Joint replacements are the #1 expenditure of Medicare. The process of approving these medical devices is flawed according to the Institute of Medicine. It is time for patients' voices to be heard as stakeholders and for public support for increased medical device industry accountability and heightened protections for patients. Post-market registry. Product warranty. Patient/consumer stakeholder equity. Rescind industry pre-emptions/entitlements. All clinical trials must report all data.
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Twitter: @JjrkCh

Wednesday, September 23, 2015

FDA Scientists Gone Wild: Fraud in Advisory Panels and Clinical Trials?

Are Your Medications Safe?

The FDA buries evidence of fraud in medical trials. My students and I dug it up.
By Charles Seife  February 9, 2015
Agents of the Food and Drug Administration know better than anyone else just how bad scientific misbehavior can get. Reading the FDA’s inspection files feels almost like watching a highlights reel from a Scientists Gone Wild video. It’s a seemingly endless stream of lurid vignettes—each of which catches a medical researcher in an unguarded moment, succumbing to the temptation to do things he knows he really shouldn’t be doing. Faked X-ray reports. Forged retinal scans. Phony lab tests. Secretly amputated limbs. All done in the name of science when researchers thought that nobody was watching.
That misconduct happens isn’t shocking. What is: When the FDA finds scientific fraud or misconduct, the agency doesn’t notify the public, the medical establishment, or even the scientific community that the results of a medical experiment are not to be trusted. On the contrary. 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 FDA has repeatedly hidden evidence of scientific fraud not just from the public, but also from its most trusted scientific advisers, even as they were deciding whether or not a new drug should be allowed on the market. Even a congressional panel investigating a case of fraud regarding a dangerous drug couldn't get forthright answers. For an agency devoted to protecting the public from bogus medical science, the FDA seems to be spending an awful lot of effort protecting the perpetrators of bogus science from the public.
Much of my research has to do with follies, foibles, and fraud in science, and I knew that the FDA wasn’t exactly bending over backward to correct the scientific record when its inspectors found problems during clinical trials. So as part of my investigative reporting class at New York University, my students and I set out to find out just how bad the problem was—and how much important information the FDA was keeping under wraps.
The silence is unbroken even when the FDA itself seems shocked at the degree of fraud and misconduct.
We didn’t have to search very hard to find FDA burying evidence of research misconduct. Just look at any document related to an FDA inspection. As part of the new drug application process, or, more rarely, when the agency gets a tipoff of wrongdoing, the FDA sends a bunch of inspectors out to clinical sites to make sure that everything is done by the book. When there are problems, the FDA generates a lot of paperwork—what are called form 483s, Establishment Inspection Reports, and in the worst cases, what are known as Warning Letters. If you manage to get your hands on these documents, you’ll see that, most of the time, key portions are redacted: information that describes what drug the researcher was studying, the name of the study, and precisely how the misconduct affected the quality of the data are all blacked out. These redactions make it all but impossible to figure out which study is tainted. My students and I looked at FDA documents relating to roughly 600 clinical trials in which one of the researchers running the trial failed an FDA inspection. In only roughly 100 cases were we able to figure out which study, which drug, and which pharmaceutical company were involved. (We cracked a bunch of the redactions by cross-referencing the documents with clinical trials data, checking various other databases, and using carefully crafted Google searches.) For the other 500, the FDA was successfully able to shield the drugmaker (and the study sponsor) from public exposure.
It’s not just the public that’s in the dark. It’s researchers, too. And your doctor. As I describe in the current issue of JAMA Internal Medicine, my students and I were able to track down some 78 scientific publications resulting from a tainted study—a clinical trial in which FDA inspectors found significant problems with the conduct of the trial, up to and including fraud. In only three cases did we find any hint in the peer-reviewed literature of problems found by the FDA inspection. The other publications were not retracted, corrected, or highlighted in any way. In other words, the FDA knows about dozens of scientific papers floating about whose data are questionable—and has said nothing, leaving physicians and medical researchers completely unaware. The silence is unbroken even when the FDA itself seems shocked at the degree of fraud and misconduct in a clinical trial.
Such was the case with the so-called RECORD 4 study. RECORD 4 was one of four large clinical trials that involved thousands of patients who were recruited at scores of clinical sites in more than a dozen countries around the world. The trial was used as evidence that a new anti-blood-clotting agent, rivaroxaban, was safe and effective. The FDA inspected or had access to external audits of 16 of the RECORD 4 sites. The trial was a fiasco. At Dr. Craig Loucks’ site in Colorado, the FDA found falsified data. At Dr. Ricardo Esquivel’s site in Mexico, there was “systematic discarding of medical records” that made it impossible to tell whether the study drug was given to the patients. At half of the sites that drew FDA scrutiny—eight out of 16—there was misconduct, fraud, fishy behavior, or other practices so objectionable that the data had to be thrown out. The problems were so bad and so widespread that, contrary to its usual practice, the FDA declared the entire study to be “unreliable.” Yet if you look in the medical journals, the results from RECORD 4 sit quietly in The Lancet without any hint in the literature about falsification, misconduct, or chaos behind the scenes. 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.
It’s not just one study, either. The FDA found major problems with sites involved in the other three clinical trials that were used to demonstrate rivaroxaban’s safety and effectiveness. RECORD 2, for example, was nearly as awful as RECORD 4: Four out of 10 sites that the FDA inspected showed evidence of misconduct, or other issues grave enough to render the site’s data worthless—including clear evidence of data falsification at one site. In aggregate, these problems raise serious doubts about the quality of all four key rivaroxaban studies—and, by extension, doubts about how seriously we should take the claim that rivaroxaban is safe and effective. The FDA is keeping mum, even as wrongful-death lawsuits begin to multiply.

The FDA’s failure to notify the public is not merely a sin of omission. In March 2009, the FDA convened a committee of outside scientific experts to mull the “robustness and meaningfulness” of the results from the four rivaroxaban trials, RECORDs 1, 2, 3, and 4. (The agency regularly calls in advisers to get advice, or, more cynically, to get cover, about a decision the agency has to make.) When the agency briefed the committee, it was (to put it mildly) coy about the problems it was finding. It said only that inspectors had found “significant issues” at two clinical sites involved in the RECORD 4 study—and that data from one of them was included in the analysis. Inspections were still ongoing, so it’s not easy to say precisely what the agency knew at that point, but it’s clear that the FDA wasn’t admitting to everything it knew. A bunch of inspections had been completed a month prior to the meeting, and we know for certain that the agency was fully aware of major issues beyond the two it revealed to the advisory committee. In a memo dated three days before the advisory committee meeting convened, the FDA detailed “falsification of data by a subinvestigator” at a RECORD 2 site. The advisory committee was not told.
By itself, this might seem like a miscommunication or an oversight, but the FDA has a history of not notifying the public about the misconduct it finds. About a decade ago, the agency got into trouble over a newly approved antibiotic, Ketek. Inspectors had found extensive problems (including fraud) affecting key clinical trials of the drug. Yet the agency did its best to hide the problems from even its most trusted advisers. As David Ross, the FDA official in charge of reviewing Ketek’s safety, put it, “In January 2003, over reviewers’ protests, FDA managers hid the evidence of fraud and misconduct from the advisory committee, which was fooled into voting for approval.” However, when the reports of misconduct at one clinical site began appearing in the press—along with stories of liver damage and blurred vision associated with the new drug—Congress stepped in, demanding information from the agency about the fraud.
But even the Senate couldn’t wring key information about the misconduct out of the FDA. “Every excuse under the sun has been used to create roadblocks,” complained an indignant Sen. Charles Grassley, “even in the face of congressional subpoenas requesting information and access to FDA employees.” The head of the FDA, Andrew von Eschenbach, attempted to explain to Congress why the agency didn’t tell its advisory committee about the problems in the Ketek study: “After considering the fact that the investigation results were preliminary ... FDA decided to hold the Advisory Committee meeting as planned ...” without notifying the committee of the potential problems. But Rep. Bart Stupak quickly pointed to an email, which, he argued, contradicted von Eschenbach's testimony. “So either you are not being forthright with us, when I believe you are, but whoever is doing your work is trying to  lead this committee down the wrong path.” And the correct path showed that site after site involved in study 3014, as well as other key Ketek studies, were tainted as well.
In the decade since the Ketek affair, it’s hard to see any change in behavior by the agency. On occasion, the FDA has even actively approved and promoted statements about drugs that, according to its own inspectors, are based upon falsehoods. At the end of 2011, the FDA learned that an audit of a Chinese site involved in a key clinical trial of a different anti-clotting agent, apixaban, had turned up evidence of fraud: Personnel had apparently been fiddling with patient records. Worse yet, the fraud appeared to invalidate one key finding of the study. Just three months earlier, the researchers running the trial proudly announced in the New England Journal of Medicine that there was a “significant reduction in mortality” among patients who took apixaban compared with those who took the old standby, warfarin. Alas, the moment you exclude the data from the Chinese fraud site, as per standard FDA procedure, that statement went out the window. Yet look at the label for apixaban—the one approved by the FDA after the fraud was discovered—and you read that “treatment resulted in a significantly lower rate of all-cause death ... than did treatment with warfarin,” backed up by the data set with the Chinese site included. In other words, the label is carrying a claim that the FDA knows is based upon fraud. In a written response to my questions on this subject, the FDA stated that, “The FDA extended the drug’s review period to address the concerns. However, the review team did conclude concluded [sic] that the data at that site and other sites in China did reflect meaningful clinical information; that was not what was considered unreliable.”
Again, this isn’t an isolated incident. I had previously encountered bogus data on FDA-approved labels when a colleague and I were looking into a massive case of scientific misconducta research firm named Cetero had been caught faking data from more than 1,400 drug trials. That suddenly worthless data had been used to establish the safety or effectiveness of roughly 100 drugs, mostly generics, that were being sold in the United States. But even after the agency exposed the problem, we found fraud-tainted data on FDA-approved drug labels. (The FDA still maintains its silence about the Cetero affair. To this day, the agency refuses to release the names of the 100-odd drugs whose approval data were undermined by fraud.)
And the FDA covers up drug-related misconduct in other, more subtle ways, too. For example, the agency publishes the canonical listing of generic drugs in the United States, known as the “Orange Book.” Prescription drugs in this book are often given what’s called a “therapeutic equivalence code.” This code is a two-letter designation that signals the quality of the scientific evidence that a generic is “bioequivalent” to the name-brand drug. The code “AB,” for example, tells pharmacists and physicians that there are solid scientific studies proving that bioequivalence. Another code, “BX,” signals that there isn’t sufficient data to prove the generic is bioequivalent to the name brand.

When the Cetero misconduct was uncovered, key bioequivalence studies for scores of generic drugs turned out to be worthless. By rights, some of those drugs should have had their designation downgraded from AB to BX. But even though the FDA updates the Orange Book monthly, there was no rash of drugs losing their AB rating in the months after the Cetero affair broke. In the year and a half after the Cetero fraud was first announced, I was able to identify a grand total of four generic drugs (in various dosages) that were downgraded to BX, none of which appeared to be linked to the Cetero problem. On the other hand, the one prescription generic drug that I knew for sure had been hit hard by the Cetero fraud—both key studies supporting its bioequivalence to the name brand were declared worthless—had no change in its designation. The FDA apparently allowed the drug to keep its AB badge for months without any valid data backing the drug’s bioequivalence. When asked, point blank, whether the agency had downgraded the bioequivalence code of any products due to the Cetero affair, officials promptly dodged the question. A written statement issued by the agency’s press office in response to my queries noted that the FDA requested additional data from the companies whose drugs were implicated in the Cetero affair and that “If the data were not provided within 6 months or the data provided did not support a finding of bioequivalence, FDA said it would consider changing the generic product’s therapeutic equivalence rating in the Orange Book from AB to BX.” Not a word about a single bioequivalence rating actually being changed.  
Why does the FDA stay silent about fraud and misconduct in scientific studies of medicine?
This, too, is a pattern of behavior rather than a one-off. In the past few weeks, another major Cetero-type case began to emerge—this time, having to do with GVK Biosciences, a firm in Hyderabad, India. The European Medicines Agency, the European equivalent of the FDA, examined more than 1,000 drugs in various dosages affected by GVK’s “data manipulations” and has suggested pulling 700 off the market. You can find the full list on the EMA website; to their credit, the Europeans are being relatively transparent as the crisis develops. Not so much on this side of the pond, alas. So far from the FDA, we’ve heard precious little, even though there are drugs on the U.S. market that rely entirely on GVK’s tests. In a written statement, the FDA admitted that there were some 40-odd drugs whose approval depended upon GVK-run studies. Which ones? The agency is keeping mum, as it did with Cetero and with other similar cases. However, the agency assures us that it inspected GVK's facility and found nothing to be concerned about; if the situation changes, “FDA will take swift and appropriate action to ensure that the drug products available to American consumers are safe and effective.”
Why does the FDA stay silent about fraud and misconduct in scientific studies of pharmaceuticals? Why would the agency allow claims that have been undermined by fraud to appear on drug labels? And why on earth would it throw up roadblocks to prevent the public, the medical community, its advisory panels, and even Congress from finding out about the extent of medical misconduct? The answers the FDA gives are fascinating—they show how an agency full of well-meaning people can do intellectual backflips to try to justify secrecy.
The most common excuse the agency gives is that exposing the details about scientific wrongdoing—naming the trials that were undermined by research misconduct, or revealing which drugs’ approvals relied upon tainted data—would compromise “confidential commercial information” that would hurt drug companies if revealed. This claim falls apart under scrutiny. The courts have ruled that when information is provided by companies involuntarily, such as the information that an FDA inspector finds, “commercial confidential information” refers to proprietary material that causes substantial, specific harm when it falls into the hands of a competitor. It doesn’t cover embarrassing peccadilloes—or misconduct that might cause bad publicity when word gets out.
Another excuse I’ve heard from the FDA is that it doesn’t want to confuse the public by telling us about problems, especially when, in the FDA’s judgment, the misconduct doesn’t pose an immediate risk to public health. For example, when my colleague and I asked the director of FDA’s Center for Drug Evaluation and Research why the agency wouldn’t name the drugs affected by the Cetero fraud, she told us that the matter “did not rise to the level where the public should be notified. We felt it would result in misunderstanding and inappropriate actions.” But even the most paternalistic philosophy of public health can’t explain why the FDA would allow drug companies to put data on its labels that the agency knows are worthless, or to fail to flag bioequivalence problems in a publication that is specifically designed for the purpose of flagging those very problems.

Charles Seife is a journalism professor at New York University. His most recent books are Sun in a Bottle: The Strange History of Fusion and the Science of Wishful Thinking and Proofiness: The Dark Arts of Mathematical Deception

FDA has a 'hearing problem'. Harmed patients (women) amplify social media voice!

FDA Reviews Essure to See if Device Causes Problems

by REUTERS  9/23, 2015
U.S. health experts will review the potential risks of Bayer AG's permanent contraceptive device, Essure, on Thursday in light of growing complaints over possible side effects, and consider whether its use should be restricted.
Some 17,000 women who had the device implanted and claim it has hurt them are members of the Facebook group "Essure Problems," run by Angela Lynch, who herself experienced problems with Essure. Complaints voiced by the women include chronic pain, heavy bleeding, fatigue and skin allergies.
The Food and Drug Administration panel will be asked to discuss potential changes to the product's label and whether further clinical studies should be conducted. The panel will not be asked to formally vote on their recommendations.
Bayer obtained the device with its $1.1 billion acquisition of Conceptus in 2013 and maintains it is safe and effective. It says roughly 750,000 units have been sold, mostly in the United States.
It's a small metal spring that goes into the fallopian tubes - an alternative to tying them.
Dr. Patricia Carney, the company's medical director for Essure, said the company welcomes the discussion.
"We want to understand as a company what is going on," she said. "We want to know whether there is a link to the product."
Already the complaints have led some physicians to re-examine their use of the device.
Dr. Sebastiaan Veersema, a gynecologist at St. Antonius Hospital Nieuwegein in the Netherlands, was an early European adopter, implanting the device in nearly 1,400 women and training dozens of practitioners in its use.
He now believes more research needs to be done to establish what, if any, relationship exists between the device and the problems relayed by some patients.
"If there is something wrong with the device I want to know," he said.
Veersema said a stronger screening process might be warranted to avoid implanting Essure in women who already have a uterine problem, such as fibroids.
Angela Lynch was 28 when she was implanted with the device. She had three children and did not want any more.
"Because I had just had a kid I wrote off all my symptoms as hormonal, my body trying to adjust," she said. "After two years I started losing hair. Then I started losing teeth, and over time it got to where my whole body was hurting."
In 2012 she had the device removed and underwent a hysterectomy.
"After three days it was like I woke up from a five-year flu," she said.
Dr. Cindy Basinski, who consults for Bayer and will be testifying on the company's behalf at the FDA meeting, has been implanting the device since 2006 and has conducted about 1,100 procedures with minimal complications.
She has had "a couple" of patients come to her with complaints and one asked for the device to be removed.
Basinski, who practices in Newburgh, Indiana, said she in "no way discounts the patients out there recounting their experience," but said it was not possible to draw scientific conclusions from anecdotal information.
For some doctors, it is not just the implantation of the device that needs to be looked at but how it is removed.
Dr. Shawn Tassone, who practices at a clinic in Austin, Texas, began implanting Essure in 2008, said there is no standardized method for removal.
"I'm hoping that all this will change the way doctors counsel their patients," Tassone said. "Instead of saying Essure is an easy procedure with no side effects, (they should) say this is a surgery and there are people reporting complications."

FDA, Medical Device Industry Profit and Harmed Women Collide With Pope Francis in DC on September 24

Essure complaints spike nearly 1,400% in 3 years


The FDA logged a nearly 1,400% spike in complaints filed over the Essure permanent female sterilization treatment made by Bayer (ETR:BAYN), according to a review released yesterday ahead of an FDA advisory panel meeting this week.
Essure, the only approved permanent birth control device in the U.S., is a small metal coil that is placed in the fallopian tubes via catheter. The FDA approved the device in November 2002.
In the near 13 years since then, the health regulator said it had received 5,093 complaints, including those of pain or menstrual irregularities after using the device, as well as complaints of the device breaking. Those adverse event reports include 5 fetal deaths in women who became pregnant after using Essure and 4 adult deaths for reasons such as infection and uterine perforation, the FDA said.
There were 152 complaints filed in the FDA’s Manufacturer & User Facility Device Experience database in 2012; last year there were 2,259 complaints filed in the MAUDE database, a 1,386% increase. So far this year there have been 1,363 MAUDE complaints filed with the FDA, the agency said. The FDA cautioned that the complaints it received had limitations such as incomplete or inaccurate data and did not necessarily directly indicate a faulty or defective device.

The FDA’s Obstetrics and Gynecology Devices advisory panel is set to meet Sept. 24 to discuss the risks and benefits of Essure and has invited feedback from presenters, panel members and the public. Some 17,000 women who had the device implanted and claim it has hurt them are members of the Facebook group “Essure Problems,” run by Angela Lynch, who herself experienced problems with Essure. Complaints voiced by the women include chronic pain, heavy bleeding, fatigue and skin allergies.
Lynch, who was 28 when she was implanted with the device, had 3 children and did not want any more.
“Because I had just had a kid I wrote off all my symptoms as hormonal, my body trying to adjust,” she said. “After 2 years I started losing hair. Then I started losing teeth, and over time it got to where my whole body was hurting.”
In 2012 she had the device removed and underwent a hysterectomy.
“After 3 days it was like I woke up from a 5-year flu,” she said.
In May, Bayer cited a 364-patient 5-year study of the device published in the Journal of Minimally Invasive Gynecology that indicated no pregnancies after 5 years and that the Essure inserts were “generally well tolerated.” Pelvic pain was reported in no more than 7% of patients, but no study participants reported persistent pelvic pain of any kind at the 3-, 4-, and 5-year follow-up visits, according to Bayer.
The study reported 3 serious adverse events “possibly related” to Essure in the trial, including irregular menstrual bleeding, lower abdominal pain and heavy periods and continuous bleeding. The latter 2 patients ended up having hysterectomies.
Dr. Patricia Carney, the company’s medical director for Essure, said Bayer welcomes the discussion. “We want to understand as a company what is going on,” she said. “We want to know whether there is a link to the product.”
In February a citizens petition lodged with the FDA asked the safety regulator to take Essure off the U.S. market, alleging that the clinical data the FDA used to approve the device was fudged and that the company concealed adverse events associated with Essure.
In July, the FDA approved using transvaginal ultrasound as an alternate test to confirm if the Essure implant has been placed properly. A month later Bayer cut the ribbon on a new plant in Costa Rica where it plans to make Essure.
Material from Reuters was used in this report.

Proto-AE: FDA Monitors Social Media

FDA panel set to vet Essure safety

On Sept. 24, the Food and Drug Administration’s Obstetrics and Gynecology Devices Panel will meet in Silver Spring, Md., to discuss the future of Bayer’s Essure permanent female sterilization coil.
FDA officials have asked the 19-member advisory panel to evaluate the currently available scientific data on the safety and effectiveness of the Essure system and make recommendations on appropriate use, product labeling, and the potential need for additional postmarket clinical studies.

Since Essure’s approval in 2002, the FDA has received more than 5,000 complaints about Essure. Most concern chronic pain, perforation, dyspareunia, device migration, menstrual problems, and possible allergic reactions to the nickel in Essure, but more than 100 adverse symptoms have been reported to the agency, according to newly posted meeting materials.
The complaints have been filed mostly in the past 2 years by patients who have organized online to share their stories and lobby to have Essure taken off the market; some are involved in legal action against Bayer. Meanwhile, Bayer maintains that, for most of the approximately 750,000 women who have received Essure, the device is safe and effective.
Advisory panel members will have their work cut out for them as they sort through the issues. The FDA has released a new 89-page review of Essure, and Bayer has submitted its own lengthy review document. Testimony is expected from Bayer, FDA reviewers, patients, and others. The meeting is scheduled to run almost 12 hours, from 8 a.m. to 7:30 p.m. Eastern time, at the agency’s White Oak Campus in Silver Spring, Md., and will be broadcast live online.
FDA noted in its review that it has been monitoring social media with automated software that scours Twitter, Facebook, patient forums, and other websites for “posts with resemblance to adverse events” or “Proto-AEs.” The program picked up 350,000 references to Essure between September 2013 and July 2015 and classified more than 20,000 as Proto-AEs, mostly related to pain, hysterectomy, malaise, pregnancy, and device removal. The social media data, however, are preliminary since the FDA has yet to remove duplications and retweets.

Saturday, September 12, 2015

Study: Hip/Knee Surgery May Be Bad for the Heart

Knee and Hip Replacements May Be Bad for the Heart

August 31, 2015
Contrary to recent reports, Boston-based researchers found that osteoarthritis patients who had total knee or hip joint replacement surgery, known as arthroplasty, were at increased risk of heart attack (myocardial infarction) in the early post-operative period. However, findings published in Arthritis & Rheumatology, a journal of the American College of Rheumatology (ACR), indicate that long-term risk of heart attack did not persist, while the risk for venous thromboembolism—blood clot in veins and lungs—remained years after the procedure.
Osteoarthritis is the most common form of arthritis, affecting 27 million Americans over the age of 25 according to the ACR. As the joint cartilage and bone deteriorates, knee or hip replacement surgery may be the only option to relieve pain and stiffness, and restore mobility. Previous studies estimate that 1.8 million arthroplasty procedures are performed each year worldwide, and that number may increase as the population ages.
“While evidence shows that joint replacement surgery improves pain, function, and quality of life for the osteoarthritis patient, the impact of cardiovascular health has not been confirmed,” explains lead study author Yuqing Zhang, D.Sc., Professor of Medicine and Epidemiology at Boston University School of Medicine in Boston, Massachusetts. “Our study examines if joint replacement surgery reduces risk of serious cardiovascular events among osteoarthritis patients.”
The present cohort study included 13,849 patients who underwent total knee replacement surgery and 13,849 matched controls who did not have surgery. Patients were 50 years of age or older and diagnosed with knee or hip osteoarthritis between January 2000 and December 2012.
Findings indicate that 306 patients in the arthroplasty group and 286 in the non-surgical group developed myocardial infarction during the follow-up period. Risk of heart attack was significantly higher during the first postoperative month in those who had knee replacement surgery compared to those in the non-surgical group, and gradually declined over time. Venous thromboembolism was a significant risk during the first month and over time for those having total knee or total hip arthroplasty.
“Our findings provide the first general population-based evidence that osteoarthritis patients who have total knee or total hip replacement surgery are at increased risk of heart attack in the immediate postoperative period,” concludes Dr. Zhang. “The long-term risk of heart attack was insignificant, but risk of blood clots in the lung remained for years after surgery to replace a hip or knee damaged by osteoarthritis.”

“Total Joint Arthroplasty and the Risk of Myocardial Infarction - A General Population, Propensity Score-Matched Cohort Study.” Na Lu, Devyani Misra, Tuhina Neogi, Hyon K.Choi and Yuqing Zhang, Arthritis & Rheumatology; Published Online: August 31, 2015 (DOI: 10.1002/art.39246).  

Tuesday, September 8, 2015

Medical device industry: "rotting from the inside out".

‘I’m rotting from the inside out’: woman tells of vaginal implant gone wrong

September 5, 2015 9:00am
Rhian DeutromThe Sunday Mail (Qld)

A BRISBANE woman whose body rejected a controversial pelvic implant at the centre of a class action has spent the past decade in agony.

Dee Nelson, 46, has been fighting for specialists around the country to address severe complications caused by a common vaginal implant.
While the mother-of-two looks perfectly healthy, she believes the tension-free vaginal tape sling, distributed by Johnson & Johnson Australia, is slowly killing her.

Ms Nelson received the implant in 2005 for weak pelvic muscles following the birth of her daughter. Two weeks later, she was rushed to the emergency department with heavy bleeding and a high fever.
According to Ms Nelson, her body rejected the implant but no one would believe her. Doctors told the mother her symptoms were “all in her head”, and at one point, a psychiatric assessment was suggested.

“I knew what the problem was, as did millions of other women across the world, but no one would listen,” Ms Nelson said.
“These people were playing with my life, but if I went back and said there was something wrong, they just wiped their hands of me.
“I have been handed around the system from one specialist to another, and in the meantime, women are dying from these foreign objects inside them.”
For the next 10 years, Ms Nelson’s health rapidly deteriorated as her nerves and muscles grew through the plastic implant, wreaking havoc with her confidence.
“I have aged so much, and I’m in constant pain,” she said.
“I can’t hold down a job, eat during the day or stand up for long periods … I feel like I’m 90 years old. It’s horrific.”
Surgeons around the country have refused to remove her implant as it has been inside her for too long.
Ms Nelson said the side effects have taken a significant toll on her family as well.
“When my children were young and needed me, I couldn’t be there for them because I was in agony,” she said.
“They have had to watch me deteriorate … it’s devastating.”

For Ms Nelson, even the thought of having sex with her husband was painful.
“I have a beautiful partner who I have been married to since I was 16 years old, but I can’t love him and he can’t love me,” she said.
“To go through life without love and not be a woman isn’t right.”
Ms Nelson is one of about 40,000 Australian women who received mesh implants before they were withdrawn from sale in 2012. Shine Lawyers’ class actions solicitor Bridget Cook told The Courier-Mail a lawsuit was filed against distributor Johnson & Johnson Australia and manufacturer Ethicon in 2012 on behalf of 400 women who suffered the devastating side effects.
“We allege the products were introduced without any pre-market testing … the implants were not fit for their purpose, Ms Cook said.
A spokeswoman for Johnson & Johnson Australia said the company was “always concerned when a patient experiences adverse medical events”.
She said Ethicon is “vigorously defending” all lawsuits concerning the allegedly faulty implants.
“We are confident the evidence will show that Ethicon acted appropriately and responsibly in the research, development and marketing of its pelvic mesh product s.
“We have made patient safety a top priority, and will continue to do so,” the spokeswoman said.
While the lawsuit inches closer to a trial, Ms Nelson remains housebound, praying to regain control of her life. Her only hope is to travel to the US to undergo $40,000 surgery to finally have the mesh removed.

Knowing what I know now, I would never have gone through with it … It’s rotting me from the inside out,” she said.

FDA historically allows fraudulent ads of pharmaceuticals and medical devices targeted to women.

Jeremy A. Greene, M.D., Ph.D., and Elizabeth S. Watkins, Ph.D.
August 19, 2015
Aside from New Zealand, the United States is the only country with a strong pharmaceutical regulatory infrastructure that allows direct-to-consumer advertising (DTCA) of prescription drugs in print, broadcast, and electronic media. U.S. consumers are accustomed to full-page ads in newspapers and magazines detailing a drug's benefits — followed by another page of fine print in which its contraindications, risks, and side effects are spelled out in minute detail and equally minute print.
That may soon change, however, as the Food and Drug Administration (FDA) moves to enact new regulations regarding risk communication in DTCA. Earlier this year, the FDA sought public comments on new guidance for pharmaceutical marketers on communicating risks to consumers in print advertisements. This proposal, which the FDA has kicked around in one form or another since 2004, responds to mounting research showing that reprinting highly technical package inserts in print ads does very little to communicate risks to consumers. The goal is to communicate those risks in a new vernacular.
Instead of reproducing the fine print meant for physicians and pharmacists, the FDA proposes that drug marketers use a new “consumer brief summary” focused “on the most important risk information . . . in a way most likely to be understood by consumers.” A summary written in everyday language might take the form of a Q&A list, for example, or a Drug Facts box like those on packaging for over-the-counter medicines. Drug marketers are being asked to use popular idiom to communicate with people with a wide range of literacy levels; to use larger fonts and more readable formats; and to use visual elements such as white space, logos, and color schemes to highlight the most relevant risks.1
Public comments on the proposal have focused on the challenges of implementation. How many risks are too many to print? How will a manufacturer — or the FDA — know when language is too simple, too technical, or pitched “just right” for average Americans? Missing from this conversation is a broader perspective on the vernacular of risk in pharmaceutical promotion — as something that is not a new DTCA-related duty for the FDA but fundamental to the origins of the category of prescription drugs and their regulation over the past half-century.
After passage of the 1938 Food, Drug, and Cosmetic Act, which established the distinction between prescription-only and over-the-counter drugs, consumers received most information about the latter through ads and most about the former from their physician or pharmacist. Indeed, the category of “prescription-only” medications enabled industry to avoid having to communicate risks directly to consumers in marketing materials. The 1938 law required drugs to carry labels providing “adequate directions for use” and “adequate warnings” to protect users from harm. Partly to sidestep this mandate, drug manufacturers restricted the sale and marketing of their products to doctors, who could comprehend highly technical presentations of indications, contraindications, toxicology, and adverse effects.2
This order of things was upset in the late 1960s, after highly publicized Senate hearings on the safety of oral contraceptives. Women's health activists demanded action after the revelation that knowledge of the health risks associated with the Pill — including potentially fatal pulmonary emboli — had often been kept from women or left for doctors to convey at their discretion. Beginning in 1970, the FDA required manufacturers to include information for patients in every package of birth-control pills. Unlike technical package inserts for pharmacists, this patient package insert (PPI) would outline the health risks of the Pill in clear, everyday prose.

The 1970 Patient Package Insert for Oral Contraceptives.
Yet as the FDA quickly discovered, there was no clear consensus on how best to provide risk information to patients. The first draft of the PPI became a flash point in debates over the relationships between the FDA, drug manufacturers, consumers, and physicians. Entitled “What You Should Know about Birth Control Pills,” the 600-word document described in lay language the health risks, side effects, and contraindications of oral contraceptives. Both the medical profession and the pharmaceutical industry vigorously opposed the proposed pamphlet, and the FDA's parent agency, the Department of Health, Education, and Welfare, advocated revising the wording to address legal issues. In response to pressure from professional, industrial, and government interests, the FDA developed a shorter, less detailed version. The revised text, 100 words long, listed just 5 symptoms of side effects, whereas the earlier draft had listed 25. Gone were statistics on increased risk for and mortality from thromboembolism; the edited version simply mentioned blood-clotting disorders as a possible complication.
During the commenting period on the PPI, the FDA received more than 800 responses, most of them complaining about inadequate disclosure of adverse effects. Yet the insert that finally went to press was even more anemic: it listed no symptoms at all, telling consumers to “notify your doctor if you notice any physical discomfort.” Four of the insert's seven sentences described the availability of an information booklet, which patients could request from physicians. This 800-word booklet, jointly written by the American Medical Association (AMA), the FDA, and the American College of Obstetricians and Gynecologists, provided more information, but very few women actually received it.
It wasn't until 1977, after the FDA mandated use of a PPI to communicate newly disclosed health risks associated with estrogen products, that consumers earned the right to routinely receive the same technical package information as physicians and pharmacists. Then, in 1979, the FDA proposed a lay-language PPI for all prescription drugs. But when physicians, pharmacists, and drug companies balked, the agency scaled back its ambitions to a 3-year pilot program for 10 types of drugs. Even this reduced mandate failed to take effect, after the Reagan administration — seeking deregulation, privatization, and smaller government — required federal agencies to review the necessity and cost-effectiveness of existing and proposed regulations. The FDA deferred implementation of the PPI program in 1981 and canceled it the next year, relying instead on a voluntary private-sector approach.
After the revocation, some written information about prescription drugs was produced by a patchwork of organizations, including the AMA, the U.S. Pharmacopeia, and the American Association of Retired Persons.3 When the FDA began in 1985 to allow drug companies to advertise in mass-market magazines and newspapers so long as they included a “fair balance of information,” as required for ads in medical journals, companies began developing their own “patient information sheets,” which often simply reprinted the text of the package insert written for physicians and pharmacists. This information provision had little to do with educating consumers and much to do with expanding marketing opportunities. The medical terminology, dense verbiage, and tiny fonts of these inserts have made them inscrutable to the average consumer and virtually useless as information sources.4
The FDA's Medication Guide program, proposed in 1995 and launched in 1999, aimed to mitigate this problem for some outpatient prescription products, with user-friendly information to be distributed at the point of sale. The most effective of these guides might serve as templates for risk communication in DTCA. Moreover, in 2015, companies could harness the power of communications technologies such as smartphone-scannable QR codes to link such information to print ads or online materials for interested consumers.
Yet the primary risk-communication challenges the FDA has faced are not technological but social. In the case of the Pill, the PPI's opponents were able to dilute and delay efforts to provide patients with clear, comprehensive risk information. The U.S. medical consumer's voice has grown stronger since the 1970s, and the FDA increasingly relies on social scientific research in its decisions. Nonetheless, the success or failure of the current proposal depends on the agency's ability to capture the interests of all stakeholders.
For all its capacity to encourage overdiagnosis and overmedication, DTCA's virtue is that it treats consumers as people who deserve to know something about the compounds they take into their bodies. After 30 years of DTCA, it's not clear that advertising is the best medium for communicating risk information,5 but marketers should at least be required to try to communicate risk information as effectively as they do their promotional messages.

Disclosure forms provided by the authors are available with the full text of this article at
This article was published on August 19, 2015, at

From the Division of General Internal Medicine and the Department of the History of Medicine, Johns Hopkins University School of Medicine, Baltimore (J.A.G.); and the Department of Anthropology, History and Social Medicine, University of California, San Francisco, School of Medicine, San Francisco (E.S.W.).

Friday, September 4, 2015

GAO to investigate FDA regulation of power morcellators.

Government Watchdog to Investigate Hysterectomy Device Found to Spread Uterine Cancer

Government Accountability Office to probe surgical device that was marketed for two decades before FDA issued warnings


The U.S. Government Accountability Office confirmed Friday that it plans to investigate a surgical device that was marketed for two decades before the Food and Drug Administration warned it can spread uterine cancer.
Twelve lawmakers wrote the GAO a letter last month asking for a probe into laparoscopic power morcellators, which are bladed, drill-shaped tools gynecologists commonly used to cut up growths called fibroids in minimally invasive surgery, most often hysterectomies. The FDA last year estimated that women who undergo these procedures face 1-in-350 odds that they harbor an undetected cancer that a morcellator could spread and worsen.
“We’ve agreed to do the work,” Katherine Siggerud, managing director for congressional relations at the GAO, confirmed Friday.
In a letter earlier this week to U.S. Rep. Mike Fitzpatrick (R., Pa.), a lawmaker at the forefront of pushing for a GAO review, Ms. Siggerud said the agency accepted his request “as work that is within the scope” of GAO authority. She said the GAO would likely have the staff available to begin its work in about five months.
She said in an interview it was too soon to tell how long a probe might take. An FDA spokeswoman said the agency will cooperate with any GAO review, and does not comment on pending or ongoing investigations.
The probe will likely add scrutiny to how the FDA handled issues with power morcellators going back to 1991—when the first one was cleared for sale in the U.S.—to last year, when the agency cited evidence that the risk of hidden uterine cancers called sarcomas was much higher than many gynecologists believed. Device applications and other records show the FDA knew early on that morcellators could spread dangerous cells, but the agency said the magnitude of that risk wasn’t recognized until the issue gained prominence starting in late 2013.
“I am glad the GAO has agreed to take up this investigation,” Mr. Fitzpatrick said in a statement. “What happened with the power morcellator should never happen again.”
Rep. Louise Slaughter (D., N.Y.) and 10 other members of Congress also signed the Aug. 7 letter to the GAO.
They asked for an investigation into issues such as the FDA’s reliance on a regulatory process used to clear all morcellators for sale in the U.S.; the process has drawn criticism for being too lenient. The lawmakers also asked to know whether groups like hospitals and device manufacturers complied with FDA rules to report problems with the devices, how doctors were trained to use them and what steps the FDA is taking to determine whether morcellators are safe to remain on the market.
The FDA has defended the regulatory process used to approve morcellators and most devices as a good way to balance innovation and safety, and said that the agency is strengthening its surveillance of devices on the market. Johnson and Johnson, formerly the largest morcellator maker before it voluntarily left the market last year, has said that it wasn’t aware of any reportable events regarding morcellators and the possibility of worsened cancer until late 2013.
The FDA in November followed up on its earlier morcellator advisory by calling for a black-box warning, its strongest caution, regarding the cancer risks. The devices still remain on sale from other companies beyond J&J, although many hospitals and health insurers have curbed their use.

My comment:  I blog on FiDA Advocate blogspot.  I was trained 9/2010 at the request of FDA/CDRH to be a Patient Representative on medical device Advisory Panels.  CDRH conducts few  Advisory Panels because most (98%) new devices are cleared through the 510(k) process that simply requires the identification of a 'predicate' device and perhaps a payment of $4000.  If an Advisory Panel is called, the FDA/OSHI - Office of Special Health Issues selects the Patient Representative and this person is a NON-voting member of the panel.  Harmed patients and their advocates are rarely a part of the equation and industry has infiltrated the regulatory sphere.  The system is rigged and patient harm-for-profit is the result.

Thursday, September 3, 2015

27 Fatalities of Implanted Device: C.R. Bard CEO Sells $7M Shares

Medical Device to Prevent Blood Clots Associated With 27 Fatalities (Video link 4:37)

September 3, 2015

Serious questions are being raised about a medical device implanted in thousands of Americans at risk for blood clots — including whether the manufacturer told all it knew about potentially fatal flaws.
At least 27 deaths have been associated with the Recovery filter — a spider-shaped apparatus that is inserted into the largest vein in the body — over the course of a decade, an NBC News investigation has found.
Government data shows approximately 300 other non-fatal problems have also been reported with the Recovery, which is one of thousands of medical products sold by C.R. Bard.
Dodi Froehlich, 45, got hers after severe injuries in a 2004 car accident put her at high risk for clots. The filter was supposed to stop them from reaching her heart or lungs; instead, it nearly killed her.
Four months after it was implanted, she developed a severe headache and passed out.
"In that two seconds of being in the ambulance, I started flat-lining," Froehlich told NBC News.

Testing revealed a piece of the filter had broken off and pierced her heart, and she had to have emergency open-heart surgery.
"My family was notified," she said. "The priest was brought in."
Surgeons were able to remove the broken piece during emergency open-heart surgery and save Froelich's life, but not all Recovery recipients have been so lucky.
Gloria Adams, then 55, needed a filter after a brain aneurysm in 2004. Her son Kevin Keech says "everything was fine" when she was discharged from the hospital — but a week later, she was dead.
An autopsy showed that instead of the filter stopping a clot, a clot pushed the entire device into her heart, puncturing it.
"I didn't get many answers at that point," her son said.

After the problems with the Recovery began, Bard hired public-relations giant Hill and Knowlton. The firm circulated a crisis management plan to Bard management, warning that "unfavorable press" could damage stock prices and ruin reputations. The company also retained an outside doctor to conduct a confidential study, which was obtained by NBC News.
The consultant found the Recovery filter had higher rates of relative risk for death, filter fracture and movement than all its competitors.
"Further urgently warranted," the doctor wrote.
But even as death and injury reports were climbing, the company decided not to recall the Recovery. Instead, Bard sold about 34,000 of them for nearly three years before replacing them with a modified version with a new name, G2.

Each year, about a quarter of a million blood clot filters are implanted in patients who can't tolerate blood thinners, most without incident. Eleven companies sell them in the U.S., but Bard's Recovery filter stood out early as a risky device.
Bard officials declined NBC News' requests for interviews but in a statement said all its filters have been "appropriately cleared by [the] FDA based on required and accurate documentation and that when used as instructed they demonstrate "significant benefits to patients."
Getting FDA clearance took more than one attempt. After the agency rejected one application for the Recovery, Bard, in 2002, recruited Kay Fuller, a veteran regulatory specialist, to help try again.
In an exclusive interview with NBC News, Fuller raised questions about how Bard handled that application.
She says the company did not give her important safety performance test results and that a small clinical trial raised red flags.
"I was pretty concerned there were going to be problems with this product," she said.
However, when she voiced those concerns, she said, the message she got was that she would be removed from the team if she continued to pursue the matter.
"I was shocked," she said.
Read Part Two of NBC News' Investigation tomorrow: Did C.R. Bard forge Kay Fuller's signature on a key document submitted to the FDA?

Insider Selling: Timothy M. Ring Sells 40,000 Shares of C R Bard Stock (BCR)
September 3rd, 2015 - 

C R Bard (NYSE:BCR) CEO Timothy M. Ring sold 40,000 shares of the stock in a transaction that occurred on Monday, August 31st. The stock was sold at an average price of $195.17, for a total value of $7,806,800.00. Following the transaction, the chief executive officer now owns 119,694 shares in the company, valued at approximately $23,360,677.98. The sale was disclosed in a filing with the Securities & Exchange Commission, which is available at this link.
Several equities research analysts recently commented on BCR shares. Zacks raised C R Bard from a “hold” rating to a “buy” rating and set a $194.00 target price for the company in a research note on Wednesday, June 24th. Goldman Sachs raised C R Bard from a “neutral” rating to a “buy” rating and lifted their price objective for the company from $193.00 to $220.00 in a research note on Thursday, August 27th. TheStreet cut C R Bard from a “strong-buy” rating to a “hold” rating in a report on Monday, August 24th. Brean Capital reiterated a “hold” rating on shares of C R Bard in a research note on Thursday, July 23rd. Finally, KeyBanc began coverage on shares of C R Bard in a research note on Thursday, August 27th. They issued a “sector weight” rating for the company. Seven investment analysts have rated the stock with a hold rating and four have issued a buy rating to the company. C R Bard presently has a consensus rating of “Hold” and a consensus target price of $193.38.
Shares of C R Bard (NYSE:BCR) traded up 2.30% during mid-day trading on Wednesday, hitting $191.86. The company had a trading volume of 512,486 shares. The stock’s 50-day moving average is $191.45 and its 200-day moving average is $176.17. The stock has a market cap of $14.24 billion and a price-to-earnings ratio of 42.34. C R Bard has a 52-week low of $141.49 and a 52-week high of $202.47.
C R Bard (NYSE:BCR) last announced its earnings results on Thursday, July 23rd. The company reported $2.27 earnings per share (EPS) for the quarter, topping the Zacks’ consensus estimate of $2.18 by $0.09. During the same period in the previous year, the firm posted $2.06 earnings per share. The business had revenue of $859.80 million for the quarter, compared to analysts’ expectations of $836.18 million. The firm’s revenue was up 4.0% compared to the same quarter last year. Equities analysts forecast that C R Bard will post $9.08 earnings per share for the current year.