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XARELTO Media Monitoring 5/31
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Dirty Clinical Trials Omit Violations
Feb 12, 2015 | Med Page Today
By Sarah Wickline Wallan
When the FDA found violations of safety or quality standards at clinical trial sites, the published peer-reviewed reports on these studies rarely mentioned the problems, according to journalism professor Charles Seife, MS, of New York University. -
FDA's lack of transparency hurts dentists and their patients
Feb 19, 2015 | Dr Bicuspid.com
By Theresa Pablos
February 19, 2015 -- The dental community should be a little more wary of articles detailing clinical trials published in peer-reviewed journals, according to a new review of clinical trials in the Journal of the American Medical Association. The author of the paper discovered that the findings of clinical trials are sometimes published without any note of their scientific misconduct found by the Food and Drug Administration (FDA). -
PharmedOut 2015
Jun 21, 2015 | HealthNewsDigest.com
By Michael D. Shaw
(HealthNewsDigest.com) - PharmedOut is a Georgetown University Medical Center project that advances evidence-based prescribing, and educates healthcare professionals about pharmaceutical marketing practices. Founded in January, 2007, it is an Internet-based alternative for doctors seeking Continuing Medical Education (CME) courses, not sponsored by the pharmaceutical industry. -
Anticoagulant red flag raised: FDA reviewer about missing date for Eliquis
Aug 7, 2015 | Naples Daily News
By John Fauber And Coulter Jones
Of the four new anticoagulant drugs billed as alternatives to warfarin, Eliquis is the only one that can claim it reduces deaths in people with atrial fibrillation. -
Is the FDA Protecting Drug Companies Instead of Patients?
Feb 11, 2015 | New Inferno
The U.S. Food and Drug Administration (FDA) exists to protect public health, but oftentimes the agency appears to be protecting drug companies rather than patients, according to an article published in Slate. Charles Seife, a journalist and professor at New York University, says that the agency repeatedly hides evidence of fraud in medical trials. “For more than a decade, the FDA has shown a pattern of burying the details of misconduct. As a result, nobody ever finds out which data is bogus, which experiments are tainted, and which drugs might be on the market under false pretenses.” the article states. -
Thousands of Xarelto Lawsuits Filed Alleging Injury, Death
May 12, 2016 | LawyersandSettlments.com
By Heidi Turner
New Orleans, LA--Thousands of Xarelto lawsuits have been filed against the makers of the blood thinner, alleging patients suffered serious injuries or even death as a result of taking the anticoagulant. Among the alleged Xarelto side effects are an increased risk of uncontrolled bleeding, which can turn into a fatal bleeding event. In addition to Xarelto, the makers of other blood thinners also face allegations of failure to adequately warn about the risks associated with their drugs.
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Dirty Clinical Trials Omit Violations
Feb 12, 2015 | Med Page Today
By Sarah Wickline Wallan
When the FDA found violations of safety or quality standards at clinical trial sites, the published peer-reviewed reports on these studies rarely mentioned the problems, according to journalism professorCharles Seife, MS, of New York University.
Seife, with the help of NYU graduate students, found 57 trials in which the FDA had cited trial investigators for serious, life-threatening incidents and data falsification, but only three of the 78 subsequent published reports on these trials acknowledged the issues, according to Seife's report in JAMA Internal Medicine.
"Given the FDA's mission to protect research subjects and the public health, it should be made possible to link the agency's inspection documents to specific trials and publications," Robert Steinbrook, MD, of Yale School of Medicine, and a consultant to the FDA's Drug Safety and Risk Management Advisory Committee, and JAMA Internal Medicine editor Rita F. Redberg, MD, wrote in an accompanying editorial.
The FDA inspects sites and records of clinical trials testing medications. During inspections, investigators check adherence to trial protocols and look for discrepancies between the researchers' progress notes and the data reported to the study sponsor. One of three grades are then issued: no action indicated; voluntary action indicated, which suggests minor problems; and official action indicated (OAI), denoting a severity warranting regulatory attention.
Without a publicly-accessible central database from which to search FDA inspection records, Seife had to file Freedom of Information Act requests. This yielded 20 OAI-rated inspections.
A creative key-word Google search yielded another 21. But the best source of OAI-related inspections came from documentation of FDA regulatory actions. "Such actions occur only when the failure to adhere to research regulations is considered particularly grave," Seife wrote.
Seife found 421 OAI-rated inspections from 1998 to 2013. Due to heavy redaction, his team was unable to tie most of the OAI grading to clinical trials and peer-reviewed published literature. Reliable and intelligible data could only be found for 57 clinical trials where inspectors found significant departures from good clinical practice, such as under-reporting of adverse events, violations of protocol, and scientific misconduct.
Among those OAIs, 39% involved falsification of data, 25% problems with adverse event reporting, 74% protocol violations, 61% poor record keeping, 53% failure to protect the safety, rights, and welfare of patients, and 35% uncategorized violations.
These uncategorized violations included delegating tasks to unauthorized personnel, poor supervision of clinical investigations, and the use of experimental compounds on patients not enrolled in the trial.
Those 57 trials were referenced in 78 articles published in peer-reviewed literature. Only three of the publications referenced the FDA inspection violations, even though 76% had been notified of the violations at least 6 months prior to publication.
Seife highlighted four of the most egregious examples:
-In a stem-cell trial with 26 patients with ischemic limbs, one patient had a foot amputated after stem-cell administration. This information never made it into the publication.-Out of 16 trial sites for the anticoagulant rivaroxaban (Xarelto), eight were issued OAIs for the "systemic discarding of medical records," unauthorized unblinding, falsification, or "concerns regarding improprieties in randomization." The FDA regarded the study, RECORD-4, as unreliable. However, none of these problems were mentioned in any of the publications addressing the trial.
-n a chemotherapy trial comparing two regimens, a researcher falsified test results to hide a patient's existing kidney and liver dysfunction, which led to the patient's death after a single dose. That researcher spent 71 months in prison for criminally negligent homicide. Additionally, the same researcher falsified data in three other studies, and journals publishing two of the subsequent reports omitted mention of the violations.
-Clinical trial sites in China, 24 in total, were reported as problematic. One in particular manipulated data in a trial of the anticoagulant apixaban (Eliquis) to show mortality benefit.
A statement from Janssen, makers of rivaroxaban, said the RECORD sites were audited and the data were re-analyzed, and the safety and efficacy conclusions remained the same as in the published manuscript.
“We continuously track the medicine’s safety performance and after more than 3 years on the U.S. market, to date, the benefit-risk profile of Xarelto remains favorable and consistent with studies completed in more than 85,000 patients,” the statement said.
A recent investigation by The BMJ found Boehringer Ingelheim, maker of the anticoagulant dabigatran (Pradaxa), had suppressed trial evidence on the dose adjustment and blood level monitoring to reduce major bleeding risk by as much as 20%.
Following that publication, BI issued a statement explaining that it had “provided regulators with the complete data set and analyses of clinical evidence demonstrating Pradaxa’s benefits and safety, and FDA and EMA [European Medicines Agency] have affirmed RE-LY’s conclusions and state that Pradaxa provides an important health benefit when used as directed.”
"The findings presented in this study should give us pause," Seife concluded. He recommended that the FDA notify Clinicaltrials.gov when an OAI is issued, with which Steinbrook and Redberg concurred.
"There is far too much critical information found by the FDA that is not linked back to the medical literature," Harlan Krumholz, MD, of Yale School of Medicine, told MedPage Todayin an email. "The outcomes and safety events presented to the FDA can differ from published articles and there is no reconciliation -- and yet the literature is the basis of reviews, chapters, guidelines -- and general information for the public."
He added, "Journal editors and the FDA must come together to find ways to determine the truth and disseminate it."
Seife reported several limitations in his study. For one, the data were descriptive, not quantitative. Also, the search strategy was limited by the heavy redaction and lack of public access.
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FDA's lack of transparency hurts dentists and their patients
Feb 19, 2015 | Dr Bicuspid.com
By Theresa Pablos
February 19, 2015 -- The dental community should be a little more wary of articles detailing clinical trials published in peer-reviewed journals, according to a new review of clinical trials in the Journal of the American Medical Association. The author of the paper discovered that the findings of clinical trials are sometimes published without any note of their scientific misconduct found by the Food and Drug Administration (FDA).
Author Charles Seife, a professor of journalism at New York University, and his investigative reporting class evaluated clinical trials with significantly objectionable conditions or practices, such as falsifying information or not reporting severe adverse effects, that were published in peer-reviewed journals. They found that about 96% of the tainted clinical trial articles, including ones for medications prescribed by the dental community, did not mention any sort of scientific misconduct.
"Such allegations [of serious research misconduct] are relevant to include in the peer-reviewed literature on which physicians and other medical researchers rely to help them choose treatments that they offer to patients and other participants," Seife noted in the paper (JAMA, February 9, 2015). "To better serve the public health, the FDA should make unredacted information about its findings of research misconduct more readily available."
Using documents accessible through the FDA's website and from Freedom of Information Act requests, Seife and his class looked for clinical trial sites that were issued an Official Action Indicated (OAI) rating from FDA investigations. The FDA gives clinical trial sites an OAI rating only when they find "objectionable conditions or practices significant enough to warrant regulatory action."
Through their research, Seife and his students identified 421 OAI-rated inspections between January 1998 and December 2013. However, only 101 trials could be identified from those because of the amount of text the FDA redacted to protect sensitive corporate information.
About one-third of clinical trials with OAI-rated inspections remained unpublished, while the rest were published in peer-reviewed journals. The researchers were able to identify 78 published clinical trial articles where the authors did not mention the FDA inspection violations, such as falsification of information and failure to protect patient safety.
While the FDA usually excludes data from studies with OAI-rated inspections when judging a drug's safety, it does not make that information readily available to the scientific community. Consequently, papers about clinical trials that have been labeled as unreliable by the FDA can get published as fact in peer-reviewed literature, as was the case with rivaroxaban (brand name Xarelto, Bayer HealthCare), an anticoagulant drug.
Unreliable rivaroxaban studies highlight serious problem
Rivaroxaban and other anticoagulants have been warranted as safe to use fornonextensive dental surgery by the University of California, Davis Health System.
When rivaroxaban was first set to enter the U.S.market, the FDA audited 16 sites that were involved with a Bayer-sponsored clinical trial of the drug called RECORD 4. Half of investigated sites resulted in OAI ratings because of grievances such as falsification of information, failure to protect patient safety, and improper record keeping.
The FDA ultimately ruled RECORD 4 completely unreliable. David Craig Loucks, MD, a key researcher at a Colorado location, was cited in 2009 for a number of egregious errors, including destroying documents, falsifying his signature, lack of proper oversight, not ensuring proper subject safety, and not mentioning 12 severe adverse effects in a timely manner for the 24-person study.
The FDA also audited a sister rivaroxaban clinical study, called RECORD 2, that proved almost as unreliable as RECORD 4. The FDA found evidence of misconduct in 4 of the 10 sites, according to Seife in a Slate article. Like RECORD 4, RECORD 2 was part of a Bayer-sponsored clinical trial of its drug.
At least four papers citing the pharmaceutical-sponsored clinical studies were published in peer-reviewed journals anyway. All four of the published papers touted the findings of the discredited studies, concluding that rivavoxaban was superior to the anticoagulant enoxaparin (New England Journal of Medicine, June 26, 2008, Vol. 358:26, pp. 2765-2775 and 2776-2786; Lancet, July 5, 2008, Vol. 372:9632, pp. 31-39, and May 16, 2009, Vol. 373:9676, pp. 1673-1680).
Perhaps unsurprisingly, the authors of all four papers were connected to Bayer, according to an analysis of the clinical studies presented at 2008 American Society of Hematology annual meeting and published in the journal Blood. Most notably, Alexander G.G. Turpie, MD, the lead author of the paper on RECORD 4, and Ajay Kakkar, MBBS, PhD, the lead author of a paper published on RECORD 2, sit on the Global Anticoagulant Registry in the Field (GARFIELD-AF) Steering Committee for the GARFIELD Registry, which is funded by an unrestricted research grant from Bayer. However, it is not known for certain if either of the papers' authors knew of the OAI-rated inspections before writing the articles.
Most concerning, wrongful death lawsuits are now being pursed against Bayer, the drug's manufacturer, and Janssen Pharmaceuticals, a Johnson & Johnson company that markets Xarelto. Rivaroxaban can cause uncontrolled bleeding from even small cuts, prompting questions of its safety for even minor dental work, according to some law websites.
Questionable IV ibuprofen study may impact future research
An FDA inspection of a site of a Cumberland Pharmaceuticals-sponsored clinical study also yielded an OAI rating. The trial looked at how well Cumberland's Caldolor intravenous ibuprofen drug reduced patient's morphine use and postoperative pain after abdominal and orthopedic surgery.
The FDA's warning letter cited the study location researchers for discrepancy in the reporting of how much morphine the patients were actually given, breaking the double-blind study through a record revealing that two patients were receiving ibuprofen and not the placebo, and not reporting that one patient was vomiting for 48 hours and required an IV.
Two papers citing the efficacy of Caldolor were published in peer-reviewed journals based on the questionable findings (Clinical Therapeutics, September 2009, Vol. 31:9, pp. 1922-1935; Pain Practice, January-February 2011, Vol. 11:1, pp. 23-32). Amy Rock, the current senior director for regulatory affairs for Cumberland Pharmaceuticals (then a senior manager), was the responsible party for the clinical trial and a co-author on both published papers. Additionally, either a lead or co-author from each publication presented their papers for Cumberland at the 2009 American Academy of Pain Management annual clinical meeting.
The promising results of this study prompted another researcher at Tufts University School of Dental Medicine to see if intravenous ibuprofen can pre-emptively prevent postoperative pain after third-molar extraction. The clinical trial, which cites one of the published papers in its description, is currently recruiting participants.
Archana Viswanath, BDS, the lead researcher of the new clinical study, could not be reached for comment by press time on whether the validity of the first clinical trial would affect her study.
Beginning to solve the problem
It is clear that when studies without good clinical practice get published as fact the entire medical community, from researchers to doctors to patients, gets hurt.
"The FDA has legal as well as ethical responsibilities regarding the scientific misconduct it finds during its inspections," Seife concluded. "Failing to notify the medical or scientific communities about allegations of serious research misconduct in clinical trials is incompatible with the FDA's mission to protect public health."
While the JAMA article was revealing, the author did admit the research was biased. Documents from certain regions of the country and time periods were easier to locate online, Seife noted. The documents the researchers found were also so redacted that they could only analyze a percentage of them. The shortcomings prevent researchers from making generalizations of their findings that apply to all clinical trials, he added.
The shortcomings, however, do not detract from the need for more transparency of clinical trials. Seife recommends that the FDA should notify journals when a site participating in a published clinical trial receives an OAI inspection. Furthermore, he recommends the agency publish more OAI-rated investigations online and to do so without the heavy redactions.
Seife's final recommendation is for peer-reviewed journals to require article authors to disclose any adverse findings during FDA inspections. While this may not solve the problem entirely, it may help the medical community to read the published material with a more critical eye.
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Jun 21, 2015 | HealthNewsDigest.com
By Michael D. Shaw
(HealthNewsDigest.com) - PharmedOut is a Georgetown University Medical Center project that advances evidence-based prescribing, and educates healthcare professionals about pharmaceutical marketing practices. Founded in January, 2007, it is an Internet-based alternative for doctors seeking Continuing Medical Education (CME) courses, not sponsored by the pharmaceutical industry.
Inasmuch as the industry derives its greatest profits from new proprietary drugs, it has a built-in tendency to tout them, even though newer is not always better. One example, cited at the time of PharmedOut's founding, came from Georgetown Ob-Gyn doctor Anthony Scialli: "Take oral contraceptives. Over the years they have increased in number, but there haven't really been any major advances since the 1970s. The newer ones are more expensive. Why do doctors prescribe them? Because of promotion and educational activities funded by the manufacturers."
Starting in 2010, PharmedOut has organized annual conferences. The theme of this year's conference (June 11-12) was "The Real Risks of Rx Drugs." Over the two days, there were 16 presentations. Let's take a look at three of them...
The endangered normal: Does anyone escape a diagnosis?----given by Georgetown's Dr. Adriane Fugh-Berman, a founder of PharmedOut. As she puts it, "the medicalization of daily life has become endemic." Whether it is a shy kid with "social anxiety disorder"; a young woman who is less horny than her partner with "hypoactive sexual desire disorder"; or someone who urinates more than four times per day with "overactive bladder syndrome," people with these common--and likely harmless--conditions create a potentially huge, if unjustified market.
Given TV drug advertising, patients are probably more susceptible to this sort of fearmongering, but doctors are not immune. To be sure, Big Pharma uses financial and non-financial inducements to influence those who prescribe. In an earlier article, Fugh-Berman noted that "Physicians fail to recognize their vulnerability to commercial influences due to self-serving bias, rationalization, and cognitive dissonance." She added that "Professionalism offers little protection; even the most conscious and genuine commitment to ethical behavior cannot eliminate unintentional, subconscious bias."
Researchers behaving badly: Misconduct in clinical trials ----given by Charles Seife, journalism professor at NYU, with a math background. In exposing wrongdoing at the FDA, Seife engaged his investigative reporting class to discover shocking examples of FDA burying evidence of research misconduct. Even though the form 483s (Establishment Inspection Reports) can be heavily redacted, if one takes the time to cross reference these with clinical trial data, it is possible in certain cases to pierce the veil of secrecy. And, pierce it they did.
Among other examples, they discuss the appalling case of "RECORD 4" (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thromboembolism and Pulmonary Embolism). In this study, the new drug rivaroxaban (Xarelto) was being compared to the non-proprietary enoxaparin. At half of the sites that drew FDA scrutiny there was misconduct, fraud, fishy behavior, or other practices so objectionable that the data had to be thrown out.
Too bad that the official report, published in The Lancet, proclaiming the superiority of rivaroxaban, makes no mention of these issues. As the lawsuits against Xarelto are counted up, the FDA may change its tune, but don't hold your breath.
Hyperglycemia, sedentary obesity, and complications of type 2 diabetes----given by Thomas Finucane, MD of Johns Hopkins. It would be safe to say that Finucane is unconvinced regarding the merits of tight glycemic control. The final sentence of the abstract for his presentation makes that pretty clear: "The massive enterprise of setting and using drugs to achieve glycemic targets is unsupported by data, biologically implausible, and massively profitable to several interests."
Finucane covered much of this ground in his August, 2012 paper, published in Journal of the American Geriatrics Society, with the legendary title "Tight Control in Geriatrics: The Emperor Wears a Thong." He goes after the diabetes industry, which ceaselessly proclaims the benefits of aggressive glycemic control--especially in light of the ad agency developed Aim-Achieve-Believe: Diabetes A1c Initiative, launched on World Diabetes Day, 2002.
Finucane comes close to joining the Type 2 Deniers Club (current members include Ernest Curtis, MD and yours truly) by shredding several highly touted studies which proclaim the gospel of glycemic control. Even better, he publicizes a relatively obscure metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. One of the findings was that the risk of a cardiovascular event rose exponentially starting at a fasting blood sugar of 75 mg/dL. Apparently, virtually all of us are doomed!
In the 2012 paper, Finucane states: "The timidity of performance-measurement initiatives, disease-focused charities, professional societies, and academics in confronting the discrepancy between the data and the public relations enterprise is a matter for serious consideration."
But does the paper's sardonic title betray his reluctance to unequivocally condemn the type 2 memes? Indeed, why does the emperor even wear a thong, and is not simply naked?
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Anticoagulant red flag raised: FDA reviewer about missing date for Eliquis
Aug 7, 2015 | Naples Daily News
By John Fauber And Coulter Jones
Of the four new anticoagulant drugs billed as alternatives to warfarin, Eliquis is the only one that can claim it reduces deaths in people with atrial fibrillation.
But is that claim real?
An FDA reviewer doesn’t think so.
In the clinical trial of Eliquis, patients getting the drug were 11 percent less likely to die from any cause than those getting warfarin, which for decades had been the only anticoagulant used to prevent strokes in people with atrial fibrillation.
But because vital data — primarily involving deaths — was missing from the trial, FDA reviewer Thomas Marciniak concluded that if there was one more death among Eliquis patients or one less warfarin death, the benefit would no longer be considered statistically significant.
In a December 2012 memo, Marciniak noted there were more than 300 Eliquis patients with missing data.
“I, like most FDA reviewers, would like to conclude that apixaban (Eliquis) is effective in atrial fibrillation — we would like to have alternatives to warfarin,” Marciniak wrote.
But the data problems “destroy our confidence” that the drug reduces deaths, he concluded.
Marciniak’s review also said the Eliquis trial was just one of many other trials — he did not name the others — that had substantial problems with data quality.
“Some of the responsibility for the data quality problems rests with us, the FDA: We have approved drugs ignoring similar data quality issues, granting superiority claims and not discussing in the labels the data quality issues,” he wrote. “We must stop doing this.”
Marciniak called for the data problems to be described at length on the drug’s label, but he was overruled by others at the FDA.
In a response memo, two other FDA officials discounted Marciniak’s comments and wrote they were “somewhat unrealistic.”
They said the missing data was not “especially large,” and it was unclear if the “missingness” favored Eliquis, actually making the death benefit more significant.
“Perhaps some (patient data) were lost to follow-up because they had a stroke or died, which potentially biases the study results,” they wrote. “However, there is no reason to believe that this was more likely in the apixaban (Eliquis) arm than in the warfarin arm. We cannot directly address whether the missing data are biased in one direction.”
In addition, they said drug companies should not have to provide a “cushion” when it comes to establishing statistical significance.
In an email, representatives of Pfizer and Bristol-Myers Squibb, which co-market the drug, said data compiled in its trial came from more than 1,000 sites in 40 countries.
The data was “thorough and complete, despite inherent challenges with following such a large and diverse population,” they said. “As the FDA ultimately decided, the small fraction of patients lost to follow-up did not adversely alter the interpretation of superior results vs. warfarin.”
However, F. Perry Wilson, an expert in clinical trial design and an assistant professor of medicine at Yale University Medical School, said Marciniak makes a valid point.
“I would tend to agree that touting this as a potential (mortality) benefit of the drug is likely very premature,” said Wilson, who reviewed the FDA documents for this story.
John Fauber is a reporter with the Journal Sentinel. Coulter Jones is a reporter with MedPage Today. This story was reported as a joint project of the Journal Sentinel and MedPage Today, which provides a clinical perspective for physicians on breaking medical news at medpagetoday.com.
TIMELINE: THE HISTORY OF WARFARIN
From its origins as a rat poison to its rise as the most common treatment for preventing strokes caused by atrial fibrillation, here is a look at the history behind the drug warfarin.
Moldy hay leads to medical discovery
1933: With cattle bleeding to death in Wisconsin and elsewhere, farmer Ed Carlson, of Deer Park, shows up at the University of Wisconsin agriculture lab with samples of moldy hay and a container of uncoagulated cow blood. From the rancid hay, UW biochemist Karl Paul Link eventually isolates a chemical anticoagulant known as dicumarol.
Warfarin marketed as rat poison
1948: UW patents Link’s research as warfarin — a name inspired by the Wisconsin Alumni Research Foundation. It is marketed, not as medicine, but as a commercial rat poison. If rodents ate it, they bled to death.
Breakthrough leads to medical use
1954: A warfarin-related agent is approved as a medicine to prevent blood clots. The compound, coumarin, is the basis for Coumadin, which becomes the most widely prescribed blood thinner in the world. Warfarin has a readily available antidote — in cases of severe bleeding, its effect can be reversed by administering intravenous vitamin K.
Eisenhower is a famous early patient
1955: President Dwight Eisenhower suffers a heart attack and is given Coumadin to help him recover.
Patent expires, ending royalties
1982: The University of Wisconsin’s patent on warfarin expires, ending the royalties it collects on sales of the drug. All told, the university collected $120 million — in today’s dollars — from the drug.
A new use for the drug
1989 to 1995: Six clinical trials show that warfarin — now a generic — is effective at preventing strokes in people with atrial fibrillation, prompting new widespread usage of the drug. An estimated 3-5 million Americans have the condition, according to a recent estimate.
Book makes Stalin, warfarin-poisoning link
2003: A book claims Soviet leader Joseph Stalin, who died of a brain hemorrhage in 1953, may have been poisoned with warfarin. The book, “Stalin’s Last Crime,” speculates that Stalin, who also suffered extensive stomach bleeding, was killed by a member of the Politburo to prevent a war with the United States. The theory has never been proven.
Warfarin continues to lead in sales
2014: With more than 31 million prescriptions, warfarin remains the most prescribed anticoagulant in the United States. However, it now competes with four new drugs that have won approval from the U.S. Food and Drug Administration since 2010. Each boasts it is more convenient, but none have an antidote for cases of dangerous bleeding.
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Is the FDA Protecting Drug Companies Instead of Patients?
Feb 11, 2015 | New Inferno
The U.S. Food and Drug Administration (FDA) exists to protect public health, but oftentimes the agency appears to be protecting drug companies rather than patients, according to an article published in Slate. Charles Seife, a journalist and professor at New York University, says that the agency repeatedly hides evidence of fraud in medical trials. “For more than a decade, the FDA has shown a pattern of burying the details of misconduct. As a result, nobody ever finds out which data is bogus, which experiments are tainted, and which drugs might be on the market under false pretenses.” the article states.
Seife points out that in documents related to an FDA inspection, critical parts are redacted. The reader is left not knowing what drug was studied, the number of the study and how the data was affected by misconduct. Seife and his students analyzed documents related to 600 clinical trials where there was a failed FDA inspection. He reports that they were only able to find the study, the drug and the identity of the pharmaceutical company in about 100 cases.
This type of omission affects both consumers as well as researchers and physicians. According to the Slate article, the FDA is aware of dozens of studies with questionable data but has not taken any action. This was the case with the RECORD 4 study, which was one of four large clinical trials used as evidence for the safety and efficacy of the anti-clotting drug Xarelto (rivaroxaban). RECORD 4 involved thousands of patients and clinical sites in more than a dozen countries around the world. The FDA inspected or had access to external audits of 16 sites, the article says. Seife calls the trial “a fiasco” and says the agency found falsified data at Dr. Craig Loucks’ site in Colorado and “systematic discarding of medical records” at Dr. Ricardo Esquivel’s site in Mexico. The agency found misconduct, fraud, suspicious behavior and other practices that were so questionable the data had to be discarded in half of the sites. “The problems were so bad and so widespread that, contrary to its usual practice, the FDA declared the entire study to be ‘unreliable.’” Seife says.
Xarelto has become the subject of safety concerns and lawsuits alleging that the drug caused uncontrollable bleeding. Plaintiffs allege that the drug was marketed as being superior to warfarin, an older drug that requires blood monitoring. Xarelto has raised safety concerns because unlike warfarin, there is no antidote to reverse bleeding if it occurs.
The article goes on to say that despite knowing this, data from RECORD 4 continues to remain in The Lancet without any indication about falsification or wrongdoings. “This means that physicians around the world are basing life-and-death medical decisions on a study that the FDA knows is simply not credible.” says Seife. According to this article, this type of behavior is not simply miscommunication or oversight. Apparently, the agency even resisted attempts by Congress to obtain more information.
“Every excuse under the sun has been used to create roadblocks,” said Sen. Charles Grassley in relation to problems with clinical trials of the antibiotic Ketek. “even in the face of congressional subpoenas requesting information and access to FDA employees.”
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Thousands of Xarelto Lawsuits Filed Alleging Injury, Death
May 12, 2016 | LawyersandSettlments.com
By Heidi Turner
New Orleans, LA--Thousands of Xarelto lawsuits have been filed against the makers of the blood thinner, alleging patients suffered serious injuries or even death as a result of taking the anticoagulant. Among the alleged Xarelto side effects are an increased risk of uncontrolled bleeding, which can turn into a fatal bleeding event. In addition to Xarelto, the makers of other blood thinners also face allegations of failure to adequately warn about the risks associated with their drugs.
According to court documents, one such lawsuit was filed in February by a woman who alleges she suffered serious side effects from using Xarelto. The plaintiff, Margaret Garvy, argues she only used Xarelto from May 8, 2014 to May 18, 2014 - 10 days. On May 18, she allegedly suffered hemorrhagic pericardial effusion, pericardial tamponade and plural effusion, requiring hospitalization and medical treatment and resulting in permanent injuries.
The lawsuit alleges patients were not adequately warned about the risks associated with Xarelto, but Garvy’s lawsuit further alleges the trials on which Xarelto was approved - the RECORD studies - were “flawed in design and conducted in a negligent manner.”
“In fact, FDA Official Action Indicated (‘OAI’) - rated inspections in 2009 disclosed rampant violations including, ‘systemic discarding of medical records,’ unauthorized unblinding, falsification, and ‘concerns regarding improprieties in randomization,’” the lawsuit claims. “As a result, the FDA found that the RECORD 4 studies were so flawed that they were deemed unreliable.”
Despite concerns about the RECORD trial, Xarelto was approved for use, partially based on a trial known as the ROCKET AF trial. That trial showed Xarelto was at least as good as warfarin in preventing stroke or systemic embolism in patients with non-valvular atrial fibrillation, according to the lawsuit. But Garvy alleges the study participants who received warfarin were not well managed, and as a result, Xarelto appeared to be non-inferior to warfarin, when the two groups could not have been adequately compared.
“The warfarin group in the ROCKET AF study was the worst managed warfarin study group in any previously reported clinical trial involving warfarin,” Garvy’s lawsuit alleges.
Of concern is that Xarelto was reportedly marketed as not requiring blood monitoring - which ensures patient’s blood plasma levels stay within certain guidelines - but critics and some patients say Xarelto is still safer if patients receive regular monitoring and dose adjustments.
As of April 15, 2015, there were 4,579 lawsuits consolidated for pretrial proceedings in MDL 2592 before US District Judge Eldon E. Fallon.
The Garvy lawsuit is Garvy v. Janssen Research & Development, et al., Case number 2:16-cv-01359, US District Court, Eastern District of Louisiana.
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