VALSARTAN U.S. SUPPLIERS IN CHINA AND INDIA ON FDA RECALL RADAR: SEE FDA WARNING LETTER TO ZHEJIANG HUAHAI PHARMACEUTICAL

 

 

 

 

 

 

 

Inspections, Compliance, Enforcement, and Criminal Investigations

Zhejiang Huahai Pharmaceutical 11/29/18

 

 

10903 New Hampshire Avenue
Silver Spring, MD 20993

Via UPS                                                          Warning Letter: 320-19-04

November 29, 2018

Mr. Jun Du

Executive Vice President

Zhejiang Huahai Pharmaceutical Co., Ltd.

Coastal Industrial Zone, Chuannan No. 1 Branch No. 9 

Donghai Fifth Avenue, Linhai, Taizhou Zhejiang 317016

CHINA

Dear Mr. Du:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Zhejiang Huahai Pharmaceutical Co., Ltd., located at Coastal Industrial Zone, Chuannan No. 1 Branch No. 9, Donghai Fifth Avenue, Linhai, Taizhou Zhejiang, from July 23 to August 3, 2018.

 This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your API are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

We reviewed your August 26, 2018, response in detail and acknowledge receipt of your subsequent correspondence.

During our inspection, our investigators observed specific deviations including, but not limited to, the following.

  1. Failure of your quality unit to ensure that quality-related complaints are investigated and resolved.

Valsartan API

Your firm received a complaint from a customer on June 6, 2018, after an unknown peak was detected during residual solvents testing for valsartan API manufactured at your facility. The unknown peak was identified as the probable human carcinogen N-nitrosodimethylamine (NDMA). Your investigation (DCE-18001) determined that the presence of NDMA was caused by the convergence of three process-related factors, one factor being the use of the solvent (b)(4)). Your investigation concluded that only one valsartan manufacturing process (referred to as the (b)(4) process in your investigation) was impacted by the presence of NDMA.

However, FDA analyses of samples of your API, and finished drug product manufactured with your API, identified NDMA in multiple batches manufactured with a different process, namely the (b)(4) process, which did not use the solvent (b)(4). These data demonstrate that your investigation was inadequate and failed to resolve the control and presence of NDMA in valsartan API distributed to customers. Your investigation also failed:

  • To include other factors that may have contributed to the presence of NDMA. For example, your investigation lacked a comprehensive evaluation of all raw materials used during manufacturing, including (b)(4).
  • To assess factors that could put your API at risk for NDMA cross-contamination, including batch blending, solvent recovery and re-use, shared production lines, and cleaning procedures.
  • To evaluate the potential for other mutagenic impurities to form in your products.

Our investigators also noted other examples of your firm’s inadequate investigation of unknown peaks observed in chromatograms. For example, valsartan intermediates (b)(4) and (b)(4) failed testing for an unknown impurity (specification ≤ (b)(4)%) with results of (b)(4)% for both batches. Your action plan indicated that the impurity would be identified as part of the investigation; however, you failed to do this. In addition, no root cause was determined for the presence of the unknown impurity. You stated that you reprocessed the batches and released them for further production.

Your response states that NDMA was difficult to detect. However, if you had investigated further, you may have found indicators in your residual solvent chromatograms alerting you to the presence of NDMA. For example, you told our investigators you were aware of a peak that eluted after the (b)(4) peak in valsartan API residual solvent chromatograms where the presence of NDMA was suspected to elute. At the time of testing, you considered this unidentified peak to be noise and investigated no further. Additionally, residual solvent chromatograms for valsartan API validation batches manufactured using your (b)(4) process, with (b)(4) in 2012 ((b)(4), and (b)(4)) show at least one unidentified peak eluting after the (b)(4) peak in the area where the presence of NDMA was suspected to elute.

Your response also states that you were not the only firm to identify NDMA in valsartan API. In your case, FDA analyses of samples identified amounts of NDMA in valsartan API manufactured at your firm that were significantly higher than the NDMA levels in valsartan API manufactured by other firms. FDA has grave concerns about the potential presence of mutagenic impurities in all intermediates and API manufactured at your facility, both because of the data indicating the presence of impurities in API manufactured by multiple processes, and because of the significant inadequacies in your investigation.

In response to this letter:

  • Submit risk assessments for all APIs and intermediates manufactured at your facility for the potential presence of mutagenic impurities.
  • Provide an update on investigations and CAPA plans initiated to address the presence of NDMA and other potential mutagenic impurities in all APIs manufactured at your firm.
  • Provide a thorough, independent assessment of your overall system for investigating deviations, discrepancies, out-of-specification (OOS) results, complaints, and other failures. In addition, provide a retrospective review of all distributed batches within expiry to determine if your firm released batches that did not conform to established specifications or appropriate manufacturing standards.
  • Provide test results for all (b)(4)and intermediates for the presence of NDMA, N-Nitrosodiethylamine (NDEA), and other potentially mutagenic impurities.

(b)(4) API

Your firm received a customer complaint on September 13, 2016, concerning (b)(4) API batches ((b)(4) and (b)(4)) that exceeded the specification for (b)(4) (≤ (b)(4)ppm). (b)(4) has been classified as a probable human carcinogen. Your customer’s test results conflicted with your (b)(4) test results, which showed the two batches meeting the specification upon release. Your complaint investigation (CC-16008) identified no clear laboratory error, and no anomalies were detected during the production of the batches. Your investigation failed to evaluate other (b)(4) API batches to determine if the presence of excess (b)(4) was an adverse trend. For example, (b)(4)batches (b)(4), and (b)(4) were OOS for (b)(4) because of production errors; however, they were not discussed in your complaint investigation.

Your response states that (b)(4) API batches (b)(4) and (b)(4) were returned, reprocessed, and released to customers in non-U.S. markets.

Your response also states that in August 2017 you implemented a new (b)(4) test method that uses a (b)(4) LC-MS/MS method, to replace the (b)(4) LC-MS method that was prone to erroneous OOS results. You failed to verify the reliability of the (b)(4) results for all (b)(4) API batches (including (b)(4) batch (b)(4)) originally released using your (b)(4) LC-MS method, which you indicated was inferior to your updated method.

In response to this letter, provide:

  • A risk assessment for all (b)(4) API batches manufactured within expiry.
  • A revised complaint handling procedure and details of any further controls your facility has implemented to ensure that all complaints are adequately documented and thoroughly investigated.
  • Procedures for accepting and reprocessing returned drugs.
  • Results of (b)(4) testing of all (b)(4)API batches released to the U.S. market using your updated (b)(4) LC-MS/MS (b)(4) test method.
  1. Failure to evaluate the potential effect that changes in the manufacturing process may have on the quality of your API.

In November 2011 you approved a valsartan API process change (PCRC – 11025) that included the use of the solvent (b)(4). Your intention was to improve the manufacturing process, increase product yield, and lower production costs. However, you failed to adequately assess the potential formation of mutagenic impurities when you implemented the new process. Specifically, you did not consider the potential for mutagenic or other toxic impurities to form from (b)(4) degradants, including the primary (b)(4) degradant, (b)(4). According to your ongoing investigation, (b)(4) is required for the probable human carcinogen NDMA to form during the valsartan API manufacturing process. NDMA was identified in valsartan API manufactured at your facility.

You also failed to evaluate the need for additional analytical methods to ensure that unanticipated impurities were appropriately detected and controlled in your valsartan API before you approved the process change. You are responsible for developing and using suitable methods to detect impurities when developing, and making changes to, your manufacturing processes. If new or higher levels of impurities are detected, you should fully evaluate the impurities and take action to ensure the drug is safe for patients.

Your response states that predicting NDMA formation during the valsartan manufacturing process required an extra dimension over current industry practice, and that that your process development study was adequate. We disagree. We remind you that common industry practice may not always be consistent with CGMP requirements and that you are responsible for the quality of drugs you produce.

Your response does not describe sufficient corrective actions to ensure that your firm has adequate change management procedures in place: (1) to thoroughly evaluate your API manufacturing processes, including changes to those processes; and (2) to detect any unsafe impurities, including potentially mutagenic impurities. For FDA’s current thinking on control of potentially mutagenic impurities, see FDA’s guidance document M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk for approaches that FDA considers appropriate for evaluating mutagenic impurities, at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM347725.pdf.

In response to this letter, provide:

  • Detailed revised change management procedures describing how your firm will assess and control all impurities, including mutagenic impurities, in API and intermediates manufactured at your facility.
  • Detailed procedures describing how your firm establishes impurity profiles for products manufactured at your firm. These procedures should contain instructions for comparing at appropriate intervals against the impurity profile in the regulatory submission, or for comparing against historical data, to detect changes to the API resulting from modifications in raw materials, equipment operating parameters, or the production process.
  • A retrospective analysis of other API and intermediates manufactured at your firm to determine if they were adequately evaluated for anticipated and unanticipated impurities, including potentially mutagenic impurities.
     

CGMP Consultant Recommended

Based upon the nature of the deviations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations and assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.

 Quality Systems Guidance

 Your firm’s quality systems are inadequate. For guidance on establishing and following CGMP compliant quality systems, see FDA’s guidances: Q8(R2) Pharmaceutical Development, at https://www.fda.gov/downloads/drugs/guidances/ucm073507.pdfQ9 Quality Risk Management, at https://www.fda.gov/downloads/Drugs/Guidances/ucm073511.pdf; and Q10 Pharmaceutical Quality System, at https://www.fda.gov/downloads/drugs/guidances/ucm073517.pdf.

 Additional API CGMP guidance

FDA considers the expectations outlined in ICH Q7 in determining whether API are manufactured in conformance with CGMP. See FDA’s guidance document Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients for guidance regarding CGMP for the manufacture of API, at https://www.fda.gov/downloads/Drugs/…/Guidances/ucm073497.pdf.

Conclusion

Deviations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these deviations, for determining the causes, for preventing their recurrence, and for preventing other deviations.

If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b) and allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.

FDA placed your firm on Import Alert 66-40 on September 28, 2018.

Until you correct all deviations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.

Failure to correct these deviations may also result in FDA continuing to refuse admission of articles manufactured at Zhejiang Huahai Pharmaceutical Co., Ltd., located at Coastal Industrial Zone, Chuannan No. 1 Branch No. 9, Donghai Fifth Avenue, Linhai, Taizhou Zhejiang, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles may be subject to refusal of admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your deviations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

 Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov or mail your reply to:

Rory K. Geyer

Compliance Officer

U.S. Food and Drug Administration

White Oak Building 51, Room 4235

10903 New Hampshire Avenue

Silver Spring, MD 20993

USA

Please identify your response with FEI 3003885745.

Sincerely,

/S/

Francis Godwin

Acting Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research

 

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The FDA 510(k) System Overhaul -Process For Medical Device Approval: Is this a win for Big Pharma?

 

IS BIG PHARMA LOBBYING DICTATING FEDERAL REGULATORY POLICY IN WASHINGTON D.C. NOW?

By Mark A. York (December 5, 2018)

 

 

 

 

 

 

 

Official FDA announcement: FDA changes 510(k) program for approval and review of medical devices Nov. 26, 2018

(MASS TORT NEXUS MEDIA) On November 26, 2018 the FDA announced an overhaul of the 510(k) system that is meant to prompt manufacturers to base new products on technologies that are 10 years old or less. Almost 20% of the products currently cleared by the system were based on devices older than 10 years. For consumer safety, the FDA is considering whether to publicize the manufacturers and their devices that are based on older products.

The FDA is supposed to protect the interests of the general public and ensure that new devices, as well as existing ones are functioning as designed. More often that is not the case, as the FDA either fails to review medical device failures or simply ignores them.

The FDA has a reporting and tracking database that permits the public to review and see what devices are unsafe or causing adverse events, see FDA Medical Device Adverse Event Report Database.

Now there seems to be an effort by the FDA to pull back on the reporting functions in their official oversight duties. This includes the reporting requirements for problematic medical devices.

But earlier this year, the FDA made a rule change that could curtail that database, which was already considered to be of limited scope by medical researchers and the FDA itself.

For the FDA Medical Device Reporting Program (MDR): FDA.gov/MedicalDevices/Safety/ReportaProblem

BIG PHARMA LOBBYING INFLUENCE

Pharmaceutical companies and medical device makers, collectively Big Pharma, spend far more than any other industry to influence politicians. Big Pharma has poured close to $2.5 billion into lobbying and funding members of Congress over the past decade.

Hundreds of millions of dollars flow to lobbyists and politicians on Capitol Hill each year to shape laws and policies that keep drug company profits growing. The pharmaceutical industry, which has about two lobbyists for every member of Congress, spent $152 million on influencing legislation in 2016, according to the Center for Responsive Politics. Drug companies also contributed more than $20m directly to political campaigns last year. About 60% went to Republicans. Paul Ryan, the former speaker of the House of Representatives was the single largest beneficiary, with donations from the industry totaling $228,670.

Over the past decade, manufacturers have also paid out at least $1.6 billion to settle charges of regulatory violations, including corruption and fraud, around the world, according to the consortium, which published its report findings on November 26, 2018.

The new FDA rule, which had been sought by medical device manufacturers, opens the door for a decrease in reported information for nearly 9 out of 10 device categories, a recent review found. It could allow manufacturers to submit quarterly summarized reports for similar incidents, rather than individual reports every time malfunctions occur, meaning there will be much less detail about individual cases.

As part of the worldwide scrutiny of medical devices and at times, the  affiliated dangers, a massive investigation known as “The Implant Files” was undertaken by a group of journalists around the world.  Led by editors and reporters from the International Consortium of Investigative Journalists, it took a year to plan and another year to complete

ICIJ partnered with more than 250 journalists in 36 countries to examine how devices are tested, approved, marketed and monitored. This included an analysis of more than 8 million device-related health records, including death and injury reports and recalls.

The Implant Files review encompassed more than 1.7 million injuries and nearly 83,000 deaths suspected of being linked to medical devices over 10 years, and reported to the U.S. alone.

Like the rest of Big Pharma, the medical device manufacturers have created an intricate web of corporate and political influence including at the Federal Drug Administration, where the FDA is charged with oversight of medical devices.

The new rule is one of several regulatory changes favoring the medical device industry that have been proposed and enacted since the beginning of the Trump administration. They are part of a decades-long campaign to decrease U.S. regulation of the pharmaceutical and medical device industry, which is a massive global business that has existed for years with minimal international scrutiny.

A recent analysis of the 10 largest publicly traded medical device companies in the U.S. found that since the start of the Trump administration, the companies have spent more than $36.5 million on efforts to influence rules and legislation. Some of these companies manufacture a variety of medical products, including pharmaceuticals and lab equipment, but four of the 10 exclusively manufacture devices and lobbying disclosures for all 10 emphasize efforts to influence policy around devices.

BUYING A PRESENCE IN WASHINGTON

The medical device industry was worth $405 billion worldwide in 2017, according to an Accenture market analysis. Despite its size, the medical device industry has only a patchwork of international oversight, even though when things go wrong with a device, the consequences can be serious.

But the single largest medical device market in the world is the U.S., worth an estimated $156 billion in 2017, according to the U.S. Department of Commerce. As the medical device market has boomed over the past several decades, the industry has built a sizable presence in Washington, D.C.

Many medical device companies have built sophisticated lobbying arms, often employing their own team of lobbyists in addition to hiring outside firms for specific issues. Several of the largest companies used between 15 and 50 lobbyists in 2017 alone, an analysis by the Center for Responsive Politics (CRP) found.

There are also two main trade groups for the industry to which device makers contribute membership fees to, both of which pack a hefty lobbying punch on their own. Since the start of 2017, the Advanced Medical Technology Association (AdvaMed), the older and larger group, has spent more than $6 million and the Medical Device Manufacturers Association (MDMA) has spent nearly $2.6 million. The groups’ policy goals echo those that individual companies list on their lobbying disclosures, among them: decreasing taxes on devices, increasing insurance coverage and reimbursement and the FDA’s approval process for bringing a device to market.

The medical device lobbying effort is vast, with lobbyists seeking to be heard on Medicare and Medicaid reimbursement codes, device purchasing policies at the Veterans Administration, even cybersecurity and trade issues. Companies regularly lobby Congress and target agencies and offices across the executive branches in D.C., from the FDA to the Center for Medicare and Medicaid and the National Security Council.

Altogether, the industry has spent more than $20 million per year for the past five years lobbying the federal government, according to an analysis of campaign finance and lobbying data from CRP.

With the change in administration in 2017, that spending increased to more than $26 million, $2.2 million more than its highest level in any of the previous four years. Based on disclosures from the first three quarters of the year, medical device lobbying in 2018 is on pace to exceed 2017 levels.

An industry spokesperson noted that the U.S. pharmaceutical industry spends more heavily on lobbying than the device industry. Big Pharma-pharmaceuticals, which was worth more than $453 billion in the U.S. in 2017, spent more than $171 million the same year, more than six times as much as the device industry, according to a Statista market analysis.

The lobbying resources of the device industry far outweigh those of consumer and patient advocates, which are often on the other side of regulatory debates on Capitol Hill.

Very few advocacy groups spend time lobbying on devices, said Dr. Diana Zuckerman, a former HHS official under Obama and president of the National Center for Health Research, a nonprofit advocacy organization based in Washington.

“When we’ve talked to congressional staff about this,” she said, “they say things like, ‘Well, we’re getting calls every day, all day long from various device companies or their lawyers,’ and the nonprofits are basically going to the Hill for visits a few hours a year.”

Zuckerman’s group is one of about a half dozen to lobby on devices over the past few years. Each of the largest spends no more than a few-hundred-thousand dollars annually to lobby on devices and all other consumer issues, according to their federal lobbying disclosures.

Trial lawyer groups, which the device industry spokesperson noted often sue device makers, also spent less than one third of what the device industry did in 2017, a CRP analysis found.

Three companies that spent the most on lobbying in the past five years were  ask about their lobbying efforts. Baxter International and Abbott Laboratories did not comment. Medtronic said, “Despite the company nearly doubling in size, our lobbying-related efforts over the last 10 years have remained relatively stable.”

Previously, Abbott, Medtronic and a half-dozen other international device makers told the International Consortium of Investigative Journalists that they conduct business with the highest ethical standards, adhere to all laws and have rigorous programs to prevent employee misconduct.

In a statement, Mark Leahey, president of MDMA, said, “As millions of Americans benefit daily from the more than 190,000 different medical devices available and in use in the United States, our members continue to work with patient groups and policy makers to advance policies that promote improved access for patients and providers. This dynamic innovation ecosystem remains committed to developing the cures and therapies of tomorrow, while reducing adverse events and learning from ongoing research and each patient’s experience.”

OBAMA – TRUMP COMPARISON

During its eight-year tenure, the Obama administration permitted some deregulation but also instituted the first FDA product ban since the 1980s.

Beginning in 2014, warning letters to industry began to drop steeply and approval of new devices to rise. By 2017, the number of FDA warning letters to device manufacturers about product safety had dropped to nearly 80 percent less than those issued in 2010, while approval numbers for new devices were more than three times as high as at the beginning of the decade. The FDA says the decrease in warning letters is due to a more interactive approach to working with violative companies, and the uptick in approvals is due to an increase in staffing and efficiency.

Under Obama, some FDA regulators responsible for overseeing the device industry pushed for deregulation. Administrators largely kept it in check, said Peter Lurie, an FDA associate commissioner during the Obama administration.

“It was accompanied by very heavy lobbying on Capitol Hill as well,” said Lurie. Priorities included faster device approval times and decreasing taxes.

During Obama’s final year in office, the FDA banned its first device in more than 30 years, a type of surgical glove and proposed a ban on a home shock collar for behavior modification. That ban is still pending.

The industry successfully pushed for changes in a proposed regulation on unique device identifiers, the identification codes for individual devices, similar to automotive vehicle identification numbers, and won the suspension of a tax on medical devices created to help fund the Affordable Care Act.

“Now with the advent of the Trump administration,” said Lurie, “the deregulatory gloves are off and we’re seeing a number of the device industry’s most desired objectives come to fruition.”

President Trump vowed to cut regulations across the government by 75 percent when he came into office.

In 2002, Congress instituted a program in which the device industry pays “user fees” to fund the FDA office that oversees it, amounts which are agreed upon in negotiations between industry and the regulator every five years. In its first year, the fees provided 10 percent of funding for the device center, but by 2018, the fees brought in more than $153 million, providing more than 35 percent of the center’s budget.

“It’s carefully negotiated for weeks and months at a time,” said Jack Mitchell, former director of Special Investigations for the FDA. “And there’s a laundry list of things that the industry gets FDA to agree to and that they’re paying for.”

If the most recent agreement, negotiated in 2017, had not gone through by the deadline, the agency would have legally been required to temporarily layoff at least one third of its device center staff. The final agreement included a decrease in approval time for certain devices.

“We do not believe user fee funding has influenced our decision making,” the FDA said in a statement, noting that other parts of the FDA are also funded by user fees.

The agency also noted that it held meetings with patient stakeholders in addition to industry when negotiating the user fee agreement, saying, “Patients are a critical part of the user fee process.”

The FDA emphasized that it does not always agree with the industry, citing as examples its support of legislation that makers of reusable devices provide instruction on how to prevent bacterial contamination, and including device identifier codes in insurance claims forms.

MAKING FDA APPROVAL EASIER FOR BIG PHARMA

The changes to how adverse events are reported was seen as an overwhelming industry success.

The FDA database in which surgical complications are entered is known as the Manufacturer and User Facility Device Experience Database (MAUDE), which includes more than 750,000 incidents per year. The adverse events range from minor malfunctions to patient deaths linked to products being used around the world.

Despite its size, it’s widely accepted that the database is only a rather limited record of the full scale of medical device complications and adverse events.

The rule went into effect in August. The FDA said in a statement in November that though the reports are valuable, they were never meant to be sole source for determining if a device is causing harm.

“This type of reporting system has notable limitations,” said the FDA, “including the potential submission of incomplete, inaccurate, untimely, unverified, or biased data.”

Patients are able to report adverse events to the database themselves, but few know to do so. Companies are required to report the events, once they are notified., which they don’t always do. The FDA said thirty-three percent (33%)  of all FDA warning letters to device makers were to companies that failed to meet rules for reporting complications with devices.

The more companies that fail to file properly, the less the database accurately reflects what is happening to patients with devices.

Under the rule change, companies could be allowed to submit quarterly summarized reports for similar incidents, rather than individual reports each time malfunctions occur. Previously, qualified manufacturers could submit summarized reports if they filed a request with the agency. Now they can do so without making a request.

“[The database] is the way we’ve learned about some very serious health issues,” said Rita Redberg, a cardiologist at the University of San Francisco who studies adverse events like Hershey’s. “It’s the most widespread and publicly available database for adverse events, which is extremely important for patient safety.”

In a public comment in support of the rule change, AdvaMed called the change a “commonsense approach” that will reduce the volume of reports manufacturers need to submit to the FDA and streamline the information the FDA receives about malfunctions.

“This process will actually make it easier for third parties to assess the malfunction data in [the database],” said Greg Crist, a spokesperson for AdvaMed. “Comparing the old alternative summary reporting program to this new initiative is comparing apples to oranges.”

In response to public comments that critical report information would be lost with the change in reporting, the FDA wrote in the published rule that, “We do not believe there will be an adverse impact on the content of information provided to FDA.”

In a statement, the agency said the new program “streamlines the process for reporting of device malfunctions and allows us to more efficiently detect potential safety issues and identify trends. It also frees up resources to better focus on addressing the highest risks.”

But Redberg, is worried that the new rule change will make searching an already unwieldy database more difficult, decreasing the ability of researchers and the public to search for misfiled reports or see accurate numbers of adverse events.

“It makes things easier for industry, it makes things worse for patients,” she said. “I really think it’s a public health crisis. We have more and more devices in use, and for many of them we really have no idea how safe they are because we don’t have accurate reporting.”

How these changes are affecting medical care in the US, and more importantly the publics right to be informed of adverse events and problems with medical devices, their approval process and who’s lobbying who and for what in the FDA should be open and transparent.  

(Certain images and text excerpts in this article were reprinted from third party media sources)

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

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.

_________________________________________________________

Controversy Surrounding ROCKET-AF: A Call for Transparency, But Should We Be Changing Practice? References
Jason D Matos1 and Peter J Zimetbaum1,,2 Arrhythm Electrophysiol Rev. 2016 May; 5(1): 12–13.; doi:  [10.15420/aer.2016.24.2]
  1. Kubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939 – an oral, direct Factor Xa inhibitor – after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61:873–80. PMID: 16328318. [PubMed]
  2. Cohen D. Rivaroxaban: can we trust the evidence? BMJ. 2016;352:i575. DOI: 10.1136/bmj.i575; PMID: 26843102. [PubMed]
  3. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91. DOI: 10.1056/NEJMoa1009638; PMID: 21830957. [PubMed]
  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.
  8. Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J. 2014;35:3346–55. DOI: 10.1093/eurheartj/ehu367; PMID: 25182247.[PubMed]
  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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Pradaxa Federal Court Trial Win: $1.25 million verdict-with punitives of $1 million in death case

Betty Erelene Knight (Deceased), Claude R. Knight   vs. Boehringer Ingelheim Pharmaceuticals, Inc.  Docket No. 3:15-cv-06424; Judge Robert C. Chambers (United States District Court-Southern District of West Virginia)

(MASS TORT NEXUS MEDIA) A federal jury has awarded the family of a deceased West Virginia woman $1.25 million after finding that Boehringer Ingelheim failed to warn of risks associated with its blood thinner Pradaxa, causing her to suffer gastrointestinal bleeding.

The federal trial in Huntington, WV, (US District Court Southern District of West Virginia) awarded $250,000 in compensatory damages to the estate of Betty Erelene Knight and her husband Claude R. Knight, and added $1,000,000 more in punitive damages. The jury added the large punitive award after plaintiff counsel showed that Boehringer Ingelheim engaged in wanton and willful acts in handling of its blockbuster drug Pradaxa, primarily in failing to warn of the risks.

The October 17th plaintiffs’ verdict was the first trial win in the country against Boehringer Ingelheim the German drugmaker, showing that the blockbuster drug is dangerous. The Pradaxa defense team had won three earlier trials for the company, and this verdict on behalf of  the estate of Erelene Knight and her surviving spouse Claude, shows that juries can be convinced of the dangers including fatal risks related to Pradaxa. Mrs. Knight, who was in her 80’s passed away while taking Pradaxa.

She suffered from an irregular heartbeat, a condition that often leads to the development of blood clots, which can travel into the brain and cause a stroke. The plaintiff’s doctor stated that she was at “high risk of stroke.”

Prior to being prescribed Pradaxa, her doctors initially prescribed Coumadin, another prescription blood thinner. Because of the risk of uncontrolled bleeding with this particular drug, the victim required “frequent monitoring” which is what the Pradaxa marketing teams focused on, when meeting with doctors while marketing Pradaxa as a “safer alternative to Coumadin.”  Eventually, the victim grew weary of the inconvenience of such monitoring and learned about Pradaxa, which performs a similar function to Coumadin, from a television commercial.

Her doctor agreed to switch her to Pradaxa, and after about 18 months on the drug, she started to suffer from severe, uncontrolled internal bleeding. At one point she required surgery, which significantly weakened her and set into motion a decline in her health. Within several months of the surgery Erelene Knight passed away. Defense vigorously attempted to point the finger at other health conditions and place blame on anything besides Pradaxa, which failed as the punitive damage award of $1 million showed that the jury clearly saw that Boehringer Ingelheim knew the risks of Pradaxa, yet continued offering the drug without sufficient warnings.

The winning plaintiff trial team consisted of the Childers, Schlueter & Smith Firm and partner  Andy Childers, Neal Moskow of Ury & Moskow, LLC and Yvette Ferrer of Ferrer Poirot & Wansbrough. Congratulations to everyone, as the mass tort world looks forward to additional plaintiff verdicts in the many other Pradaxa cases pending in dockets around the country.

WHAT IS PRADAXA?

·        Pradaxa is an anticoagulant medication used to reduce the risk of stroke and blood clots in patients with non-valvular atrial fibrillation (AF), the most common type of heart rhythm abnormality.

·        The safety and efficacy of Pradaxa were studied in a clinical trial comparing Pradaxa with the anticoagulant warfarin. In the trial, patients taking Pradaxa had fewer strokes than those who took warfarin.1

·        From approval in October 2010 through August 2012, a total of approximately 3.7 million Pradaxa prescriptions were dispensed, and approximately 725,000 patients received a dispensed prescription for Pradaxa from U.S. outpatient retail pharmacies.2

Rulings Prior to Trial

The estate’s lawsuit against Boehringer Ingelheim, focused on Pradaxa’s label, asserting claims that the company knew that “certain blood plasma concentrations of Pradaxa increased the risk of a major bleed without contributing any additional stroke prevention benefit.” This risk was actually disclosed on labels for Pradaxa in Europe, but not the United States at the time of the victim’s care. Boehringer also knew that patients should not take Pradaxa if they also use P-gp inhibitor drugs, which Erelene Knight did. And while the company later altered its label to include this information, it did not directly inform doctors of the risk.

Based on all this, the judge presiding over the case ruled the estate presented sufficient evidence to submit the question of liability for “failure to warn” to the jury. Defense protested that at the relevant time, Pradaxa contained a general warning that the drug “can cause serious and, sometimes, fatal bleeding.” But whether or not this was an “adequate” warning given what BI allegedly knew, but failed to disclose on the original U.S. label, will be for the jury to decide.

How the favorable verdict predicts future trial outcomes in not only Pradaxa cases currently pending around the country, but in the more than 25,000 Xarelto blood thinner cases that are filed in the Xarelto MDL 2592 litigation, see Mass Tort Nexus Briefcase XARELTO-(rivaroxaban)-MDL-2592-USDC-ED-Louisiana (Judge Eldon Fallon), and in the Philadelphia Court of Common Pleas, see XARELTO-Case-No-2349-in-Philadephia-Court-of-Common-Pleas–Complex-Litigation-(PA-State-Court). There are several bellwether trials set for the Philadelphia Xarelto cases in 2019, where Laura Feldman and Rosemary Pinto of the Philadelphi firm of Feldman & Pinto, will be co-lead counsel for the trial team.

Michael Brady Lunch will speak on the Pradaxa litigation as well as the status of Xarelto 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  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.

WWW.MASSTORTNEXUS.COM

 

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Essure Litigation Against Bayer Survives Preemption Challenge – Cases Remanded to Pennsylvania State Court

Philadelphia Court of Common Pleas Is Now The Venue for Filing “Essure” Cases

By Rosemary Pinto, Esq. Feldman & Pinto

And Mark A. York, Mass Tort Nexus

(September 27, 2018)

 

 

 

 

 

 

(MASS TORT NEXUS MEDIA) Bayer Corp. and its entities, the makers of Essure, a permanent contraceptive implant subject to thousands of injury reports and repeated safety restrictions by regulators ,said  recently that it will stop selling the device in the U.S., the only country where it remains available.

On July 23, 2018, U.S. District Senior Judge, John R. Padova of the Eastern District of Pennsylvania, ruled  that the federal court did not have jurisdiction over the cases against Bayer Healthcare Pharmaceuticals Inc., and the legal claims over the Essure contraceptive device.

The cases were originally filed in Philadelphia court but were removed by Bayer with the company claiming the removals were proper because the plaintiffs’ claims involved an interpretation of federal law, including Food and Drug Administration regulations.

The company cited a 2017 ruling by a U.S. District Court in North Carolina in another Essure case, Burrell v. Bayer, in which it found that it had federal question jurisdiction because “the labeling of FDA-approved medical devices is governed by the FDA under the MDA, and [the] state law is generally pre-empted under 21 U.S.C. Section 360k.”

But Padova instead followed the lead of courts in the Eastern District of Kentucky and the Eastern District of Missouri, finding that “Congress intended for the state courts to resolve cases such as this one, which ask whether a defendant violated state laws that parallel federal requirements applicable to Essure.”

Bayer argued that the cases were of federal concern because the Essure devices were subject to “stringent federal scrutiny” as Class III medical devices.

“We certainly agree with Bayer that Congress has a significant interest in the regulation of Class III medical devices,” Padova said. Nevertheless, Padova added, the Medical Device Amendments of 1976 “permit individuals to bring state law causes of action alleging violations of duties that parallel the federal requirements. It would be entirely inconsistent with this structure to conclude that Congress intended all such state law causes of action to be brought in federal court.”

Padova also said Bayer failed to identify any disputed federal issue, noting that “the central claims in the complaints are that Bayer violated state law and the complaints merely reference federal law to rebut any argument that their state law claims are preempted.

Feldman Pinto In Philadelphia Provides Insight

Essure Litigation Survives Preemption Challenge, Cases Remanded to State Court

Essure is a birth control device composed of two metal coils implanted in a patient’s fallopian tubes. Women injured by the device have filed more than 16,000 lawsuits against Bayer Healthcare, alleging, among other things, that Bayer failed to provide adequate warnings of severe Essure complications suffered by plaintiffs from device breakage, migration, and / or expulsion. Complications include perforation of fallopian tubes, uteri, rectums, colons, and other organs; severe and chronic pelvic or abdominal pain; and autoimmune diseases.

Essure Claims for Negligent Misrepresentation and Negligent Failure to Warn Survive Preemption Challenge

All of the approximately 16,000 Essure lawsuits in state and federal court exist as individual legal actions rather than class actions or multidistrict litigation. Five such cases were consolidated in the U.S. District Court for the Eastern District of Pennsylvania. Defendants filed motions in all five cases, requesting dismissal of plaintiffs’ claims on the basis of express or implied preemption, failure to state a plausible claim, or failure to plead fraud with particularity.

In March 2016, the court denied defendants’ motions to dismiss plaintiffs’ claims of negligent misrepresentation and negligent failure to warn, holding that the state law claims set forth plausible claims for relief and were not preempted by federal law.

Consolidated Essure Cases Remanded to State Court

In July 2018, the Eastern District of Pennsylvania remanded 19 Essure injury cases to the Philadelphia Court of Common Pleas. The district court found that it lacked both diversity of citizenship and federal question subject-matter jurisdiction over the consolidated individual actions and remanded them to state court.

 Essure Statute of Limitations

Defendants in Essure personal injury cases may argue that the statute of limitations period in all Essure cases should begin on November 18, 2016, the date the FDA approved a black box warning (its strongest warning level) for Essure. In reality, the dates triggering Essure limitation periods will vary. The beginning of each plaintiff’s limitation period will depend on the plaintiff’s individual claims and state law applicable to the particular case.

Bayer Stops USA Sales

Bayer announced in June 2018 that it would voluntarily discontinue U.S. sales of Essure by the end of this year “for business reasons” but earlier this month affirmed the safety profile of the device. Last week, Bayer took Netflix to task over the accuracy of its medical device documentary “The Bleeding Edge.” The tide was turning for Bayer at that point, sales were already down 70% after the 2016 FDA warning and the public became aware of the risks of using Essure.

Bayer received FDA approval to sell Essure in 2002 and promoted it as a quick and easy permanent solution to unplanned pregnancies. Essure consists of two thin-as-spaghetti nickel-titanium coils inserted into the fallopian tubes, where they spur the growth of scar tissue that blocks sperm from fertilizing a woman’s eggs.

Because of the reported complaints, the FDA added its most serious warning to the device in 2016 and ordered the company to conduct a 2,000-patient study. FDA Commissioner Scott Gottlieb said Friday, the agency would work with Bayer to continue the study, but noted “Bayer will not be able to meet its expected enrollment numbers” for new patients. The study was designed to follow patients for three years to better assess complications.

Gottlieb said the FDA will continue to monitor adverse events reported to its database after Essure is removed from the market.  He stated “I also want to reassure women who’ve been using Essure successfully to prevent pregnancy that they can continue to do so,” and added “Those who think it’s causing problems, such as persistent pain, should consult with their doctors,” with Gottlieb further noting that device removal “has its own risks.”

Essure’s original label warned that the device’s nickel can result in allergic reactions. Its current labeling lists hives, rash, swelling and itching as possible reactions.

But many women have attributed other problems to the implant, including mood disorders, weight gain, hair loss and headaches. Those problems are listed in the current FDA labeling for the device, with the qualifier: “It is unknown if these symptoms are related to Essure or other causes.”

Informational material Bayer supplied to doctors and patients lists potential problems and states the devices are meant to be permanent. It also says removal may require complicated surgery, including a hysterectomy, that might not be covered by insurance.

Non-Profit Weighs In

Diana Zuckerman, president of the nonprofit National Center for Health Research, said Essure is among medical devices approved without “clear evidence of safety or effectiveness. As a result, when thousands of women reported serious complications from Essure, there was no unbiased long-term research to refute or confirm those reports” she also stated, “If patients had been listened to when the first clinical trials were conducted on Essure, better research would have been conducted to determine exactly how safe and effective Essure is.”

 Feldman & Pinto is Representing Plaintiffs in Essure Litigation

The Philadelphia personal injury firm of Feldman & Pinto concentrates its practice in plaintiffs’ drug and medical device injury litigation. Each of the firm’s attorneys has more than 20 years’ experience trying personal injury and wrongful death cases in state and federal court. Feldman & Pinto currently represents plaintiffs in approximately 20 Essure injury cases in the Philadelphia Court of Common Pleas.  Attorney Rosemary Pinto can be contacted at rpinto@feldmanpinto.com.

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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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Why Does the FDA Ignore “Off-Label” Drug Marketing?

“BY REMOVING FDA OVERSIGHT BIG PHARMA RUNS AMOK”

By Mark A. York (August 1, 2018)

(MASS TORT NEXUS MEDIA)  In 2017 and continuing into 2018, Big Pharma has been fighting major legal battles related to off-label marketing of drugs for unintended uses. They also engaged in a parallel strategy, where they were influencing the FDA and other policy making agencies behind the scenes in Washington DC. Big Pharma was paying millions to lobbyists, making campaign donations and generally buying influence as they always have. It was a foregone conclusion that with the Trump administration view of , “no regulatory oversight required” that there would be some loosening of the FDA regulatory shackles.

Big Pharma was getting ready for freedom to sell, sell, sell their drugs in any way they could, including off-label marketing of the drugs for unintended use purposes. A corporate policy, that’s technically illegal, yet results in billions of dollars in profits every years for Big Pharma. Then the FDA rolled out an unexpected new proposed rule, in March 2017 cracking down on “off-label’ marketing of drugs. This new rule change wasn’t in Big Pharma’s bests interests, sending the drug industry into a furious lobbying scramble. Bring in the Trump camp and on January 12, 2018 Big Pharma and the army of lobbyists and elected officials that were recruited, seem to have succeeded in stopping the FDA rules change that would have tightened up “off label” marketing of drugs.

Trump stops FDA enforcement rule change: January 12, 2018 Food and Drug Administration Press Release: FDA Delays Change to “Off-Label” Drug Use Enforcement Rules

This seems to be further evidence of the Trump administration permitting private corporations to control what goes on behind the scenes in federal regulatory agencies these days. The same loosening of enforcement rules has been seen in the EPA as well as in Dept. of Energy oversight enforcement authority. Whatever else you might think about the ramped up Trump vs. Obama administration mindset, this rule delay is an example of the new FDA leadership doing what is in the best interests of those they are supposed to be regulating, the drug makers, and not in the interests of the US consumers.

To put this into perspective, consider the current “Opioid Crisis” gripping the entire country, where “off-label” marketing of opiates for the last 20 years by drug makers, has resulted in thousands of deaths each year, unknown financial losses and the related social impact felt in every state across the country. Another result is the Opiate Prescription Litigation MDL 2804, (see OPIOID CRISIS BRIEFCASE: MDL 2804 OPIATE PRESCRIPTION LITIGATION) where litigation started when hundreds of counties, states and cities and other entities impacted by the catastrophic expense related to combatting the opiate healthcare crisis fought back. The various parties have filed lawsuits against opioid drug makers and distributors, demanding repayment of the billions of dollars spent on addressing the massive costs related to opioid abuse, primarily due to opioid based prescription drugs flooding the country.

When the Obama administration ended on January 9, 2017, the FDA issued a Final Rule on “Clarification of When Products Made or Derived from Tobacco are Regulated as Drugs, Devices, or Combination Products; Amendments to Regulations Regarding ‘Intended Uses.’” That “clarification” was meant to enable additional enforcement and control over drug makers rampant “off -label” marketing of drugs for purposes that were never FDA approved. This was an attempt by the FDA to have the ability to punish off-label promotions, where previously the process was a two-step regulatory review, whereby off-label promotions are said to prove an indicated use not included in the label and, thus, not accompanied by adequate directions for use – making the product misbranded. These regulations have been around since the 1950s, but a recent series of court decisions invoking the First Amendment called into question the FDA’s interpretation of “intended use” and its efforts to shut down truthful medical-science communications about potential benefits from off-label use.

In a 2015 proposed rule, the FDA referred to striking the language from regulations permitting the FDA to consider a manufacturer’s mere knowledge of actual use as evidence of intended use, which would have further enabled Big Pharma drug marketing abuses to go unchecked. But then, the FDA’s January 9, 2017 proposal reversed course, stating that retained knowledge of off-label use as evidence of intended use, clarified that any relevant source of evidence, whether circumstantial or direct could demonstrate intended use, and ultimately invoked the dreaded “totality of the evidence” standard. This would have enable the FDA to begin oversight and enforcement of practices such as the blatant and wide open “off-label” marketing of opioid prescription drugs that started in the mid-1990’s and never stopped.

Instead of putting a check on Big Pharma abuses, we have the Trump administration placing a hold on new regulations, and delaying the “intended use” regulation change to March 19, 2018, so that comments could be received and considered, and thereby enabling the Big Pharma “lobby machine” to become fully engaged across all DC circles, ensuring that the FDA changes are effectively put to rest.

The bottom line is that the FDA is now proposing to “delay until further notice” the portions of the final rule amending the FDA’s existing regulations on “off-label” drug use, when describing the types of evidence that may be considered in determining a medical product’s intended uses.  The FDA will receive comments on this proposal through February 5, 2018.

Here is the official FDA publication of January 16, 2018:

The Federal Register:  https://www.federalregister.gov/documents/2018/01/16/2018-00555/clarification-of-when-products-made-or-derived-from-tobacco-are-regulated-as-drugs-devices-or

WHAT IS “OFF-LABEL” MARKETING?

Global health care giant Johnson & Johnson (J&J) and its subsidiaries will pay more than $2.2 billion to resolve criminal and civil liability arising from allegations relating to the prescription drugs Risperdal, Invega and Natrecor, including promotion for uses not approved as safe and effective by the Food and Drug Administration (FDA) and payment of kickbacks to physicians and to the nation’s largest long-term care pharmacy provider.  The global resolution is one of the largest health care fraud settlements in U.S. history, including criminal fines and forfeiture totaling $485 million and civil settlements with the federal government and states totaling $1.72 billion.

“The conduct at issue in this case jeopardized the health and safety of patients and damaged the public trust,” stated Eric Holder, then US Attorney General, “This multibillion-dollar resolution demonstrates the Justice Department’s firm commitment to preventing and combating all forms of health care fraud.  And it proves our determination to hold accountable any corporation that breaks the law and enriches its bottom line at the expense of the American people” he added.

The resolution includes criminal fines and forfeiture for violations of the law and civil settlements based on the False Claims Act arising out of multiple investigations of the company and its subsidiaries.

“When companies put profit over patients’ health and misuse taxpayer dollars, we demand accountability,” said Associate Attorney General Tony West.  “In addition to significant monetary sanctions, we will ensure that non-monetary measures are in place to facilitate change in corporate behavior and help ensure the playing field is level for all market participants.”

The Federal Food, Drug, and Cosmetic Act (FDCA) protects the health and safety of the public by ensuring, among other things, that drugs intended for use in humans are safe and effective for their intended uses and that the labeling of such drugs bear true, complete and accurate information.  Under the FDCA, a pharmaceutical company must specify the intended uses of a drug in its new drug application to the FDA.  Before approval, the FDA must determine that the drug is safe and effective for those specified uses.  Once the drug is approved, if the company intends a different use and then introduces the drug into interstate commerce for that new, unapproved use, the drug becomes misbranded.  The unapproved use is also known as an “off-label” use because it is not included in the drug’s FDA-approved labeling.

“When pharmaceutical companies interfere with the FDA’s mission of ensuring that drugs are safe and effective for the American public, they undermine the doctor-patient relationship and put the health and safety of patients at risk,” said Director of the FDA’s Office of Criminal Investigations John Roth.  “Today’s settlement demonstrates the government’s continued focus on pharmaceutical companies that put profits ahead of the public’s health.  The FDA will continue to devote resources to criminal investigations targeting pharmaceutical companies that disregard the drug approval process and recklessly promote drugs for uses that have not been proven to be safe and effective.”

 J&J RISPERDAL MARKETING ABUSE

In a related civil complaint filed today in the Eastern District of Pennsylvania, the United States alleges that Janssen marketed Risperdal to control the behaviors and conduct of the nation’s most vulnerable patients: elderly nursing home residents, children and individuals with mental disabilities.  The government alleges that J&J and Janssen caused false claims to be submitted to federal health care programs by promoting Risperdal for off-label uses that federal health care programs did not cover, making false and misleading statements about the safety and efficacy of Risperdal and paying kickbacks to physicians to prescribe Risperdal.

“J&J’s promotion of Risperdal for unapproved uses threatened the most vulnerable populations of our society – children, the elderly and those with developmental disabilities,” said U.S. Attorney for the Eastern District of Pennsylvania Zane Memeger.  “This historic settlement sends the message that drug manufacturers who place profits over patient care will face severe criminal and civil penalties.”

In its complaint, the government alleges that the FDA repeatedly advised Janssen that marketing Risperdal as safe and effective for the elderly would be “misleading.”  The FDA cautioned Janssen that behavioral disturbances in elderly dementia patients were not necessarily manifestations of psychotic disorders and might even be “appropriate responses to the deplorable conditions under which some demented patients are housed, thus raising an ethical question regarding the use of an antipsychotic medication for inappropriate behavioral control.”

The complaint further alleges that J&J and Janssen were aware that Risperdal posed serious health risks for the elderly, including an increased risk of strokes, but that the companies downplayed these risks.  For example, when a J&J study of Risperdal showed a significant risk of strokes and other adverse events in elderly dementia patients, the complaint alleges that Janssen combined the study data with other studies to make it appear that there was a lower overall risk of adverse events.  A year after J&J had received the results of a second study confirming the increased safety risk for elderly patients taking Risperdal, but had not published the data, one physician who worked on the study cautioned Janssen that “[a]t this point, so long after [the study] has been completed … we must be concerned that this gives the strong appearance that Janssen is purposely withholding the findings.”

The complaint also alleges that Janssen knew that patients taking Risperdal had an increased risk of developing diabetes, but nonetheless promoted Risperdal as “uncompromised by safety concerns (does not cause diabetes).”  When Janssen received the initial results of studies indicating that Risperdal posed the same diabetes risk as other antipsychotics, the complaint alleges that the company retained outside consultants to re-analyze the study results and ultimately published articles stating that Risperdal was actually associated with a lower risk of developing diabetes.

The complaint alleges that, despite the FDA warnings and increased health risks, from 1999 through 2005, Janssen aggressively marketed Risperdal to control behavioral disturbances in dementia patients through an “ElderCare sales force” designed to target nursing homes and doctors who treated the elderly.  In business plans, Janssen’s goal was to “[m]aximize and grow RISPERDAL’s market leadership in geriatrics and long term care.”  The company touted Risperdal as having “proven efficacy” and “an excellent safety and tolerability profile” in geriatric patients.

In addition to promoting Risperdal for elderly dementia patients, from 1999 through 2005, Janssen allegedly promoted the antipsychotic drug for use in children and individuals with mental disabilities.  The complaint alleges that J&J and Janssen knew that Risperdal posed certain health risks to children, including the risk of elevated levels of prolactin, a hormone that can stimulate breast development and milk production.  Nonetheless, one of Janssen’s Key Base Business Goals was to grow and protect the drug’s market share with child/adolescent patients.  Janssen instructed its sales representatives to call on child psychiatrists, as well as mental health facilities that primarily treated children, and to market Risperdal as safe and effective for symptoms of various childhood disorders, such as attention deficit hyperactivity disorder, oppositional defiant disorder, obsessive-compulsive disorder and autism.  Until late 2006, Risperdal was not approved for use in children for any purpose, and the FDA repeatedly warned the company against promoting it for use in children.

The government’s complaint also contains allegations that Janssen paid speaker fees to doctors to influence them to write prescriptions for Risperdal.  Sales representatives allegedly told these doctors that if they wanted to receive payments for speaking, they needed to increase their Risperdal prescriptions.

In addition to allegations relating to Risperdal, today’s settlement also resolves allegations relating to Invega, a newer antipsychotic drug also sold by Janssen.  Although Invega was approved only for the treatment of schizophrenia and schizoaffective disorder, the government alleges that, from 2006 through 2009, J&J and Janssen marketed the drug for off-label indications and made false and misleading statements about its safety and efficacy.

As part of the global resolution, J&J and Janssen have agreed to pay a total of $1.391 billion to resolve the false claims allegedly resulting from their off-label marketing and kickbacks for Risperdal and Invega.  This total includes $1.273 billion to be paid as part of the resolution announced today, as well as $118 million that J&J and Janssen paid to the state of Texas in March 2012 to resolve similar allegations relating to Risperdal.  Because Medicaid is a joint federal-state program, J&J’s conduct caused losses to both the federal and state governments.  The additional payment made by J&J as part of today’s settlement will be shared between the federal and state governments, with the federal government recovering $749 million, and the states recovering $524 million.  The federal government and Texas each received $59 million from the Texas settlement.

NURSING HOME PATIENT ABUSES BY J&J

The civil settlement also resolves allegations that, in furtherance of their efforts to target elderly dementia patients in nursing homes, J&J and Janssen paid kickbacks to Omnicare Inc., the nation’s largest pharmacy specializing in dispensing drugs to nursing home patients.  In a complaint filed in the District of Massachusetts in January 2010, the United States alleged that J&J paid millions of dollars in kickbacks to Omnicare under the guise of market share rebate payments, data-purchase agreements, “grants” and “educational funding.”  These kickbacks were intended to induce Omnicare and its hundreds of consultant pharmacists to engage in “active intervention programs” to promote the use of Risperdal and other J&J drugs in nursing homes.  Omnicare’s consultant pharmacists regularly reviewed nursing home patients’ medical charts and made recommendations to physicians on what drugs should be prescribed for those patients.  Although consultant pharmacists purported to provide “independent” recommendations based on their clinical judgment, J&J viewed the pharmacists as an “extension of [J&J’s] sales force.”

J&J and Janssen have agreed to pay $149 million to resolve the government’s contention that these kickbacks caused Omnicare to submit false claims to federal health care programs.  The federal share of this settlement is $132 million, and the five participating states’ total share is $17 million.  In 2009, Omnicare paid $98 million to resolve its civil liability for claims that it accepted kickbacks from J&J and Janssen, along with certain other conduct.

“Consultant pharmacists can play an important role in protecting nursing home residents from the use of antipsychotic drugs as chemical restraints,” said U.S. Attorney for the District of Massachusetts Carmen Ortiz.  “This settlement is a reminder that the recommendations of consultant pharmacists should be based on their independent clinical judgment and should not be the product of money paid by drug companies.”

OFF-LABEL USE OF HEART DRUG NATRECOR

The civil settlement announced today also resolves allegations that J&J and another of its subsidiaries, Scios Inc., caused false and fraudulent claims to be submitted to federal health care programs for the heart failure drug Natrecor.  In August 2001, the FDA approved Natrecor to treat patients with acutely decompensated congestive heart failure who have shortness of breath at rest or with minimal activity.  This approval was based on a study involving hospitalized patients experiencing severe heart failure who received infusions of Natrecor over an average 36-hour period.

In a civil complaint filed in 2009 in the Northern District of California, the government alleged that, shortly after Natrecor was approved, Scios launched an aggressive campaign to market the drug for scheduled, serial outpatient infusions for patients with less severe heart failure – a use not included in the FDA-approved label and not covered by federal health care programs.  These infusions generally involved visits to an outpatient clinic or doctor’s office for four- to six-hour infusions one or two times per week for several weeks or months.

The government’s complaint alleged that Scios had no sound scientific evidence supporting the medical necessity of these outpatient infusions and misleadingly used a small pilot study to encourage the serial outpatient use of the drug.  Among other things, Scios sponsored an extensive speaker program through which doctors were paid to tout the purported benefits of serial outpatient use of Natrecor.  Scios also urged doctors and hospitals to set up outpatient clinics specifically to administer the serial outpatient infusions, in some cases providing funds to defray the costs of setting up the clinics, and supplied providers with extensive resources and support for billing Medicare for the outpatient infusions.

As part of today’s resolution, J&J and Scios have agreed to pay the federal government $184 million to resolve their civil liability for the alleged false claims to federal health care programs resulting from their off-label marketing of Natrecor.  In October 2011, Scios pleaded guilty to a misdemeanor FDCA violation and paid a criminal fine of $85 million for introducing Natrecor into interstate commerce for an off-label use.

“This case is an example of a drug company encouraging doctors to use a drug in a way that was unsupported by valid scientific evidence,” said First Assistant U.S. Attorney for the Northern District of California Brian Stretch.  “We are committed to ensuring that federal health care programs do not pay for such inappropriate uses, and that pharmaceutical companies market their drugs only for uses that have been proven safe and effective.”

Non-Monetary Provisions of the Global Resolution and Corporate Integrity Agreement

In addition to the criminal and civil resolutions, J&J executed a five-year Corporate Integrity Agreement (CIA) with the Department of Health and Human Services Office of Inspector General (HHS-OIG).  The CIA includes provisions requiring J&J to implement major changes to the way its pharmaceutical affiliates do business.  Among other things, the CIA requires J&J to change its executive compensation program to permit the company to recoup annual bonuses and other long-term incentives from covered executives if they, or their subordinates, engage in significant misconduct.  J&J may recoup monies from executives who are current employees and from those who have left the company.  The CIA also requires J&J’s pharmaceutical businesses to implement and maintain transparency regarding their research practices, publication policies and payments to physicians.  On an annual basis, management employees, including senior executives and certain members of J&J’s independent board of directors, must certify compliance with provisions of the CIA.  J&J must submit detailed annual reports to HHS-OIG about its compliance program and its business operations.

“OIG will work aggressively with our law enforcement partners to hold companies accountable for marketing and promotion that violate laws intended to protect the public,” said Inspector General of the U.S. Department of Health and Human Services Daniel R. Levinson.  “Our compliance agreement with Johnson & Johnson increases individual accountability for board members, sales representatives, company executives and management.  The agreement also contains strong monitoring and reporting provisions to help ensure that the public is protected from future unlawful and potentially harmful off-label marketing.”

FEDERAL AND STATE JOINT CRIMINAL INVESTIGATIONS

This resolution marks the culmination of an extensive, coordinated investigation by federal and state law enforcement partners that is the hallmark of the Health Care Fraud Prevention and Enforcement Action Team (HEAT) initiative, which fosters government collaborations to fight fraud.  Announced in May 2009 by Attorney General Eric Holder and Health and Human Services Secretary Kathleen Sebelius, the HEAT initiative has focused efforts to reduce and prevent Medicare and Medicaid financial fraud through enhanced cooperation.

The criminal cases against Janssen and Scios were handled by the U.S. Attorney’s Offices for the Eastern District of Pennsylvania and the Northern District of California and the Civil Division’s Consumer Protection Branch.  The civil settlements were handled by the U.S. Attorney’s Offices for the Eastern District of Pennsylvania, the Northern District of California and the District of Massachusetts and the Civil Division’s Commercial Litigation Branch.  Assistance was provided by the HHS Office of Counsel to the Inspector General, Office of the General Counsel-CMS Division, the FDA’s Office of Chief Counsel and the National Association of Medicaid Fraud Control Units.

This matter was investigated by HHS-OIG, the Department of Defense’s Defense Criminal Investigative Service, the FDA’s Office of Criminal Investigations, the Office of Personnel Management’s Office of Inspector General, the Department of Veterans Affairs, the Department of Labor, TRICARE Program Integrity, the U.S. Postal Inspection Service’s Office of the Inspector General and the FBI.

One of the most powerful tools in the fight against Medicare and Medicaid financial fraud is the False Claims Act.  Since January 2009, the Justice Department has recovered a total of more than $16.7 billion through False Claims Act cases, with more than $11.9 billion of that amount recovered in cases involving fraud against federal health care programs.

The department enforces the FDCA by prosecuting those who illegally distribute unapproved, misbranded and adulterated drugs and medical devices in violation of the Act.  Since 2009, fines, penalties and forfeitures that have been imposed in connection with such FDCA violations have totaled more than $6 billion.

The civil settlements described above resolve multiple lawsuits filed under the qui tam, or whistleblower, provisions of the False Claims Act, which allow private citizens to bring civil actions on behalf of the government and to share in any recovery.  From the federal government’s share of the civil settlements announced today, the whistleblowers in the Eastern District of Pennsylvania will receive $112 million, the whistleblowers in the District of Massachusetts will receive $27.7 million and the whistleblower in the Northern District of California will receive $28 million.  Except to the extent that J&J subsidiaries have pleaded guilty or agreed to plead guilty to the criminal charges discussed above, the claims settled by the civil settlements are allegations only, and there has been no determination of liability

With the Trump Administration still claiming that no regulatory oversight is needed to monitor the US drug industry, that they can self-regulate, it appears that there will be no letup in the rampant “off-label: and unintended use marketing of pharmaceutical drugs in the United States.  The one way that Big Pharma is held accountable is in the courtroom, although financial damages and penalties against the drug companies amounting to billions of dollars each year being awarded by juries, wont change FDA policy, it does provide a small amount of official recognition that there are ongoing abuses by the pharmaceutical industry in the USA.

 

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Purdue Pharma Executives and the Sackler Family Named in Massachusetts Opioid Crisis Lawsuit

Oxycontin Founding Family Are Now Forced to Defend Profits In Court

Complaint: “State of Massachusetts vs. Purdue Pharma and the Sackler Family” June 13, 2018

By Mark A. York (June 20, 2018)

 

 

 

 

 

 

 

 

 

(MASS TORT NEXUS MEDIA) As more states and federal agencies continue to scrutinize the opioid drug manufacturers across the country, a clear high value target is emerging in Purdue Pharma, L.P.  and the Sackler family that founded the company. The family has profited to the tune of about $13 billion to date, and have somehow avoided the legal spotlight for the last 10 years. The Sackler family have always been protected by the company shield, even though their most profitable selling opioid drug Oxycontin and its boardroom coordinated marketing campaign was the brainchild and a direct result of the Purdue Pharma company founders, the Sackler brothers and their tried and true business model.

Complaint: “State of Massachusetts vs. Purdue Pharma and the Sackler Family” June13, 2018

That is now changing, as the State of Massachusetts, filed a lawsuit against Purdue Pharma and the Sackler family as well as various Purdue executives over the prescription painkiller OxyContin. Oxycontin is now recognized as the opioid fuse that ignited America’s opioid crisis. This is the first time where Purdue’s leading executives and members of the multibillionaire Sackler family, now known to be feuding over the opioid crisis have been named in civil litigation.

The Sacklers named in the lawsuits include Theresa and Beverly, widows of Purdue founders, brothers Mortimer and Raymond Sackler and Ilene, Kathe and Mortimer David Alfons Sackler, three of Mortimer’s children; Jonathan and Richard Sackler, Raymond’s two sons; and David Sackler, Raymond’s grandson. The Sackler family is worth conservatively, an estimated$13 billion, according to Forbes, which has been generated from sales of OxyContin.  As is normal procedure by the Sackler family and the company itself, the Sackler family feuding members always decline requests for comment on the catastrophic opioid crisis and avoid discussing any Purdue Pharma links to how the crisis came about.

PURDUE PHARMA NAMED IN 600 OPIOID LAWSUITS

Dozens of states, counties and local governments have independently sued opioid drugmakers in both state and federal courts across the country, (see OPIOID-CRISIS-BRIEFCASE-MDL-2804-OPIATE-PRESCRIPTION-LITIGATION by Mass Tort Nexus) with claims alleging all opiate drug makers, distributors and now the pharmacies engaged in fraudulent marketing to sell the powerful painkillers. They also failed to monitor and report the massive increases in opioid prescriptions flooding the US marketplace. Which has now resulted in fueling the nationwide epidemic, that’s reported to have killed over a quarter million people. The now organized approach steps up those efforts as officials sift evidence and are now holding not only the companies, but the executives and owners culpable in the designing the opioid crisis.

Purdue Pharma is facing a legal assault on many fronts, as cities, counties and states have either filed suit or are probing the company for an alleged role in the United States’ opioid and addiction epidemic. Now, a lawsuit from Massachusetts’ attorney general Maura Healey is the first to bring the company’s current and former execs into the mix, including the billionaire family with sole ownership of Purdue.

At a news conference this week, Healey said she’s filing suit against the drugmaker, plus current and former executives and board members, “for their role in creating and profiting from this epidemic that has killed so many.” The suit alleges Purdue downplayed risks and overstated benefits of opioid painkillers, including OxyContin. It seeks to link the deaths of 670 Massachusetts residents to actions at the company.

A Purdue spokesman said the company shares concern about the opioid crisis. Purdue is “disappointed, however, that in the midst of good faith negotiations with many states, the Commonwealth has decided to pursue a costly and protracted litigation process,” he said.

Purdue is no stranger to litigation, in 2007 Purdue agreed to pay $19.5million in civil penalties, but did not admit wrongdoing, to settle lawsuits with 26 states – including Massachusetts – and the District of Columbia after being accused of aggressively marketing OxyContin to doctors while downplaying the risk of addiction. This is a consistent pattern, including the 2007 criminal indictment and plea of senior Purdue Pharma executives, where they agreed to pay over $600 million and plead guilty to a greatly reduced charge of “mislabeling drugs” which seems to have set the stage for the Purdue legal strategy of throwing money at all claim of abuse, thereby setting the Purdue Pharma marketing model loose on the US consumers and the healthcare industry, see USA vs. Purdue Criminal Plea “Oxycontin” usdc.virginia.gov/OPINIONS July 2007

PURDUE PHARMA FIRES ENTIRE SALES FORCE

In what is either an amazing coincidence or a look at corporate political maneuvering, just a week after the Sacklers and company executives were named individually in the latest Purdue Pharma opiate lawsuit, the OxyContin maker laid off its entire sales force.  This puts an end to an era for Purdue that at one point, was the top-selling opioid drug in the country, and became synonymous with the nation’s opioid crisis, while the Sacklers collected billions in profits from Oxycontin sales.

Purdue, had already laid off half of its 600 sales reps in February 2018, as part of the corporate political maneuvering to curry favor with the numerous state and federal investigation that were taking place, when it announced that it would no longer be promoting OxyContin to doctors. On July 19, 2018 six days after the State of Massachusetts filed a complaint naming the company, the founding Sackler family and the executive suite as defendants in a an opioid litigation complaint,  Purdue Pharma confirmed that they had terminated the the remaining 220 employees in its sales force.

While Purdue still manufactures Oxycontin, which accounts for more than 80 percent of the company’s, they will be shifting its focus away from the highly lucrative opiate painkiller market, according to company sources.

PURDUE PHARMA DENIES ALL CLAIMS

We vigorously deny the Commonwealth’s allegations and look forward to presenting our substantial defenses to these claims,” Purdue’s spokesman said in a statement.

Executives named in the suit are current and former Purdue CEOs Craig Landau, John Stewart and Mark Timney, as well as current and former members of the Purdue board of directors, including members of the Sackler family. Dr. John Purdue Gray and George Frederick Bingham founded the company in 1892, and Mortimer and Raymond Sackler purchased Purdue in 1952, which is now owned solely by the Sackler family,.

The lawsuit alleges the company violated Massachusetts’ consumer protection statute, created a public nuisance, and that it was negligent. It seeks restitution, damages and penalties related to the alleged actions, plus injunctive relief. The company has generated more than $500 million in revenue in Massachusetts since 2008, the AG says.

“Time after time, in doctor visit after doctor visit—and there were thousands of doctor visits made to hundreds of doctors around this state—there were misrepresentations,” Healey said at a news conference. “There were lies about the efficacy, about the safety, about the supposed nonaddictive nature of their product.”

The State of Massachusetts lawsuit is the latest in a wave of complaints against the company and Big Pharma opiate drug makers involved in making and distributing opioids. Hundreds of cities and counties have filed lawsuits, and the cases are now grouped in federal court in Cleveland in MDL 2804, Opiate Prescription Litigation in front of Judge Daniel Polster. Early this year, the judge in the multidistrict litigation indicated that the sides might be able to reach a settlement, but the negotiations later hit “barriers.” The judge charted a course for a few cases to go to bellwether trials.

Aside from cities and counties, dozens of state officials and the feds have gotten involved. Attorneys general from 41 states are investigating and discussing a possible settlement with the company. Last month, six states sued Purdue over its role in the epidemic, according to USA Today. The U.S. Department of Justice is also backing cities and counties in their legal efforts.

The Sackler family name graces some of the nation’s most prestigious bastions of culture and learning — the Sackler Center for Arts Education at the Guggenheim Museum, the Sackler Lefcourt Center for Child Development in Manhattan and the Sackler Institute for Developmental Psychobiology at Columbia University, to name a few.

Now for the first time since the opioid crisis came to the attention of America, the Sackler name is front and center in a lawsuit accusing the family and the company they own and run, Purdue Pharma, of helping to fuel the deadly opioid crisis that has killed thousands of Americans.

Congratulations to the Massachusetts Attorney General Maura Healey took the unusual step of naming the eight members of the Sackler family listed above as part of the conspiracy that profited from and cause the catastrophic opioid crisis that’s gripping the USA to this day.

The 80-page complaint (Complaint: “State of Massachusetts vs. Purdue Pharma and the Sackler Family” June13, 2018) that accuses Purdue Pharma of spinning a “web of illegal deceit” to boost profits.

While prosecutors in more than a dozen other states hit hard by the opioid epidemic have sued Purdue Pharma, Healey is the first to name individual Sackler family members, along with eight company executives.

(The Sackler family regularly notes that Arthur Sackler, whose philanthropy got his name on the Smithsonian’s Sackler Gallery in Washington and other cultural institutions, died before Purdue began selling OxyContin. Several of his nieces and nephews help run the company.)

Filed on behalf of 670 Massachusetts residents who were prescribed OxyContin, became addicted to opioids and later died, the suit alleges that Purdue deceived doctors and patients about the risks, pushed prescribers to keep patients on the drugs and aggressively targeted veterans and the elderly.

The civil suit doesn’t name a dollar figure, but Healey asked a judge to order the Sacklers and Purdue to “pay full and complete restitution to every person who has suffered any ascertainable loss by reason of their unlawful conduct.”

Mike Moore, the former Mississippi attorney general who took down Big Tobaccotwo decades ago and is now going after Big Pharma, called Healey’s move “a brilliant legal strategy.”

“It pulls up the corporate curtain of protection that these people hide behind,” Moore said in an email to NBC News. “The Sacklers personally made billions of dollars while tens of thousands of overdose deaths were occurring as a direct result of their lies about the addictiveness and effectiveness of OxyContin, the drug they created and marketed. Just as these folks like to be honored when they write big checks to museums and have their names inscribed on plaques for their contributions to so many causes, they should be held accountable for how they made that money in the first place.”

SACKLER FAMILY KNOWN FOR PHILANTHROPY

Juliet Sorensen, a former federal prosecutor in Chicago who is now a professor at Northwestern University’s Pritzker School of Law, said that the Sacklers are known for their philanthropy — “not for being the driving force behind the opioid epidemic through which they gained their billions.”

“The Sacklers’ collective silence signals a lack of remorse for their role in the opioid epidemic,” she said in an email. “The complaint is a form of exposure.”

“If the Sacklers were not actually defendants that were sued, but rather named and discussed in the body of the complaint, that would be naming and shaming but without legal consequences,” she said. “In this case, however, they are named as defendants, so the naming and shaming ‘pitiless publicity’ effect comes along with potential legal liability.”

The Sacklers named in the complaint are now used to defending thensleves individually and when asked to cooment, the standard Purdue reply was offered by Purdue Pharma spokesman Bob Josephson in an email not a personal quote, “Not at this time.”

Purdue Pharma denied the allegations in the lawsuit, saying it was “disappointed” that, amid negotiations with other states that have sued, Massachusetts “decided to pursue a costly and protracted litigation process.”

“We will continue to work collaboratively with the states towards bringing meaningful solutions,” the company said.

MASSACHUSETTS HOLDS SACKLERS LIABLE

Emalie Gainey, a spokeswoman for Healey, said the attorney general’s intent in naming the Sacklers was “to hold them individually liable for the role we allege they played.”

“Not only did we name the company today, but we’ve also chose to name executives and directors,” Healey said when the lawsuit was announced. “Ours is the first lawsuit in the country to name those executives personally and tell the story of how they contributed to this deadly crisis.”

Mississippi was the first state to sue Purdue Pharma and the other big pharmaceutical companies, and the state’s attorney general, Jim Hood, said he approved of the message Massachusetts is sending.

“No individual should be above the law and allowed to hide behind corporate protections to shield them from personal responsibility,” Hood said via a spokeswoman. “That includes the Sackler family. Mississippi applauds the efforts of Massachusetts in joining our efforts and seeking accountability wherever it lies.”

In Ohio, the second state to go after the drug companies, including Purdue Pharma, Dan Tierney, a spokesman for Attorney General Mike DeWine, said individual Sackler family members “would certainly be covered” by the state’s action.

The Sackler family is the 19th richest in the nation, with an estimated fortune of $13 billion, according to Forbes.

The Sacklers involved with Purdue Pharma are the descendants of brothers Mortimer and Raymond Sackler. Their eldest brother, Arthur, died in 1987, well before Purdue began making and selling OxyContin. Arthur also worked in pharmaceuticals and developed a reputation for cleverly marketing new drugs directly to doctors, convincing them to prescribe medications including tranquilizers to their patients.

Arthur was inducted into the Medical Advertising Hall of Fame after his death, but he has also been criticized for originating “most of the questionable practices that propelled the pharmaceutical industry into the scourge it is today,” as Allen Frances, the former chair of psychiatry at Duke University School of Medicine, told the New Yorker last year.

Arthur’s family has made a point of noting that he was not involved in the sale of OxyContin and would prefer him to be remembered for his philanthropy, including funding the Arthur M. Sackler Gallery of Chinese Stone Sculpture at The Metropolitan Museum in Manhattan and the Arthur M. Sackler Museum at Harvard University.

“None of the charitable donations made by Arthur prior to his death, nor that I made on his behalf after his death, were funded by the production, distribution or sale of OxyContin or other revenue from Purdue Pharma,” his widow, Jillian Sackler, said in a February statement. “Period.”

Seven of the Sacklers named in the suit have been on the Purdue board since the 1990s, according to the suit, while David Sackler, the grandson, has served since 2012.

The board met on a weekly — sometimes daily — basis while the company was being investigated by 26 states and the Justice Department from 2001 to 2007, according to the lawsuit. In 2007, the board settled and agreed to pay a $700 million fine after the company’s CEO at the time, Michael Friedman, and two other high-ranking company officials pleaded guilty to misleading doctors and patients about opioids.

KENTUCKY LEGAL FIGHT TO KEEP SACKLER TESTIMONY SEALED

In an example of the past coming back to haunt the present, in 2015 Purdue Pharma agreed to pay $24 million to settle a lawsuit filed by Kentucky, December 22, 2015 Purdue Pharma Settlement With State of Kentucky,  which Purdue thought would end that problem by paying a fine and moving on, which isn’t the case it seems. See Purdue Pharma settles with Kentucky over Oxycontin claim(statnews.com/pharmalot) for information on the claims in Kentucky.

That state court litigation is now subject to an ongoing legal battle in the Kentucky courts where Purdue is fighting to keep the original court records from that settlement sealed, due to the only deposition testimony of one of the Sackler brothers is known to be located. The Purdue court records were unsealed by Pike County Judge, Stephen Combs in May 2016 and Purdue immediately appealed with oral arguments taking place June 26, 2017 in front of a three judge panel of the Kentucky Court of Appeals, which as of June 20, 2018 has not issued a ruling on releasing the records. The original Kentucky vs. Purdue docket information is case no. 07-CI-01303, Judge Stephen Combs, Pike County Circuit Court of Kentucky.

OxyContin was hailed as a medical marvel when it debuted in 1995. Pitched as balm for people suffering from moderate to severe pain, it reportedly generated more than $35 billion in revenue for Purdue Pharma.

But its chief ingredient is oxycodone, a cousin of heroin. And prosecutors say Purdue played down the dangers of addiction while getting hundreds of thousands of Americans hooked on opioids.

Purdue has argued that OxyContin is approved by the Food and Drug Administration and accounts for just 2 percent of the opioid prescriptions nationwide.

There are now more than 600 lawsuits naming Purdue Pharma, LP as a defendant in both federal and state court actions, this does not include the potential criminal indictments of not only the company but the Purdue family members that may be emerging. Damages are expected to easily exceed $100 billion versus the company and now that the Sacklers and company executives have been named individually the whole scope of litigation may be changing for the better, as those who profited most from the opioid crisis are now being held accountable.

 

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New York And Other State Court Opioid Litigation Moves Forward Along With Federal Opiate Rx MDL 2804

“LAWSUIT FLOOD VERSUS ENTIRE OPIOID INDUSTRY IS GETTING BIG PHARMA’S ATTENTION”

By Mark A. York (June 11, 2018)

 

 

 

 

 

 

Opioid litigation in New York and other state courts, where hundreds of counties and cities have filed lawsuits against opioid manufacturers and distributors,  are now moving forward even with the explosion in the Federal Opiate Litigation MDL 2804 OPIOID-CRISIS-BRIEFCASE -MDL-2804-OPIATE-PRESCRIPTION-LITIGATION, where more than 500 states, counties, cities as well as unions, hospitals and individuals have filed lawsuits against the opioid industry as a whole.

At one point, the opiate industry attempted to raise arguments stating that the Food and Drug Administration hasn’t yet determined whether narcotic painkillers are unnecessarily dangerous – a central question in any litigation, which was quickly denied and seems to show that Opiate Big Pharma is once again attempting to hide behind the FDA shield.

In a two-page order issued in March by Judge Jerry Garguilo of the Suffolk County Supreme Court, New York where he ruled that there is “no compelling reason to impose a stay of proceedings” until the FDA completes its own review of the benefits and risks of opioids. The lawsuits by most of the counties in New York, which have been consolidated in Garguilo’s court, are “backward-looking” toward allegedly fraudulent marketing materials and tactics the drug companies used to convince doctors and patients their products had low risk of addiction.

In another state court, the first of many opioid litigation trials to be scheduled is now set in Oklahoma, where Cleveland County District Judge Thad Balkman set May 28, 2019 for the start of the trial. ate has been set for a lawsuit by a state against pharmaceutical companies over the opioid epidemic, according to Oklahoma‘s attorney general. See Original Complaint – State of Oklahoma vs. Purdue Pharma et al, June 30, 2017 (Cleveland County, OK District Court)

Oklahoma, one of at least 20 states besides New York that have opioid lawsuit dockets against drugmakers, alleges fraudulent marketing of drugs that fueled the opioid epidemic in the lawsuit filed in June 2017, and seeks unspecified damages from Purdue Pharma, Allergan, Janssen Pharmaceuticals, Teva Pharmaceuticals and several of their subsidiaries.

The New York state court lawsuits are joined by another somewhat unique group of plaintiffs in the legal battle over the opioid-epidemic with class actions filed by consumers who claim they’re seeing skyrocketing health insurance costs as a result of the crisis.

The suits, filed in New York and four other states, were brought by individual persons against opioid manufacturers and distributors, and are among the few class actions filed against drug makers and marketers. The vast majority of cases have been separate actions brought by government entities like cities and counties.

The plaintiffs in this new wave of cases have filed across the country in federal courts in  USDC SD New York (Complaint) , a New Jersey Complaint,  a Massachusetts Complaint, an Illinois Complaint as well as a California Complaint  where they’ve filed lawsuits on behalf of those who paid increased health insurance costs–including higher premiums, deductibles and co-payments–because of effects attributable to the opioid epidemic.

The proposed classes include businesses and individuals who paid for health insurance as part of employer-sponsored plans.

“We don’t know anyone who in the litigation is addressing the private sector harms to consumers and businesses from increased premiums and other insurance costs that flow to anyone in the health insurance market as a result of the fact that insurers are paying more for addictions,” said Travis Lenkner, one of the plaintiffs attorneys filing the cases.

The opioid cases add a new type of plaintiff into the wide-reaching opioid litigation, which have also includes states, Native American tribes, pension funds and hospitals.

John Parker, senior vice president of the Healthcare Distribution Alliance, speaking on behalf of distributors AmerisourceBergen Drug Corp., Cardinal Health Inc. and McKesson Corp., all named as defendants, called the opioid epidemic a “complex public health challenge.”

“Given our role, the idea that distributors are responsible for the number of opioid prescriptions written defies common sense and lacks understanding of how the pharmaceutical supply chain actually works and is regulated,” he said in a statement. “Those bringing lawsuits would be better served addressing the root causes, rather than trying to redirect blame through litigation.”

Purdue Pharma spokesman Bob Josephson noted that his company’s products account for less than 2 percent of all opioid prescriptions. Johnson & Johnson’s Janssen Pharmaceuticals defended the labels on its prescription opioids and called the allegations “baseless and unsubstantiated.”

Representatives of the other manufacturing defendants, which include Endo Health Solutions, Teva Pharmaceutical Industries and Insys Therapeutics Inc., did not respond to requests for comment.

It is now fairly common knowledge in the legal world that there is more than enough data that links increased health insurance costs to the opioid epidemic as well as the overall catastrophic impact of the flood of opioids into the America marketplace.

The suits cite statistics. In California, for instance, health insurance premiums for family coverage increased 233.5 percent from 2002 to 2016. Monthly premiums for the plaintiff in that case, Jordan Chu, jumped from $160.52 in 2016 to $240.76 this year. New Jersey residents with private health insurance spent $5,081 in insurance premiums in 2014, up from $2,454 in 2001. And an average family plan in New York with annual costs of $9,439 in 2003 had jumped to $19,375 in 2016.

Plaintiff counsel stated that they will be filing suits in more states and fight any attempts to transfer these cases to the Northern District of Ohio, where U.S. District Judge Dan Polster is overseeing the opioid multidistrict litigation, MDL 2804, even though the cases were filed in federal courts. A damaging discovery win for the plaintiffs was the order of May 18, 2018, see DEA ARCOS Database Access Order May 8, 2018 MDL 2804, where Judge Polster ordered the DEA to turn over distribution data for all 50 states based on the revelations in a prior DEA related order where the Opioid Drug distribution data provided very solid information on all the parties involved in creating the opioid crisis over the last 15 years.

The New York court docket parallels the federal and many other opioid based complaints, filed in state courts across the country where parties have decided to pursue their claims in their state courts versus the federal docket. These filings in both state and federal courts, will only increases the pressure on manufacturers and wholesalers to either win dismissal of these cases or prepare for an accelerated trial schedule.

There are currently more than 500 of the nation’s 3,200 counties have sued and plaintiff lawyers hope to soon get that number to 1,500, which some lawyers consider critical mass for a settlement.

The defendant companies argue they can’t be held liable for selling a legal product sold only with a doctor’s prescription whose distribution was controlled and overseen, from manufacturing to retail sales, by federal and state regulators.

The plaintiffs argue manufacturers used a variety of tactics, including misleading marketing materials and highly paid physician-influencers, to convince prescribing physicians their products were safe for treating chronic pain when, in fact, they were highly addictive.

In the March order, Judge Garguilo rejected the defendants’ claim that the FDA has exclusive authority to determine whether, in effect, opioids should be sold for anything other than relieving the pain of terminal illness. Regardless of what the FDA determines, the judge said, the municipal plaintiffs have the right to seek redress for their costs associated with addiction.

“Because the focus of this lawsuit is on the state of scientific knowledge that existed when the defendants made their marketing claims, there is no risk of inconsistent rulings, and none of the current studies will have any bearing on whether the defendants’ representations were misleading when made,” the judge wrote. The court isn’t being asked to decide the risks and benefits of opioids but whether the defendants misrepresented those risks and benefits, he added.

In case the defendants didn’t grasp the judge’s ultimate goal, the judge restated his “previously expressed desire” for a “prompt resolution of this matter.” The federal judge overseeing multidistrict litigation in Ohio, Judge Dan Aaron Polster, has similarly urged defendants to engage in settlement talks, although a global resolution of the litigation could prove difficult to negotiate.

In addition to hundreds of cases consolidated in federal court, the defendants face a wave of litigation in state court, like the New York cases, as well as lawsuits and investigations by 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 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.

For those looking to tap into the opioid litigation or learn what the current status is in both state and federal court opioid litigation, please visit www.opioidcrisissummit.com where Mass Tort Nexus is hosting national political leaders and lead opiate counsel who are active in the day to day opioid crisis and have the most up to date case information during the two day event taking place July 21-22, 2018 in Fort Lauderdale.

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