lou Gehrig’s disease (ALS). The manufacturer of Nuedexta, Avanir, had its sales force focus on expanding the drug’s use with elderly patients struggling with dementia and Alzheimer’s disease. See the following graphic from CNN on the number of Nuedexta pills dispensed to long-term facilities.

Nuedexta is approved by the Food and Drug Administration (FDA) to treat anyone with PBA, including those with a variety of neurological conditions such as dementia. But geriatric physicians, dementia researchers and other medical experts told CNN that PBA is extremely rare in dementia patients; several said it affects 5% or less. And state regulators have found doctors inappropriately diagnosing nursing home residents with PBA to justify using Nuedexta to treat patients whose confusion, agitation and unruly behavior make them difficult to manage.

CNN identified dozens of examples across the country where the use of Nuedexta was questionable. In one Los Angeles nursing home, regulators found that 28% of its 162 residents had been placed on Nuedexta. A facility psychiatrist, who is a paid speaker for Avanir, had given a talk about the drug to nursing home employees. An employee at another Southern California facility admitted a resident was given a diagnosis of PBA in order to justify the use of Nuedexta, “even though its intended purpose was to control the resident’s “mood disturbances” and yelling out.” An Ohio doctor has come under investigation for allegedly receiving kickbacks for fraudulently diagnosing PBA in order to get Medicare coverage for Nuedexta.

The federal government foots the bill for a big portion of the money being spent on Nuedexta in the form of Medicare Part D prescription drug funding, for people 65 and over and the disabled. In 2015, the most recent year for which data is available, this Medicare program spent $138 million on Nuedexta — up more than 400% from just three years earlier.

The only FDA approved medication for patients with PBA is Nuedexta. “So experts say that Medicare coverage of the drug, which has been crucial to its financial success, relies on the diagnosis of this single condition.” Off-label prescribing of Nuedexta to treat patients with behavioral issues who were not diagnosed with PBA would likely not be covered. CNN analysis found that almost half of the Nuedexta claims filed with Medicare in 2015 “came from doctors who had received money or other perks from the company [Avanir].”

During the FDA approval process, two doctors on the committee raise concerns about Nuedexta being used for PBA in Alzheimer’s patients. “They both strongly recommended that Nuedexta only be approved for PBA in patients with MS or ALS.” Evidence, they argued, that it would be effective in other conditions was weak; and not enough was known about the safety of the drug in the elderly. Despite these concerns, the FDA did not limit its use as recommended. “The agency approved Nuedexta in 2010 for treating PBA in patients who have neurological conditions such as dementia.”

Soon after it hit the market, Neudexta was getting reports of potential harm, ranging from dizziness and falls to coma and death. “Nuedexta was listed as a ‘suspect’ medication in nearly 1,000 so-called adverse event reports received by the FDA detailing side effects, drug interactions and other issues.” It was listed by caregivers as a potential cause of 133 hospitalizations (which included 8 cases that also resulted in death), 51 deaths, 102 incidents of sedation and sleepiness and 101 of dizziness, confusion and falls. A nurse practioner reported on an 86-year-old Alzheimer’s patient who rapidly declined after Nuedexta was added to her Zoloft (an antidepressant), Xanax (an antianxiety medication) and Risperidone (an antipsychotic). Almost immediately she declined and became almost unresponsive, ultimately dying.

Nuedexta is a combination of two generic drugs, dextromethorphan and quinidine that are respectively a cough suppressant and antiarrhythmic drug (it slows rapid heartbeat and helps your heart beat regularly). They were once available from specialty pharmacists for less than $1 a pill. The FDA-approved medication now costs as much as $12.60 a pill; more than $9,000 a year. “Medicare Part D spending on the drug averaged $3,400 per patient in 2015.” It gained public attention through a television commercial featuring actor Danny Glover cycling through fits of laughing and crying.

Avanir executives have wanted to secure FDA approval for Nuedexta’s use to treat dementia patients who don’t have PBA, “setting their sights on the more widespread condition of agitation in dementia and Alzheimer’s patients, characterized by emotional and physical outbursts and restless behaviors.” A study has been completed that looked at the efficacy, safety and tolerability of Neudexta for the treatment of agitation in Alzheimer’s patients, but the results haven’t been posted. “Without additional FDA approval for the drug’s use in those conditions, salespeople cannot promote Nuedexta for that purpose. They can only market its use for dementia patients who also have PBA.”

Across the country, the use of Nuedexta in nursing homes has prompted concerns among state regulators whose job is to ensure adherence to federal guidelines and protect residents from being given unnecessary drugs — especially those used as chemical restraints. But to date, the red flags raised by these regulators have been largely left buried in nursing home inspection reports and have drawn little public attention. CNN identified more than 80 cases in 19 states since 2013 where inspectors cited nursing homes for inappropriate monitoring and use of Nuedexta — often because residents hadn’t exhibited any symptoms of PBA. Many of the cases — about 40% — were clustered in Southern California, where Avanir is based and where former employees said there has been aggressive marketing.

Currently there are no FDA-approved drugs to treat dementia-related agitation. But those who care for the elderly are eager to find tools to manage agitated and aggressive patients. Staff increases could reduce the need for medications. But these measures don’t always work and they are expensive. So some facilities use pharmaceuticals to help make their patients easier to treat. Helen Kales, a geriatric psychiatrist said: “”Rather than taking someone off an antipsychotic … providers search for a different ‘magic bullet.'”

McKnight’s Long-Term Care News reported that The Centers for Medicare & Medicaid Services said that it met its goal of reducing the national rate of antipsychotic use among long-term residents by 20% by the end of 2016. However, Winter et al. reported in Clinical Gerontologist there was a 12% increase for the combined rates of schizophrenia, Tourette’s and Huntingdon’s among long-term residents. The increase began in 2012 at a rate almost triple that of the general long-term nursing home population. Most of the increase was in the rates of schizophrenia reported. The increased “identification” of these psychiatric conditions seems new “and concentrated in residents on antipsychotics.”

Since antipsychotics prescribed for schizophrenia, Tourette’s, and Huntington’s are excluded from quality-measure auditing, apparent reductions in inappropriate long-stay antipsychotic use since the National Partnership may be exaggerated.

Sadly it seems that despite the clear evidence of adverse effects from antipsychotics and Nuedexta with the elderly, long-term care facilities have simply conjured up a diagnosis to justify their use.