FDA To McKesson – You Failed In Opioid Diversion Reporting: “FDA Cites Proof Of Failure To Report In-House Diversion”

McKesson Corp. Failed In Opioid Diversion Reporting: “By Failing To Report In-House Diversion”

(MASS TORT NEXUS MEDIA) In a very clear and direct statement, the FDA has issued a formal warning letter to McKesson Corp. where “failure to monitor and report” diversion of prescription opiates including when the diversion took place within McKesson’s in-house control. Examples of opiate deliveries to Rite-Aid pharmacies containing naproxen instead of opiates were delivered in broken-seal containers. Even after Rite-Aid reported the diversions on more than one occasion, there was a failure by McKesson to report the diversion to authorities as required by law, as well as failing to conduct a proper internal investigation.

A December 2018 congressional report on prescription pill dumping squarely placed the blame on U.S. prescription drug distributors and the Drug Enforcement Administration for not doing enough to help mitigate the nation’s opioid addiction and overdose crisis.

The report released by the House Energy and Commerce Committee followed an 18-month investigation and focused on the three largest U.S. wholesale drug companies, McKesson Corp., Cardinal Health and AmerisourceBergen, and regional distributors outlines a pattern of total avoidance at the highest levels where opioid prescription reporting was required by law.

The report cited examples of massive pill shipments to West Virginia, which has a population of 1.8 million and has by far the nation’s highest death rate from prescription drugs. McKesson shipped an average of 9,650 hydrocodone pills per day in 2007 to a now-closed pharmacy in Kermit, which has a population of about 400. The shipments were 36 times above a monthly dosage shipment threshold the company had established that year. Why there was no reporting on the catastrophic numbers remains a matter to be resolved in litigation, because McKesson offers no realistic explanation for their bad conduct in failure to report as required by law.

The report cited  prior federal records that showed drug wholesalers shipped 780 million hydrocodone and oxycodone pills to West Virginia from 2007 to 2012, a period when 1,728 people fatally overdosed on the painkillers. For instance, drug companies collectively poured 20.8 million hydrocodone and oxycodone pills into the small city of Williamson, West Virginia, between 2006 and 2016, according to a set of letters the committee released Tuesday. Williamson’s population was just 3,191 in 2010, according to US Census data.  These numbers are outrageous, and we will get to the bottom of how this destruction was able to be unleashed across West Virginia,” committee Chairman Greg Walden (R-Ore.) and ranking member Frank Pallone Jr. (D-N.J.) said in a joint statement to the Charleston Gazette-Mail.

The nation is currently grappling with an epidemic of opioid addiction and overdose deaths. The Centers for Disease Control and Prevention estimate that, on average, 115 Americans die each day from opioid overdoses. West Virginia currently has the highest rate of drug overdose deaths in the country. Hardest hit have been the regions of West Virginia, Ohio and Kentucy where for some reason the opioid industry chose to focus their efforts, the how and why of their focus is being addressed in the federal and state courts across the country, with the primary cases being filed in the “Opiate Prescription Multidistrict Litigation MDL 2804” , being heard in the US District Court-Northern District of Ohio, in front of Judge Dan Polster, see Opiate Prescription MDL 2804 Briefcase.

It would now seem that McKesson will have to defend their failed diversion reporting conduct not only in the thousands of lawsuits they are facing, but in the renewed scrutiny that comes along with being outed as on eof the primary causes of the existing opioid crisis in America.

THE FULL FDA WARNING LETTER TO MCKESSON CORPORATION DATED FEBRUARY 7, 2019 IS BELOW

 

 

 

 

 

 

 

Via SIGNATURE CONFIRMED DELIVERY
February 7, 2019

John H. Hammergren

Chief Executive Officer

McKesson Corporation

One Post Street

San Francisco, California 94104

 

Dear Mr. Hammergren:

From June 25 to July 3, 2018, U.S. Food and Drug Administration (FDA) investigators conducted an inspection at your corporate headquarters located at One Post Street, San Francisco, California.  FDA investigators also inspected your distribution center facility at 9700 SW Commerce Circle, Wilsonville, Oregon, from June 26 to 29, 2018.

This warning letter summarizes significant violations of the verification requirements found in section 582(c)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360eee(c)(4)). These verification requirements are intended to help preserve the security of the supply chain for prescription drug products, thereby protecting patients from exposure to drugs that may be counterfeit, stolen, contaminated, or otherwise harmful.  The verification requirements at issue include those that apply to wholesale distributors when they determine or are notified that a product is suspect or illegitimate.[1]

FDA issued a Form FDA 483 to McKesson Corporation at its San Francisco corporate headquarters on July 3, 2018.  FDA reviewed your firm’s responses, dated July 25, 2018, September 25, 2018, and November 4, 2018.

During FDA’s inspection, FDA investigators observed that your firm failed to have systems in place to enable compliance with the verification requirements of section 582(c)(4) of the FD&C Act. Specific violations include, but may not be limited to, the following:

  1. Your firm failed to respond to illegitimate product notifications as required, which includes identifying all illegitimate product subject to such notifications in your possession or control and quarantining such product (section 582(c)(4)(B)(iii)).

      2. Your firm failed to quarantine and investigate suspect product (section 582(c)(4)(A)(i)).

      3. Your firm failed to keep, for not less than 6 years, records of the investigation of suspect product and the disposition of        illegitimate product (sections 582(c)(4)(A)(iii) and 582(c)(4)(B)(v)).

Failure to comply with any of the requirements under section 582 of the FD&C Act is a prohibited act under section 301(t) of the FD&C Act (21 U.S.C. 331(t)).

Example 1: In September and October 2016, McKesson was notified by your pharmacy trading partner, Rite Aid, that three separate Rite Aid pharmacies received illegitimate product, which they reported had been distributed by McKesson. Initially, McKesson was notified by Rite Aid on September 1, 2016, that their pharmacy located in Milford, Michigan, received a bottle labeled as containing 100 tablets of oxycodone hydrochloride (NDC 0406-8530) manufactured by Mallinckrodt. The seal of the bottle was broken, and the bottle contained no oxycodone hydrochloride.  The bottle contained only 15 tablets, which were later determined to be naproxen.  Rite Aid reported to McKesson that it had received this product through a transaction with McKesson.  Mallinckrodt submitted an illegitimate product notification (via Form 3911) to FDA about this oxycodone hydrochloride, noting that “the tablets that were in the bottle were foreign tablets.”

Rite Aid’s pharmacy located in Waterford, Michigan, also received illegitimate product, which they reported had been distributed by McKesson.  The pharmacy received one bottle, also labeled as containing 100 tablets of oxycodone hydrochloride, which had a broken seal and did not contain oxycodone hydrochloride.  The bottle’s contents were also replaced with 15 tablets of naproxen.  Rite Aid reported to McKesson that it had received this product through a transaction with McKesson. On September 15, 2016, Rite Aid alerted McKesson by email about this discovery of product with missing tablets.  Mallinckrodt submitted an illegitimate product notification to FDA (via Form 3911) about the oxycodone hydrochloride, noting that the Rite Aid pharmacy in Waterford “reported that upon opening a bottle of Mallinckrodt Oxycodone 30mg the seal was broken and 100 tablets of Oxycodone 30mg were missing.  Fifteen tablets of generic Aleve ([n]aproxen sodium 220mg tablets) manufactured by Amneal Pharmaceuticals were inside the bottle.”

On October 6, 2016, Rite Aid’s pharmacy located in Warren, Michigan, also received illegitimate product, which they reported had been distributed by McKesson.  The pharmacy had ordered five bottles of oxycodone hydrochloride.  In three of the bottles they received, all the oxycodone hydrochloride had been removed.  These three bottles contained various combinations of naproxen and ciprofloxacin hydrochloride.  Mallinckrodt submitted an illegitimate product notification (via Form 3911) to FDA about these products, noting that “three bottles were missing all 100 tablets of [o]xycodone [h]ydrochloride 30mg tabs and contained foreign tablets.”

Your firm’s investigation of these three incidents of illegitimate product determined that, because of the lack of evidence of tampering with these packages and the proximity of these three Rite Aid pharmacies, it was likely that the oxycodone hydrochloride was replaced with other product while the packages were in the possession or control of McKesson.

These instances illustrate your firm’s failure to have systems in place to enable compliance with the requirements of section 582(c)(4) of the FD&C Act. After receiving illegitimate product notifications from Rite Aid, your firm was required to respond by identifying all illegitimate product subject to such notification that was in its possession or control, including any product that was subsequently received (section 582(c)(4)(B)(iii)). McKesson was then required to quarantine such product within its possession or control from product intended for distribution until such product was dispositioned (section 582(c)(4)(B)(i)(I)), dispose of any illegitimate product within its possession or control (section 582(c)(4)(B)(i)(II)), take reasonable and appropriate steps to assist trading partners to dispose of illegitimate product not in the possession of McKesson (section 582(c)(4)(B)(i)(III)), and notify within 24 hours FDA and all immediate trading partners that may have received such illegitimate product (section 582(c)(4)(B)(ii)). Your firm was also required to keep, for not less than 6 years, records of the disposition of illegitimate product (sections 582(c)(4)(B)(v)).

Although your firm conducted an investigation related to these bottles of oxycodone hydrochloride, your firm was unable to demonstrate that you met key obligations under section 582(c)(4). For example, you did not demonstrate that you identified all illegitimate product subject to the notification, such as by searching for product with the same lot number or NDC, or that you quarantined any such product. Similarly, your firm failed to demonstrate that you notified your immediate trading partners who may have received product with the same lot number or NDC. This is particularly troubling because your firm’s investigation noted that the oxycodone hydrochloride was likely replaced with different product at a McKesson distribution center. Also troubling is that during the FDA inspection of your firm’s San Francisco headquarters, a McKesson representative stated that incidents involving stolen or diverted controlled substances are not treated as Drug Supply Chain Security Act (DSCSA) verification events within the firm. In fact, DSCSA explicitly defines illegitimate product to include “a product for which credible evidence shows that the product is counterfeit, diverted, or stolen.”[2] Finally, your firm provided no records to demonstrate the disposition of these illegitimate products.

Corrective Actions

FDA has reviewed your firm’s responses to the Form FDA 483 and subsequent correspondence.

  1. Your firm’s response to the Form FDA 483 states that while you investigated “incidents related to potential diversion and theft issues … the incidents were not necessarily related to suspect or illegitimate products.”  This response parallels your representative’s statement to FDA investigators at your San Francisco headquarters that incidents involving stolen or diverted controlled substances are not treated as DSCSA verification events within the firm.  These statements demonstrate a lack of understanding of the definitions of suspect and illegitimate products, and of your firm’s responsibilities when notified of an illegitimate product by a trading partner.  All prescription drug products in finished dosage form for administration to a patient[4]– including those containing controlled substances – are subject to DSCSA verification requirements in section 582(c)(4). Moreover, the statute defines illegitimate product to include “a product for which credible evidence shows that the product is counterfeit, diverted, or stolen.”[5] Under the law, your firm must treat incidents involving suspect and illegitimate products as subject to DSCSA requirements, including products that are controlled substances.
  2. Your firm’s response to the Form FDA 483 cannot be evaluated because it lacks sufficient supporting documentation.  Your response states that McKesson plans to make procedural updates to its standard operating procedures, without describing what these updates are or providing new standard operating procedure documents for review.  FDA does not have enough information to conclude that future investigations of suspect or illegitimate product by McKesson will be conducted in a manner compliant with DSCSA.  Your firm’s response dated November 4, 2018, contains similar information as your previous response; namely regarding updates you have made to various policy documents.  Again, however, your firm provided no supporting documentation for review.
  3. Although your November 4, 2018, response to FDA states that you intend to form a “Product Safety Committee that will be responsible for coordination of all actions related to suspect or illegitimate product,” your firm provided no information about the composition of this committee or the procedures under which the committee will function.  As a result, your response does not demonstrate how the proposed change will improve McKesson’s compliance with DSCSA verification requirements.

 Conclusion

The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facilities. You are responsible for investigating and determining the causes of the violations identified above, and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law.

Failure to promptly correct these violations may result in legal action without further notice, including injunction. Unresolved violations in this warning letter may also prevent other federal agencies from awarding contracts.

Within fifteen (15) working days of your receipt of this letter, please notify this office in writing of the specific steps that you have taken to (1) correct the violations identified in this warning letter, and (2) identify and conduct appropriate investigations and follow-up related to other reports of suspect or illegitimate product that you have identified or received. Please include an explanation of each step being taken to prevent the recurrence of violations and include copies of related documentation. In addition, provide the steps your firm has taken to prevent incidents of theft and diversion. If you disagree with the characterization of the violations of the FD&C Act in this warning letter, include your reasoning and any supporting infom,ation for our consideration. If you cannot complete corrective actions within fifteen (15) working days, state the reason for the delay and the time within which you will complete the corrections.
Please send your electronic reply to ORAPHARM4_Responses@FDA.HHS.GOV or mail your reply to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
U.S. Food & Drug Administration
19701 Fairchild Rd.
Irvine, California 92612-2506
Sincerely,

Alonza Cruse

Director

Office of Pharmaceutical Quality Operations

Office of Regulatory Affairs

 

 

 

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How Johnson & Johnson Hid Asbestos In J&J Baby Powder Products For Over 40 Years

“Why Did Johnson & Johnson Hide Asbestos In Baby Powder Products?” 

By Mark A. York  (January 2, 2019)

 

 

 

 

 

 

  (Mass Tort Nexus Media) Johnson & Johnson has hidden the fact that they’ve known its raw talc and finished powders tested positive for quantities of asbestos, with the company’s doctors and lawyers being fully aware of the findings but failed to alert regulators or consumers.  This may currently be due to the Talc based litigation docket that’s quickly becoming a major mass tort, but in looking back over 40 years, it seems that J&J simply chose to ignore the science and hide the data from the public.

Among the recent documents unsealed in court indicates that in May 1974, an official at Johnson & Johnson’s Windsor mine in Vermont recommended “the use of citric acid in the depression of chrysotile asbestos” from talc extracted from the site.

“The use of these systems is strongly urged by this writer to provide protection against what are currently considered to be materials presenting a severe health hazard and are potentially present in all talc ores in use at this time,” the mine’s director of research and development wrote then.

See also “New Evidence of Johnson & Johnson Bad Conduct Moved LA Jury to Award $417 Million Talc Verdict”.

Johnson & Johnson stock — up 6 percent for the year — plunged 11 percent on news of the report, based on memos, internal documents and confidential memos that the maker of Johnson’s Baby Powder had been compelled to share with attorneys for some 11,700 plaintiffs who claim the company’s powder products caused their cancers. The cases include thousands of women with ovarian cancer.

Johnson & Johnson is facing thousands of lawsuits across the country including in a federal multi-district litigation in New Jersey, see Johnson & Johnson Talcum Powder MDL 2738 (USDC New Jersey). This litigation is related primarily to the ovarian cancer claims brought by women, who claim that J&J talcum powder products cause ovarian cancer, which combined with the emerging talc mesothelioma lawsuits, would open an entire new area of mass tort litigation for J&J and its affiliates to defend.

Any exposure to asbestos is a health risk, according to the World Health Organization and other medical groups.  ompany documents, along with deposition and trial testimony, show that from at least 1971 to the early 2000s, tests showed small amounts of asbestos could sometimes be found in the company’s raw talc and finished powders, Reuters reported.

At the same time, company executives, mine managers, scientists, doctors and lawyers worried about the problem and how to address it but did not disclose the issue to regulators or the public.

https://www.cbsnews.com/video/johnson-johnson-vows-to-appeal-4-7-billion-talcum-products-verdict/

An examination of the documents also revealed how J&J succeeded in curbing regulators’ plans to curtail asbestos in cosmetic talc products as well as scientist research on talc’s health effects, Reuters stated.

Johnson & Johnson denied reports in a statement to the Associated Press. J&J said “thousands of independent tests by regulators and the world’s leading labs prove our baby powder has never contained asbestos.”

The New Brunswick, New Jersey, company  also has publicly maintained in recent years there is no science to back alleged links between its powder and cancer. J&J has won several recent court cases alleging liability and damages, and is appealing other judgments, including $4.6 billion awarded in July to 22 women who claimed its product caused their ovarian cancer.

J&J dominated the talc powder market for more than a century, with its talc products adding $420 million to the company’s $76.5 billion in sales in 2017. While contributing a relatively small portion to overall revenue, Johnson’s Baby Powder is seen as a major component of J&J’s image as a caring company — a “sacred cow,” as one 2003 internal email cited by Reuters put it.

SCIENCE SAYS TALC IS DANGEROUS

The debate over talc began decades ago. In the early 1970s, scientists discovered talc particles in ovarian tumors. In 1982, Harvard researcher Daniel Cramer reported a link between talcum powder and ovarian cancer. His study was followed by several more finding an increased risk of ovarian cancer among regular users of talcum powder. Cramer, who at one point advised J&J to put a warning on its products, has become a frequent expert witness for women suing the company. J&J ignored and suppressed Mr. Cramer’s attempts to show them the study data then publicly declared this research as flawed, which J&J still continues to this day.

DOES J&J TALCUM POWDER CAUSE CANCER?

Johnson & Johnson has been ordered to pay nearly $1 billion in total damages after just 5 trials, alleging its baby powder is causing ovarian cancer, all jury verdicts have been in state courts in Missouri and California, see J&J Talc Trials St. Louis Missouri.

Talc, a mineral composed of magnesium, silicon, oxygen and hydrogen, is used extensively in cosmetics and personal care products. Women sometimes use talcum powder on their genital areas, sanitary napkins or diaphragms to absorb moisture and odor – contrary to the guidance of most physicians. (Asbestos, linked to lung cancer, was once an impurity in talc, but it has been banned for several decades.)  J&J is notorious for using any means possible to influence scientific data and opinion as well as manipulating research reports and public media commentary by industry experts. The recent California trial showed payments made to previously perceived impartial Science Council members, who were declaring publicly that J&J talcum powder does not pose a cancer risk, the Los Angeles jury did not agree with J&J and other pro-talc defense team members, as over $300 million of the total $417 million judgment was for punitive damages, usually awarded for intentional misconduct, see “New Evidence of Johnson & Johnson Bad Conduct Moved LA Jury to Award $417 Million Talc Verdict”.

His studies and the many others that have found a relationship used a case-control approach. A group of women diagnosed with ovarian cancer and a group without it were asked to recall their past diet and activities, and the results were then compared.

Critics say these kinds of studies have serious drawbacks, particularly “recall bias.” Women may forget what they did or, if diagnosed with cancer, might inadvertently overestimate their use of a suspect substance. People without a serious disease may be less motivated to remember details.

Three other studies – considered cohort studies – did not find any overall link. Unlike the case-control studies, these efforts began with a large group of women who did not have cancer and followed the progress of their health, with participants recording what they were doing in real time. The results of this approach, most scientists say, are stronger because they aren’t subject to the vagaries of memory.

One such study included more than 61,000 women followed for 12 years as part of the National Institutes of Health’s well-respected Women’s Health Initiative.

WILL “MESOTHELIOMA TALC” BE THE NEW MASS TORT?

Two recent verdicts for asbestos contamination demonstrate the risk to cosmetic talc defendants, when a Los Angeles County jury awarded $18M to Philip Depolian against Whittaker, Clark & Daniels finding it 30% responsible for his mesothelioma due to his alleged exposure to various cosmetic talc products used at his father’s barbershops that contained asbestos. The jury apportioned liability against various cosmetic talc defendants that had settled and several other cosmetic talc product defendants that sold products including Old Spice, Clubman, Kings Men and Mennen Shave Talc.

In 2015, another Los Angeles jury awarded Judith Winkel $13M against Colgate-Palmolive for mesothelioma allegedly caused by exposure to talc in its baby powder. The jury rejected Colgate and its experts’ claims that the cosmetic talc at issue was not contaminated by asbestos and that the talc in question were non-fibrous “cleavage fragments” unlikely to be inhaled or embedded in the lungs. Although details of the trial are not readily verified, at least one report indicated that evidence presented at trial showed that the talc contained 20% asbestos fibers.

These cases are particularly important because the defendants were held responsible for cosmetic talc containing asbestos and for having caused mesothelioma and not ovarian cancer as in the earlier J&J talc cases. Further, both juries found that the defendants acted with malice. However, the cases were confidentially settled before the respective punitive damage phases.

Will “Talc Mesothelioma” be the next mass tort against Johnson & Johnson and its affiliates? Mass Tort Nexus will continue to report on this as additional information becomes available.

 

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The Opioid Epidemic and State Courts – Why some aren’t filing into Opiate MDL 2804

Florida, Texas, Nevada, North Carolina, North Dakota, Oklahoma, Tennessee, Massachusetts and others have started  their own Opioid Litigation in state courts across the country

By Mark A. York (December 10, 2018)

 

 

 

 

 

 

 

(MASS TORT NEXUS MEDIA) Opioid abuse has been steadily increasing in the United States, and now state courts are becoming the legal venue of choice for filing lawsuits against the “opioid industry” and there may be a need for partnerships with other organizations to confront this epidemic. Lawsuits have already been filed in federal courts and by 22 U.S. states and Puerto Rico against Opiate Big Pharma. 

For a look at the Federal Opiate Litigation MDL 2804 see “OPIOID-CRISIS-BRIEFCASE -MDL-2804-OPIATE-PRESCRIPTION-LITIGATION” where states, counties, cities, indian tribes as well as unions, hospitals and individuals have filed more than 1000 lawsuits against the opioid industry as a whole.

BILLIONS IN PROFITS

The pharmaceutical industry spent a vast $6.4 billion in “direct-to-consumer” advertisements to hype new drugs in 2016, according tracking firm Kantar Media. That figure has gone up by 62% since 2012, Kantar Media says. This number may seem large at first but compared to the multi-billions in yearly profits just by opioid manufacturers over the last 15 years, the numbers is small.  Corporate earnings have risen every year since the push to increase opioid prescriptions in every way possible, to became an accepted business model in Big Pharma boardrooms across the country.

Opioids were involved in more than 42,000 overdose deaths in 2016, the last year for which data was available, according to the U.S. Centers for Disease Control and Prevention. Kentucky, one of the nation’s hardest-hit states, lost more than 1,400 people to drug overdoses that year.

A NEW INFANT NAS MDL 2872

Kevin Thompson of the Opioid Justice Team, has filed a motion for a new prescription opiate related multidistrict litigation, which was heard in front of the JPML panel on November 28, 2018 in New York City, where the panel was requested to designate MDL No. 2872 (INFANTS BORN OPIOID-DEPENDENT PRODUCTS LIABILITY LITIGATION) as a new and separate litigation focused on infants born addicted to opiates and suffering from what’s commonly knows as Neonatal Abstinence Syndrome (NAS) and numerous other long-term medical issues.

The current Opiate MDL 2804 is not moving litigation related to individuals forward in any way. Thompson’s team is requesting that the infant cases be carved out from the sprawling lawsuit in Cleveland and transferred to a federal judge in West Virginia, one of the hardest hit states where roughly 5 percent of all babies are born dependent on opioids. The overall Infant NAS MDL 2872 docket can be viewed here MDL 2872 Infant NAS Re-infants-born-opioid-dependent-products-liability-litigation docket.

The misuse of opioids starting with the flood of prescription pain medicines, which has cast a wide net to now include heroin, fentanyl, morphine, and other drugs both legal and illegal is a serious national problem. In 2015 one in ten Americans reported using an illicit drug in the past 30 days.[1] Marijuana use and the misuse of prescription pain relievers account for the majority of illicit drug use. Of the 21.5 million Americans 12 or older who had a substance-use disorder in 2014, 1.9 million had a substance-use disorder involving prescription pain relievers, and 586,000 had a substance-use disorder involving heroin.[2]

 

Widespread use of opioids has had a devastating impact on many communities. In 2014, more people died from drug overdoses than in any year on record, with 78 Americans dying every day from an opioid overdose. Drug overdose now surpasses motor-vehicle crashes as the leading cause of injury death in the United States. Most opioid-related overdoses involve prescription painkillers, but a growing number are the result of a powerful combination of heroin and fentanyl, a synthetic opioid often packaged and sold as heroin. Some of the largest concentrations of overdose deaths were in Appalachia and the Southwest, according to county-level estimates by the Centers for Disease Control and Prevention.[3]

One contributing factor behind the opioid epidemic is the increase in the use of prescription painkillers nationally. From 1991 to 2011, the number of opioid prescriptions dispensed by U.S. pharmacies tripled from 76 million to 219 million.[4] This increase in the use of opioids is unique to America. The United States represents less than 5 percent of the world’s population but consumes roughly 80 percent of the world’s supply of opioid drugs.[5] There is also wide variation from one state to another in opioid-prescribing rates. In 2012 twelve states had more opioid prescriptions than people: Alabama (142.9 per 100 people), Tennessee (142.8), West Virginia (137.6), Kentucky (128.4), Oklahoma (127.8), Mississippi (120.3), Louisiana (118), Arkansas (115.8), Indiana (109.1), Michigan (107), South Carolina (101.8), and Ohio (100.1).[6]

The impact of the opioid epidemic touches every aspect of our public safety and judicial system. Drug-related arrests involving opioids are skyrocketing. In many communities, court dockets and probation caseloads are filled with individuals with opioid-use disorders. Access to treatment, particularly medication-assisted treatment combined with cognitive behavioral interventions, is limited—particularly in rural communities. This epidemic also comes at a price. In 2015 the Ohio Department of Mental Health and Addiction Services began providing substance-abuse treatment in Ohio’s prisons, spending an estimated $30 million per year on drug treatment in prisons, $4 million on housing for individuals in recovery, and $1 million over two years for naloxone to reverse drug overdoses. The Ohio State Highway Patrol spent over $2 million to expand and improve their crime lab to keep up with substance testing.

In addition to the impact of opioid abuse on the criminal courts, the nation’s family courts and child welfare system are being deeply impacted. A recent report by the Administration for Children and Families shows that after years of decline, the number of children in foster care is rising. Nearly three-quarters of all states reported an increase in the number of children entering foster care from 2014 to 2015. The largest increases occurred in Florida, Indiana, Georgia, Arizona, and Minnesota. From 2012 to 2016, the percentage of removals nationally due to parental substance abuse increased 13 percent to 32.2 percent.

In addition to hundreds of cases consolidated in federal court in Opiate MDL 2804, the defendants face a wave of litigation in state courts as well as civil and criminal investigations by numerous state attorneys general and the federal government. Any settlement would have to protect the defendant companies from future lawsuits over the same issue and that may be difficult to negotiate given all the concurrent litigation in different courts.

The primary federal litigation involving many cities and counties was consolidated by the JPML in December 2017 in a federal court in Cleveland, Ohio, in front of Judge Daniel Polster. The defendants include Purdue, J&J, Teva, Endo, AmerisourceBergen, Cardinal Health and McKesson. The federal litigation is growing daily see, Opiate Prescription MDL 2804, US District Court of Ohio link.

The time has now arrived for Opioid Big Pharma, in all forms to face the facts that for close to 20 years they have flooded the mainstream commerce of America with massive amounts of opiates with little to no oversight, which whether caused by a catastrophic systemic failure on many levels, or simple greed, the time has now come for the opiate industry to face the music of complex litigation in state and federal court venues across the country.

The judiciary can play a critical role in addressing the opioid epidemic. In August 2016, representatives from the Kentucky, Illinois, Indiana, Michigan, Ohio, Pennsylvania, Tennessee, Virginia, and West Virginia courts convened for the first-ever Regional Judicial Opioid (RJOI) Summit. The judicial summit brought together multidisciplinary delegates from each state to develop a regional action plan and consider regional strategies to combat the opioid epidemic. RJOI member states continue to work both within their home states and regionally to share promising practices, as well as to implement the objectives of the regional action plan. Courts are encouraged to work with partners in similar ways to:

  • Invest in local, state, and regional multidisciplinary, system-level strategic planning to identify policies or practice changes that can improve treatment engagement and reduce the risk of overdose death. Judges are particularly effective at using their convening power to bring together a variety of agencies and community stakeholders. The sequential intercept model is an effective approach to identifying gaps and opportunities for diverting criminal-justice-involved people to treatment. Communities are encouraged to not focus singularly on heroin use but to focus on substance-use disorders in general. A recent CDC study found that nearly all people who used heroin also used at least one other drug; most used at least three other drugs.[7]
  • Implement law-enforcement diversion programs, prosecutor diversion programs, or both to deflect or divert individuals with substance-use disorders from the criminal justice system into treatment at the earliest possible point.
  • Expand court diversion and sentencing options that provide substance-abuse treatment as an alternative to incarceration. Problem-solving courts, such as adult drug courts or veterans treatment courts, are the most notable examples of effective approaches.  
  • Incorporate strategic screening questions designed to identify criminal-justice-involved individuals at high-risk for overdose death into all criminal-justice-agency intake forms. Specifically, research suggests that individuals with a history of non-fatal overdoses, individuals with a history of opioids in combination with benzodiazepines like Xanax (alprazolam) and Soma (Carisoprodol), and individuals with an opioid-use disorder recently released from a confined environment (e.g., residential treatment or incarceration) are at particular risk for overdose death. This population should be prioritized for treatment and overdose-prevention services, such as naloxone access.

On January 24, 2017, the Bureau of Justice Assistance released funding for a “Comprehensive Opioid Abuse Program.” Through this solicitation, courts and their partners may implement overdose outreach projects, technology-assisted treatment programs, and diversion and alternatives to incarceration.

What remains to be seen is where and how the directly affected “individuals” who were prescribed millions of addictive opiates and subsequently became addicted and where thousands more overdosed and died, remains to be seen.

Who will be the advocate to make sure that these individuals as well as their children, families and communities as a whole are placed on the road to recovery. Historically, Big Pharma is not an industry to put the best interests of the paying consumer at the forefront of their agendas.

__________________________________________________________________________________________

[1] Center for Behavioral Health Statistics and Quality, “Key Substance Use and Mental Health Indicators in the United States: Results from the 2015 National Survey on Drug Use and Health” (HHS Publication No. SMA 16-4984, NSDUH Series H-51), report prepared for the Substance Abuse and Mental Health Services Administration, Rockville, Maryland, 2016. Retrieved from http://www.samhsa.gov/data/.

[2] Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality, Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health (Rockville, MD: Substance Abuse and Mental Health Services Administration, 2015).

[3] L. M. Rossen, B. Bastian, M. Warner, D. Khan, and Y. Chong, “Drug Poisoning Mortality: United States, 1999–2014,” National Center for Health Statistics, 2016.

[4] National Institute on Drug Abuse, “Prescription Opioids and Heroin,” Research Report Series, Department of Health and Human Services, National Institutes of Health, Washington, D.C., 2015. Retrieved from https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/rx_and_heroin_rrs_layout_final.pdf.

[5] L. Manchikanti and A. Singh, “Therapeutic Opioids: A Ten-Year Perspective on the Complexities and Complications of Escalating Use, Abuse, and Nonmedical Use of Opioids,” Pain Physician 11, 2nd supp. (2008): S63-S88.

[6] L. J. Paulozzi, K. A. Mack, and J. M. Hockenberry, “Vital Signs: Variation Among States in Prescribing Pain Relievers and Benzodiazepines—United States,” Center for Disease Control and Prevention, Atlanta, 2014.

[7] National Survey on Drug Use and Health, 2011-2013.

 

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MEDICAL DEVICE IMPLANT OVERSIGHT BY FDA IS NOT HAPPENING: WHY?

WHY THE MOTTO OF “PROFITS BEFORE PATIENTS” IS STILL THE BANNER: 

HERE’S A FULL REPORT

 By Mark A. York (November 26, 2018)

 

 

 

 

 

 

 

 

 

 

(MASS TORT NEXUS MEDIA) For years, medical device companies have stated that the products they are developing and placing into the marketplace are safe and helping patients in the USA and worldwide. That is often not the case and people around the world are suffering.

Medical device makers and compensated doctors have touted FDA approved implants and other devices as the surgical cure for millions of patients suffering from a wide range of pain disorders, making them one of the fastest-growing products in the $400 billion medical device industry. Companies and doctors aggressively push them as a safe antidote to the deadly opioid crisis in the U.S. and as a treatment for an aging population in need of chronic pain relief and many other afflictions.

Why Device Makers Tout FDA Approvals

Manufacturer headlines like these instill consumer confidence that medical devices are safe and effective. After all, they have the FDA’s stamp of approval, right? NO!

The reality is, the FDA seldom requires rigorous evidence that a device works well–and safely–before allowing it onto the market. Medical devices are the diverse array of non-drug products used to diagnosis and treat medical conditions, from bandages to MRI scanners to smartphone apps to artificial hips.

This low standard of evidence applies to even the highest risk devices such as those that are implanted in a person’s body. Surgical mesh, pacemakers and gastric weight loss balloons are just a few examples of devices that have had serious safety problems.

Devices are subject to weaker standards than drugs because they’re regulated under a different law. The Medical Device Amendments of 1976 was intended to encourage innovation while allowing for a range of review standards based on risk, according to legal expert Richard A. Merrill. An array of corporate lobbying has since prompted Congress to ease regulations and make it easier for devices to get the FDA’s approval.

In 2011, an Institute of Medicine panel recommended that the “flawed” system be replaced, because it does not actually establish safety and effectiveness. At the time the FDA said it disagreed with the group’s recommendations.

Defective devices cleared through this system have included hip replacements that failed prematurely, surgical mesh linked to pain and bleeding and a surgical instrument that inadvertently spread uterine cancer.

FDA Does Not Do What’s Needed

Congress, FDA Poised to Loosen Oversight of Medical Devices, June 20, 2017

When makers of medical devices learn that one of their products has malfunctioned in a way that could kill or seriously injure people, they are required to file a report with the Food and Drug Administration (FDA). The reports are meant to alert regulators that patients may be in danger.

However, in the future, under a deal the FDA has negotiated with industry lobbyists, manufacturers could generally wait three months before reporting malfunctions, and they could report malfunctions in “summary” form, according to an FDA document.

This 2017 deal apparently means that the government and the public could receive less detailed and less timely warnings.

To see how many FDA recalls take place daily see the FDA recall database link: https://www.fda.gov/MedicalDevices/Safety/default.htm

Spinal Cord Stimulator Failures

Jim Taft listened intently as his pain management doctor described a medical device that could change his life, it wouldn’t fix the nerve damage in his mangled right arm, but a spinal-cord stimulator would cloak his pain, making him “good as new.”

Taft’s stimulator failed soon after it was surgically implanted. After an operation to repair it, he said the device shocked him so many times that he couldn’t sleep and even fell down a flight of stairs. Today, the 45-year-old Taft is virtually paralyzed.

“I thought I would have a wonderful life,” Taft said. “But look at me.” Taft is just one of the thousands of patients who have been injured by an implanted medical device, almost always by a device that was made in the USA.

A recent global investigation has found that hundreds of thousands of unsafe medical devices have been implanted in patients around the world and device failures are considered very normal.

A recent worldwide investigation was carried out by the International Consortium of Investigative Journalists (ICIJ) in coordination with the British Medical Journal and various media outlets including the Guardian newspaper and BBC Panorama.

The probe found that pacemakers, artificial knees, hips and rods to support the spinal cord are among the faulty devices that were implanted in patients and that failed. These unsafe medical devices have resulted in thousands of injuries and deaths and quite often patients are forced to undergo removal or revision surgeries.

The investigation found that many of the unsafe medical devices did not complete patient trials before their commercial launch, adding  that some of the pacemakers were implanted when the manufacturers were aware of the problems, while some devices were approved on the basis of a regulatory nod secured in other countries.

Poor regulations across countries, lenient testing standards and lack of clarity allowed these faulty medical devices to reach the market.

In the UK alone, the regulators received 62,000 “adverse incident” reports associated with medical devices between 2015 and 2018. About 1,004 of such cases even resulted in the death of patients.

In the USA, the Food and Drug Administration (FDA) has been notified of 5.4 million ‘adverse events’ over the last ten years. Faulty devices were linked to approximately 1.7 million injuries and 83,000 deaths.

Even though these medical devices are made in the USA, the U.S. Food and Drug Administration had not, and still has not, deemed them good enough for Americans. The FDA has permitted sales overseas of unproven devices and products via an obscure FDA provision in which products are registered as an “export only” device, requiring far less FDA scrutiny than for devices that are sold domestically.

An example is PyroTITAN, by Intergra LifeSciences of New Jersey, among the biggest medical device companies in the world and maker of more than a dozen export-only devices with troubled track records identified as “export only” which is a U.S.-made implant for losing weight that instead led to  numerous emergency surgeries, stents that could cut into arteries and heart valves sold in Spain and Italy that, according to the FDA, caused severe infections and may have caused a five-year-old child to die. These items were found by analyzing and comparing databases in 10 countries, and a lack of international standards for identifying devices means it is difficult to know how many other troubled devices exist.

For U.S. companies, exporting medical devices is big business, valued last year at more than $41 billion. Currently about 4,600 devices are registered with the FDA as “export only” devices. Several executives for medical device makers said registering the devices is faster, less expensive and has involved less oversight than getting them approved for sale inside the U.S. The troubled devices identified by NBC News have been sold around the world. The destinations range from the Netherlands to Namibia, Chile to Canada, Japan to Germany.

Recently, NBC probed export-only devices as part of the same global project organized by the International Consortium of Investigative Journalists, a news organization notable for its work on the Panama Papers, to examine the medical device industry. More than 250 reporters in 36 countries worked on stories that began publishing Sunday.

Worldwide US Device Exports are Often Substandard

Zimmer Biomet is one of the big medical device companies named in the investigation. The company has previously had to discontinue sales of a metal-on-metal hip implant system which was cause to flesh-rotting via metallosis poisoning. The company seems to have maintained the tried and true Big Pharma mantra of “we do what the FDA requires, therefor we are excluded from accepting responsibility for defective medical products” which is often pushed as a coverall statement by medical device makers when they are under scrutiny.

“We adhere to strict regulatory standard, and work closely with the FDA and all applicable regulatory agencies in each of our regions as part of our commitment to operating a first-rate quality management system across our global manufacturing network.

Abbott has also come under scrutiny for its Nanostim pacemaker, which has received complaints about implant battery failures and parts of the device falling off inside patients.  The company released the following statement: “In accordance with the European CE Mark approval process, the Nanostim leadless pacing system was approved based on strong performance and safety data.”

Johnson & Johnson (J&J) is another one of the big medical device companies to be named in the investigation. Earlier this year, J&J agreed to work with the Indian government to offer compensation to patients who were affected by faulty hip implants.

Although there are roughly 4,000 types of medical devices in the FDA’s data, just six of them accounted for a quarter of device injury reports since 2008.

 

Spinal Cord Stimulator Misinformation:

Medical device companies and doctors tout spinal-cord stimulators to treat patients suffering from a wide range of pain disorders. But an investigation by AP found the devices rank third in injury reports to the FDA in 10 years.

But the stimulators — devices that use electrical currents to block pain signals before they reach the brain — are more dangerous than many patients know, an Associated Press investigation found. They account for the third-highest number of medical device injury reports to the U.S. Food and Drug Administration, with more than 80,000 incidents flagged since 2008.

Patients report that they have been shocked or burned or have suffered spinal-cord nerve damage ranging from muscle weakness to paraplegia, FDA data shows. Among the 4,000 types of devices tracked by the FDA, only metal hip replacements and insulin pumps have logged more injury reports.

The FDA data contains more than 500 reports of people with spinal-cord stimulators who died but details are scant, making it difficult to determine if the deaths were related to the stimulator or implant surgery.

An animated look at the spinal cord stimulator, its benefits and potential problems. (AP Animation/Peter Hamlin)

Medical device manufacturers insist spinal-cord stimulators are safe — some 60,000 are implanted annually — and doctors who specialize in these surgeries say they have helped reduce pain for many of their patients.

Most of these devices have been approved by the FDA with little clinical testing and the agency’s data shows that spinal-cord stimulators have a disproportionately higher number of injuries compared to hip implants, which are far more plentiful.

The AP reported on spinal stimulators as part of a year long joint investigation of the global medical devices industry that included NBC, the International Consortium of Investigative Journalists and more than 50 other media partners around the world. Reporters collected and analyzed millions of medical records, recall notices and other product safety warnings, in addition to interviewing doctors, patients, researchers and company whistleblowers.

The media partners found that, across all types of medical devices, more than 1.7 million injuries and nearly 83,000 deaths were reported to the FDA over the last decade.

The investigation also found that the FDA — considered by other countries to be the gold standard in medical device oversight — puts people at risk by pushing devices through an abbreviated approval process, then responds slowly when it comes to forcing companies to correct sometimes life-threatening products.

Devices are rarely pulled from the market, even when major problems emerge, and the FDA does not disclose how many devices are implanted in the U.S. each year — critical information that could be used to calculate success and failure rates.

The FDA acknowledges its data has limitations, including mistakes, omissions and under-reporting that can make it difficult to determine whether a device directly caused an injury or death, but it rejects any suggestion of failed oversight.

“There are over 190,000 different devices on the U.S. market. We approve or clear about a dozen new or modified devices every single business day,” Dr. Jeffrey Shuren, the FDA’s medical device director said at an industry conference in May. “The few devices that get attention at any time in the press is fewer than the devices we may put on the market in a single business day. That to me doesn’t say that the system is failing. It’s remarkable that the system is working as it does.”

In response to reporters’ questions, the FDA said last week that it was taking new action to create “a more robust medical device safety net for patients through better data.” ″Unfortunately, the FDA cannot always know the full extent of the benefits and risks of a device before it reaches the market,” the agency said. In the last 50 years, the medical device industry has revolutionized treatment for some of the deadliest scourges of modern medicine, introducing devices to treat or diagnose heart disease, cancer and diabetes.

Medical device companies have “invested countless resources — both capital and human — in developing leading-edge compliance programs,” said Janet Trunzo, head of technology and regulatory affairs for AdvaMed, the industry’s main trade association.

At the same time, medical device makers also have spent billions to try to influence regulators, hospitals and doctors.

In the United States, where drug and device manufacturers are required to disclose payments to physicians, the 10 largest medical device companies paid nearly $600 million to doctors or their hospitals last year to cover consulting fees, research, travel and entertainment expenses, according to an AP and ICIJ analysis of data from the Centers for Medicare & Medicaid Services. This figure doesn’t include payments from device manufacturers like Johnson & Johnson and Allergan, which also sell other products.

On top of that, lobbying records show that the top four spinal-cord stimulator manufacturers have spent more than $22 million combined since 2017 to try to influence legislation benefiting their overall business, which includes other medical devices.

Some companies have been fined for bribing physicians, illegally promoting products for unapproved uses and paying for studies that proclaim the safety and effectiveness of their products, according to the joint investigation.

In a 2016 case, Olympus Corp. of the Americas, the largest U.S. distributor of endoscopes and related medical equipment, agreed to pay $623.2 million “to resolve criminal charges and civil claims relating to a scheme to pay kickbacks to doctors and hospitals,” according to the U.S. Justice Department. Olympus said that it “agreed to make various improvements to its compliance program.”

In a case the previous year involving spinal-cord stimulators, Medtronic,Inc. agreed to pay $2.8 million to settle Justice Department claims that the company had harmed patients and defrauded federal health care programs by providing physicians “powerful” financial inducements that turned them into “salesmen” for costly procedures. Medtronic denied wrongdoing. “As a matter of policy, Medtronic does not comment on specific litigation,” the company said in a statement. “We do stand behind the safety and efficacy of our Spinal Cord Stimulators and the strong benefits this technology provides to patients, many of whom have tried all other therapy options to no benefit.”

Some doctors enthusiastically promote spinal-cord stimulators without disclosing to patients they’ve received money from medical device manufacturers. Some experts say doctors are not legally required to disclose such payments, but they have an ethical obligation to do so. Sometimes the money goes to the doctors’ hospitals, and not directly to them.

As for Taft, he said he just wanted to get better, but he has lost hope. “This is my death sentence,” Taft said, stretched out beneath his bed’s wooden headboard on which he’s carved the words “death row.”

“I’ll die here,” he said.

Why Hasn’t The FDA Learned From Past Failures?

A generation ago, tens of thousands of women were injured by the Dalkon Shield, an intrauterine device that caused life-threatening infections. Consumer advocates demanded testing and pre-market approval of medical devices to prevent deaths and injuries associated with defective products.

So in 1976, Congress passed the Medical Device Amendment, a law meant to assure Americans that devices recommended by their doctors would do good and not harm.

“Until today, the American consumer could not be sure that a medical device used by his physician, his hospital or himself was as safe and effective as it could or should be,” President Gerald Ford said when he signed the bill into law.

Charged with carrying out the law, the FDA created three classes of medical devices. High-risk products like spinal-cord stimulators are designated to be held to the most rigorous clinical testing standards. But the vast majority of devices go through a less stringent review process that provides an easy path to market for devices deemed “substantially equivalent” to products already approved for use.

As designed by Congress, that process should have been phased out. Instead, it became the standard path to market for thousands of devices, including hip replacements implanted in tens of thousands of patients that would later be recalled because metal shavings from the devices made some people sick.

The AP found that the FDA has allowed some spinal-cord stimulators to reach the market without new clinical studies, approving them largely based on results from studies of earlier spinal stimulators.

Spinal stimulators are complex devices that send electrical currents through wires placed along the spine, using a battery implanted under the skin. An external remote controls the device.

The four biggest makers of spinal-cord stimulators are Boston Scientific Corp., based in Marlborough, Massachusetts; Medtronic, with headquarters in Ireland and the U.S.; Nevro, in Redwood City, California; and Illinois-based Abbott, which entered the market after its $23.6 billion purchase of St. Jude Medical, Inc.

St. Jude’s application to go to market with its first spinal stimulator contained no original patient data and was based on clinical results from other studies, while Boston Scientific’s application for its Precision spinal-cord stimulator was based largely on older data, though it did include a small, original study of 26 patients who were tracked for as little as two weeks.

Once approved, medical device companies can use countless supplementary requests to alter their products, even when the changes are substantial.

For example, there have been only six new spinal-cord stimulator devices approved since 1984, with 835 supplemental changes to those devices given the go-ahead through the middle of this year, the AP found. Medtronic alone has been granted 394 supplemental changes to its stimulator since 1984, covering everything from altering the sterilization process to updating the design.

“It’s kind of the story of FDA’s regulation of devices, where they’re just putting stuff on the market,” said Diana Zuckerman, president of the National Center for Health Research, who has studied medical devices for nearly 30 years.

Medical device manufacturers have cited multiple industry-funded studies showing the effectiveness of spinal-cord stimulation in the treatment of chronic pain. Experts say treatment is considered successful if pain is reduced by at least half, but not every patient experiences that much pain reduction.

A 2016 study looking at different stimulation systems found “significant evidence” that they were “a safe, clinical and cost-effective treatment for many chronic pain conditions.”

But Zuckerman noted that the more extensive studies came after the devices were being widely used on people. “These patients are guinea pigs,” she said.

FDA said in a statement that it approves, clears or grants marketing authorization to an average of 12 devices per business day and its decisions are “based on valid scientific evidence” that the devices are safe and effective.

Dr. Walter J. Koroshetz, director at the neurological disorders and stroke division at the National Institutes of Health, said trials for medical devices like spinal-cord stimulators are generally small and industry-sponsored, with a “substantial” placebo effect.

“I don’t know of anyone who is happy with spinal-cord technology as it stands,” Koroshetz said. “I think everybody thinks it can be better.”

Why Device Makers Don’t Reveal Adverse Product Issues  

Every time Jim Taft walked into his pain management doctor’s office, he would glance at the brochures touting spinal-cord stimulators — the ones with pictures of people swimming, biking and fishing.

Inside the exam room, Taft said, his doctor told him the device had been successful for his other patients and would improve his quality of life.

On lifetime worker’s compensation after his right arm was crushed as he was hauling materials for an architectural engineering company, Taft had been seeing the doctor for five years before he decided to get a stimulator in 2014. What finally swayed him, he said, was the doctor’s plan to wean him off painkillers.

Taft said his pain management doctor praised the technology, saying stimulators had improved the quality of life for his patients. But four years later, Taft is unable to walk more than a few steps.

Taft is one of 40 patients interviewed by the AP who said they had problems with spinal-cord stimulators. The AP found them through online forums for people with medical devices. Twenty-eight of them said their spinal-cord stimulators not only failed to alleviate pain but left them worse off than before their surgeries.

Zuckerman, who has worked at the U.S. Department of Health and Human Services and as a senior policy adviser to then-first lady Hillary Rodham Clinton, said no doctor wants to think they’re harming patients.

“But there’s a tremendous financial incentive to downplay, ignore or forget bad patient experiences and just focus on how happy patients are,” she said.

More than half the patients interviewed by the AP said they felt pressured to get stimulators because they feared their doctors would cut off their pain medications — the only thing helping them.

Stimulators are considered a treatment of “last resort” by insurance companies, as well as Medicare and Medicaid. That means doctors must follow a protocol before insurance will pay for the device and implantation.

Physicians must show that conservative treatments failed to help, and patients also undergo psychological assessments to evaluate the likelihood of success. They then typically undergo a trial period lasting three days to a week with thin electrodes inserted under the skin. If patients say they got relief from the external transmitter sending electrical pulses to the contacts near their spines, they have surgery to implant a permanent stimulator.

Taft said his three-day trial helped reduce his pain so, a few days before his surgery, he began preparing for a new life. He ordered lumber to refurbish a patio and deck for his wife, Renee, as thanks for her years of support.

In April 2014, Boston Scientific’s Precision stimulator was implanted in Taft by Jason Highsmith, a Charleston, South Carolina, neurosurgeon who has received $181,000 from the company over the past five years in the form of consulting fees and payments for travel and entertainment. A Boston Scientific sales representative was in the operating room — a common practice, the AP found.

Highsmith would not comment on the payments. Other doctors have defended the practice, saying they do important work that helps the companies — and ultimately patients — and deserve to be compensated for their time.

From the time Taft was cut open and the device placed inside his body, he had nothing but problems, according to hundreds of pages of medical records reviewed by the AP. The device began randomly shocking him, and the battery burned his skin.

Taft and his wife complained repeatedly, but said his doctors and a Boston Scientific representative told them that spinal-cord stimulators don’t cause the kind of problems he had.

That runs counter to Boston Scientific’s own literature, which acknowledges that spinal stimulators and the procedures to implant them carry risks, such as the leads moving, overstimulation, paralysis and infections.

That also is not reflected in the AP’s analysis of FDA injury reports, which found shocking and burning had been reported for all major models of spinal-cord stimulators. For Boston Scientific devices, infection was the most common complaint over the past decade, mentioned in more than 4,000 injury reports.

In response to questions, the company called infection “unfortunately a risk in any surgical procedure” that the company works hard to avoid. It added that the FDA’s data “shouldn’t be interpreted as a causal sign of a challenge with our device. In fact, many examples of reportable infections include those that were caused by the surgical procedure or post-operative care.”

“In our internal quality assessments, over 95 percent of the injury reports were temporary or reversible in nature,” the company added.

Taft said had he known the devices hurt so many people, he would have reconsidered getting one. A Boston Scientific sales representative tried reprogramming the device, he said, but nothing worked.

“I told them that it feels like the lead is moving up and down my spine,” Taft said. “They said, ‘It can’t move.’” But in July 2014, X-rays revealed the lead indeed had moved — two inches on one side.

Highsmith told the AP the electrode broke from “vigorous activity,” though Taft said that would not have been possible due to his condition. Taft said he was in such bad shape after his surgery that he was never able to redo the patio and deck for his wife or do anything else vigorous.

That October, Highsmith said, he operated on Taft to install a new lead, tested the battery and reinserted it.

Still, Taft’s medical records show that he continued to report numbness, tingling and pain. During a January 2015 appointment, a physician assistant wrote that the device “seemed to make his pain worse.”

The stimulator was surgically removed in August 2015. The following June, Taft got a second opinion from a clinic that specializes in spinal injuries, which said he had “significant axial and low back pain due to implantation and explantation” of the stimulator.

Highsmith said other doctors have documented severe arthritis in Taft and that, while he has not examined Taft in more than three years, it’s “likely his current condition is the result of disease progression and other factors.”

He did not answer questions about whether he informed Taft of the risks associated with stimulators.

The doctor said the overwhelming majority of his spinal-cord stimulator patients gain significant pain relief.

“Unfortunately, in spite of the major medical breakthroughs with devices like these, some patients still suffer from intractable pain,” he said.

Renee Taft, a paralegal, reached out to Boston Scientific in 2017, but said the company refused to help because her husband’s stimulator had been removed and blamed Taft for his problems, also saying he had engaged in “rigorous physical activity” after surgery.

In the letter from the company’s legal department, Boston Scientific also noted that federal law shielded manufacturers from personal liability claims involving medical devices approved by the FDA.

In response to questions from investigators, Boston Scientific again blamed Taft’s “activity level” but didn’t elaborate. The company also said other factors could contribute to his problems such as “hyperalgesia, a phenomenon associated with long-term opioid use which results in patients becoming increasingly sensitive to some stimuli.”

Since 2005, there have been 50 recalls involving spinal stimulators, averaging about four per year in the last five years. Roughly half the recalls involved stimulators made by Medtronic, the world’s largest device manufacturer, though none warned of a risk of serious injury or death.

The experience of nearly all the 40 patients interviewed by the AP reflected one common fact. Their pain was reduced during the trial but returned once their stimulators were implanted.

Experts say the answer may be a placebo effect created when expectations are built up during the trial that only the stimulator can offer relief from pain, exacerbated by patients not wanting to disappoint family members, who often have been serving as their caregivers.

“If patients know this is a last resort, a last hope, of course they will respond well,” said Dr. Michael Gofeld, a Toronto-based anesthesiologist and pain management specialist who has studied and implanted spinal-cord stimulators in both the U.S. and Canada.

By the time the trial ends, the patient is “flying high, the endorphin levels are high,” Gofeld said.

Manufacturer representatives are heavily involved during the entire process. Along with often being in the operating room during surgery in case the physician has questions, they meet with patients to program the devices in the weeks following surgery.

Most of the patients interviewed by the AP said the adjustments to their devices were performed by sales representatives, often with no doctor or nurse present. That includes one patient who was billed for programming as if the doctor was in the room, though he was not.

“People who are selling the device should not be in charge of maintenance,” Gofeld said. “It’s totally unethical.”

In a 2015 Texas case, a former Medtronic sales representative filed suit contending she was fired after complaining that the company trained employees to program neurostimulators without physicians present. She also claimed that a Medtronic supervisor snatched surgical gloves away from her when she refused to bandage a patient during a procedure, pushed her aside and then cleaned and dressed the patient’s wound. Medtronic denied the allegations, and the case was settled on undisclosed terms.

In the Justice Department case involving Medtronic, a salesman who said he earned as much as $600,000 a year selling spinal-cord stimulators claimed sales representatives encouraged physicians to perform unnecessary procedures that drove up the costs for Medicare and other federal health programs.

“While there have been a few instances where individuals or affiliates did not comply with Medtronic’s policies, we acted to remedy the situation in each case once discovered and to correct any misconduct,” the company said.

Gofeld said he believes stimulators do work, but that many of the problems usually arise when doctors don’t choose appropriate candidates. And he thinks the stimulators are used too often in the U.S.

Nevro, one of the four big manufacturers, has cited estimates that there are as many as 4,400 facilities in the U.S where spinal-stimulation devices are implanted by a variety of physicians, including neurosurgeons, psychiatrists and pain specialists.

It’s a lucrative business . Analysts say stimulators and the surgery to implant them costs between $32,000 and $50,000, with the device itself constituting $20,000 to $25,000 of that amount. If surgery is performed in a hospital, the patient usually stays overnight, and the hospital charges a facility fee for obtaining the device. Costs are typically covered by insurance.

The AP found that doctors can make more money if they perform the surgery at physician-owned outpatient surgery centers, since the doctor buys the device, marks it up and adds on the facility fee.

In Canada, where Gofeld now works, he said the surgeries are done only by those who specialize in the procedures. He said spinal-cord stimulators should be used when pain starts and not after failed back surgeries.

“By then,” he said, “it’s too late.”

When Surgeries Never Stop

While manufacturers and top FDA officials tout stimulators as a weapon in the battle against opioids, neurosurgeons like Steven Falowski are the front-line evangelists.

“Chronic pain is one of the largest health-care burdens we have in the U.S. It’s more than heart disease, cancer and diabetes combined,” Falowski said in an interview. If they’re used early enough for pain, they can prevent people from going on opium-based pain killers, said Falowski, who speaks at neuromodulation conferences and teaches other doctors how to implant stimulators.

Since 2013, device manufacturers have paid Falowski — or St. Luke’s University Health Network in Fountain Hill, Pennsylvania, where he works — nearly $863,000, including $611,000 from St. Jude or its new parent company, Abbott, according to the Centers for Medicare and Medicaid Services database. The payments range from consulting fees to travel and entertainment expenses.

Falowski said he has conducted research and done other work for manufacturers, adding, “The contracts with industry are with my hospital and not with me.”

St. Luke’s told the AP that it keeps the majority of the payments from device makers, but that Falowski “may receive a portion of these payments through his annual compensation.” AP’s analysis showed Abbott products were more likely than other major models to include reports of a hot or burning sensation near the site of the battery, with about 5,600 injury reports since 2008 referring to the words “heat” or “burn.”

Abbott said that many of the “adverse events” reports in the FDA’s data stemmed from a device that was voluntarily recalled in 2011. The company added that feeling a temperature increase at the implant site “is often a reality for rechargeable spinal-cord stimulation systems,” which is why the company is now concentrating on devices that do not need to be recharged.

 

Falowski said doctors do important work for medical device companies, and he has been involved in device development, education, clinical trials and research.

“You’re trying to help patients and you realize as a physician by yourself you’re not going to generate $200 million to make the next best implant for a patient and it’s going to take a company to do that,” he said. “So I think the important part in that relationship is transparency and disclosures.”

Experts interviewed by the AP said doctors are not legally required to tell their patients about financial relationships with medical device manufacturers, but that it would be the right thing to do.

“The patient should be fully informed before consenting to a procedure,” said Genevieve P. Kanter, an assistant professor at the University of Pennsylvania who specializes in internal medicine, medical ethics and health policy.

Abbott Issues Warning After Surgeries For Thousands of Patients

In October 2016, Abbott notified physicians and patients that a subset of ICD and cardiac resynchronization therapy defibrillator (CRT-D) devices manufactured between January 2010 and May 2015 could potentially experience premature battery depletion due to short circuits from lithium clusters.

The potential for premature battery depletion in the affected devices is low. The new Battery Performance Alert can be used as a tool to further assist in identifying the potential for these devices to experience premature battery depletion.

It’s a voluntary recall, so patients are being told to consult with their doctors before coming in for the procedure — which thankfully consists of a simple 3-minute wireless firmware update (using a wand, according to the pamphlet) instead of anything invasive.

The FDA-approved firmware update actually includes a pair of important-sounding fixes. In addition to some enhanced security, the update also comes with a way to detect if a device’s battery drains abnormally quickly and alert the patient.

The FDA and Abbott say they haven’t had issues with any of the 50,000 firmware updates they’ve installed on devices like this so far.

Summary:

Based on historical results as well as litigation related to adverse events with medical device FDA approvals and disclosures by device makers, it would seem that the reality of the dangers related to this device and thousands of other FDA approved devices, we may never know the truth on how dangerous these products really are.

(Images and text excerpts have been taken from NBC News and Associated Press media releases) 

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XARELTO RECENT LABEL CHANGE: Is Rat Poison Safer?

A WHITE PAPER REPORT BY MASS TORT NEXUS

(The following information and conclusions are based on opinions formed after a review of relevant facts and data by John Ray and edited by Lisa Powell, Mass Tort Nexus www.masstortnexus.com)

XARELTO LABEL CHANGE AND CLINICAL TRIAL BACKGROUND

On October 11, 2018, Janssen Pharmaceuticals, Inc. (a division of Johnson & Johnson) changed its Xarelto® drug safety label as follows:

Monitoring for the anticoagulation effect of rivaroxaban using a clotting test (PT, INR or aPTT) for anti-factor XA (FXa) activity is not recommended.

Rivaroxaban is an anticoagulant medication. Anticoagulants thin blood. Rivaroxaban is sold under its trade name, Xarelto®. Xarelto® is used to prevent and/or treat blood clots that could result in strokes in patients with non-valvular atrial fibrillation, in patients undergoing knee and hip reconstruction or replacement surgery, and for secondary prevention in patients who have had an Acute coronary syndrome event.

Prior to FDA approval in 2011, clinical trials were conducted to test the safety and efficacy of Xarelto® and to compare it to other anticoagulants. Trial administrators measured both the medication’s effectiveness in thinning the blood and how long it took to be within the therapeutic range. A blood test is used to measure the international randomized ratio (INR). The INR was used to determine the appropriate dose and dosage (i.e., amount and rate of administration) specific to each patient; or, in this case, each trial participant.

The safety label update made last week by the drug maker, Janssen Pharmaceuticals, Inc. (a division of Johnson & Johnson) in effect states that the INR test used to gain FDA approval—and that doctors continue to use to dose and monitor the effects of Xarelto® in their patients—is arguably defective. Not only would this render the clinical trial results invalid but also bolster plaintiffs’ new and existing claims that the drug maker(s) failed to adequately inform doctors that there was no means by which to determine the correct dose and dosage for any given patient. Essentially a doctor would have to wait until the patient bleeds out or throws a clot before determining that the patient may not be on the right dose and/or dosage. In other words, the INR test likely has no diagnostic value and is no more effective than a shot in the dark.

Summary of Facts and Subsequent Findings

  • On October 11, 2018, the Xarelto® drug safety label was changed to “not” recommend INR testing to monitor the effects Xarelto® on patients
  • INR testing was used in clinical trials to establish the safety and efficacy of Xarelto® and to compare it to other anticoagulants prior to FDA approval and market release in 2011
  • Title 21 of the U.S. Code of Federal Regulation requires that drug labels include a summary of essential scientific information including a statement of the recommended or usual dosage
  • Results from Xarelto® clinical trials using INR testing are at best, questionable, and at worst, invalid
  • A change to the Xarelto® drug safety label likely indicates that the drug makers failed to adequately warn that there was no means by which to determine correct dosage for any given patient
  • A pharmaceutical product for which correct dose and dosage cannot be established for a given patient is arguably defective in a significant way
  • Physicians that rely on INR testing without knowing that it may render inaccurate results could lead them to incorrectly dose Xarelto® potentially causing significant harm to their patients

Methodology Flaws in the Xarelto Clinical Trials

INR testing was used in the original Xarelto® clinical trials known as the ROCKET-AF and EINSTEIN DVT/PE trials. These trials were paid for by the drug makers—Bayer Healthcare and Janssen Pharmaceuticals, Inc. (a division of Johnson & Johnson). These trials were conducted to establish the safety and efficacy of Xarelto® and to compare it to other anticoagulants.

The following is an excerpt from the EINSTEIN DVT/PE clinical trial results:

EINSTEIN DVT/PE trial design: Randomized, phase 3, multicenter, open-label, parallel group,

active-controlled, event-driven noninferiority studies (EINSTEIN DVT and EINSTEIN PE) with patients receiving XARELTO® at an initial dose of 15 mg twice daily with food for the first 3 weeks, followed by XARELTO® 20 mg once daily with food or enoxaparin 1 mg/kg twice daily for at least 5 days with VKA, then VKA only after target INR (2.0-3.0) was reached. Patients were treated for 3, 6, or 12 months at HCP discretion.

In other words, Xarelto® was administered to trial participants and after a target INR was reached, they received a different anticoagulant—a VKA (i.e., vitamin K antagonist).

Given the drug safety update added to the Xarelto® label by Janssen on October 11, 2018:

Monitoring for the anticoagulation effect of rivaroxaban using a clotting test (PT, INR or aPTT) for anti-factor Xa (FXa) activity is not recommended.

Results from Xarelto® clinical trials using INR testing are at best, questionable, and at worst, invalid.

Thank You for Sharing. Not!

In May 2017—17 months before Janssen changed the Xarelto® label—Clinical Therapeutics, an international peer-reviewed journal, published an article entitled, “International Normalized Ratio Is Significantly Elevated with Rivaroxaban and Apixaban Drug Therapies: A Retrospective Study Published.” An excerpt from the article follows (emphasis added):

Purpose

Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself. [Emphasis added.]

Methods

The data collected from 218 hospitalized patients׳ charts included PT and INR taken on admission, patients׳ characteristics, laboratory results, other medications regularly used, and coexisting clinical conditions.

Findings

No statistically significant association between INR elevation and the parameters examined was found in our study. INR was significantly elevated in both drug groups (P < 0.001), with 84.2% of rivaroxaban patients and 78.3% of apixaban patients presenting with INR levels above the higher limit of the normal range. Furthermore, INR was significantly higher in the rivaroxaban group than in the apixaban group (P < 0.001).

Implications

Both of the reviewed drugs significantly elevated INR. Moreover, rivaroxaban elevates INR significantly more than apixaban, and there are apparently no other factors affecting INR but the drugs themselves. Larger prospective studies are needed to confirm and clarify the clinical significance of these results.

In that the common tests used to determine the correct administration of Xarelto® are not recommended by the drug maker, how are doctors to determine what dose and dosage of Xarelto® is correct vs. what dose and dosage may render a patient over anticoagulated and more likely to experience severe bleeding, or under anticoagulated, leaving patients more likely to suffer the adverse events Xarelto® is intended to treat?

In other words, doctors have relied on—and may continue to rely on—the test that the makers of Xarelto® now say is not recommended to determine the blood-thinning effects of the drug without knowing that these tests were likely rendering inaccurate results which could lead to their treating patients in a manner likely to cause them significant harm.

If the means to determine the correct dosage to administer to a given patient does not exist, the product is arguably defective. In addition, it would be impossible for a drug maker to comply with the requirements of Title 21, as follows:

21 CFR § 201.56 (a)(1): The labeling must contain a summary of the essential scientific information needed for the safe and effective use of the drug.

21 CFR § 201.100(b)(2): Requires labels for prescription drugs bear a statement of the recommended or usual dosage.

Janssen’s Misleading Advertising Campaign

There are three types of anticoagulants used in the United States. Xarelto® is a direct factor Xa inhibitor type. Benefits claimed by its U.S. manufacturer, Janssen Pharmaceuticals, Inc., include once daily administration of an oral pill, no dietary restrictions, and less testing requirements resulting in fewer blood draws. Warfarin, another type of anticoagulant, is a vitamin K inhibitor.  If a patient’s blood becomes too thin after taking warfarin, vitamin K is administered to reverse its blood-thinning effects (i.e., an antidote or reversal agent). While the INR measurement is an effective test to dose and monitor warfarin in patients, Janssen’s advertising campaign touting less testing requirements for Xarelto® as a benefit is laughable given that the INR test used repeatedly to demonstrate the safety and efficacy of Xarelto® “is not recommended.” Until early 2018—approximately seven years after its market release–Xarelto® did not have a reversal agent, and to date, there is not a “recommended” test for doctors to accurately dose and monitor the effects of Xarelto® in their patients.

In 2014, the FDA required Janssen to add new language to its official warnings and precautions including an update to its “black box” because the test equipment used to measure the INR during clinical trials was deemed faulty. The black box is the strongest and most urgent FDA warning added to an official drug label. The update notifies patients and caregivers about certain risks and potentially dangerous side effects from Xarelto®. A year earlier, the FDA cited Johnson & Johnson for its misleading advertising campaign in contradiction to U.S. laws and regulations.

According to Recall Center, a consumer protection organization:

Since the drug’s release, there have been multiple updates to the label warning users of possible risks. In 2013, the FDA issued a determination letter to Johnson & Johnson advising them that their print advertising published in WebMD magazine earlier that year was misleading. They cited the following deficiencies:

  • Effects of the drug to potential patients were downplayed
  • Efficacy claims appeared to be disassociated from the potential risks
  • Assertions that Xarelto has “no dosage adjustments,” which the FDA noted is inaccurate according to the product information’s section on warnings and precautions, as well as its section on dosage and administration.

Because of these allegations, the FDA declared Johnson & Johnson to be in violation of U.S. laws and regulations that oversee drug marketing. [U.S. Food & Drug Administration. “Letter to Roxanne McGregor-Beck, RE: NDA #202439.” (June 6, 2013) FDA.gov. Accessed Oct. 27, 2014]

According to a 2017 PR Newswire press release published by Business Insider (emphasis added):

Johnson & Johnson (NYSE: JNJ), Janssen Pharmaceuticals and Bayer Healthcare (OTC: BAYRY) are accused of downplaying the risks of taking Xarelto and aggressively marketing the drug as an alternative for warfarin in patients needing blood thinners to reduce the risk of dangerous clots. The companies positioned the drug as more convenient, calling for a once-a-day dose and eliminating the need for regular monitoring of a patient’s blood. However, the lawsuits charge that doctors and patients were not fully informed of the risks.

While Janssen’s Xarelto® advertising campaign claims:

And with XARELTO® you can

  • Spend your time how you want to spend it, with no regular blood monitoring

MISLEADING. A more accurate statement would arguably be:

Regular blood monitoring would be useless because it will not identify whether a patient is under anti-coagulated [i.e. clotting too much] or over anti-coagulated [i.e., bleeding too much].

  • Enjoy a full variety of healthy foods with no known dietary restrictions

TRUE.

  • Know it’s working, with no frequent dosage adjustments

MISLEADING. A more accurate statement would arguably be:

There is no means by which to determine if a dosage adjustment is needed in that the common tests to make such a determination are inaccurate in patients who have been administered Xarelto®.

It bears repeating:

A pharmaceutical product for which correct dosage cannot be established or determined for any given patient is arguably defective in a significant way.

With Testing, Rat Poison Can Be Correctly Dosed for Benefit

There may be no better example of why correctly dosing an anticoagulant is important than warfarin. Warfarin first came into commercial use as a rat poison in 1948. Correctly dosed, warfarin is an effective anticoagulant for humans; incorrectly dosed, warfarin is poison.

Unlike Xarelto®, INR testing is reliable for dosing warfarin. To optimize the therapeutic effect without risking dangerous side effects such as bleeding, close monitoring of the degree of anticoagulation is required. During the initial stage of treatment, the INR is checked daily. Intervals between tests can be lengthened if the patient manages stable therapeutic INR levels on an unchanged warfarin dose. Newer point-of-care testing is available and has increased the ease of INR testing in the outpatient setting. Instead of a blood draw, the new INR point-of-care test involves a simple finger prick.

Therefore, an anticoagulant that cannot be accurately dosed is arguably not as safe as rat poison.

———-

The foregoing is an observation of statistics and data related to Xarelto®. The conclusions contained herein are based on opinions formed by the author after a review of the relevant data. We acknowledge that others could draw differing conclusions and opinions based on the same observations.

 References:

https://www.clinicaltherapeutics.com/article/S0149-2918(17)30242-4/pdf

https://www.recallcenter.com/xarelto/fda-news/

https://markets.businessinsider.com/news/stocks/report-more-than-15-000-adverse-events-linked-to-xarelto-in-2016-1002203317

https://www.xareltohcp.com/dvt-pe/clinical-trials

Read More

XARELTO INITIAL ROCKET & EINSTEIN CLINICAL TRIALS NOW SEEN AS FLAWED: ADD THE MAY 2018 FAILURE OF TWO LATEST BAYER/JANSSEN STUDIES = BAD SCIENCE

Xarelto Study Red Flags Ignored: Why were medical research professionals ignored when red flags were raised over the viability of the Xarelto Rocket AF and Einstein DVT study results? Now the clinical trials for both are considered flawed, and the two most recent studies, the “Commander HF” and “Mariner,” failed to produce clear evidence that Xarelto is able to reduce the rate of blood clots in certain high-risk patients or after an acute decline in their condition.

By Mark A. York (October 23, 2018)

 

 

 

 

 

 

 

 

(MASS TORT NEXUS MEDIA) Xarelto (rivaroxaban) is a prescription blood thinner created by Bayer and Janssen Pharmaceuticals that was approved by the Food and Drug Administration (FDA) in 2011. This drug is an anticoagulant for preventing blood from clotting, often used to treat deep vein thrombosis, atrial fibrillation, pulmonary embolism, stroke, and other conditions.

More than one study has shown Xarelto can cause a higher rate of internal bleeding, than other anticoagulant drugs and until very recently, there was no available “antidote” for stopping internal bleeding in patients taking Xarelto. With warfarin, vitamin K has been shown to stop bleeding but there is no vitamin K “parallel” for people taking Xarelto. For Xarelto, it can take 24 hours for a dose to get out of the body. That means that if internal bleeding starts, the patient may simply have to wait it out and hope it stops on its own.

What The Medical Studies Say About Xarelto?

The FDA has received thousands of adverse event reports regarding Xarelto and medical studies have examined the safety of this drug:

  • New England Journal of Medicine (2011): Published the ROCKET-AF study, which compared Xarelto to Warfarin in patients suffering from atrial fibrillation. This was the biggest clinical trial of this medication and it compared the effects of Xarelto to the effects of a similar drug known as Warfarin in over 14,000 patients. The study concluded that “there was not significant between-group difference in the risk of major bleeding.”
  • Archives of Internal Medicine (2012): The study discussed the risk of uncontrollable bleeding outweighing the benefits for several different blood thinners including Xarelto. The researchers in this study found that there was a tripled risk of bleeding among the patients, who were given the drug, and no improvement in overall survival rates.
  • Institute for Safe Medication Practices (2012): Issued a report based on FDA data from the first quarter of 2012. During this period, the FDA received 356 adverse event reports of Xarelto side effects including “serious, disabling, or fatal injury.” Additionally, 158 reports indicated blood clots were the serious side effect.
  • New England Journal of Medicine (2013): Published the results of the ROCKET study, which found that Xarelto may carry an increased risk of bleeding.
  • Medscape (2013): Xarelto is associated with a higher risk of bleeding in certain patients. It caused a nearly 3-fold increase of the risk of bleeding in “acutely ill patients” and 4-fold increased risk of major bleeding in patients that had “Acute Coronary Syndrome” (ACS).

Drug Makers Failed To Disclose Faulty Device In Xarelto Trials

 Rivaroxaban and the ROCKET AF trial issue chronicles: A closer look at benefit risk profile of the drug.

  • BMJ2016354 doi: https://doi.org/10.1136/bmj.i5131 (Published 28 September 2016)Cite this as: BMJ 2016;354:i5131
  • Study Analysis: There has been a lot of hue and cry over the recent question raised about the ROCKET AF[1] trial for rivaroxaban which was the only trial used by the company for drug approval from USFDA. This is indeed a very important concern as it directly impacts the well-being of the patients who are at the receiving end of this very highly prescribed anticoagulant drug in 2014.[2] The main concern with this whole confusion surrounding the ROCKET AF trial is that the device used for measuring the INR in trial arm of warfarin patient was faulty and gave lower INR values than it should have, leading to over dosing of warfarin and thereby increasing bleeding problems with the same, compared to the trial arm of rivaroxaban. However, there has been a reanalysis done by the ROCKET AF researchers, which again reinforced the prior result database of the trial and which was accepted by FDA as well[3]. In the reanalysis, the US FDA clearly mentioned that the effect of the faulty device results in causing bleeding episodes, both minor and major, was minimal.[4]
  • However, following this reanalysis, not everyone who raised the question in the first place was convinced and there was a demand that the data of the complete ROCKET AF trial should be made public for everyone to assess and understand the risks. But since the trial was done and results released before the principles on responsible clinical trial data sharing came into effect, the parent pharmaceutical company for rivaroxaban refused to share the patient level details, citing concerns on privacy and transparency policy [5].
  • In spite of everything said and written for and against this issue, a simple question arises, regarding the amount of belief, honesty and hard work that goes without questioning when you bring a new chemical entity to the research stage, get it approved and then bring it to market. For this to happen, there have to be maintained a very fine balance between pharmaceutical companies, drug regulatory authorities and marketing people. In this case, after initial suspicions, the drug regulatory authorities have cleared and supported the approval of rivaroxaban after reanalysis and that should have a say, in case we want to continue trust with this process of drug entry into the market.
  • Rivaroxaban has shown its efficacy and safety both in patients who required adequate anticoagulation e.g. those who had atrial fibrillation and underwent cardioversion. There are few other trials where rivaroxaban has performed better or equally good than warfarin in terms of both efficacy and safety [6]. These results lead us to believe that all was not wrong with the ROCKET AF trial results. All these, combined with personal experiences of those physicians who had been using the drug rivaroxaban for the last couple of years with a hugely favorable result clearly imply that the drug rivaroxaban is holding its side strongly in the midst of all the controversies surrounding its approval and efficacy and it is here to stay. Adding a last word to all this discussion is that rivaroxaban will always hold an upper hand compared to warfarin when prescribed because of its very favorable and easy to use once daily dosing. We cannot discard all the positive reports and positive experiences associated with this drug, based on real time data, only because of the question raised by some, and considering the fact that the question had been satisficatorily answered with a re analysis with no change in the result.

What Did Or Didn’t The FDA Do About Xarelto?

  • In July, 2011, the U.S Food and Drug Administration (FDA) initially approved the medicine for sale on the market for a limited group of people. This included people who had knee or hip replacement surgery because they were considered to be at a higher risk of blood clotting. Read the FDA News Release here.
  • In November, 2011, Xarelto was approved for a larger group of people, including people with an abnormal heart rhythm, and was used to prevent stroke. Read further.
  • In June, 2012, an FDA advisory panel voted against approving this medicine for the treatment of acute coronary syndrome.
  • In November, 2012, Xarelto was later approved for general treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) after a fast track regulatory review by the FDA. Read more.
  • October 22, 2014, the FDA issued a recall for approximately 13,500 bottles of Xarelto after receiving a customer complaint about contamination in a sales sample.
  • January 12, 2015 – An antidote may have been discovered by Portola Pharmaceuticals for Xarelto. A late-stage clinical trial of the intravenous medication, andexanet alfa, met its goal of “immediately and significantly” reversing Xarelto.

The approval history for Xarelto was actually pretty controversial. FDA reviewers originally said that they recommended against approval, then there was an FDA advisory committee (independent group of key opinion leaders) and they voted in favor, so the FDA approved the drug. Their concern was with how the Phase III trials were run and whether Xarelto had really proved its efficacy. The tests compared patients on warfarin to patients on Xarelto, but the patients on the warfarin run had poor TTR. That means the patients weren’t well controlled on warfarin to begin with, which skews the data in favor of Xarelto.

During the approval process, Xarelto actually wanted a superiority label, which would say that the drug was better than warfarin and other blood thinners. Because of the concerns with the Phase III data, the FDA only gave them a non-inferior label, which says they’re essentially the same in terms of effectiveness.

The INRatio device was the subject of two FDA warning letters about inaccurate readings just as the trial was starting in 2005 and 2006. In 2014, the device was recalled. The use of the INRatio device may have skewed the results with inaccurate readings, making Xarelto look better in comparison with warfarin.

In a 2017 annual report issued by the Institute for Safe Medication Practices (ISMP), it was stated that oral anticoagulant drugs, including Xarelto (rivaroxaban), showed “unacceptably high risks,” according to two government data sources, the FAERS adverse events reports for 2016 and a new systematic study by the Centers for Disease Control and Prevention (CDC).

Overall, the CDC found in its systematic study that the FDA’s FAERS voluntary reporting underestimates anticoagulant drug-related injuries. The CDC discovered that approximately 228,600 emergency department visits occur each year due to the use of blood thinner drugs, including Xarelto, which is 10 times more than the FAERS total number of voluntary reports.

Xarelto Clinical Trial Red Flags

Controversy Surrounding ROCKET-AF: A Call for Transparency, But Should We Be Changing Practice?

Jason D Matos1 and Peter J Zimetbaum1,,2

Arrhythm Electrophysiol Rev. 2016 May; 5(1): 12–13.

doi:  [10.15420/aer.2016.24.2]

Prior to the emergence of novel oral anticoagulants (NOACS), nearly all patients were prescribed vitamin K antagonists for thromboembolic prophylaxis in non-valvular atrial fibrillation (AF). Rivaroxaban (Xarelto, Bayer/Johnson & Johnson), an oral factor Xa inhibitor, is now one of the most frequently prescribed NOACs used for this indication.1,2

ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), published in the New England Journal of Medicine in 2011, demonstrated the non-inferiority of rivaroxaban compared with warfarin for the primary prevention of stroke or systemic embolism in patients with AF. This double-blinded randomised trial, which included 14,264 patients across 45 countries, also showed no significant difference in the risk of major bleeding between these two groups.3

Rivaroxaban use in AF has become widespread since the publication of this trial and US Food and Drug Administration (FDA) approval. Two additional Factor Xa inhibitors, apixaban and edoxaban, have also been evaluated in similar randomised trials and have demonstrated non-inferiority to warfarin for stroke or systemic embolism prophylaxis in patients with non-valvular AF with no significant difference in major bleeding.4,5

In recent months, the results of ROCKET-AF have come into question after the FDA issued a recall notice for the device used to obtain International Normalised Ratio (INR) measurements in the warfarin control group. The FDA found that lower INR values were seen with the ‘point-of-care’ INRatio Monitor System (Alere) compared with a plasma-based laboratory in patients with certain medical conditions.2 These conditions included abnormal haemoglobin levels, abnormal bleeding and abnormal fibrinogen levels.6Since the FDA recall of this device, there has been widespread concern that falsely low INR readings in ROCKET-AF may have led to warfarin overdosing. Inappropriately high warfarin dosing could have increased bleeding rates in the control group and therefore made the rivaroxaban arm appear falsely favourable.7 This point-of-care device recall also highlighted a lack of transparency of the specifics of devices used in large clinical trials.

In response, the authors from ROCKET-AF released a correspondence in February 2016, citing the FDA recall. They also provided a post hoc analysis of patients who may have been affected by the recall. They found that major bleeding was greater in patients with conditions affected by the recall, but, reassuringly, the bleeding risk was greater in those who were on rivaroxaban and not warfarin.6

Despite this post hoc analysis, concern has arisen regarding the generalisability of ROCKET-AF given the faulty point-of-care INR readings. There has been a call for complete transparency of the data from this trial and a better explanation of the mechanism of the incorrect INR measurements.7

Once published, the data supporting an FDA-approved treatment should be available for independent analysis. One issue is that rivaroxaban was approved in the US prior to 1 January 2014, before a new transparency policy on clinical trial data sharing was approved by the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA).2 Drug companies are refusing to share any data on pharmaceuticals approved before 2014.

A device malfunction in a large clinical trial also should raise concern, especially when that trial has altered clinical practice for millions of patients. On review of Patel et al’s correspondence regarding the point-of-care malfunction, there is inadequate explanation of the mechanism of these faulty readings. Why are they only seen only in patients with abnormal haemoglobin and fibrinogen levels? How inaccurate could the readings be – within 0.1 or 1.0 of a gold standard value? Most alarming is the revelation that the manufacturer had evidence of faulty readings in similar models dating back to 2002.2

Despite legitimate concerns regarding the absence of data transparency and the faulty point-of-care device, rivaroxaban need not be removed from clinical practice for AF patients. In ROCKET-AF, the drug demonstrated non-inferiority to warfarin in preventing thromboembolic events. In addition, data has shown that patients potentially affected by the faulty point-of-care device actually bled more on rivaroxaban than warfarin.6 Therefore, the original risk–benefit ratio presented in ROCKET-AF remains true.

There are other, albeit smaller, randomised trials with shorter follow-up times that compare rivaroxaban and warfarin for thromboembolic prophylaxis.8,9 For example, Cappato et al in 2014, randomised 1,504 patients to show that oral rivaroxaban was non-inferior to warfarin in preventing a composite endpoint of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction and cardiovascular death in patients with AF undergoing cardioversion. Major bleeding rates in the rivaroxaban and warfarin arms were similar (0.6 % versus 0.8 % respectively).8

The prospective observational trial XANTUS (Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation) followed 6.784 patients on rivaroxaban for AF during a mean time of 329 days at 311 different hospitals. Major bleeding occurred in 128 patients (2.1 events/100 patient years) and 43 patients (0.7 events/100 patient years) suffered a stroke. These numbers are more reassuring than those seen in ROCKET-AF, though the patient population had a lower risk profile, with an average CHADS2 score of 2.0 compared with 3.5 in ROCKET-AF.10

To further mitigate concern regarding inaccuracies of bleeding rates in the ROCKET-AF control group, it is helpful to compare bleeding rates in the warfarin arms of the other major NOAC trials. The RE-LY (Randomised Evaluation of Long-Term Anticoagulation Therapy) trial, had a warfarin-arm major bleeding rate of 3.4%/year.11 The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, had a warfarin-arm major bleeding rate of 3.1%/year.4 The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial, had a warfarin-arm major bleeding rate of 3.4 %/year.5The warfarin arm of ROCKET-AF had a 3.4 %/year major bleeding rate, comparable to the other studies. Furthermore, the ROCKET-AF patients are known to be at higher risk for stroke and bleeding; their average CHADS2 score was highest among these studies (3.5 compared with 2.1–2.8).3 In addition, ROCKET-AF had a very high percentage of patients with a HAS-BLED score ≥3 (62 %) compared with the other studies (23 % in ARISTOTLE and 51 % in ENGAGE AF-TIMI 48).1214

Several large randomised trials have compared the safety and efficacy of rivaroxaban versus warfarin for venous thromboembolic disease. The warfarin arm of the EINSTEIN-PE trial (Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients with Acute Symptomatic Pulmonary Embolism), which randomised patients with pulmonary embolism to warfarin or rivaroxaban, had a major bleeding rate of 2.2 %. The bleeding rate was lower in the rivaroxaban arm (1.1 %) and notably patients received a higher loading dose of rivaroxaban for the first 3 weeks (15 mg twice daily) compared with the daily 20 mg daily in ROCKET-AF.15

The recent uncertainties surrounding ROCKET-AF demonstrate the need for widespread data transparency for major trials with the capability of so greatly affecting patients’ lives. These are complicated issues both for the companies’ manufacturing products and the clinical trial organisations who carry out these studies and analyse the data. Ultimately the goal of full transparency to allow increased confidence in trial results should be sought. In this instance there is no compelling evidence of imminent danger of excessive bleeding with rivaroxaban. We should take notice of the recent findings, but there is no need to change practice.

What Are Xarelto Side Effects?

The most dangerous Xarelto side effect is uncontrollable bleeding. Blood thinning drugs have also been associated with bleeding complications. Other side effects include:

  • Blood clots
  • Gastrointestinal bleeding
  • Spinal bleeding
  • Intracranial bleeding
  • Epidural bleeding
  • Cerebral bleeding
  • Stroke
  • Difficulty breathing

For Information on Xarelto and other mass torts see:

Michael Brady Lunch will speak on the Xarelto litigation as well as the status of Pradaxa litigation and related issues at the upcoming Mass Tort Nexus “CLE Immersion Course”

November 9 -12, 2018 at The Riverside Hotel in Fort Lauderdale , FL.

For class attendance information please contact Jenny Levine at 954.520.4494 or Jenny@masstortnexus.com.

  • For the most up to date information on all MDL dockets and related mass torts visit  masstortnexus.com and review our mass tort briefcases and professional site MDL briefcases.
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REFERNCES CITED IN STUDIES SHOWN ABOVE

 Rivaroxaban and the ROCKET AF trial issue chronicles: A closer look at benefit risk profile of the drug. References:
BMJ 2016354 doi: https://doi.org/10.1136/bmj.i5131 (Published 28 September 2016)Cite this as: BMJ 2016;354:i5131
  1. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883-891. Article
    2. Top 50 pharmaceutical products by global sales. PMLiVE, Available here.
    3. FDA analyses conclude that Xarelto clinical trial results were not affected by faulty monitoring device.https://www.fda.gov/Drugs/DrugSafety/ucm524678.htm
    4. ROCKET AF Reanalysis Reviews.http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202439Orig1s000Ro…
    5. Joint EFPIA-PhRMA Principles for Responsible Clinical Trial Data Sharing Become Effective.http://www.efpia.eu/mediaroom/132/43/Joint-EFPIA-PhRMA-Principles-for-Re…
    6. Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014; 35:3346-3355.

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Controversy Surrounding ROCKET-AF: A Call for Transparency, But Should We Be Changing Practice? References
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  2. Cohen D. Rivaroxaban: can we trust the evidence? BMJ. 2016;352:i575. DOI: 10.1136/bmj.i575; PMID: 26843102. [PubMed]
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  4. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92. DOI: 10.1056/NEJMoa1107039; PMID: 21870978.[PubMed]
  5. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104. DOI: 10.1056/NEJMoa1310907; PMID: 24251359. [PubMed]
  6. Patel MR, Hellkamp AS, Fox KA, et al. Point-of-care warfarin monitoring in the ROCKET AF Trial. N Engl J Med. 2016;374:785–8. DOI: 10.1056/NEJMc1515842; PMID: 26839968. [PubMed]
  7. Mandrola J. Rivaroxaban: It’s not time to cut the rope, yet. Medscape. 9 February 2016. Available at: www.medscape.com/viewarticle/858648. (accessed 6 May 2016.
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  9. Cappato R, Marchlinski FE, Hohnloser SH, et al. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J. 2015;36:1805–11. DOI: 10.1093/eurheartj/ehv177; PMID: 25975659. [PMC free article] [PubMed]
  10. Camm AJ, Amarenco P, Haas S, et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J. 2016;37:1145–53.DOI: 10.1093/eurheartj/ehv466; PMID: 26330425. [PMC free article] [PubMed]
  11. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51. DOI: 10.1056/NEJMoa0905561; PMID: 19717844.[PubMed]
  12. Sherwood MW, Nessel CC, Hellkamp AS, et al. Gastrointestinal bleeding in patients with atrial fibrillation treated With rivaroxaban or warfarin: ROCKET AF trial. J Am Coll Cardiol. 2015;66:2271–81.DOI: 10.1016/j.jacc.2015.09.024; PMID: 26610874. [PubMed]
  13. Lopes RD, Al-Khatib SM, Wallentin L, et al. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial. Lancet. 2012;380:1749–58. DOI: 10.1016/S0140-6736(12)60986-6; PMID: 23036896. [PubMed]
  14. Eisen A, Giugliano RP, Ruff CT, et al. Edoxaban vs warfarin in patients with nonvalvular atrial fibrillation in the US Food and Drug Administration approval population: An analysis from the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial. Am Heart J. 2016;172:144–51. DOI: 10.1016/j.ahj.2015.11.004; PMID: 26856226. [PubMed]
  15. EINSTEIN-PE Investigators, Buller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287–97. DOI: 10.1056/ NEJMoa1113572. PMID: 22449293. [PubMed]

 

 

 

 

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Why Isn’t Medical Cannabis Used to Treat Opioid and Substance Abuse Disorders More Often? 

Will Medical Marijuana Become A Viable Addiction Treatment Option?

By Mark A. York (September 28, 2018)

 

 

 

 

 

 

(MASS TORT NEXUS MEDIA) More and more medical treatment professionals, politicians and others have joined in the quickly emerging role of medical marijuana to help in treatment by patients struggling with opioid addiction. Now, two studies are reflecting this emerging treatment to be viable.

Will medical marijuana become a viable option in the long term treatment programs that may be coming out of the Opiate Prescription Litigation MDL 2804 and the many state court opioid based lawsuits filed across the country? See Mass Tort Nexus Briefcase Re: National-Prescription-Litigation-MDL-2804-USDC-ND-Ohio, where the various opioid litigation dockets and court rulings are provided.

Recent studies, published journal JAMA Internal Medicine, compared opioid prescription patterns in states that have enacted medical cannabis laws with those that have not. One of the studies looked at opioid prescriptions covered by Medicare Part D between 2010 and 2015, while the other looked at opioid prescriptions covered by Medicaid between 2011 and 2016.

Additionally, three states have approved Medical Cannabis for alternative treatments related to both pain management and substance abuse disorders, where cannabis has been determined as an appropriate treatment. Pennsylvania, New Jersey and Illinois are at the forefront of using changes to state laws regarding medical cannabis in the most effective clinical settings when possible.

PENNSYLVANIA CANNABIS BASED OPIOID ADDICTION TREATMENT

The Pennsylvania Department of Health approved major changes to the state’s medical marijuana program, when the  health department added opioid addiction to the list of conditions eligible for treatment with medicinal cannabis. With that decision, Pennsylvania joins New Jersey and Illinois as the only states that have done so.

Pennsylvania Secretary of Health Dr. Rachel Levine told local media that marijuana won’t be the first treatment for addiction to opioids. Instead, doctors will try more traditional therapies first.

“It’s important to note that medical marijuana is not a substitute for proven treatments for opioid use disorder,” Dr. Levine said. “In Pennsylvania, medical marijuana will be available to patients if all other treatment fails, or if a physician recommends that it be used in conjunction with traditional therapies.”

A related positive note by Pennsylvania is the Department of Health has approved cannabis research licenses for five Philadelphia area medical schools on Monday. With one topic of research at the institutions being the potential role of cannabis in addiction treatment as a normal treatment protocol.

The schools that received approval to study cannabis are Drexel University College of Medicine, Lewis Katz School of Medicine at Temple University, Sidney Kimmel Medical College at Thomas Jefferson University, Perelman School of Medicine at the University of Pennsylvania, and Philadelphia College of Osteopathic Medicine.

JAMA STUDY RESULTS

The researchers found that states that allow the use of cannabis for medical purposes had 2.21 million fewer daily doses of opioids prescribed per year under Medicare Part D, compared with those states without medical cannabis laws. Opioid prescriptions under Medicaid also dropped by 5.88% in states with medical cannabis laws compared with states without such laws, according to the studies.

“This study adds one more brick in the wall in the argument that cannabis clearly has medical applications,” said David Bradford, professor of public administration and policy at the University of Georgia and a lead author of the Medicare study.

“And for pain patients in particular, our work adds to the argument that cannabis can be effective.”

Medicare Part D, the optional prescription drug benefit plan for those enrolled in Medicare, covers more than 42 million Americans, including those 65 or older. Medicaid provides health coverage to more than 73 million low-income individuals in the US, according to the program’s website.

“Medicare and Medicaid publishes this data, and we’re free to use it, and anyone who’s interested can download the data,” Bradford said. “But that means that we don’t know what’s going on with the privately insured and the uninsured population, and for that, I’m afraid the data sets are proprietary and expensive.”

Republicans Support Legalizing Medical Cannabis

Earlier this year, the National Academy of Sciences, in a 395-page report, refuted the official US Department of Justice position that cannabis is a “gateway drug” and that using marijuana can lead to opioid addiction and instead found evidence of cannabis having therapeutic and health benefits. Joe Schrank, a social worker who worked at various detox centers and clean houses, is now practicing the report’s findings at High Sobriety treatment center in Los Angeles, where he offers clients medical and therapeutic sessions, and daily doses of marijuana to treat a variety of addictions.

The Opioid Crisis Is Here

The new research comes as the United States remains entangled in the worst opioid epidemic the world has ever seen. Opioid overdose has risen dramatically over the past 15 years and has been implicated in over 500,000 deaths since 2000 — more than the number of Americans killed in World War II.

“As somebody who treats patients with opioid use disorders, this crisis is very real. These patients die every day, and it’s quite shocking in many ways,” said Dr. Kevin Hill, an addiction psychiatrist at Beth Israel Deaconess Medical Center and an assistant professor of psychiatry at Harvard Medical School, who was not involved in the new studies.

“We have had overuse of certain prescription opioids over the years, and it’s certainly contributed to the opioid crisis that we’re feeling,” he added. “I don’t think that’s the only reason, but certainly, it was too easy at many points to get prescriptions for opioids.”

Today, more than 90 Americans a day die from opioid overdose, resulting in more than 42,000 deaths per year, according to the US Centers for Disease Control and Prevention. Opioid overdose recently overtook vehicular accidents and shooting deaths as the most common cause of accidental death in the United States, the CDC says.

 

 

 

 

 

 

Doctors must lead us out of our opioid abuse epidemic

Like opioids, marijuana has been shown to be effective in treating chronic pain as well as other conditions such as seizures, multiple sclerosis and certain mental disorders, according to the National Institute on Drug Abuse. Research suggests that the cannabinoid and opioid receptor systems rely on common signaling pathways in the brain, including the dopamine reward system that is central to drug tolerance, dependence and addiction.

“All drugs of abuse operate using some shared pathways. For example, cannabinoid receptors and opioid receptors coincidentally happen to be located very close by in many places in the brain,” Hill said. “So it stands to reason that a medication that affects one system might affect the other.”

But unlike opioids, marijuana has little addiction potential, and virtually no deaths from marijuana overdose have been reported in the United States, according to Bradford.

“No one has ever died of cannabis, so it has many safety advantages over opiates,” Bradford said. “And to the extent that we’re trying to manage the opiate crisis, cannabis is a potential tool.”

Comparing states with and without medical marijuana laws

  • Researchers compared prescription patterns in states with and without medical cannabis laws
  • States with medical marijuana had 2.21 million fewer daily doses of opioids prescribed per year
  • Opioid prescriptions under Medicaid dropped by 5.88% in states with medical cannabis laws

In order to evaluate whether medical marijuana could function as an effective and safe alternative to opioids, the two teams of researchers looked at whether opioid prescriptions were lower in states that had active medical cannabis laws and whether those states that enacted these laws during the study period saw reductions in opioid prescriptions.

Both teams, in fact, did find that opioid prescriptions were significantly lower in states that had enacted medical cannabis laws. The team that looked at Medicaid patients also found that the four states that switched from medical use only to recreational use — Alaska, Colorado, Oregon and Washington — saw further reductions in opioid prescriptions, according to Hefei Wen, assistant professor of health management and policy at the University of Kentucky and a lead author on the Medicaid study.

“We saw a 9% or 10% reduction (in opioid prescriptions) in Colorado and Oregon,” Wen said. “And in Alaska and Washington, the magnitude was a little bit smaller but still significant.”

Cannabis legalization by the numbers

The first state in the United States to legalize marijuana for medicinal use was California, in 1996. Since then, 29 states and the District of Columbia have approved some form of legalized cannabis. All of these states include chronic pain — either directly or indirectly — in the list of approved medical conditions for marijuana use, according to Bradford.

The details of the medical cannabis laws were found to have a significant impact on opioid prescription patterns, the researchers found. States that permitted recreational use, for example, saw an additional 6.38% reduction in opioid prescriptions under Medicaid compared with those states that permitted marijuana only for medical use, according to Wen.

The method of procurement also had a significant impact on opioid prescription patterns. States that permitted medical dispensaries — regulated shops that people can visit to purchase cannabis products — had 3.742 million fewer opioid prescriptions filled per year under Medicare Part D, while those that allowed only home cultivation had 1.792 million fewer opioid prescriptions per year.

“We found that there was about a 14.5% reduction in any opiate use when dispensaries were turned on — and that was statistically significant — and about a 7% reduction in any opiate use when home cultivation only was turned on,” Bradford said. “So dispensaries are much more powerful in terms of shifting people away from the use of opiates.”

The impact of these laws also differed based on the class of opioid prescribed. Specifically, states with medical cannabis laws saw 20.7% fewer morphine prescriptions and 17.4% fewer hydrocodone prescriptions compared with states that did not have these laws, according to Bradford.

 

 

 

 

 

 

This is fentanyl: A visual guide

Fentanyl prescriptions under Medicare Part D also dropped by 8.5% in states that had enacted medical cannabis laws, though the difference was not statistically significant, Bradford said. Fentanyl is a synthetic opioid, like heroin, that can be prescribed legally by physicians. It is 50 to 100 times more potent than morphine, and even a small amount can be fatal, according to the National Institute on Drug Abuse.

“I know that many people, including the attorney general, Jeff Sessions, are skeptical of cannabis,” Bradford said. “But, you know, the attorney general needs to be terrified of fentanyl.”

MAKING CANNABIS AVAILABLE

This is not the first time researchers have found a link between marijuana legalization and decreased opioid use. A 2014 study showed that states with medical cannabis laws had 24.8% fewer opioid overdose deaths between 1999 and 2010. A study in 2017 also found that the legalization of recreational marijuana in Colorado in 2012 reversed the state’s upward trend in opioid-related deaths.

“There is a growing body of scientific literature suggesting that legal access to marijuana can reduce the use of opioids as well as opioid-related overdose deaths,” said Melissa Moore, New York deputy state director for the Drug Policy Alliance. “In states with medical marijuana laws, we have already seen decreased admissions for opioid-related treatment and dramatically reduced rates of opioid overdoses.”

Sessions: DOJ looking at ‘rational’ marijuana policy

Some skeptics, though, argue that marijuana legalization could actually worsen the opioid epidemic. Another 2017 study, for example, showed a positive association between illicit cannabis use and opioid use disorders in the United States. But there may be an important difference between illicit cannabis use and legalized cannabis use, according to Hill.

“As we have all of these states implementing these policies, it’s imperative that we do more research,” Hill said. “We need to study the effects of these policies, and we really haven’t done it to the degree that we should.”

The two recent studies looked only at patients enrolled in Medicaid and Medicare Part D, meaning the results may not be generalizable to the entire US population.

But both Hill and Moore agree that as more states debate the merits of legalizing marijuana in the coming months and years, more research will be needed to create consistency between cannabis science and cannabis policy.

“There is a great deal of movement in the Northeast, with New Hampshire and New Jersey being well-positioned to legalize adult use,” Moore said. “I believe there are also ballot measures to legalize marijuana in Arizona, Florida, Missouri, Nebraska and South Dakota as well that voters will decide on in Fall 2018.”

Hill called the new research “a call to action” and added, “we should be studying these policies. But unfortunately, the policies have far outpaced the science at this point.”

There are no U.S. Food and Drug Administration (FDA)-approved painkillers derived from marijuana, but companies such as Axim Biotechnologies Inc, Nemus Bioscience Inc and Intec Pharma Ltd have drugs in various stages of development.

The companies are targeting the more than 100 million Americans who suffer from chronic pain, and are dependent on opioid painkillers such as Vicodin, or addicted to street opiates including heroin.

Opioid overdoses, which have claimed the lives of celebrities including Prince and Heath Ledger as victims, contributed to more than 33,000 deaths in 2015, according to the Centers for Disease Control and Prevention.

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A New Opiate MDL Was Requested For Benefit of Opioid Addicted Babies On September 20, 2018

THE JPML HAS BEEN REQUESTED TO CONSOLIDATE A NEW ADDICTED INFANT MULTIDISTRICT LITIGATION

By Mark A. York (September 21, 2018)

 

 

 

 

 

 

 

 

 

Have the most vunerable plaintiffs in the opiate litigation been underserved by firms primarily focused on representing governmental entities in Opiate MDL 2804 and state court consolidations? What about the epidemic of NAS affected babies who have been born addicted to prescription opiates?

Link to Mass Tort Nexus Briefcase Re: OPIOIDS-Children-Born-Opioid-Dependent-(NAS)-JPML-MDL-(PENDING)

(MASS TORT NEXUS MEDIA) Lawyers representing addicted infants in the opiate litigation have now filed a Motion for Transfer and Consolidation of Children Born Opioid Dependent with the JPML on September 21, 2018. To read the entire JPML Motion and Brief in Support, see our briefcase Re: masstortnexus.com/News/4335/Motion-for-New-Infant-NAS-Opioid-Dependant-MDL-Filed-With-JPML-September-20-2018.

Plaintiffs lawyers have also filed class actions in nine states on behalf of infants, and other “individuals” affected by opiate use and subsequent addiction, with very limited input into the federal litigation process. On May 21, 2018 a coalition of nine law firms filed court papers asking MDL 2804 Judge Dan Polster (USDC ND Ohio) for permission to request a separate discovery and litigation track for the baby cases, which was summarily denied without comment by the court on June 28, 2018.

Lawyers and public health officials have estimated that there could be more than 1 million babies diagnosed with “neonatal abstinence syndrome,” which occurs when infants are born to mothers who used opioids. There is a request seeking a trust of more than $1 billion to help pay for medical monitoring of the children over the next few decades.

“There has been no large-scale attempt to find out what happens to these children, and there are thousands at this time, perhaps over 1 million, progressing now through the school system and growing up,” said Scott Bickford, a principal at Martzell, Bickford & Centola in New Orleans. “Theoretically, these kids are born addicted and may stay addicts for life.”

Treatment and Prognosis for Opioid Addicted Newborns

The course of treatment will be determined by factors such as:

  • Baby’s gestational age, medical history, and health
  • Severity of the disorder and expectation of the effects it will have
  • Baby’s tolerance of the therapies, procedures, or medications
  • Parents’ preference

Immediate treatment for withdrawal effects focuses on comfort and thriving. Babies suffering from opioid withdrawal often have trouble resting and eating, so treatment involves:

  • Swaddling for comfort
  • Adding extra calories to account for energy used through restlessness and increased activity
  • Intravenous fluids for dehydration
  • Medication to relieve discomfort and eliminate symptoms like seizures

Long-term treatment involves treating physical and behavioral effects and can involve:

  • Monitoring and treating vision and hearing impairments
  • Therapy for behavioral problems
  • Language therapy
  • Treatment for chronic ear infections
  • Interventions for cognitive deficits
  • Treatment for sleep disturbance

Babies are the latest segment of the opioid epidemic to attempt to get a front-row seat in the legal case against manufacturers and distributors. More than 1,000 lawsuits have been coordinated in multidistrict litigation in Cleveland before U.S. District Judge Dan Polster of the Northern District of Ohio, who has allowed a limited amount of discovery to go forward, (see Mass Tort Nexus Briefcase OPIOID-National-Prescription-Litigation-MDL-2804-USDC-Northern-District-of-Ohio) for case docket information.

The vast majority of plaintiffs are cities and counties seeking to recoup the costs of medical treatment and law enforcement, but Native American tribes, hospitals and others have elbowed into the case. New plaintiffs are emerging, such as class actions—including eight filed this week—filed on behalf of individuals alleging the opioid epidemic caused their health insurance premiums to skyrocket.

At least 11 cases have been brought on behalf of babies, many of whom suffer from addiction and learning disabilities. Bickford said the cases are in states that have medical monitoring laws, which include New York and California. According to the case filed in New York Supreme Court for Niagara County, for instance, lifetime medical costs could include treatment of developmental, psychiatric, emotional or behavioral disorders associated with addiction.

THIS IS A MUCH BIGGER PROBLEM

Dr. Shawn Hollinger, neonatologist at Niswonger Children’s Hospital, cradled baby Jayden’s head in an effort to comfort him. After 35 days in the neonatal intensive care unit, Jayden was ready to go home.

The number of children needing intensive treatment for NAS has become so overwhelming that the hospital opened a new ward this year just to care for them. Since 2009, hospital staff have treated over 1,800 babies with NAS. In the past 12 months, Hollinger has seen 351 infants with NAS come through the NICU.

After birth, children exposed to drugs in the womb experience a multitude of symptoms, including tremors and seizures. Even after being released from the hospital, some children may still have to be treated with medication and physical therapy. It can cost upwards of $60,000 to treat one baby.

“The intent would be to construct a trust that would deliver financial assistance directly to the custodians of these children,” he said. Custodians could include other family members, foster parents or birth parents who have kicked the habit, he said.

The defendants in all the baby cases include opioid manufacturers Purdue Pharma, Johnson & Johnson, Endo Health Solutions and Teva Pharmaceuticals, as well as distributors McKesson Corp., AmerisourceBergen Corp. and Cardinal Health Inc. The New York complaint also named Insys Therapeutics Inc.

Johnson & Johnson spokeswoman Wanda Moebius wrote in an email: “Our actions in the marketing and promotion of these medicines were appropriate and responsible. The labels for our prescription opioid pain medicines provide information about their risks and benefits, and the allegations made against our company are baseless and unsubstantiated. In fact, our medications have some of the lowest rates of abuse among this class of medications.”

Endo spokeswoman Heather Zoumas Lubeski said, “We deny the allegations contained in these lawsuits and intend to vigorously defend the company.”

Representatives of the other defendants either did not respond or declined to comment.

It’s not the first time the coalition of law firms tried to get Polster to create a separate “baby track.” On June 28, the judge denied an earlier request.

“We’ve asked the court to reconsider our motion for a separate baby track for babies with neonatal abstinence syndrome,” Bickford said. “We don’t think the present MDL and the people in it who essentially represent state and local governments really have the children’s interests at heart.”

The plaintiffs’ executive committee in charge of the opioid MDL has refused to provide information about discovery and depositions, he said. His request described the discovery process as operating under a “cloak of secrecy” and included an attached email exchange in which executive committee member Jayne Conroy of Simmons Hanly Conroy called his request to monitor depositions “not necessary” and “burdensome.”

Conroy said in a statement: “All our legal efforts are directed at the companies who caused the opioid epidemic.  Any success will benefit all victims.”

Earlier this summer, the Judge charged with control over the federal MDL involving government entities’ claims against opioid manufacturers and distributors rejected a request for the inclusion of NAS baby cases within a special litigation track. The request would create a nationwide medical monitoring trust fund for NAS babies within the existing MDL litigation regarding prescription opioid

On May 31, 2018 counsel for the baby/NAS addicted plaintiffs filed a Motion for Leave to Establish a Separate Track for Opioid Baby Claims, with the court denying the request via text order entry below.

06/28/2018 Order [non-document] denying Motion for leave to File Motion for Order to Establish Separate Track for Opioid Baby Claims filed by Melissa Ambrosio, Darren Flanagan, Elena Flanagan, Ceonda Rees, Deric Rees, Virginia Salmons, Walter Salmons, Roxie Whitley, Rache l Wood(Related Doc # 540 ). Judge Dan Aaron Polster (MDL 2804) on 6/28/18.(P,R) (Entered: 06
Court Response to Previous Attempt to Get a Baby Track in Opiate MDL 2804

 Tens of thousands of infants born in the U.S. each year now have NAS, and a recent Centers for Disease Control report said the rate of NAS deliveries at hospitals quadrupled during the past 15 years.

The period of hospitalization for NAS infants averages 16 days and hospital costs for a typical newborn with NAS are $159,000$238,000 greater than those of healthy newborns, according to the attorneys representing the NAS babies.

Dr. Kanwaljeet J. S. “Sunny” Anand, the nation’s foremost expert on opioids in infants and a Professor of Pediatrics, Anesthesiology, Perioperative & Pain Medicine at Stanford University School of Medicine, is a medical expert to the legal team. “There is an unprecedented epidemic of opioid addiction sweeping across the U.S.,” said Dr. Anand. “Newborn babies are the most vulnerable citizens, their lives and developmental potential are disrupted by NAS, but arrangements for their short-term and long-term care have been ignored until now. These babies need strong advocacy and legal action to ensure that their rights are protected, and that they urgently receive essential medical care and rehabilitation. On average, one infant with NAS is hospitalized every hour in the U.S.”

Named as defendants in the class actions are an array of pharmaceutical manufacturers, distributors and retailers, all of whom netted billions of dollars due to unfair and deceptive trade practices that preyed on all Americans, including the unborn, say the attorneys.

“A medical monitoring fund would document and address the medical problems these children will have to face for a lifetime,” said Mr. Bickford. The filing today objects to current settlement negotiations engaged by the opioid MDL which ignore the NAS babies’ interests.

“Legal precedent recognizes the difference between present and future claims in negotiations of this magnitude,” said Mr. Bickford. “Without being at the table, the legal representatives of NAS babies and children will not be heard and the due process rights of these infants and children will be denied.”

The filing says only government, hospital and third-party payors are at the table in negotiating a settlement through the MDL, though no agreement has yet been reached. The attorneys representing the NAS babies have raised concerns that outcomes similar to the Tobacco MDL settlement, where money was diverted to state budget deficits instead of the intended victims, might happen here.

 Born to women addicted to drugs, newborns suffer through withdrawal

Babies suffering through opioid withdrawal have a distinct way of crying: a short, anguished, high-pitched wail, repeated over and over. It echoes through the neonatal therapeutic unit of Cabell Huntington Hospital in Huntington, West Virginia. A week-old girl has been at it, inconsolably, since six o’clock this morning. At 10 o’clock Sara Murray, the unit’s soft-spoken, no-nonsense nurse manager, sighs. “This may be a frustrating day,” she says.

The opioid epidemic in the United States is painfully evident in hospital newborn units across the country. In 2012 nearly 22,000 babies were born drug dependent, one every 25 minutes, according to the most recent federal data. As the opioid crisis has escalated dramatically over the past five years, those numbers have surely climbed.

West Virginia, at two and a half times the national average, has the highest rate of deaths from drug overdose—mostly from opioids. Cabell County, which averaged about 130 overdose calls to 911 annually until 2012, received 1,476 calls last year and is on pace to reach around 2,000 this year. Emergency workers saved many of those people, including an 11-year-old, but inpatient treatment programs have long waiting lists. At Cabell Huntington Hospital, one in five newborns has been exposed to opioids in the womb.

“What you’re seeing here is the tip of the iceberg of substance use,” says neonatologist Sean Loudin, the unit’s medical director.

In 2012 the neonatal intensive care unit became so overwhelmed by drug-dependent babies that it had to turn away newborns with other medical needs. The hospital opened this specialized unit to treat withdrawal. It typically has 18 babies. On this day there are 23.

The babies shake, sweat, vomit, and hold their bodies stiff as planks. They eat and sleep fitfully. Swaddled, they lie in bassinets or in the arms of nurses, parents, or volunteers. The place doesn’t have the hustle or beeping machinery of an ICU. Instead there are dim lights and hushed conversations because the babies need calm and quiet. Many also need methadone or other medication to relieve their symptoms. They are weaned from it over days or weeks.

“OK,” Murray whispers to a bleating 41-day-old boy. She gently lifts him to her chest, cradles him firmly, and places a green pacifier in his mouth. He sucks it fast and hard, like a piston.

Opioids pass readily from a pregnant woman’s bloodstream through the placenta and across the fetal blood-brain barrier. When birth abruptly shuts down the flow of the drug, the baby’s nervous system can trigger the agitating symptoms of withdrawal. Studies show that 55 percent to 94 percent of newborns exposed to opioids develop symptoms. Prenatal exposure to other widely used drugs, including benzodiazepines and certain antidepressants, also can lead to withdrawal shortly after birth.

The condition is called neonatal abstinence syndrome (NAS). Experts don’t consider it to be addiction, which, by definition, means a person persists in compulsive drug use despite terrible consequences. By the same logic, NAS is also a misnomer—abstaining, or just saying no, is different from experiencing the physical anguish of withdrawal. But medical experts have come to accept the NAS label because it’s less fraught with stigma than words like “addiction” and “withdrawal.”

In some cases the mothers themselves are in recovery. They didn’t misuse opioids during pregnancy but took methadone or buprenorphine, the frontline medications for treating opioid addiction. The American Congress of Obstetricians and Gynecologists recommends their use during pregnancy despite the risk of NAS, for the obvious reason that sobriety is safer and healthier for a woman than shooting heroin or popping painkillers or trying to go cold turkey on her own. It’s also much better for her child. But encouraging as it is, the growing use of medication-assisted addiction treatment means that even when the opioid crisis eases, hospitals like Cabell Huntington will continue to be swamped with babies in withdrawal.

To manage the condition, most hospitals use an assessment tool developed at the height of the heroin outbreak in the 1970s. Babies are rated every four hours on the severity of 31 symptoms, including excessive crying, sweating, tremors, and frequent yawning. The scores help doctors determine whether to put babies on methadone or other medication. In most cases the scores support drug therapy. Now some researchers are challenging that approach.

“It’s archaic,” says Elisha Wachman, a neonatologist at Boston Medical Center and an assistant professor of pediatrics at Boston University School of Medicine. “What ends up happening is that babies get overmedicated.” Too often, she says, they experience withdrawal from their treatment, which prolongs their misery and their hospital stay.

A handful of researchers around the country are revamping NAS treatment to rely less on medication and more on parental bonding. Wachman has abandoned the old score sheet for assessing the babies. “I couldn’t care less how many times they yawn,” she says. Instead, she evaluates them on just three measures: eating, sleeping, and being consoled. Rather than transfer babies to an ICU or a specialty unit, Boston Medical Center keeps them with their moms throughout their stay. Wachman encourages the women to breastfeed and clutch their babies skin to skin. One hundred fifty volunteers—most of them medical students and hospital employees—put in two-hour shifts as cuddlers. The waiting list to hold babies has 200 names.

Before the hospital changed its approach, 86 percent of the babies with NAS it treated received medication. Now it’s 30 percent. The babies generally spend nine days in the hospital, down from 19 days under the old protocol. The average cost of a hospital stay for a baby with NAS is $19,655 at Boston Medical Center, compared to a national average of $67,000.

Wachman says sound treatment for the babies must go hand in hand with compassionate, comprehensive care for their mothers. The medical center runs a prenatal clinic for women with addiction. The obstetricians prescribe buprenorphine and prepare women for the possibility that their babies will have NAS. The clinic also offers counseling, social services, psychiatric help, peer support, and education about infant care. “When the moms come in to deliver, they’re in the best shape they can be,” Wachman says. In July the medical center opened a clinic that provides pediatric care for babies born with NAS and addiction services for their mothers.

It’s not clear how opioid exposure affects long-term brain development. Surprisingly little research has been done, and most of it predates the current crisis and the widespread use of highly potent synthetics, such as fentanyl. Some studies show subtle cognitive and behavioral differences among children who were exposed to opioids before birth, but the problems are less severe than the intellectual and attention deficits associated with fetal alcohol exposure. The studies don’t answer a key question: Do the neurodevelopment issues stem from drug exposure or poverty or other chronic stresses? Some researchers believe that social factors and a stable environment are bigger influences on a child’s future than NAS.

“We keep hearing about the babies, and that it is important, but there needs to be much more of a focus on women and making sure they’re taken care of well,” says Uma Reddy, a maternal-fetal medicine expert at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Mass Tort Nexus will provide updates on the Infant NAS MDL request to the JPML as well the Opiate Prescription MDL 2804 on a daily basis.

For the most up to date information on all MDL dockets and related mass torts visit www.masstortnexus.com and review our mass tort briefcases and professional site MDL briefcases.

To obtain our free newsletters that contain real time mass tort updates, visit www.masstortnexus.com/news and sign up for free access.

 

 

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Motion for New Infant/NAS Opioid Dependant MDL 2872 Filed With JPML on September 20, 2018

A group of plaintiff attorneys have filed a new motion for consolidation of an “Infant/NAS Opioid Addicted Baby MDL” to be separate from the existing Opiate Prescription MDL 2804 due to the lack of “individuals/baby cases” being offered a prominent role in MDL 2804

 

 

 

 

 

 

 

 

 

September 20, 2018 Motion and Brief in Support Filed With the Joint Panel on Multidistrict Litigation:

BEFORE THE UNITED STATES JUDICIAL PANEL ON MULTIDISTRICT LITIGATION

IN RE: CHILDREN BORN                                                           MDL – 2872

OPIOID-DEPENDENT

 

MOTION FOR TRANSFER OF ACTIONS PURSUANT TO 28 U.S.C. §

1407 FOR COORDINATED OR CONSOLIDATED PRETRIAL PROCEEDINGS

 

Plaintiffs[1] respectfully move that the Judicial Panel on Multidistrict Litigation (“Panel”), pursuant to 28 U.S.C. § 1407 and Rule 6.2 of the Rules of Procedure of the Panel, transfer the actions on behalf of children born opioid-dependent listed in the attached Schedule of Actions and subsequent tag-along actions to a separate MDL before the Southern District of West Virginia.  Alternatively, Plaintiffs request transfer to the Southern District of Illinois.  Transfer is appropriate for the following reasons:

  1. Movants seek transfer and coordination or consolidation of all cases filed on behalf of opioiddependent infants into a separate MDL for the reasons laid out in the Doyle plaintiffs’ recently filed Motion to Vacate CTO-47 (JPML 2804 Rec. Doc. 2398).[2] As discussed therein, the cases of the opioiddependent infants are unique, and further, Movants have grave concerns that the due process rights of opioid-dependent infants are not being protected in MDL 2804 and that the interests of the governmental and corporate parties represented by the MDL leadership are fundamentally in conflict with those of these infants. The question now posed to the Panel, argued in the accompanying brief in support of this Motion, is not whether these cases should be held outside of the MDL as presently structured (they must be), but whether they should be consolidated in a separate MDL.
  2. Presently, there are substantially similar class action suits filed on behalf of opioid-dependent infants pending in the Southern District of West Virginia, the Southern District of Ohio, as well as eight cases currently caught up in MDL 2804 in the Northern District of Ohio. Undersigned counsel anticipates that several more substantially similar opioid-dependent infant class action suits will be filed across the country in the coming months.
  3. The actions on behalf of the opioid-dependent infants assert substantially similar claims and seek substantially similar relief. These suits seek to establish a fund for medical monitoring, damages related to acute neonatal abstinence syndrome (NAS) treatment and long-term treatment of these innocent victims of the Opioid Crisis.
  4. The convenience of the courts, witnesses, parties, and counsel will all be served by transfer of these cases to the Southern District of West Virginia, or in the alternative, the Southern District of

Illinois.

  1. Absent transfer, the opioid-dependent infants’ unique interests will remain unprotected and these young victims risk losing the opportunity to achieve a productive adulthood.
  2. In support of this Motion, Movants file:
    1. A Brief supporting their Motion;
    2. A numbered Schedule of Actions providing (i) the complete name of each action involved, listing the full name of each party included as such on the district court’s docket sheet; (ii) the district court and division where each action is pending; (iii) the civil action number of each action; and, (iv) the name of the Judge assigned to each action;
    3. A copy of all complaints and docket sheets for all actions listed on the schedule;
    4. Statement Regarding Oral Argument; and,
    5. Proof of Service.

WHEREFORE, Movants respectfully request that the Panel grant their motion and transfer these cases, for coordinated and consolidated pre-trial proceedings, to the Southern District of West Virginia. Alternatively, Plaintiffs request transfer to the Southern District of Illinois.

Respectfully submitted,

/s/ Scott R. Bickford

MARTZELL, BICKFORD & CENTOLA

Scott R. Bickford (LA 1165)

Spencer R. Doody (LA 27795)

338 Lafayette Street

New Orleans, LA 70130

Telephone: 504-581-9065 Facsimile: 504-581-7635 sbickford@mbfirm.com srd@mbfirm.com

usdcndoh@mbfirm.com

CERTIFICATE OF SERVICE

             I HEREBY CERTIFY that on this 19th day of September, 2018, a true and correct copy of the foregoing has been electronically filed with the Clerk of Court using the CM/ECF system, which provides an electronic service notification to all counsel of record registered as CM/ECF users.

/s/Scott Bickford___________________________

Scott Bickford

 

[1] Movants are: Deric Rees and Ceonda Rees, individually and as next friend and guardian of Baby T.W.B. on behalf of themselves and all others similarly situated (Illinois Class); Darren and Elena Flanagan, individually and as adoptive parents and next friends of Baby K.L.F., on behalf of themselves and all others similarly situated (Tennessee Class); Rachel Wood, individually and as next friend and adopted mother of Baby O.W., on behalf of themselves and all others similarly situated (Missouri Class); Melissa Ambrosio, individually and as next friend of Baby G.A., and on behalf of themselves and all others similarly situated (California Class); Shannon Hunt, individually and as next friend of Baby S.J., on behalf of themselves and all others similarly situated (Maryland Class); Bobbi Lou Moore on behalf of Baby R.R.C., and all other similarly situated (West Virginia Class); Walter and Virginia Salmons, individually and as the next friend or guardian of Minor W.D. and on behalf of all others similarly situated (National Class).

[2] All arguments in Motion to Vacate CTO-47 (JPML 2804 Rec. Doc. 2398) are adopted in support of this Motion.

 

___________________________________________________________________________________________________________________________________

BEFORE THE UNITED STATES JUDICIAL PANEL ON MULTIDISTRICT LITIGATION

IN RE: CHILDREN BORN                       MDL – _________

OPIOID-DEPENDENT

 

BRIEF IN SUPPORT OF PLAINTIFFS’ MOTION FOR TRANSFER OF

ACTIONS PURSUANT TO 28 U.S.C. § 1407 FOR COORDINATED OR

CONSOLIDATED PRETRIAL PROCEEDINGS

Plaintiffs[1] respectfully move that the Judicial Panel on Multidistrict Litigation (“Panel”), pursuant to 28 U.S.C. § 1407 and Rule 6.2 of the Rules of Procedure of the Panel, transfer the actions on behalf of children born opioid-dependent listed in the attached Schedule of Actions and subsequent tag-along actions to a separate MDL before the Southern District of West Virginia.; alternatively, Plaintiffs request transfer to the Southern District of Illinois.

I.        Children Born Opioid-Dependent Need A Separate MDL From MDL 2804

Movants seek transfer and coordination or consolidation of all cases filed on behalf of opioiddependent infants into a new MDL for the reasons laid out in the Doyle plaintiffs’ recently filed Motion to Vacate CTO-47 (JPML 2804 Rec. Doc. 2398).[2] As discussed therein, Movants bring unique claims on behalf of opioid-dependent infants, distinct from the claims of the government and corporate plaintiffs in MDL 2804. These suits bring direct claims on behalf of innocent victims for past and future damages suffered, in contrast to claims for reimbursement. Plaintiffs’ claims do not wholly sound in public nuisance but also in state medical monitoring and product liability causes of action. Further, Movants have grave concerns that the due process rights of opioid-dependent infants are not being protected in MDL 2804 and that the interests of the governmental and corporate parties represented by the MDL leadership are fundamentally in conflict with those of these infants.

Movants established in their Motion to Vacate that concerns for due process, conflicts of interest, and the protection owed to children under the law compel this Panel to exclude such claims from MDL 2804 as it is presently structured.  Movants have also established that despite their counsel’s numerous attempts to address these concerns with the leadership of the MDL, the status quo remains.  Absent a structural change within the MDL, the question before the Panel is not whether these cases should be held outside of the MDL (they must be), but whether they should be consolidated in their own MDL.

The prospect of a separate MDL for a non-governmental plaintiff group was explicitly and favorably discussed at this Panel’s November 30, 2017 hearing:[3]

JUDGE BREYER: Well, there’s another option that maybe your colleagues can address for you which is they all go to Judge X. There are common issues. Judge X conducts the discovery with respect to the common issues. And Judge X has the option of addressing the panel, one way or another, or the lawyers do, to create another MDL with this group or that group because the issues aren’t really amenable to the MDL that they are in.

  1. TELLIS: I think that is a fine idea.

JUDGE BREYER: You like that idea?

  1. TELLIS: I like that idea.

JUDGE BREYER: I’m glad you came up with that idea.

JUDGE VANCE: It’s not infeasible to think there could be a personal injury MDL or a third-party payor.

It has become abundantly clear that MDL 2804 is not amenable to the issues affecting opioid dependent infants, making a separate MDL for this group of innocent, injured plaintiffs necessary.

Presently, there are substantially similar opioid-dependent infant class action suits pending in the Southern District of West Virginia, the Southern District of Ohio, as well as eight cases currently caught up in MDL 2804 in the Northern District of Ohio. These state by state class actions filed to date conservatively represent approximately 40% of the children born opioid-dependent in the country. Undersigned counsel anticipates that several other substantially similar opioid-dependent infant class action suits will be filed across the country in the coming months. The actions on behalf of the opioid-dependent infants assert substantially similar claims and seek substantially similar relief.

These suits seek to establish a fund for medical monitoring, damages related to Neonatal Abstinence Syndrome (NAS) treatment and long-term treatment of these innocent victims of the Opioid Crisis.

The medical issues involved in the opioid-dependent infant cases and the relief sought are distinct from those of the governmental and corporate cases of MDL 2804.  The unique issues of these infants’ cases require discovery to be undertaken in areas including the following:

  • Studies regarding the effect of Defendants’ opioid products upon the health of pregnant mothers and their children in utero, and effects after birth.
  • Knowledge regarding the effects of methadone (and other addiction treatment drugs) taken by pregnant mothers on their children in utero.
  • Studies regarding which medications are appropriate for pregnant mothers dealing with opioid addiction.
  • Knowledge of the diversionary opioid market’s impact on pregnant mothers.
  • Discovery relevant to Movants’ products liability claims.

 

To the extent there is overlap of factual allegations and common issues regarding the opioid drug manufacturers’ and distributors’ conduct between the opioid-dependent infant lawsuits and the suits in MDL 2804, Movants envision that discovery in the infants’ MDL would be coordinated with Judge Polster in MDL 2804 in accord with 28 U.S.C. § 1407.

Absent transfer to a separate MDL, the opioid-dependent infants’ unique interests will remain unprotected and these innocent young victims risk losing the opportunity to achieve a productive adulthood.

II. The Southern District of West Virginia is the Most Appropriate Forum for Transfer and Consolidation or Coordination

 

The Southern District of West Virginia, where the suit of Bobbi Lou Moore on behalf of Baby R.R.C. v. Purdue Pharma L.P., No. 2:18-cv-01231 (S.D.W. Va.) is currently pending, is the most appropriate forum for Multidistrict Litigation. Southern West Virginia is the epicenter of the Opioid Crisis– where it began and where its most profound impacts are being felt. West Virginia has some of the highest rates of fetal opioid exposure and Neonatal Abstinence Syndrome (NAS) in the country.

The West Virginia Department of Health and Human Resources (DHHR) recently released data for

2017 showing the overall incidence rate of NAS was 50.6 cases per 1,000 live births (5.06%) for West

Virginia residents, with the rate as high as 106.6 cases per 1,000 live births (10.66%) in one county.[4]  According to the CDC, there are many more opioid prescriptions than people in West Virginia– 138 prescriptions for every 100 people.[5] A congressional investigation revealed that from 2008 to 2012, pharmaceutical distributors sent more than 780 million pills of hydrocodone and oxycodone to West Virginia, a state with only 1.8 million people.[6] Southern West Virginia was especially hard hit: 20.8 million opioid pills were shipped from 2006 to 2016 to Williamson (population 2,900).[7] One pharmacy in Kermit (population 400) ranked 22nd in the U.S. in the number of hydrocodone pills it received in 2006.[8] The grave impact of this flood of prescription opioids on southern West Virginia and the children born there cannot be overstated.

The Courts of the Southern District of West Virginia have a proven track record in administering Multidistrict Litigation, as demonstrated by the Pelvic Repair System Products Liability Litigation. The Southern District of West Virginia provides a well-prepared, well-staffed, and overall top-notch staff and Clerk’s office. As discussed below, the District’s judges have a wealth of experience in complex litigation, particularly pharmaceutical litigation. The convenience of the courts, witnesses, parties, and counsel will all be served by transfer of these cases to the Southern District of West Virginia.

Judge Robert C. Chambers has the requisite experience to manage this complex litigation.  He previously served as Chief Judge for this District from 2012-2017, and has presided over 500 cases involving pharmaceutical companies.  Judge Chambers is currently presiding over products liability actions involving claims against the manufacturer of prescription anticoagulant drugs.[9]  He has also presided over a case featuring complex pharmaceutical litigation, W. Virginia ex rel. Morrisey v. Pfizer, Inc., 969 F. Supp. 2d 476, 479 (S.D.W. Va. 2013).  Prior to being appointed to the federal bench by President Clinton, Judge Chambers was in private practice in Charleston for twenty years, and served as legal counsel to the West Virginia State Senate.

Senior Judge David A. Faber, appointed to the federal bench in 1991 by President George H.W. Bush, served as Chief Judge at the Southern District of West Virginia from 2002 to 2007. He has served as a Senior Judge in the district since 2008. He has handled 79 cases involving pharmaceuticals, including several opioid cases.[10] Senior Judge Faber also presided over a case involving medical products liability.[11] Prior to becoming a federal judge, Senior Judge Faber worked in both private practice and served in the military as a JAG, and achieved the rank of Colonel. He attended Yale for law school where he was a National Law Scholar, and holds an L.L.M. degree from the University of Virginia.

Chief Judge Thomas E.  Johnston in the Charleston Division has over a decade of experience as a federal judge. He oversees some of the suite of cases collected in the MDL related to the Pelvic Repair System Products Liability Litigation.[12]  Chief Judge Johnston has extensive experience presiding over medical cases, including 216 cases involving health care, and 28 cases specifically involving pharmaceuticals, as well as products liability claims.[13] He had previously served as U.S. Attorney for the Northern District of West Virginia from 2001 to 2006 before being appointed to the bench by President George W. Bush.

In the alternative, Movants would propose transfer and consolidation in the Southern District of Illinois before the Judge Staci M. Yandle. Judge Yandle was appointed to the federal bench in 2014 after an illustrious career in private practice and a distinguished record of public service, including serving on the Illinois Advisory Committee to the United States Commission on Civil Rights. This Panel has previously commended the Southern District of Illinois as convenient due in part to its geographically central location.[14]

III.     Conclusion

For the above-stated reasons and the reasons stated in the Motion to Vacate filed by the Doyle plaintiffs, Movants respectfully request that the Panel transfer the actions on behalf of opioid dependent infants recited on the attached Schedule and all subsequently filed tag-along cases for coordinated and consolidated pretrial proceedings in a separate MDL in the Southern District of West Virginia. Alternatively, Movants request transfer to the Southern District of Illinois, and assignment to Judge Staci M. Yandle.

 

Respectfully submitted,

 

/s/ Scott R. Bickford

MARTZELL, BICKFORD & CENTOLA

Scott R. Bickford (LA 1165)

Spencer R. Doody (LA 27795)

338 Lafayette Street

New Orleans, LA 70130

Telephone: 504-581-9065 Facsimile: 504-581-7635 sbickford@mbfirm.com srd@mbfirm.com

usdcndoh@mbfirm.com

 

 

/s/ Celeste Brustowicz

COOPER LAW FIRM, LLC

Celeste Brustowicz (LA 16835)

Barry J. Cooper, Jr. (LA 27202)

Stephen H. Wussow (LA 35391)

Victor Cobb (LA 36830)

1525 Religious Street

New Orleans, LA 70130

Telephone: 504-399-0009 Cbrustowicz@sch-llc.com

swussow@sch-llc.com

 

 

/s/ Kevin W. Thompson

THOMPSON BARNEY LAW FIRM

Kevin W. Thompson David R. Barney, Jr.

2030 Kanawha Boulevard, East

Charleston, WV 25311

Telephone: 304-343-4401

Facsimile: 304-343-4405

Kwthompsonwv@gmail.com

 

 

/s/ James F. Clayborne

CLAYBORNE, SABO & WAGNER, LLP

Sen. James F. Clayborne (IL 45627)

525 West Main Street, Suite 105

Belleville, Il 62220

Telephone:  618-239-0187

Facsimile:  618-416-7556

jclayborne@cswlawllp.com

 

 

/s/ Jack W. Harang

LAW OFFICES OF JACK W. HARANG

Jack W. Harang (LA 15083)

2433 Taffy Drive

Kenner, LA 70065 Telephone: 504-810-4734

jwharang@gmail.com

 

 

/s/ Kent Harrison Robbins

THE LAW OFFICES OF KENT HARRISON

ROBBINS, P.A.

Kent Harrison Robbins (FL 275484)

242 Northeast 27th Street

Miami, FL 33137

Telephone: 305-532-0500

Facsimile: 305-531-0150

Primary: Khr@khrlawoffices.com

Secondary: ereyes@khrlawoffices.com

Tertiary: assistant@khrlawoffices.com

 

 

/s/ Donald Creadore

THE CREADORE LAW FIRM, P.C.

Donald Creadore (NY 2090702)

450 Seventh Avenue – 1408

New York, NY 10123

Telephone: 212-355-7200

Facsimile: 212-583-0412

Primary: donald@creadorelawfirm.com

Secondary: donald@aol.com

 

 

/s/ Warren Perrin

PERRIN, LANDRY, deLAUNAY

Warren Perrin

251 La Rue France

  1. O. Box 53597

Lafayette, LA 70505

Telephone: 337-233-5832

[1] Movants are: Deric Rees and Ceonda Rees, individually and as next friend and guardian of Baby T.W.B. on behalf of themselves and all others similarly situated (Illinois Class); Darren and Elena Flanagan, individually and as adoptive parents and next friends of Baby K.L.F., on behalf of themselves and all others similarly situated (Tennessee Class); Rachel Wood, individually and as next friend and adopted mother of Baby O.W., on behalf of themselves and all others similarly situated (Missouri Class); Melissa Ambrosio, individually and as next friend of Baby G.A., and on behalf of themselves and all others similarly situated (California Class); Shannon Hunt, individually and as next friend of Baby S.J., on behalf of themselves and all others similarly situated (Maryland Class); Bobbi Lou Moore on behalf of Baby R.R.C., and all other similarly situated (West Virginia Class); Walter and Virginia Salmons, individually and as the next friend or guardian of Minor W.D. and on behalf of all others similarly situated (National Class).

[2] All arguments in Motion to Vacate CTO-47 (JPML 2804 Rec. Doc. 2398) are adopted in support of this Motion.

[3] JPML 2804 Rec. Doc. No. 382 at 16-17, Transcript of November 30, 2017 Hearing.

[4] https://dhhr.wv.gov/News/2018/Pages/DHHR-Releases-Neonatal-Abstinence-Syndrome-Data-for-2017-.aspx

[5] CDC, “Opioid Use Disorder Documented at Delivery Hospitalization – United States 1999-2014,” August 10, 2018, at 2. “West Virginia, for example, had a prescribing rate estimated at 138 opioid prescriptions per 100 persons in 2012, suggesting that individual persons might receive more than one opioid prescription per year.”

[6] https://www.usnews.com/news/politics/articles/2018-05-08/hill-panel-probing-opioids-abuse-targets-distributorfirms

[7] Id.

[8] Id.

[9] Knight v. Boehringer Ingelheim Pharm., Inc., 2018 WL 3037442 (S.D.W. Va. June 19, 2018).

[10] See, e.g., City of Huntington v. AmerisourceBergen Drug Corp., No. CV 3:17-01362, 2017 WL 3317300 (S.D.W. Va. Aug. 3, 2017); The Town of Clendenin, West Virginia v. AmerisourceBergen Drug Corporation et al., No. 2:18-CV-01284, (S.D.W. Va.

Sept. 10, 2018); Adkins v. Purdue Pharma, L.P. et al., No. 18-CV-00477, (S.D.W. Va. Mar. 23, 2018).

[11] Walker v. Medtronic, Inc., No. CIV.A. 2:07-00317, 2010 WL 4822135 (S.D.W. Va. Nov. 24, 2010), aff’d, 670 F.3d 569 (4th Cir. 2012).

[12] See MDL No. 2187, In Re C. R. Bard, Inc., Pelvic Repair System Products Liability Litigation.

[13] See, e.g., Raab v. Smith & Nephew, Inc., 150 F. Supp. 3d 671 (S.D.W. Va. 2015).

[14] In re: Pradaxa (dabigatran etexilate) Prod. Liab. Litig., 883 F. Supp. 2d 1355, 1356 (U.S. Jud. Pan. Mult. Lit. 2012) (“The Southern District of Illinois’ geographically central location and accessibility also commend it for this nationwide products liability litigation.”).

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XARELTO STUDIES FAIL IN BAYER/J&J ATTEMPTS TO EXPAND MARKET CONTROL

THE RECENT FAILURE OF TWO XARELTO STUDIES STOPPED BAYER AND JOHNSON & JOHNSON ATTEMPTS TO INCREASE BLOOD THINNER MARKET-SHARE

By Mark A. York (August 28, 2018)

 

 

 

 

 

 

 

Two recent Xarelto studies fail to show additional benefits when Bayer and Johnson & Johnson’s attempted to expand the patient group for their heart drug Xarelto.

The recent Xarelto blood thinner “Commander HF” study, (see  https://clinicaltrials.gov/ct2/Bayer/J&J (Commander AF Study), could not show any statistical improvements in helping heart failure patients after an acute decline in their condition, results from the so-called study showed on Monday. The primary study goal of reduction in the risk of death, heart attack and stroke was unsuccessful.

A second Bayer/J&J study known as “Mariner” also failed to produce clear evidence that Xarelto is able to reduced the rate of blood clots in certain high-risk patients after a hospital release.

Bayer earned $3.84 billion in sales of Xarelto revenues last year, primarily from stroke prevention in the elderly, with projected annual sales to rise above $5 billion in 2019 and beyond.

Bayer retains marketing rights for Xarelto outside the United States while partner J&J sells Xarelto in the U.S., with Bayer being eligible for royalties on U.S. sales of 20 to 30 percent.

Both Bayer and J&J’s Janssen R&D are facing thousands of lawsuits across the country over failure to warn and disclose the significant dangers of being prescribed Xarelto and the inability to stop the bleeding as there hasn’t been an antidote for Xarelto until 2018.

XARELTO MDL 2804 AND PHILADELPHIA COMPLEX LITIGATION DOCKET

Between the Xarelto MDL 2804 federal docket of 25,000 plus and the 1,700 in Philadelphia Court of Common Pleas there seems to be significant concern for the use of Xarelto when a comparison is made to the pre-Xarelto blood thinners i.e. Coumadin and Warfarin which required additional monitoring, are not known as a drug that can kill you.

Mass Tort Nexus Briefcase Re: XARELTO-Case-No-2349-in-Philadephia-Court-of-Common-Pleas–Complex-Litigation-(PA-State-Court)

Mass Tort Nexus Briefcase Re: XARELTO-MDL-2592-US-District-Court-ED-Louisiana

HOW XARELTO WAS APPROVED BY THE FDA

Xarelto was first approved by the FDA July 2011, representing a major advancement in blood thinning (anticoagulant) medication according to Bayer and Johnson & Johnson, developed to prevent serious conditions that sometimes arise after surgeries (such as artificial hip and knee surgeries). As an anticoagulant, it was intended to prevent pulmonary embolism (PE) and deep vein thrombosis (DVT) and strokes. Xarelto was also intended to help those patients with atrial fibrillation, a group of people more vulnerable to PE, DVT, and stroke after surgery. Eventually, the FDA expanded approval of Xarelto to treat all patients with PE, DVT and atrial fibrillation.

More than one study has shown Xarelto can cause a higher rate of internal bleeding, than other anticoagulant drugs and there is no available “antidote” for stopping internal bleeding in patients taking Xarelto. With warfarin, vitamin K has been shown to stop bleeding, but there is no vitamin K “parallel” for people taking Xarelto. For Xarelto, it can take 24 hours for a dose to get out of the body. That means that if internal bleeding starts, the patient may simply have to wait it out and hope it stops on its own.

 MAYO CLINIC XARELTO STUDY RESULTS NOT POSITIVE

In the journal Gastroenterology, a team of physicians and researchers from the Mayo Clinic studied thousands of patients who took Xarelto (rivaroxaban), Pradaxa (dabigatran), and Eliquis (apixaban). The goal was to figure out which of these three anticoagulant drugs had “the most favorable GI safety profile,” which is medical-research-speak for “which one of these drugs is least likely to hurt patients.”

This is how the study worked: The researchers studied health insurance administrative claims information on thousands of patients between October 1, 2010 and February 28, 2015. These patients had atrial fibrillation, or Afib, which is a heart arrhythmia, a quivering or irregular heartbeat. Afib can lead to serious health problems such as stroke, blood clots, heart failure and other health complications. The researchers looked at the incidents of gastrointestinal bleeding among the thousands of patients who took Xarelto or Pradaxa or Eliquis.

MAYO STUDY SHOWS NEGATIVE RESULTS

Patients who took Xarelto had a higher incidence of gastrointestinal (GI) bleeding patients who took Pradaxa or Eliquis. The statistics show that patients taking Xarelto may have a 20% greater risk of internal bleeding than with those taking Pradaxa or Eliquis, with the rates of GI bleeding increased in patients over seventy-five (75) years old. Turns out, Eliquis “had the most favorable GI safety profile among all age-groups.” While clearly showing Xarelto, unfortunately, had the “least favorable” safety profile among the three prescription anticoagulant drugs.

FDA Investigation of Xarelto Trials

The approval history for Xarelto was actually pretty controversial. FDA reviewers originally said that they recommended against approval, then there was an FDA advisory committee (independent group of key opinion leaders) and they voted in favor, so the FDA approved the drug. Their concern was with how the Phase III trials were run and whether Xarelto had really proved its efficacy. The tests compared patients on warfarin to patients on Xarelto, but the patients on the warfarin run had poor TTR. That means the patients weren’t well controlled on warfarin to begin with, which skews the data in favor of Xarelto.

During the approval process, Xarelto actually wanted a superiority label, which would say that the drug was better than warfarin and other blood thinners. Because of the concerns with the Phase III data, the FDA only gave them a non-inferior label, which says they’re essentially the same in terms of effectiveness.

One of the clinical trials that played a key role in its approval for stroke prevention in patients with atrial fibrillation is now under investigation by the FDA. This trial compared Xarelto’s performance to warfarin’s, but it used a device called INRatio to test the warfarin patients.

The INRatio device was the subject of two FDA warning letters about inaccurate readings just as the trial was starting in 2005 and 2006. In 2014, the device was recalled. The use of the INRatio device may have skewed the results with inaccurate readings, making Xarelto look better in comparison with warfarin.

The FDA’s medical experts originally recommended against improving the drug due to concerns about its efficacy. They found that Xarelto was not as effective as warfarin. However, a review board eventually approved the drug over the objections.

The FDA has issued a number of warnings about Xarelto and has required the makers of the drug to change its labeling multiple times. Specifically, the FDA warned about the risks of uncontrolled bleeding. It also added a black-box warning, its most serious kind of warning, about the increased risk of stroke when patients prematurely stop taking Xarelto and about the increased risk for swelling and damage associated with the use of epidural anesthesia while taking Xarelto.

The makers of Xarelto recently applied to the FDA to expand the approved uses of the drug to include treatment for acute coronary syndrome (ACS). For the third time, the FDA unanimously denied the expansion. Johnson & Johnson and Bayer are expected to continue to apply for approval due to the high value of that market. More than 1 million patients are hospitalized with ACS each year. That offers serious potential for growth for Xarelto, which already earns almost $1 billion in sales annually.

Johnson & Johnson also is claiming that Xarelto helps patients with peripheral artery disease (PAD) in reducing their heart attack and blood clot risks.

WHAT THE VETERANS ADMINISTRATION SAYS ON XARELTO USE

“The good news is you now have an alternative to warfarin … The bad news is you can kill a patient as easily with the new drug as you could with the old drug.”Dr. Alan Jacobson, Director of anti-coagulation services at the VA in Loma Linda, Calif.

The makers of Xarelto say it takes time for doctors to get up to speed on new types of treatments and how to best administer them outside the controls of clinical trials.

“This is a shift in medical practice,” said Dr. John Smith, senior vice president for clinical development at Boehringer. “Individual physicians have to determine what the follow-up plan will be, to use common medical-sense judgment.”

XARELTO MAKERS SAY NO FOLLW-UP CARE REQUIRED

Dr. Peter Wildgoose, a senior director of clinical development at J&J, said the company has not provided special advice on follow-up care for patients on Xarelto.

“There’s nothing more than for any other drug that people regularly take,” he said, adding that most atrial fibrillation patients probably see their doctors on a regular basis. “These drugs have been tested long term, for several years at a time, with very good outcomes.”

Johnson & Johnson officials stressed there was far less evidence in trials of brain bleeding – the most worrisome side effect of anti-coagulants – in patients taking Pradaxa and Xarelto than those taking warfarin.

WAS XARELTO EVEN NEEDED?

Even though warfarin (Coumadin) has been the standard in anticoagulant (blood thinner) drugs for more than 50 years, it lacked perfection, making way for a new generation of blood thinners, including Xarelto. In clinical studies, Xarelto was shown to be more effective than warfarin in treating patients with atrial fibrillation (AF) who are at an increased risk for stroke. And while Xarelto had less cranial hemorrhage (bleeding in the brain) incidents than warfarin, it was shown to have a similar overall number of bleeding incidences when compared to the number of bleeding events in patients taking warfarin.

Despite this finding, and – until recently – its lack of antidote (reversal agent) for serious bleeding, Xarelto rose to popularity, making up a significant portion of the billion-dollar anticoagulant drug industry in the United States. Even after an investigation into into the clinical trial ROCKET-AF study, upon which its U.S. Food and Drug Administration (FDA) approval hinged, the drug continues to be prescribed by doctors to patients with AF and as a prophylaxis for deep vein thrombosis (DVT), which can lead to pulmonary embolism (PE) after total hip and knee replacement surgeries.

But as more evidence surfaced regarding the drug risks for patients taking Xarelto, including an increased risk of wound complications following surgical procedures, severe bleeding with no easily available antidote to stop its serious consequences, as well as reports of platelet deficiencies, hepatitis and Stevens-Johnson syndrome (SJS) (a severe skin reaction), some heart doctors are becoming a bit more cautious with the blood thinner.

Xarelto and Internal Bleeding?

Janssen and parent company Johnson & Johnson market its anticoagulant drug Xarelto as a safe and more convenient choice in blood thinners compared to warfarin. But pre-market clinical studies and post-marketing reports have shown that taking Xarelto leaves many patients vulnerable to internal bleeding that can result in death for some users.

In a 2017 annual report issued by the Institute for Safe Medication Practices (ISMP), it was stated that oral anticoagulant drugs, including Xarelto (rivaroxaban), showed “unacceptably high risks,” according to two government data sources, the FAERS adverse events reports for 2016 and a new systematic study by the Centers for Disease Control and Prevention (CDC).

XARELTO ACCOUNTS FOR 75 PERCENT OF ALL AE’s IN ANTI-COAGULANTS

Of the 22,000 reports of serious injuries resulting from anticoagulant drugs, Xarelto accounted for 15,043 cases alone, the FDA said.

“According to an analysis of 2016 FDA adverse event data conducted by the ISMP, anticoagulant (blood thinner) drugs accounted for nearly 22,000 reports of serious injuries in the United States, led by Xarelto, which accounted for 15,043 cases alone. These numbers also included 3,018 reported deaths, with most injuries being the result of hemorrhages, making bleeding one of the most adverse events.”

Gastrointestinal hemorrhages made up the MOST INJURIES, followed by cerebral hemorrhages. From early testing, hemorrhage has always been an apparent increased risk associated with lowering the risk of strokes from blood clots.

In late 2016, the CDC released a separate study that found that “anticoagulant drugs accounted for more emergency department visits for outpatient adverse effects than any other class of drugs currently in therapeutic use, including opioids (non-abuse visits), antibiotics and diabetes drugs.” Most of these adverse events were severe, with nearly 50 percent requiring a hospital stay. The ISMP estimated in its QuarterWatch report that just over 6 percent of patients using anticoagulants for one year will need to visit the emergency room, with about half of those patients requiring hospitalization. That is a major number of injuries that can be attributed to a drug that is advertised as life saving and designed to prevent injuries.

Overall, the CDC found in its systematic study that the FDA’s FAERS voluntary reporting underestimates anticoagulant drug-related injuries. The CDC discovered that approximately 228,600 emergency department visits occur each year due to the use of blood thinner drugs, including Xarelto, which is 10 times more than the FAERS total number of voluntary reports.

The Symptoms of Internal Bleeding

At its onset, unless it’s a severe hemorrhage, internal bleeding may not cause any symptoms apparent to the patient taking Xarelto. However, dependent on where the bleed is located in the body, the patient will soon begin exhibiting signs and symptoms that will be their indication to seek immediate medical attention. Patients who are in poor health or are over the age of 64 and the targeted audience seem more likely to suffer serious, potentially life-threatening bleeding complications.

The end result of Bayer and J&J’s attempts to secure the blood thinner market may continue unabated until the more than 25,000 lawsuits over the injuries and deaths that are affiliated with taking Xarelto will force both companies to come to either the settlement table or begin trying the Xarelto MDL 2592 lawsuits being remanded back to original courts for trials and blocks of 1200 cases at a time. Xarelto MDL Judge Eldon Fallon, USDC Eastern District of Louisiana has already started the remand process for 23,000 cases pending in his federal court, due to the lack of progress in settlements and cooperation by Bayer and Johnson & Johnson.

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