Could One Company Be . . . Medtronic? St. Jude?

Replacing Faulty Heart Devices Costs Medicare $1.5 Billion in 10 Years

By FRED SCHULTE and CHRISTINA JEWETT   OCT. 2, 2017  The New York Times

WASHINGTON — Medicare paid at least $1.5 billion over a decade to replace seven types of defective heart devices, a government watchdog says. The devices apparently failed for thousands of patients.

A report released on Monday by the inspector general’s office for Health and Human Services said officials needed to do a better job tracking these costly product failures to protect patients from harm. More detailed reporting could lead to earlier recognition of serious problems with medical devices and faster recalls of all types of “poorly performing” ones, the inspector general’s office said.

The report marks the first effort by anyone in government to assess the losses to taxpayers and patients 65 and older from medical gear that proves faulty.

Officials said the $1.5 billion lost from the seven devices from 2005 through 2014 was a “conservative estimate.” Patients also paid $140 million in out-of-pocket costs for this care, the report noted.

The report found that nearly 73,000 people on Medicare had one of the seven devices replaced because of recalls, premature failures, medically necessary upgrades or infections. It did not outline specific injuries that patients suffered as a result.

The inspector general did not identify the manufacturers of the seven devices, but officials said they included implanted cardio defibrillators and a pacemaker that had either been recalled because of flaws or had “prematurely failed.” Pacemakers and implantable defibrillators are small devices placed under the skin to help treat irregular heartbeats.

How best to identify these defects and cut Medicare spending associated with fixing them has been under consideration at various times since 2007, according to the report. But it remains a contentious issue.

The inspector general recommended that hospitals and doctors be required to submit detailed information identifying failed devices, like serial and batch numbers, during the billing process.

“This could help reduce Medicare costs by identifying poorly performing devices more quickly, which could also protect beneficiaries from unnecessary costs and improve their chances of receiving appropriate follow-up care more quickly,” the report said.

David Lamir, an official in the inspector general’s Boston office, said the $1.5 billion figure represented a “drop in the bucket” of the true costs to Medicare from medical products that malfunction. He said device failures not only waste money, but also can expose patients to a “high risk of illness,” including needless surgeries.

The report said that medical device recalls nearly doubled from 2003 through 2012 and noted that they have probably cost Medicare billions of dollars. In the past five to six years, more than 200 cardiac devices have been recalled, according to the inspector general’s office. In most cases, manufacturers withdrew their products voluntarily after reports surfaced of injuries or malfunctions. Device makers are required to report problems they learn of, often from doctors and hospitals, to a database run by the Food and Drug Administration.

Diana Zuckerman, president of the National Center for Health Research who has testified before Congress on device safety, said her organization supports making hospitals report malfunctioning devices when they seek Medicare payments to cover an implant surgery. She said the change would help officials pinpoint faulty devices before issuing a recall for tens of thousands of products in patients.

“It would be much more obvious much more quickly which implanted devices were causing problems,” she said.

Ms. Zuckerman noted that the report did not touch on other high-profile device failures, like metal-on-metal hip implants or vaginal mesh.

Medical device companies and some doctors have opposed tighter reporting, arguing that it would be costly and difficult to integrate with existing payment claim forms and might not yield useful information.

“It is abundantly clear that data collected in electronic health records is a far superior and more cost-effective method for monitoring the performance of medical devices,” said Mark Leahey, who heads the Medical Device Manufacturers Association. The trade group represents nearly 300 device companies.

Mr. Leahey said that the electronic health record “captures the full clinical history of the patient, their changing health status and detailed information on their medical treatments,” including any surgically implanted devices.

A spokesman for the Centers for Medicare and Medicaid Services said the agency had not seen the report and would have no comment.

But in written remarks included in the report, Seema Verma, the agency’s administrator, said the tighter reporting requirement was “under consideration” and that the agency would “carefully evaluate the potential that this policy would impose a burden on physicians unnecessarily.”

This article was produced in collaboration with Kaiser Health News, an editorially independent program of the Kaiser Family Foundation. 

• https://www.nytimes.com/2017/10/02/health/heart-devices-medicare.html?_r=0

Dr. Amy Reed Dies at Age 44, Mother of 6 Children and Advocate for Safe Medical Devices

Amy Reed, Doctor Who Fought a Risky Medical Procedure, Dies at 44

By DENISE GRADY

MAY 24, 2017  (FiDA highlight)

Dr. Amy J. Reed, a physician and cancer patient who turned a personal calamity into a crusade to spare other women from the medical procedure that harmed her, died on Wednesday night at home in Yardley, Pa. She was 44.

Dr. Amy J. Reed and her husband, Dr. Hooman Noorchashm, in 2014. (MATTHEW CAVANAUGH FOR THE NEW YORK TIMES)

Her husband, Dr. Hooman Noorchashm, said the cause was leiomyosarcoma of the uterus, a type of cancer.

Dr. Reed and her husband fought for years to ban the use of a surgical tool called a power morcellator, which has a spinning blade that slices up tissue so it can be extracted through small incisions. Though the device is regarded as a great boon to minimally invasive surgery, if a patient has cancer, as Dr. Reed did, morcellation can spread the disease.

Dr. Reed and Dr. Noorchashm (pronounced NOOR-chasm) won some notable victories. Because of their efforts, the Food and Drug Administration studied morcellation and in 2014 recommended that it not be used in the “the vast majority” of women having surgery for uterine fibroids, a common tumor that is usually benign but that can hide a dangerous type of cancer.

Some insurers began declining coverage for morcellation, and one major manufacturer took its morcellators off the market. Use of the technique dropped.

Dr. Reed, an anesthesiologist and the mother of six children, underwent surgery involving morcellation in 2013, when, at 40, she had her uterus removed because of fibroids. The operation was performed at Brigham and Women’s Hospital in Boston, which is affiliated with Harvard Medical School, where both Dr. Reed and Dr. Noorchashm had teaching positions. A biopsy after the operation found that Dr. Reed had a hidden leiomyosarcoma, an aggressive type of cancer.

Only then were Dr. Reed and her husband told that her surgeon had used a power morcellator to slice up her uterus. The device allows doctors to work through small slits rather than big, open incisions, so that patients can heal faster and run less risk of bleeding and infection.

At that time, morcellation was performed on 50,000 women a year in the United States to help remove fibroids, or to remove the entire uterus.

The device had sprayed malignant cells around inside Dr. Reed’s abdomen, leaving her with an advanced, Stage 4 cancer.

As physicians, Dr. Reed and Dr. Noorchashm knew at the time that her morcellation procedure could be a death sentence. As a surgeon himself, Dr. 

Dr. Reed quickly embarked on a series of aggressive treatments, but she still suffered one recurrence after another, in her abdomen, lungs and spine. She had several major operations and received arduous courses of chemotherapy, radiation, immunotherapy and experimental treatment.

The couple fought the medical establishment as fiercely as they did the cancer, seeking to ban morcellation. They sent thousands of emails to the F.D.A., device makers, hospitals, legislators, professional societies and individual doctors, and they reached out to news organizations to publicize their cause.

Dr. Noorchashm also collected the names and histories of women whose cancer had spread after morcellation, enlisting them, or their survivors, in the crusade.

Dr. Amy Reed with her husband, Dr. Hooman Noorchashm, and their children in their backyard in Yardley, Pa., in the summer of 2015.

JENNIFER CAPOZZOLA

Their activism, alienating some colleagues and aggravating administrators, came at a price. Dr. Noorchashm had been a rising star in cardiothoracic surgery at Brigham and Women’s, where his wife had the operation, but as he continued to criticize its gynecology department, his career there began to stall.

He and Dr. Reed were both hired by the University of Pennsylvania, and moved there in 2014. Both had extended family in and around Philadelphia.

They had apparently burned their bridges at Harvard. At one point, when Dr. Reed needed to return to Brigham and Women’s for a medical procedure, she and Dr. Noorchashm were stunned to find that the hospital had assigned a guard to inspect their bags and escort them at all times, for security reasons. Dr. Noorchashm called a lawyer. A judge put a stop to the escort, issuing a restraining order against the hospital.

The gynecology profession also fought back against Dr. Noorchashm and Dr. Reed, insisting that leiomyosarcoma was so rare that the benefit of morcellation — the ability to have minimally invasive surgery — far outweighed any risk.

Before 2013, the F.D.A. had received no reports of uterine cancers being spread by morcellators. But after Dr. Reed and her husband went public — interviewed by newspapers, magazines and TV news shows — reports began to pour in. Dr. Reed, with her hair gone and her youngest child sometimes climbing onto her lap during interviews, was a sympathetic figure.

The couple’s efforts gained traction. The F.D.A. responded by studying published and unpublished medical data on morcellation. Before then, estimates of how many women with fibroids would have undiagnosed leiomyosarcomas or other uterine sarcomas were based on studies of varying reliability, and ranged from 1 in 10,000 to in 1 in 500. But the F.D.A. concluded in April 2014 that hidden sarcomas were more common than earlier estimates had stated — and probably occurred in about one in 350 women with fibroids. The tumors are extremely difficult to detect without surgery.

Soon after the F.D.A. issued its findings, one maker of morcellators, Johnson & Johnson, pulled its devices off the market. But others remained.

In November 2014, the F.D.A. went further, recommending that power morcellators not be used in the vast majority of women having fibroid surgery. Using the device in women with undetected sarcomas, it said, “may spread cancer and decrease the long-term survival of patients.” The F.D.A. portrayed the statement as a “safety communication,” not as an announcement of a new regulation.

Morcellator use dropped significantly, but many gynecologists still favored it, and the devices remained available. Dr. Noorchashm and Dr. Reed would not settle for less than a complete ban, and continued to agitate. They prodded legislators to ask the Government Accountability Office to investigate morcellation.

In a report issued in February, the G.A.O. criticized the F.D.A.’s method of collecting data on problems stemming from morcellation, noting that the system was dependent on voluntary reports from doctors, who frequently fail to report bad outcomes.

The F.D.A. said it agreed that it needed a better system to detect harm to patients. By September 2016, the agency had received 285 reports of uterine cancer being spread by morcellation.

Amy Josephine Reed was born on March 22, 1973, in Bristol, Pa. Her mother, the former Joann Tunis, was a pharmacist and executive at the drug company Pfizer. Her father, William Reed, was a health insurance consultant.

Dr. Reed graduated from Pennsylvania State University in 1995 and went on to the University of Pennsylvania, where she earned a Ph.D. in immunology and a degree in medicine. She specialized in anesthesia and critical-care medicine.

She and Dr. Noorchashm met as graduate students and married in 2001. In 2011, both were offered teaching posts at the Harvard Medical School and clinical positions at its affiliated hospitals — Dr. Noorchashm at Brigham and Women’s and Dr. Reed at Beth Israel Deaconess. She treated victims of the Boston Marathon bombing in 2013, as well as the surviving bomber.

Besides Dr. Noorchashm, Dr. Reed is survived by her parents; her daughters, Nadia and Ava; her sons, Joseph, Joshua, Luke and Ryan; and seven siblings: Alison Perate, Andrea Kealy, Amber Trainer, Matthew Reed, Justin Reed, Daniel Trainer and Sarah Trainer.

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They Can Run, But They Can't Hide! J&J Halo Products Shielding Medical Device Failure

Johnson & Johnson Is Urged to Slim Down

By ROBERT CYRAN JUNE 2, 2016  @rob_cyran  The New York Times

Johnson & Johnson weighs heavy. The bulging health care conglomerate is swallowing the hair-care company Vogue International for $3.3 billion in defiance of calls to break up. Johnson & Johnson’s $312 billion market value makes it a hard target for activists. Yet its size has created ailments, including poor merger-and-acquisition activity and mediocre shareholder returns.

Over the last decade shareholders have largely come to the conclusion that pharmaceutical firms should focus on developing medicines. After all, there’s little in common between using science to discover a cure for Alzheimer’s and selling shampoo. That has led Abbott Laboratories to spin off the pharmaceutical division AbbVie; Pfizer and Merck each to sell their consumer-goods business;and GlaxoSmithKline to divest nutritional drinks. The results have been largely favorable to investors too, because the cash thrown off by consumer goods companies is coveted by yield-starved investors.

Johnson & Johnson has resisted the trend. About one-fifth of its revenue comes from selling consumer health and beauty products such as Band-Aids and Listerine. Over 40 percent comes from cutting-edge drugs, and the rest from medical devices. The diversity may produce relatively steady results, but investors aren’t terribly appreciative of the fish-fowl hybrid. The company is valued at about 11.5 times estimated earnings before interest, taxes, depreciation and amortization, or Ebitda, over the next 12 months. That’s lower than the multiples attached to the consumer goods maker Colgate and the drug maker Eli Lilly, which trade between 14 and 15 times Ebitda, and the medical device firm Medtronic, at 12.5 times.

This has not escaped investors. Artisan Partners tried to pressure Johnson & Johnson to split earlier this year. However, Artisan owned well under 1 percent of its stock; combined with Johnson and Johnson’s scattered investor base, the activist had almost no power to battle its giant target.

The company’s girth comes at a cost. The drug business is faring well, but the other divisions are not. The consumer-goods unit’s margins are below rivals’ and some of its factories still operate under regulatory oversight from the Food and Drug Administration after a wave of product recalls a few years ago. The medical device division’s profits have been essentially stagnant since 2010 despite buying a rival, Synthes, for around $20 billion five years ago. Slimming down, or even splitting into three, would serve Johnson & Johnson well.

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FDA Commissioner Dr. Califf: The Fox is in the Henhouse!

F.D.A. Asks If Faulty Blood Monitor Tainted Xarelto Approval

By KATIE THOMAS FEB. 22, 2016

The Food and Drug Administration is investigating whether a faulty blood-testing device may have compromised the results of a clinical trial that led to the approval of Xarelto, a blockbuster anticlotting drug that has been prescribed to millions of Americans since it arrived on the market in 2011.

The agency has asked the drug’s manufacturer, Johnson & Johnson, detailed questions about whether there was evidence that the device was malfunctioning while the trial was underway, according to a legal brief filed in federal court on Monday by lawyers for patients and their families who say they were injured by the drug. The lawyers also cited internal company documents that they said showed doctors were complaining to the trial leadership during the course of the study.

The clinical trial, known as Rocket AF, was led by Dr. Robert M. Califf, currently President Obama’s nominee for head of the Food and Drug Administration. It involved more than 14,000 patients worldwide and took place from 2006 to 2010.

Xarelto, which is also known by its scientific name, rivaroxaban, is one of a new class of drugs that are seen as a replacement for warfarin, a cumbersome 60-year-old drug used to prevent strokes in people with a heart-rhythm disorder known as atrial fibrillation. Warfarin requires careful monitoring of a patient’s diet and drug regimen, and frequent blood tests to ensure that is working. If patients receive too little of the drug, they could experience a stroke. But if they receive too much, their lives could be threatened by catastrophic bleeding.

Questions about the trial have been stirring since last fall, when Johnson & Johnson and Bayer, which sells Xarelto overseas, notified regulators that the device that was used in the trial had been recalled in 2014 because it was understating patients’ risk of bleeding. The device, the INRatio sold by Alere, was used in the trial to help doctors gauge whether patients were getting the right dose of warfarin. The trial compared the number of strokes and bleeding events experienced by patients taking Xarelto to those of patients who were given warfarin.

Regulators are looking at whether the malfunctioning device might have led doctors to give patients the wrong dose of warfarin, which could have led to additional bleeding episodes and given an unfair advantage to Xarelto.

This month, researchers with the Duke Clinical Research Institute, which oversaw the trial, published their own analysis in the New England Journal of Medicine and concluded that the faulty device did not affect the trial’s outcome. A few days later, an analysis by the European Medicines Agency, the F.D.A.’s European counterpart, came to the same conclusion.

But rather than settling the matter, the analyses have raised additional questions and have come under harsh criticism from some medical experts. The Duke researchers, for example, never mentioned the existence of central laboratory tests — taken at two points during the trial — that could have been used to assess whether the device’s readings were accurate. And the analysis released by the European drug agency, while it did include those readings, was done by the companies themselves and not by independent statisticians.

“There are so many questions that are yet unaddressed,” said Dr. Harlan M. Krumholz, a cardiologist and director of the Yale University Open Data Access Project, which has an agreement with Johnson & Johnson to make the company’s data from clinical trials available to outside researchers. He has asked the company for access to the trial data, he said, and the company has agreed — but Bayer has refused.

Dr. Krumholz called on Alere to release more information about its device. “We do not know why the device did not work well,” he said.

In a statement, a spokeswoman for the F.D.A. said that while the agency was looking into the issue, it had not changed its recommendations for the drug, which “provides an important health benefit when used as directed.”

A spokeswoman for Alere declined to comment, and a representative for Duke referred to an earlier statement detailing the results of its reanalysis.

Johnson & Johnson said the INRatio device was selected because it was F.D.A.-approved and easy to use. It said it was not informed of the device recall until last September, when it and Bayer “acted with urgency, diligence and in the best interests of patients and prescribers.” The company said that it has provided answers to the questions the F.D.A. asked and that the analysis published in the New England Journal of Medicine confirmed the safety and efficacy of the drug.

A spokesman for Bayer said the company was confident in the results of the trial and dismissed the issue as being driven by plaintiffs’ lawyers, saying, “They have cherry-picked testimony and documents divorced from any context.”

Dr. Califf is the former director of the Duke Clinical Research Institute, which conducted the trial, and served as the study’s co-chairman. He has since left Duke and is now a deputy commissioner of the F.D.A. Dr. Califf, who did not respond to an email, has no role in the inquiry into the Rocket AF trial, the F.D.A. has said. The Senate was expected to vote Tuesday on whether to confirm his nomination as head of the agency.

Just as the trial was getting underway in 2006, the INRatio was facing scrutiny by the F.D.A. In 2005 and 2006, the agency sent warning letters to HemoSense, then the manufacturer of INRatio, claiming that the devices were generating “clinically significant” erroneous values and that the company, which was later acquired by Alere, was not properly investigating the complaints.

In 2014, Alere recalled the INRatio monitors, saying that they might provide inaccurate results.

However, the connection to the Rocket trial was not made public until this past fall, when a journalist for the British Medical Journal began asking the companies about it. A spokesman for Johnson & Johnson told the journal that the company had been unaware of the recall. The revelation led to the reanalysis by the Duke researchers as well as inquiries by the European Medicines Agency and the F.D.A.

But while the European agency concluded that the trial outcome was not affected by problems with the device, the F.D.A. appears to be taking a closer look, asking pointed questions about whether the company had evidence that the device was malfunctioning during the trial and what actions it took, according to the legal document, which was filed with Judge Eldon E. Fallon in the Eastern District of Louisiana.

The legal motion filed on Monday also cited internal emails that, the lawyers said, showed that some doctors were questioning the accuracy of the device while the trial was underway. The lawyers said so many concerns were raised about the device that a special program was set up to investigate the malfunctions, but none of these details were provided to the F.D.A. when Johnson & Johnson responded to the agency this month.

The Rocket trial has previously come under criticism. In 2011, the F.D.A.’s medical reviewers recommended against approval of Xarelto, citing concerns that the patients receiving warfarin during the trial were being poorly managed, which could give an unfair advantage to Xarelto.

An outside advisory committee later voted to approve the drug — although several members cited reservations — and the agency allowed it to go on the market. It has since become the best-selling drug in its class, bringing in $1.9 billion in the United States in 2015, according to Johnson & Johnson.

Some said the fact that Xarelto has been on the market since 2011 gave them faith in the safety of the product. “The real world has already made the case for this drug,” said Dr. Jürgen vom Dahl, a German cardiologist who served as an investigator in the trial, who said he did not recall encountering any problems with the device.

Dr. vom Dahl also said that he and his German colleagues have wondered whether Dr. Califf’s F.D.A. nomination was playing a role in the renewed questions about the trial. “We don’t know what is real science, and what is more politics,” he said.

But others say that plenty of questions remain, and that they are disheartened by a seeming reluctance by Duke, Johnson & Johnson and Bayer to be forthright about the problem.

“It depends on where you put the flashlight,” said Robert Powell, a clinical pharmacologist who has worked in the drug industry, as well as for six years at the F.D.A. “I think they were directing people away from the problem.”

Sabrina Tavernise contributed reporting.

Any COI? Dr. Robert Califf: FDA Commissioner and former Duke University researcher.

Document Claims Drug Makers Deceived a Top Medical Journal

By KATIE THOMAS MARCH 1, 2016

It is a startling accusation, buried in a footnote in a legal briefing filed recently in federal court: Did two major pharmaceutical companies, in an effort to protect their blockbuster drug, mislead editors at one of the world’s most prestigious medical journals?

Lawyers for patients suing Johnson & Johnson and Bayer over the safety of the anticlotting drug Xarelto say the answer is yes, claiming that a letter published in The New England Journal of Medicine and written primarily by researchers at Duke University left out critical laboratory data. They claim the companies were complicit by staying silent, helping deceive the editors while the companies were in the midst of providing the very same data to regulators in the United States and Europe.

Duke and Johnson & Johnson contend that they worked independently of each other. Bayer declined to comment. And top editors at The New England Journal of Medicine said they did not know that separate laboratory data existed until a reporter contacted them last week, but they dismissed its relevance and said they stood by the article’s analysis.

But the claim — that industry influence led to the concealing of data — carries echoes, some experts said, of an earlier era of drug marketing, when crucial clinical data went missing from journal articles, leading to high-profile corrections and a wave of ethics policies to limit the influence of drug companies on medical literature.

“It just feels like it’s a real ethical breach,” said Dr. Lisa Schwartz, a professor of medicine at Dartmouth, of the failure to include the lab data in the letter. “If you know the direct answer to this question, then how can you not provide it to be able to give insight?”

Xarelto, which is sold in the United States by Johnson & Johnson and overseas by Bayer, had nearly $2 billion in United States sales last year and is the best seller in a new category of drugs seeking to replace warfarin, an older blood thinner. The two companies hired the Duke Clinical Research Institute to run a three-year clinical trial involving more than 14,000 patients that led to Xarelto’s approval by regulators. But those results have come under scrutiny since September, when the companies notified regulators that a blood-testing device used in the study had malfunctioned.

The trial compared the number of strokes and bleeding events experienced by patients taking Xarelto with those of patients using warfarin. The concern is that the faulty results may have led doctors to give patients the wrong dose of warfarin, which could have favored Xarelto.

Last month the Duke researchers published an analysis in The New England Journal of Medicine and concluded that the problems with the device did not change the trial’s results.

But some in the medical community questioned their findings because their method required them to essentially guess which groups of patients were more likely to be affected by the malfunctioning device.

A better way to evaluate the device, other researchers said, would be to compare the device readings with test results that were done at a central laboratory. Investigators did that at two points in the trial, drawing blood from more than 5,000 of the patients who took warfarin and sending the samples for testing. The blood was taken 12 and 24 weeks after patients enrolled in the trial.

But the Duke researchers made no mention of the lab data in their letter. In an interview, journal editors said they did not know about the lab data until last Tuesday, when a reporter for The New York Times asked them about it.

“At the time we published the letter, we didn’t know that it existed,” said Dr. Jeffrey M. Drazen, editor in chief of The New England Journal of Medicine.

Dr. Drazen disputed the lawyers’ claim that the editors had been misled about the data, and said it was not relevant to the letter that was published.

Last week, lawyers in the case against Johnson & Johnson and Bayer filed a legal brief in federal court in New Orleans, asking a judge to unseal documents in the case, which involves more than 5,000 lawsuits filed by patients and their families who claim they were harmed by Xarelto. Of those, 500 involve patient deaths.

In a footnote, the lawyers said that during the process of vetting the Duke researchers’ letter, a peer reviewer asked about the existence of lab data that would allow a comparison with the device’s readings.

“Despite being provided this opportunity to respond to the peer reviewers,” the lawyers said, the “defendants remained silent on this point, thereby misleading the NEJM.”

Dr. Drazen confirmed that a peer reviewer, whose identities are kept confidential, had asked about such data, but said the editors had rephrased the question to ask whether such data was available throughout the course of the trial. Duke then answered no, he said.

The letter’s three authors, two from Duke and one affiliated with the University of Edinburgh in Scotland, declined to comment, as did a spokesman for Duke.

Dr. Drazen questioned the value of comparing lab results taken at only two points during the trial, noting that people’s blood-clotting levels can vary greatly over time. “There’s so much variation among people that it probably wouldn’t be clinically informative,” he said.

However, he said, the Duke researchers had since agreed to conduct an analysis of the lab data.

Dr. Drazen also said that the editors had not been in contact with either Johnson & Johnson or Bayer. A spokeswoman for Johnson & Johnson said the analysis by Duke was conducted independently of the company. Although a company employee serves on the trial’s executive committee, she said he recused himself “from the conduct of the reanalysis, the drafting of the research letter, and provided no feedback before it was submitted.” Bayer declined to comment.

In a previous statement, Duke said it had conducted its research separately from the two companies. But this fall, Bayer submitted an analysis to the European Medicines Agency that was nearly identical to the approach used by the Duke researchers, comparing the outcomes of patients who had specific medical conditions with outcomes of those who did not. And the legal document filed last week cites a document obtained from one of the companies that describes the peer-review process.

Some experts say this case is reminiscent of other instances in which drug companies concealed or altered drug-trial data in medical journals. In 2005, for example, The New England Journal of Medicine published a rare Expression of Concern after it learned that researchers had failed to include three heart attacks in a study of the painkiller Vioxx, made by Merck, which has since been withdrawn from the market. In that case, editors learned that data had been deleted from the trial manuscript two days before it was submitted to the journal.

Such controversies led to changes in the way that journal articles are published. Authors are now required to disclose their outside financial interests and the role that drug companies played in articles’ publication.

Several researchers said they were surprised that Duke and the editors at the journal did not see value in comparing the lab data, especially since Bayer and Johnson & Johnson have submitted such information to regulators in Europe and the United States.

“I think it’s always important to make sure that you have all the information to answer the scientific question before publication,” said Dr. Rita F. Redberg, a cardiologist who is also editor of the medical journal JAMA Internal Medicine.

Less than a week after the Duke letter was published, the European Medicines Agency released its own report, which contained analyses using the independent lab comparisons. The agency concluded the device most likely did not affect the trial’s outcome, but it did find that the device was highly inaccurate.

Dr. Steven Nissen, a cardiologist at the Cleveland Clinic, served on the Food and Drug Administration advisory panel that voted to approve Xarelto in 2011. He was one of two members who voted against the drug. He expressed doubt that any after-the-fact analysis would give doctors and patients answers. “Given the fact that the device was inaccurate, there is no way anybody can tell you what would have happened in the trial,” he said.

“Corporate criminals routinely escape meaningful prosecution for their misconduct.”

Elizabeth Warren: One Way to Rebuild Our Institutions

By ELIZABETH WARREN JAN. 29, 2016 The New York Times   The Opinion Pages | OP-ED CONTRIBUTOR

WASHINGTON — WHILE presidential candidates from both parties feverishly pitch their legislative agendas, voters should also consider what presidents can do without Congress. Agency rules, executive actions and decisions about how vigorously to enforce certain laws will have an impact on every American, without a single new bill introduced in Congress.

The Obama administration has a substantial track record on agency rules and executive actions. It has used these tools to protect retirement savings, expand overtime pay, prohibit discrimination against L.G.B.T. employees who work for the government and federal contractors, and rein in carbon pollution. These accomplishments matter.

Whether the next president will build on them, or reverse them, is a central issue in the 2016 election. But the administration’s record on enforcement falls short — and federal enforcement of laws that already exist has received far too little attention on the campaign trail.

I just released a report examining 20 of the worst federal enforcement failures in 2015. Its conclusion: “Corporate criminals routinely escape meaningful prosecution for their misconduct.”

In a single year, in case after case, across many sectors of the economy, federal agencies caught big companies breaking the law — defrauding taxpayers, covering up deadly safety problems, even precipitating the financial collapse in 2008 — and let them off the hook with barely a slap on the wrist. Often, companies paid meager fines, which some will try to write off as a tax deduction.

The failure to adequately punish big corporations or their executives when they break the law undermines the foundations of this great country. Justice cannot mean a prison sentence for a teenager who steals a car, but nothing more than a sideways glance at a C.E.O. who quietly engineers the theft of billions of dollars.

These enforcement failures demean our principles. They also represent missed opportunities to address some of the nation’s most pressing challenges. Consider just two areas — college affordability and health care — where robust enforcement of current law could help millions of people.

When the Education Management Corporation, the nation’s second-largest for-profit college, signed up tens of thousands of students by lying about its programs, it saddled them with fraudulent degrees and huge debts. Those debts wrecked lives. Under the law, the government can bar such institutions from receiving more federal student loans. But EDMC just paid a fine and kept right on raking in federal loan money.

When Novartis, a major drug company that was already effectively on federal probation for misconduct, paid kickbacks to pharmacies to push certain drugs, it cost taxpayers hundreds of millions of dollars and undermined patient health. Under the law, the government can boot companies that defraud Medicare and Medicaid out of those programs, but when Novartis got caught, it just paid a penalty — one so laughably small that its C.E.O. said afterward that it “remains to be seen” whether his company would actually consider changing its behavior.

Enforcement isn’t about big government or small government. It’s about whether government works and who it works for. Last year, five of the world’s biggest banks, including JPMorgan Chase, pleaded guilty to criminal charges that they rigged the price of billions of dollars worth of foreign currencies. No corporation can break the law unless people in that corporation also broke the law, but no one from any of those banks has been charged. While thousands of Americans were rotting in prison for nonviolent drug convictions, JPMorgan Chase was so chastened by pleading guilty to a crime that it awarded Jamie Dimon, its C.E.O., a 35 percent raise.

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To be fair, weak enforcement is sometimes a result of limited authority. Despite the company’s history of egregious safety failures, for example, the former C.E.O. of Massey Energy was convicted only of a single misdemeanor in the deadly Upper Big Branch mine disaster that killed 29 miners in West Virginia in 2010, because federal mining laws are too weak. It’s on Congress to stiffen such penalties.

But in many instances, weak enforcement by federal agencies is about the people at the top. Presidents don’t control most day-to-day enforcement decisions, but they do nominate the heads of all the agencies, and these choices make all the difference. Strong leaders at the Environmental Protection Agency, the Consumer Financial Protection Bureau and the Labor Department have pushed those agencies to forge ahead with powerful initiatives to protect the environment, consumers and workers. The Special Inspector General for the Troubled Asset Relief Program, a tiny office charged with oversight of the post-crash bank bailout, has aggressive leaders — and a far better record of holding banks and executives accountable than its bigger counterparts.

Meanwhile, the Securities and Exchange Commission, suffering under weak leadership, is far behind on issuing congressionally mandated rules to avoid the next financial crisis. It has repeatedly granted waivers so that lawbreaking companies can continue to enjoy special privileges, while the Justice Department has dodged one opportunity after another to impose meaningful accountability on big corporations and their executives.

Each of these government divisions is headed by someone nominated by the president and confirmed by the Senate. The lesson is clear: Personnel is policy.

Legislative agendas matter, but voters should also ask which presidential candidates they trust with the extraordinary power to choose who will fight on the front lines to enforce the laws. The next president can rebuild faith in our institutions by honoring the simple notion that nobody is above the law, but it will happen only if voters demand it.

Elizabeth Warren is a Democratic senator from Massachusetts.

NYT Editorial: FDA/CDRH STOP Bayer Essure Harm!

Safety Questions About a Birth Control Device

By THE EDITORIAL BOARD OCT. 14, 2015

The Food and Drug Administration convened a panel of experts last month to examine the safety and effectiveness of a device for permanent birth control that has generated thousands of complaints from women who say they were harmed by it.

The device, known as Essure, is implanted in a woman’s fallopian tubes to induce scar tissue formation to block the tubes and prevent eggs from being fertilized. It is an alternative to procedures that tie or cut fallopian tubes, and some 750,000 women have received the device around the world, mostly in the United States.

The American College of Obstetricians and Gynecologists considers Essure as effective as surgical procedures and safer in some respects. Planned Parenthood considers it an important option.

More than 5,000 women have reported harmful effects to the F.D.A. (this is very likely an undercount since many problems go unreported). According to the advisory committee’s summary, patients have reported persistent pain, bleeding, allergic reactions and the need to remove a faulty device and repair any damage. There have also been hundreds of unwanted pregnancies. The risks of removal are unknown because various techniques have not been evaluated in clinical studies. Many women out of desperation had hysterectomies, which they said eased their symptoms.

In addition to these complaints, a petition has been submitted to the F.D.A. by a Florida law firm claiming that the small company that developed the device committed fraud by manipulating data in the clinical trials that led to F.D.A. approval. The F.D.A. sent the complaint to its own compliance office. That is not good enough. The charges need to be investigated by an independent office free of influence from the F.D.A., like the inspector general of the Department of Health and Human Services.

The manufacturer, Bayer HealthCare Pharmaceuticals, which acquired the device in 2013, argues that the percentage of women reporting problems is low and that many of the problems are unrelated to the device.

All birth control measures carry risks and benefits. What women and doctors need to know is how this device compares with surgical procedures and intrauterine devices in preventing pregnancies and causing minimal harm. The F.D.A. needs to look hard for ways to get that information and should consider suspending sales of Essure until better data is available.

http://nyti.ms/1ZDcQCZ

US Senate Must NOT Pass 21st Century Cures Bill

How Not to Fix the F.D.A.

By THE EDITORIAL BOARD      JULY 20, 2015

A bill passed by the House and ostensibly designed to streamline the Food and Drug Administration is loaded with bad provisions and may not even be necessary. The Senate should either eliminate or rewrite the flawed provisions before passing its version of the legislation.

The bill would weaken the F.D.A.’s already flimsy regulation of medical devices, posing a threat to future patients who have devices implanted that cannot easily be removed if found defective. It would allow a drug to be tested on humans based on only limited evidence that it is safe and effective.

It would expedite the use of new antibiotics by providing financial incentives to hospitals to use them — benefiting manufacturers but also driving up costs and encouraging overuse, potentially breeding resistant superbugs. It would extend exclusive rights for manufacturers to market high-priced, brand-name drugs if they gain a new approval to treat a rare condition. And it would open a wide loophole in rules requiring companies to report payments they make to doctors to get them to prescribe their drugs.

While the bill has some valuable provisions — like making experimental drugs available more quickly to patients who have illnesses that cannot be cured, and promoting the development of treatments based on an individual’s genetic data — those elements don’t justify the bill’s passage in its current form.

The F.D.A. was once routinely vilified for sluggishness and timidity, but with the help of industry funding it has made enormous progress in speeding up its reviews and approvals. The agency testified in April that its drug review times are consistently faster than those of all other advanced regulatory agencies around the world, with the result that American patients receive new drugs sooner than people elsewhere. In 2014, the F.D.A. approved the largest number of new drugs in almost 20 years and also reduced the review times for devices.

A big reason the bill won bipartisan support in the House is that it would increase funding for the National Institutes of Health by $8.75 billion over the next five years, ending a decade of mostly stagnant funding. And any improved Senate version should certainly include new money.

Special interest money also played a role, with many of the top supporters of the legislation having received hundreds of thousands of dollars in contributions from the pharmaceutical industry and the medical device industry last year, according to the nonpartisan Center for Responsive Politics.

The Senate will take up a similar bill later this year. When it does, it needs to cure its many flaws, while also providing sufficient funds to the F.D.A. to meet its ever-increasing workload.

http://www.nytimes.com/2015/07/20/opinion/how-not-to-fix-the-fda.html?emc=edit_tnt_20150720&nlid=50639700&tntemail0=y&_r=0

The FDA's Medical Device Problem

The F.D.A.’s Medical Device Problem

By RITA F. REDBERG and SANKET S. DHRUVA              JULY 17, 2015

THE Food and Drug Administration has been regulating the approval of medical devices since 1976, but its regulatory oversight has not kept pace with the increasing complexity of this technology. Many high-risk medical devices today are approved on the basis of just one clinical trial (as opposed to new medications, which usually require two trials). And only a small minority of clinical studies of medical devices are randomized, controlled and blinded — the gold standard for reliable evidence (and the benchmark to which studies of drugs are held).

As a result, there have been many warnings about, and recalls and withdrawals of, medical devices that were found to be dangerous only after they were on the market. (In 2009, for example, the Sprint Fidelis defibrillator, which by that time had been implanted in hundreds of thousands of heart patients, was recalled because it frequently malfunctioned, harming many patients and leading to numerous deaths.) And because the F.D.A.’s oversight of medical devices once they are on the market is also weak, it is very likely that many malfunctions and other problems remain undetected.

Incredibly, legislation that the House of Representatives passed last week would severely weaken, not strengthen, the F.D.A.’s already ineffective regulatory scheme for medical devices. The device industry may stand to benefit from this legislation, but the health of the public does not.

The legislation, disingenuously titled the 21st Century Cures Act, would make it possible for companies that produce high-risk medical devices to submit evidence of safety and efficacy based on sources other than clinical trials, including case histories (i.e., the experiences of individual patients). In other words, anecdotal evidence, rather than the scientific studies, could be used to approve devices.

This act would also create a new, faster approval process for “breakthrough technologies” that are believed — but not necessarily proved — to offer significant advantages over existing alternatives. This would allow a device to be approved based on even lower standards of evidence than are currently used, on the theory that the need outweighs the risk. The legislation defines “breakthrough” loosely, creating a perverse incentive for manufacturers to use this term both to take advantage of the faster approval process and as a marketing gimmick.

In general, the proposed law is likely to shift the burden of evidence to clinical studies that are conducted only after the devices have been put on the market. Unfortunately, such studies are often delayed months to years after a device is approved. Many are never completed (and even when they are, their findings are often not publicly available). Although the proposed law alludes to “timely postmarket data collection,” that vague directive needs to be clearly defined — and more important, enforced — by the F.D.A. In fact, according to a 2014 journal article co-written by one of us, the F.D.A. has never issued a warning letter or penalty for a postmarket study delay.

Even if a postmarket clinical study deems a medical device dangerous, it still can be difficult to remove it from the marketplace. In 2005, for example, an intracranial stent called the Wingspan was approved on an expedited basis to prevent recurrent strokes. When a high-quality clinical trial was finally completed, in 2011, it found that patients who had the device implanted were more likely to have another stroke and to die than those just receiving medical management. Despite this evidence, the F.D.A. did not withdraw the device (though it did narrow its recommended uses). The Wingspan continues to be marketed and implanted today, putting patients at unnecessary risk.

Once a medical device is developed and approved, its manufacturer often makes small changes intended as enhancements (such as using a different size wire or new material). Currently, the F.D.A. is the arbiter responsible for ensuring that these changes result in a safe and effective device. But alarmingly, the 21st Century Cures Act would establish a third-party program of nongovernment authorities to assess whether a company is permitted to make such changes. The act would enable the device manufacturer itself to select — and pay — the third party from an approved list. This flagrant conflict of interest would make it impossible for physicians or patients to have trust in the safety or effectiveness of updated medical devices.

The 21st Century Cures Act would subject millions of Americans to unsafe or untested medical devices. We urge the Senate, as it takes up the bill, to avoid these dangerous provisions. Unlike medical drugs, which can readily be discontinued if problems are found, many medical devices are permanently implanted and cannot easily be removed if found to be defective. Stricter evidence standards and increased federal funding of the F.D.A. are needed to ensure that innovative medical devices lead to better health.

Rita F. Redberg is a cardiologist at the University of California, San Francisco, Medical Center. Sanket S. Dhruva, a cardiologist, is a clinical scholar at Yale University.

http://www.nytimes.com/2015/07/17/opinion/the-fdas-medical-device-problem.html?emc=edit_tnt_20150717&nlid=50639700&tntemail0=y&_r=0