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.

F.B.I. Investigates: Are Medical Device Adverse Events Reported?

F.B.I. Investigates Whether Harm From Surgical Power Tool Was Ignored

By DENISE GRADY and KATIE THOMAS MAY 27, 2015

The Federal Bureau of Investigation has begun looking into whether medical device makers, doctors and hospitals broke the law by failing to report problems linked to a power tool used during gynecologic surgery, according to two people who said they were interviewed by investigators.

The tool, called a morcellator, has rapidly spinning blades that cut tissue into pieces that can be removed from the body through the tiny slits made during minimally invasive surgery. Morcellators have often been used in surgery to remove the uterus, but in some women with undetected cancers they have sprayed malignant cells around inside the abdomen like seeds, speeding the progression of the disease.

The inquiries were first reported on Wednesday by The Wall Street Journal, which said the agents worked out of the F.B.I. office in Newark, N.J.

Celeste Danzi, a spokeswoman for the F.B.I.’s Newark office, declined to confirm the inquiry. “We just don’t comment on the existence or nonexistence of any investigation,” she said.

In an interview with The New York Times, Dr. Hooman Noorchashm, whose wife, Dr. Amy Reed, was harmed by the device, confirmed that they had spoken a number of times to an F.B.I. agent from Newark. A retired pathologist from Pennsylvania, Dr. Robert W. Lamparter, also said he had spoken to investigators. Both men declined to name the agent, saying they had been warned that disclosing too much information could interfere with the investigation.

Dr. Reed, 42, an anesthesiologist, had a hysterectomy because of fibroid tumors in her uterus in October 2013 at Brigham and Women’s Hospital in Boston. Fibroids are benign, but they sometimes hide cancer. A biopsy after Dr. Reed’s surgery found a hidden sarcoma, an aggressive type of cancer. The tumor spread, resulting in advanced Stage 4 cancer. Dr. Reed underwent numerous rounds of chemotherapy and radical surgery, but the cancer recurred in March of this year, near her spine, requiring still more surgery.

The couple, who have six children, have conducted a ceaseless nationwide campaign to ban morcellation. Gynecology groups have resisted, saying that sarcomas are uncommon and that morcellation makes surgery less invasive and safer for the majority of women.

In November, the Food and Drug Administration said that morcellators should no longer be used in “the vast majority” of women. But the agency did not take the devices off the market or ban their use.

Dr. Noorchashm said he contacted an agent from the Newark F.B.I. office last fall, because he suspected that morcellator manufacturers and some doctors and hospitals using the devices had violated a federal law requiring that adverse events be reported to the F.D.A. He said that he and his wife spoke with the agent a number of times over a few months, and that the F.B.I. seemed increasingly interested.

Dr. Lamparter said that he had also recently spoken to the F.B.I., and that the conversation had focused on his 2006 correspondence with Ethicon, the unit of Johnson & Johnson that sold power morcellators. At that time, he warned Ethicon of the potential for the morcellators to spread undetected cancer, according to email correspondence he provided to The Times and other news outlets. Johnson & Johnson withdrew its morcellators from the market last July.

Johnson & Johnson has said that after Dr. Lamparter raised his concerns, it added new language to the instructions for use of the device, and that the company had already recommended that, in patients where a cancer was suspected, doctors should use a special bag to remove the tissue.

In a telephone interview Wednesday, Dr. Lamparter said that he considered the change a “legal fig leaf” and that the gynecologists at his hospital, Evangelical Community Hospital in Lewisburg, Penn., reported that the training they received from the company in using the device did not substantially change after he raised his alarm.

Dr. Lamparter said he initially believed that the morcellator could still be used, but not on women at high risk for cancer. However, he added, “I’ve come to believe that the morcellator, as it is used now, is just a bad idea.”

Ernie Knewitz, a Johnson & Johnson spokesman, said it was unaware of any investigation.

Kate Zernike contributed reporting.

http://www.nytimes.com/2015/05/28/business/fbi-investigates-whether-harm-from-surgical-power-tool-was-ignored.html?emc=edit_tnt_20150527&nlid=50639700&tntemail0=y&_r=0

Patient Last To Know About Implant Danger

September 7, 2012  The New York Times

Unpredictable Danger Looms Close to the Heart

By KATIE THOMAS

Monsters attacked Avery de Groh when she was 4. That is how she remembers the day in 2007 when the defibrillator in her chest misfired, sending nine electric shocks through her body in less than 30 minutes.

Molly de Groh and her children Oliver, left, and Avery all have defibrillators implanted. When Avery’s misfired, repeatedly shocking her, doctors tried to fix it. Now they fear it could do it again.

Today, Avery is a chatty 9-year-old who just learned to roller-skate. She is old enough to know that she was not really attacked by monsters. The culprit was a broken wire from the defibrillator that keeps her heart beating normally. Like her mother and two brothers, she has an inherited condition that makes her prone to a fatal heart rhythm. After Avery’s episode, doctors removed the faulty wire, made by Medtronic, and replaced it with a new one made by St. Jude Medical.

Now it is possible that one is damaged, too. The wire, or lead, known as the Riata, was recalled in December after St. Jude warned doctors that internal cables were poking through the outer casing, causing unwanted shocks or failing to work when needed. Nearly 20 percent of the 128,000 people worldwide who have the Riata may be affected, according to the company.

Molly de Groh, Avery’s mother, said she worried that Avery’s new lead would also malfunction. “When I think about how scary it was for her,” she said, “I feel like, give that to me, and let her be fine.”

Heart device specialists have struggled for months to determine how best to treat patients with damaged leads. There is no easy fix: removing the wires can be dangerous, but so can leaving them in. In August, the Food and Drug Administration recommended that all patients with the Riata undergo imaging to see if their lead was failing. But the guidelines did little to settle the matter after some doctors questioned the wisdom of the advice.

Patients are caught in the middle, forced to grapple with life-or-death decisions for which there are no easy answers.

Mark Ulrich has decided not to wait. Several years ago, Mr. Ulrich’s defibrillator misfired in reaction to a medication he was taking. “I was pretty well barbecued,” said Mr. Ulrich, who is 68 and lives in Manhattan. “I would rather not be turned into a shish kebab.”

Dr. Jeffrey N. Rottman, a heart device specialist at Vanderbilt University, said most of his patients with damaged leads had elected to have them removed. “I think people who have a defibrillator already have a ‘just fix it’ type of approach,” he said.

That was Jacob Everidge’s attitude. Mr. Everidge, a 23-year-old from Athens, Ala., who has a condition that thickens the heart muscle, had his Riata removed by Dr. Rottman on Aug. 20. “I would much rather go ahead and get it out,” he said. “It wasn’t even a decision.”

For now, Ms. de Groh said, she will follow her doctor’s advice to wait and see if Avery’s lead begins to fail. But that raises other painful questions. Should the de Grohs cancel a family vacation in the Catskills, where they’ll be a half-hour from the nearest hospital? Can they send Avery to a sleepover? “As a mom of a fourth grader, I’ve got to send her to school,” said Ms. de Groh, a nurse in McHenry, Ill., a small town northwest of Chicago. But “for her not to be in my sight at all times is scary.”

Ms. de Groh and all three of her children were born with Long QT syndrome, which can cause their hearts to beat abnormally. She has a defibrillator made by Boston Scientific. Her 5-year-old son, Oliver, has the Durata, a newer lead made by St. Jude, whose safety has also been questioned recently. Her younger son, 3-month-old Monty, is too young for the operation, but he will eventually need a defibrillator, too. Because of her family history, Ms. de Groh has traveled twice to Washington to lobby lawmakers on device safety, but said she learned of the Riata recall only in August, after reading a newsletter written by a patient advocacy group.

She said she was angry at the F.D.A. and St. Jude for not contacting patients directly. “When something is implanted in a body, especially a child’s body, how can I find out about it through a newsletter?” she asked. Avery’s doctor, Marc Ovadia, said he chose not to tell Ms. De Groh about the recall because Avery’s lead is functioning “perfectly” and replacing it would require cracking open her chest. Telling patients about the recall, he said, could lead to unnecessary worry. “We want to make sure before we yell ‘fire’ in a crowded theater that this is fire,” he said. Still, he said, he regrets that Ms. de Groh found out about the recall the way she did. “These are tough, tough issues,” he said.

Mrs. de Groh’s frustration echoed that of consumer advocates who have criticized manufacturers and the F.D.A. for what they said was inadequate testing of medical devices before approval and a chaotic system for identifying problems once they are on the market.

In one example of the conflicting information about the devices, St. Jude reported last November that the problem with the Riata leads was affecting less than 1 percent of patients. But an internal report by an F.D.A. employee that month challenged that assessment, arguing that the company was underestimating the problem. The agency did not publicize the report, which was obtained through a Freedom of Information Act request and provided to The New York Times by a lawyer whose client is suing St. Jude.

The F.D.A. analysis proved to be correct: in July, a new St. Jude study found that the Riata showed signs of failing in 19 percent of patients.

The F.D.A. declined to comment on the report, other than to say that it was not unusual for the agency and the manufacturer to evaluate safety risks differently. Mitchell Shein, a manager in the F.D.A.’s division of cardiovascular devices, said deciding when to communicate with the public was often a tough call. “We’re very, very cautious to enter the public discourse on a medical issue unless we think we have something to add to that,” he said.

In addition to its recommendations that all patients with the Riata undergo imaging tests, the agency also ordered St. Jude to conduct additional studies on the Riata, which is no longer sold, and the Durata. Both were designed to be thinner than competing leads sold by Boston Scientific and Medtronic, making them easier to guide through blood vessels.

The Durata is made with a new coating that the company said seemed to have fixed the issue, but a study by a leading heart researcher has recently called that into question.

When a defibrillator is implanted, the lead is threaded through a blood vessel until it reaches the heart. In time, scar tissue can build up around it, making removal risky. The agency advised against removing the leads pre-emptively and said patients who had not experienced problems should undergo regular monitoring.

Some doctors have challenged the recommendation against routinely removing the leads, arguing that they can cause other problems when left in, like interfering with replacement leads. “There are potential risks associated with all options,” said Dr. Laurence Epstein, a heart device specialist at Brigham and Women’s Hospital in Boston.

Dr. Ovadia, a heart device specialist at Advocate Lutheran General Children’s Hospital outside of Chicago, said he did not know that the F.D.A. was recommending that all Riata patients undergo imaging tests until a reporter told him about the agency’s advice. And he said a St. Jude sales representative did not inform him of the new recommendations in a conversation in late August.

A St. Jude spokeswoman said the company notified doctors about the F.D.A. recommendations in a letter posted to its Web site, which it also sent to St. Jude field representatives. The letter explained the F.D.A.’s position on imaging, but also noted the issue was “complex and needs to take into account additional patient circumstances.”

In a separate statement, St. Jude said the company “continues to work closely with the F.D.A. and communicate important information with accuracy and integrity in a timely manner to inform patient care.”

Ms. de Groh said her thoughts had been turning to her baby, Monty. For now, he takes beta blockers to regulate his heartbeat. Common sense would tell her that he should receive a defibrillator when he is old enough. After all, medical devices fail in only a tiny percentage of cases.

“They’re supposed to save their life, but all it’s done in our family is cause problems,” Ms. de Groh said. “So you’re really conflicted as a parent on how to treat your kid if these devices are going to constantly be a source of fear and worry.
 

Smarmy corporate action: surgical mesh

http://www.nytimes.com/2012/06/06/business/johnson-johnson-unit-will-stop-selling-urinary-implants.html?emc=tnt&tntemail1=y

June 5, 2012

Johnson & Johnson Unit to Halt Urinary Implants

By KATIE THOMAS  New York Times  (FiDA blog bold)

Johnson & Johnson’s Ethicon division will stop selling four types of mesh implants used to treat urinary incontinence, the company announced in a letter to judges overseeing two large groups of lawsuits filed by women who claim the devices caused serious injury.

In a statement Tuesday, the company stressed that the move was not a recall, but was based on the products’ commercial viability “in light of changing market dynamics, and is not related to safety or efficacy.”

The announcement comes after years of controversy over the implants, which are used to treat incontinence caused by muscle weakening and a condition called pelvic organ prolapse, in which organs descend and press against the vaginal wall. The devices have been linked to serious injuries in women, including infections, pain and other complications. In 2008, the Food and Drug Administration warned that use of the implants was associated with complications but that the problems were rare. But between 2008 and 2010, the agency reported a fivefold increase in reports related to the use of the devices. In January, the F.D.A. ordered makers of the implants to study their risks in patients.

“This is very good news for women because it takes several products off the market that have harmed a lot of women,” said Diana Zuckerman, president of the National Research Center for Women and Families, a public health advocacy group. However, she said, “the bad news is that there are many other surgical meshes still on the market that are just as dangerous.”

Other device makers that also sell surgical mesh products include Boston Scientific, C. R. Bard and W. L. Gore & Associates. In a statement, a spokeswoman for Boston Scientific said the company believed that using such products “is and remains an important treatment option for patients.”

The four products Ethicon will discontinue are the Gynecare TVT Secur system, the Gynecare Prosima, the Gynecare Prolift and the Gynecare Prolift+M. Ethicon will stop selling the products over the next three to nine months, with a goal of ending sales worldwide by the first quarter of 2013. A spokesman for Ethicon declined to say how many women were implanted with the products.

Johnson & Johnson has undergone a series of product withdrawals and recalls in recent years, including the recall of artificial hips, contact lenses and other products, and the recent decision to end its line of drug-coated heart stents.