Category Archives: News Stories & Editorials

Women’s Health Advocates Question FDA About Missing Safety Data on Silicone Breast Implants

News Stories & Editorials
Associated Press: January 5, 2012

WASHINGTON — Consumer safety advocates are questioning the Food and Drug Administration about seemingly incomplete and erroneous data used to affirm the safety of silicone breast implants last year.

The FDA concluded last summer that the silicone-gel implants are basically safe as long as women understand they come with complications. More than one in five women who get implants for breast enhancement will need to have them replaced within five years, the agency’s report concluded.

In August, an outside panel of physicians affirmed the FDA’s decision that the devices should remain available for both breast enhancement and reconstruction.

But the National Research Center for Women and Families says the FDA did not present information that showed women reported lower emotional, mental and physical well-being after implantation. Additionally, the group questions why figures presented by the FDA appear to show implant complications declining over time. The implants are known to fail over time.

“This shows problems with the data, since the complication rates are reported to be cumulative and should therefore stay the same or increase over time,” states Diana Zuckerman, the group’s president, in a letter to the head of FDA’s medical device division.

Most of the FDA’s data on the safety and effectiveness of breast implants comes from long-term studies conducted by the two U.S. manufacturers of the devices, Allergan Inc. of Irvine, Calif., and Mentor, a unit of Johnson & Johnson, based in New Brunswick, N.J.

When the FDA reviewed the initial applications for the devices in 2005, women using Allergan’s implants scored lower on nine out of 12 quality-of-life measures, including mental, social and general health. Women did report higher scores on measures of sexual attractiveness-body esteem.

Women implanted with J&J’s implants also scored worse on measures of physical and mental health. In the 11-page letter, Zuckerman questions why that information was not presented at FDA’s public meeting in August.

“Breast implants are widely advertised and promoted as a way to increase women’s self-esteem and positive feelings about themselves,” said Zuckerman, in an interview with the Associated Press. “But the implant companies’ own data, which the FDA made public in 2005 but ignored last year, shows the opposite.”

Silicone gel breast implants have traveled a long, winding regulatory path at the FDA over the last 20 years. The FDA banned the silicone-gel type in 1992 amid fears they might cause cancer, lupus and other diseases. For more than a decade, only saline-filled implants were available. But when research ruled out most of the disease concern with silicone, regulators returned the implants to the market in 2006 — with the requirement that manufacturers continue studying patients to see how they fare long-term.

When the FDA revisited the devices’ safety last year they relied on eight and 10-year follow-up data from J&J and Allergan, respectively. This followed up on similar data submitted in 2005.

Breast implants are known to rupture and break down over time. But Zuckerman points out in her letter that the company data seem to defy this trend, with complication rates falling over time.

For instance, Allergan’s reported rate of swelling among patients fell from 23 percent in 2005 to 9 percent reported in 2011. Rates of scarring similarly fell from 8 percent to 4 percent.

“This again raises questions about the accuracy of reporting, and whether patients with complications were excluded from the 10-year sample,” writes Zuckerman.

FDA staffers did not immediately respond to a request for comment Thursday.

The questions about FDA’s review of breast implants come amid a wave of recalls and warnings over similar devices across Europe and South America. The implants from French company Poly Implant Prothese are being pulled from the market amid fears they could rupture and leak silicone into the body.

French investigators say the now-defunct company used cheap industrial silicone, not medical-grade silicone, and that more than 1,000 women in France have had one or two implants burst. French health officials have agreed to pay for an estimated 30,000 women in France with the implants have them removed.

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Insight: Breast Implant Scandal Shows Regulators in Dark on Risk

News Stories & Editorials
Anna Yukhananov, Reuters: December 29, 2011

(Reuters) – Long before the latest global breast implant scare, American health officials were toying with the idea of building a registry that would track patients with implants.

The registry would give a better idea of the number of complications over time, such as rupture or infection.

But to this day, none exists for the world’s largest healthcare market, which often serves as a global model for regulatory practice. Some individual countries in Europe have made their own attempts but with only limited success, and there is no continent-wide registry.

In the wake of the current scandal surrounding France’s Poly Implant Prothese (PIP), which used industrial grade silicone instead of medical grade silicone in implants placed surgically in some 300,000 women worldwide, advocates for a registry are again pushing the idea.

The French government has advised the 30,000 women in France who bought the implants to have them removed and governments in several other countries, such as Britain and Brazil, have asked women to visit their doctors for checks.

“If we had had registries, we would have known years ago if it’s true that PIP implants break sooner,” said Diana Zuckerman, president of the National Research Center for Women & Families. “We would have known if Mentor ones break sooner or later than Allergan’s,” she said, referring to the two largest makers of breast implants.

There were almost 400,000 breast enlargement or reconstruction procedures in the United States in 2010, according to the American Society of Plastic Surgeons. That includes silicone and saline implants.

The U.S. Food and Drug Administration has relied on company-funded efforts to track the safety of implants since allowing the silicone versions back on the market in 2006. It had banned silicone implants in 1992 after some U.S. women said the devices leaked and made them chronically ill.

Failed to Meet Goals

The approval given to Allergan and Johnson & Johnson’s Mentor unit was conditional on the companies each following 40,000 women who received the implants for 10 years, as well as extending smaller pre-approval studies.

In August, Allergan said it had only collected two-year data for 60 percent of participants, while Mentor only had three-year data for 21 percent.

Consumer and patient groups have criticized the two companies for failing to meet the goals. They have asked the FDA to revoke Mentor’s marketing approval and to force Allergan to conduct further studies.

In addressing low response rates, representatives of both companies said the studies may have tried to keep track of too many patients and included overly cumbersome requirements, such as filling out a 27-page questionnaire each year.

Allergan offered patients $20 to participate in the study, and $100 for each office visit, while doctors were paid $200 for enrolling each patient. Mentor did not offer any cash incentives to patients but gave doctors $100 for each participant.

In August, Mentor attributed its low response rate to a switch in policy. While it initially required patients to participate in the study if they wanted to buy an implant, it later made that participation voluntary.

Mentor and Allergan both expressed support for a registry at the FDA’s meeting in August. But the companies, physicians and regulators have so far failed to reach an agreement over who will pay for it, how information will remain private and whether participation will be mandatory.

The concept of a registry is a good one, but carrying it out is complicated, said Allergan spokeswoman Caroline Van Hove.

“There has been already plenty of discussion with the FDA to really logistically figure out how you would do this,” she said. There has been no agreement on a methodology and a system that would work for all implants and all patients, Van Hove added.

Mentor said it is committed to working with the FDA to monitor implant safety, through registries or clinical studies.

So far, the companies’ studies have found similar rates of complications such as rupture and hardening of the device, and no apparent link between silicone implants and connective tissue disease, breast cancer or reproductive problems – though the FDA said the low level of participation meant this wasn’t conclusive.

Little Incentive to Keep Track

The FDA said enrolling patients in follow-up studies was a challenge, and that the agency would work to involve different groups, including advocacy groups and physicians, to make sure patients understand the benefits of sharing information. The agency said the implants were safe enough to stay on the market.

“You can have the most well-meaning company, but if the patients don’t want to participate in the study, that’s out of their control,” said Dr William Maisel, deputy director of the FDA’s devices division, at the time.

Some critics say that companies cannot be relied on to track this data, and that a more systematic effort is needed, especially as the FDA itself says women are likely to need to replace their implants every 10 years due to the risk of complications.

“They have fiddled around with this issue (of registries) for over 20 years, and nothing has been done,” said Sybil Niden Goldrich, a consumer advocate on breast implants. “We still don’t have an accurate rupture rate on these products.”

In the late 1980s, Goldrich’s own silicone implants, used to reconstruct her breasts after a mastectomy, ruptured and migrated to different locations on her body. She campaigned for the FDA to require implant manufacturers to conduct clinical trials and since 1988, has called for a registry to be created.

Registry Models

The FDA and other groups have proposed different models for registries that can track all medical devices, from following patients through their insurance company to allowing patients to voluntarily report complications via an online database.

Patients can currently report problems with implants to the FDA’s MedWatch program, a system for keeping track of complaints about drugs and devices, which the agency can theoretically use to detect problems.

But many are not aware it exists. At the FDA meeting in August, the vast majority of the dozens of women who testified on problems with breast implants had not reported their complaints to MedWatch.

Manufacturers and facilities such as hospitals and nursing homes are required to tell the agency of device-related deaths. Reports of serious injuries from devices only have to go to the manufacturer, who then decides what to report to the FDA within a 30-day period.

Europe’s Experience

Denmark set up a registry in 1999, and data from the first 1,600 women has been used for studies that look at implants’ safety. France has no registry for implants.

In Britain, a registry to track breast implant issues was set up in 1993, funded by the government. Reporting was voluntary on the part of the patient, surgeon and hospital.

But few women were willing to take part, and after funding dried up, the registry was shut down in March 2006. An independent review group had previously recommended that the registry be compulsory.

Surgeons and campaigners are now keen to restart it, though they say a better solution would be to have a database that tracks all implants in Europe.

“If we could have a register that was European-wide that would be wonderful,” said Douglas McGeorge, a consultant plastic surgeon and a former president of the British Association of Aesthetic Plastic Surgeons. “It would mean that wherever in Europe you were treated, you could always get access to your information.”

A European registry may be bolstered by government-run health systems in many countries. But in the U.S., it may not be a panacea, as many implants are not covered by insurance.

U.S. patients and their doctors may not have enough incentives to stay in studies, especially if they have to fill out lengthy questionnaires every year, or do expensive tests to see if their implant has ruptured.

Given those disincentives, Dr. Caroline Glicksman, a New Jersey-based surgeon, said a registry should be mandatory.

“I cannot get women to come back (for follow-up) when everything is fine,” said Glicksman, who is now conducting research on Allergan implants. “A registry is valuable. When an implant deflates or things go wrong, it’s very important to have because these are not life-long devices.”

(Additional reporting by Kate Kelland in London, Alina Selyukh in Washington, Lewis Krauskopf in New York, and Debra Sherman in Chicago; Editing by Michele Gershberg and Martin Howell)

The original article can be found here.

FDA Revokes Avastin Approval for Breast Cancer. Decision Leaves Some Devastated. Drug Will Remain Available to Treat Other Cancers.

News Stories & Editorials
Rob Stein, Washington Post: November 19, 2011

The Obama administration revoked approval on Friday of the top-selling cancer drug Avastin for treating advanced breast cancer, despite appeals from distraught women, some patient advocates and the company that makes the drug.

Food and Drug Administration Commissioner Margaret A. Hamburg issued a 69-page decision that said a review had clearly shown the drug was harming women more than it was helping them. Studies have found that Avastin can increase the risk of dangerous bleeding, heart attacks and other problems.

“Sometimes, despite the hopes of investigators, patients, industry and even the FDA itself, the results of rigorous testing can be disappointing,” Hamburg said. “This is the case with Avastin when used for the treatment of metastatic breast cancer.”

While medical advances have reduced the death toll from breast cancer, the malignancy remains the most common cancer among women, and the decision leaves few last-ditch options for many of those fighting the most advanced form of the disease. As a result, the fate of the drug had sparked one of the more emotional and acrimonious debates in years over a medical treatment among patients, oncologists, women’s health advocates, health-care policymakers, politicians and the pharmaceutical industry.

Some patients likened the FDA decision to a death sentence. Advocates of quicker access to new treatments and critics fearing health-care rationing called it a prime example of government overstepping. But many leading researchers, public health analysts and even prominent breast cancer doctors and advocates praised the decision. They saw it as a crucial demonstration that careful examination of the scientific evidence trumped emotion and intense public pressure.

Despite the revocation, Avastin will remain available to treat other cancers, enabling doctors to prescribe it “off-label” for breast cancer patients. But several insurance companies have already stopped paying for the drug for breast cancer, and the decision will probably prompt more to follow. Avastin costs about $99,000 a year per patient. Breast cancer patients also will lose eligibility for a program sponsored by drugmaker Genentech that caps the annual cost at about $58,000 for women making less than $100,000 a year and helps cover insurance co-payments.

Medicare, however, will continue to pay for Avastin, at least for now, officials said. Genentech’s foundation also will help women who do not have insurance or whose insurance refuses to pay for it, and will refer women to other charitable groups that could help them, said company spokeswoman Charlotte Arnold.

“We are disappointed with this outcome. We remain committed to the many women with this incurable disease and will continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment,” she said.

The decision was condemned by some patient advocacy groups.

“By not recognizing the fact that a subgroup of women with metastatic breast cancer respond well to Avastin, we have yet another tragic mistake by the FDA,” said Frank Burroughs, founder of the Abigail Alliance, which advocates for greater access to new treatments. “Because of FDA drug rejections like Avastin for breast cancer, the terribly slow FDA approval of lifesaving therapies and the FDA’s blocking of compassionate access, we are losing thousands of lives of cancer patients and others with serious life-threatening illnesses each year.”

‘I am stunned’

Individual patients also expressed outrage and despair.

“I am devastated,” said Patricia Howard, 66, of Summerfield, Fla., who pleaded with the FDA’s advisory committee to retain the approval. “I am stunned by the lack of compassion of the FDA for those of us who are successful on this drug. . . . Every time I sit in the infusion chair I worry if this will be my last infusion.”

In a statement, J. Leonard Lichtenfeld, deputy chief medical officer of the American Cancer Society, said he hoped that, at the very least, insurance companies would continue to pay for the drug for women “with metastatic breast cancer who are currently on the drug and who are showing a benefit from its use.”

Several major insurance companies contacted Friday said they were reviewing their positions on Avastin in light of the FDA’s revocation.

The decision was praised by many others, including several leading breast cancer advocacy groups and experts who said it was important for the agency to base its decisions on the results of careful clinical studies, not emotional appeals, especially when lives are at stake and controlling health-care costs is so crucial to the nation’s economy.

“We should be using our time and resources to find drugs that work. It is unfortunate that Avastin does not,” said Fran Visco, president of the National Breast Cancer Coalition, a patient advocacy group. “Marketing campaigns and appeals by the public devastated by breast cancer cannot change that. These women deserve drugs that well-designed research tells us will prolong their lives. Let’s focus our attention on making that happen.”

Among the costliest

The FDA is not supposed to acknowledge cost in drug approvals, and officials have stressed that the price was irrelevant. But coming amid a continuing national debate over President Obama’s health-care overhaul, the fight about Avastin has become entangled in the politically sensitive struggle over medical spending and effectiveness.

“The fact remains that thousands of women today depend on Avastin as a vital tool in their fight against breast cancer, and the FDA should not have taken that option off the table by rationing access,” said Sen. David Vitter (R-La.)

Avastin is among the costliest of a new generation of anti-cancer medications that appear to offer some patients perhaps a few extra months of life. It was the first drug designed to fight cancer using a new strategy – inhibiting blood flow to tumors – and was approved for treating several malignancies. Evidence is much clearer that the approach is effective for colon, lung, kidney and brain cancer.

Avastin for breast cancer has been controversial since its approval in 2008. Only one study found that the drug appeared to slow the growth of an advanced breast tumor, delaying progression by about 51 / 2 months. It remained unclear whether patients lived longer or enjoyed a better quality of life. So the FDA authorized Avastin under a special program designed to make advances in treatment available to patients quickly. The deal was that Genentech must validate the risk-benefit ratio with additional studies.

The agency moved in December to revoke the approval based on a July 2010 advisory committee conclusion that the new studies had not shown that the drug extends life and had indicated that it slowed tumor growth for far less time – perhaps as little as a month.

At the same time, the drug increased the risk for life-threatening bleeding and hemorrhaging, heart attacks, heart failure, severe high blood pressure and perforations in different parts of the body, including the nose, stomach and intestines.

Genentech immediately challenged that decision. That led the agency to convene a two-day meeting in June, which was marked by unusually tense exchanges between representatives of Genentech and agency officials. In the end, the six-member committee concluded that the drug was doing more harm than help.

New research vowed

On Friday, the company vowed to start a new study of Avastin in combination with another drug in metastatic breast cancer patients to “evaluate a potential biomarker that may help identify which people might derive a more substantial benefit from Avastin,” Arnold said.

Before the FDA announced initial plans to revoke Avastin’s approval for breast cancer, the drug was being prescribed annually to about 60 percent of the 29,000 U.S. women with breast cancer who were eligible. Globally, Avastin had annual sales of about $5.5 billion in 2010, making it the world’s best-selling cancer drug and one of the top-selling products for Genentech and Roche, its Swiss owner.

Genentech has waged an unprecedented campaign to keep U.S. approval of the drug for breast cancer. But as questions have been raised about its safety and effectiveness, sales and use of the drug have dropped significantly for breast cancer in the United States, falling to about 20 percent of eligible women, according to Genentech.

“The science is clear: Breast cancer patients are more likely to be harmed than helped by Avastin,” said Diana Zuckerman, president of the National Research Center for Women & Families. “The risks of the drug are very substantial and can be fatal, killing patients long before they would otherwise die from the disease. FDA made a scientific decision, and it was absolutely the right decision.”

Staff writer N.C. Aizenman contributed to this report.

FDA Revokes Avastin Approval

News Stories & Editorials
Lauran Neergaard, Associated Press: November 18, 2011
By LAURAN NEERGAARD, AP Medical Writer

The government delivered a blow to some desperate patients Friday as it ruled the blockbuster drug Avastin should no longer be used to treat advanced breast cancer.

Avastin is hailed for treating colon cancer and certain other malignancies. But the Food and Drug Administration said it appeared to be a false hope for breast cancer: Studies haven’t found that it helps those patients live longer or brings enough other benefit to outweigh its dangerous side effects.

“I did not come to this decision lightly,” said the FDA’s commissioner, Dr. Margaret Hamburg. But she said, “Sometimes despite the hopes of investigators, patients, industry and even the FDA itself, the results of rigorous testing can be disappointing.”

Avastin remains on the market to treat certain colon, lung, kidney and brain cancers. Doctors are free to prescribe any marketed drug as they see fit. So even though the FDA formally revoked Avastin’s approval as a breast cancer treatment, women could still receive it — but their insurers may not pay for it. Some insurers already have quit in anticipation of FDA’s long-expected ruling.

However, “Medicare will continue to cover Avastin,” said Brian Cook, spokesman for the Centers for Medicare & Medicaid Services. The agency “will monitor the issue and evaluate coverage options as a result of action by the FDA but has no immediate plans to change coverage policies.”

Including infusion fees, a year’s treatment with Avastin can reach $100,000.

The ruling disappointed patients who believe Avastin is helping to curb their incurable cancer.

“It’s saved my life,” said a tearful Sue Boyce, 54, of Chicago. She’s taken Avastin in addition to chemotherapy since joining a research study in 2003. Her breast cancer eventually spread to her lungs, liver and brain, but Boyce says she is stable and faring well.

“So I’m hoping the insurance company will grandfather me in to continue taking it,” she said.

The Avastin saga began in 2008, when an initial study suggested the drug could delay tumor growth for a few months in women whose breast cancer had spread to other parts of the body. Over the objection of its own advisers and to the surprise of cancer groups, FDA gave Avastin conditional approval — it could be sold for such women while manufacturer Genentech tried to prove it really worked.

The problem: Ultimately, the tumor effect was even smaller than first thought. Across repeated studies, Avastin patients didn’t live longer or have a higher quality of life. Yet the drug causes some life-threatening risks, including severe high blood pressure, massive bleeding, heart attack or heart failure and tears in the stomach and intestines, the FDA concluded. In two public hearings — one last year and one this summer — FDA advisers urged the agency to revoke that approval.

“The science is clear: Breast cancer patients are more likely to be harmed than helped by Avastin,” said Diana Zuckerman of the National Research Center for Women and Families in Washington.

Genentech had argued the drug should remain available while it conducted more research to see if certain subsets of breast cancer patients might benefit, and some patients and their doctors had argued passionately for the drug.

“There certainly are patients who benefit tremendously,” said Boyce’s oncologist, Dr. Melody Cobleigh of Rush University Medical Center. “We’ll just be battling with the insurance companies.”

“For those not fortunate enough to be on Medicare or an insurance plan that covers it, it’s a death sentence,” Christi Turnage of Madison, Miss., said of the FDA’s decision. Her breast cancer had moved into her lungs before she began Avastin three years ago and the spreading stopped, but Turnage said her insurer is ending coverage and she will seek financial help from Genentech’s access program.

Hamburg said that she considered those arguments but that scientifically there are no clues yet to identify who those rare Avastin responders would be — putting a lot of people at risk in order for a few to get some as-yet-unknowable benefit. She urged Genentech to do that research, saying the FDA “absolutely” would reconsider if the company could find the right evidence.

Genentech, part of Swiss drugmaker Roche Group, pledged to begin that research.

“We are disappointed with the outcome,” said company chief medical officer Dr. Hal Barron. “We remain committed to the many women with this incurable disease and will continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment in the United States.”

The breast cancer organization Susan G. Komen for the Cure said that it respected the FDA’s decision and that it was time for researchers to concentrate on finding so-called biomarkers that would tell which drug is right for which patient.

“Each type of cancer is very different from another in important ways, and in the end it’s no surprise that Avastin’s effectiveness may not be equivalent against all types of cancer,” said Dr. Neal Meropol of University Hospitals Case Medical Center in Cleveland, who has long used Avastin for colon cancer.

Associated Press writer Marley Seaman in New York contributed to this report.

FDA Eyes Registry for Breast Implants Problems

News Stories & Editorials
Anna Yukhananov, Reuters: August 31, 2011

U.S. health regulators said they would consider setting up a registry that tracks safety problems with breast implants, after too many patients dropped out of company-funded studies.

But the U.S. Food and Drug Administration emphasized on Wednesday that silicone implants were safe and would stay on the market, despite calls for their removal by consumer groups.

Expert advisers who held a two-day meeting to discuss post-approval safety studies for silicone implants urged the FDA to establish a registry.

“We believe it’s a good idea to have a conversation about a breast implant registry. … (But) we believe implants are safe and effective and should remain on the market,” Dr William Maisel, deputy director of the FDA’s devices division, told reporters after the meeting.

In 2006 the FDA approved silicone gel-filled breast implants sold by Allergan and Johnson & Johnson’s Mentor unit on condition both companies follow 40,000 women for 10 years to look at safety issues, as well as extend smaller pre-approval studies.

So far, Allergan has collected preliminary two-year data for 60 percent of participants, while Mentor has collected three-year data for only 21 percent — well below the 65 percent the FDA said would be acceptable.

“It’s very inefficient to enroll 40,000 patients, and only get data on 400 on them (for rare symptoms). So having registries is a much more high-value approach,” said Jason Connor, a biostatistician on the advisory panel.

There were almost 400,000 breast enlargement or reconstruction procedures in the United States in 2010, according to the American Society of Plastic Surgeons. That includes silicone and saline implants.

In June, the FDA said the risks of breast implants are well understood, after looking at the companies’ results as well as reports of negative events and scientific literature. It said women who get silicone implants are likely to need additional surgery within 10 years.

The agency had banned silicone implants for most U.S. women in 1992 after some said the devices leaked and made them chronically ill.

The companies and FDA advisers said patients and their doctors may not have enough incentives to stay in the company-funded studies, especially if they have to fill out a 27-page questionnaire every year, or do expensive medical procedures such as MRIs that test if their implant has ruptured.

A registry, which would track any patient who has had a breast implant, can provide broader data, making it easier to identify any complications, such as rupturing of the device.

Panel members said women should be encouraged to enroll in the registry by linking participation to the warranty on their devices, or to their surgeons’ certification.

Maisel also said it was important to involve different groups, including advocacy groups and physicians, to make sure patients understand the benefits of sharing information about their implants.

“What we’ve heard over the last two days is that it takes a whole community,” Maisel said. “You can have the most well-meaning company, but if the patients don’t want to participate in the study, that’s out of their control.”

However, some groups said the agency was letting manufacturers, especially Mentor, off the hook.

“You can’t ignore the fact that Allergan has three times more patients participating than Mentor. You can’t not hold Mentor responsible for that,” said Diana Zuckerman, president of the National Research Center for Women & Families.

FDA: Breast Implant Safety Studies Will Continue

News Stories & Editorials
Brenda Goodman, Web MD: August 31, 2011

Officials Say They Will Work With Companies to Improve Follow-Up Rates

After two days of testimony on what the FDA should do about troubled long-term safety studies of silicone-gel breast implants, agency officials said the studies would continue.

“The current post-approval studies will continue,” said William Maisel, MD, MPH, chief scientist in the FDA’s Center for Devices and Radiological Health, in remarks after the meeting. “The FDA is committed to seeing them completed and making sure the follow-up rates improve.”

The safety studies in question, of nearly 100,000 women with breast implants, which the FDA said were the largest ever required of manufacturers after their devices were marketed to the public, have lost track of up to 79% of the women they enrolled just three years into planned 10-year efforts.

As a result, FDA epidemiologists testified yesterday, the studies had lost the ability to find rare complications, including connective tissue diseases, that they were designed to look for.

Save or Scrap Troubled Studies?

In a second day of testimony, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to the FDA heard plenty of opinions about what should happen with the studies.

Some panelists felt the companies should be compelled by the FDA to finish the studies they had agreed to complete as a condition of the approval of their devices. They asked FDA officials what regulatory powers the agency could wield to do that.

“If you do not meet the conditions of approval the FDA does have regulatory authority to either impose civil penalties or other regulatory actions,” said Mark N. Melkerson, director of the Division of Surgical, Orthopedic and Restorative Devices at the FDA’s Center for Devices and Radiological Health.

The agency said it was not considering taking silicone breast implants off the market.

Some consumer advocates thought that option ought to be on the table, however.

“It has now been 25 years since FDA declared silicone breast implants a class III device, and in that period, only weak attempts have been made to assess the safety of these implants,” said Kate Ryan, of the nonprofit Breast Cancer Action, which is based in San Francisco.

“Follow-up rates on the two large studies are dismal,” Ryan said in testimony. “Given that these studies were a condition of approval, Mentor should have done much more to ensure it had the technical skills to locate women and provide women with incentives to participate in this important research.”

Manufacturers Respond

Manufacturers fired back against the notion that they weren’t doing enough to complete the studies.

“To imply that patient safety is not first on our radar is simply inaccurate,” said Caroline Van Hove, a spokeswoman for Allergan. She said the company hoped that the meeting would give the FDA an opportunity to more fully appreciate the complexity of the required studies.

“In general, we are highly committed to collecting quality data in a way that is possible for them and possible for us,” she said.

In other testimony, panelists heard from plastic surgeons like Dennis Hammond, MD, of Cedar Rapids, Mich., who participated in the clinical trials of Mentor’s Memory Gel implants.

In contrast to the 21% of patients retained overall by one of the Mentor studies, Hammond said he’d kept track of about 76% of the women he was following.

Panelists asked him how he did it.

“You’ve got to have dedicated surgeons that are really interested in making this study work,” Hammond said. He said he had one staff member devoted to follow-up with women in the clinical trial and that he allocated about half a day of clinical time each week to seeing women in the study for follow-up visits.

Additionally, “A really compelling part would be if the patient had some sort of compensation. It doesn’t have to be wild, really, just something they get back to compensate for the drive in.”

Allergan, the maker of Natrelle implants, which had a 60% follow-up rate with patients after two years, said they paid women a small amount of money for filling out annual questionnaires and coming back to scheduled office visits. Mentor did not.

“While it was certainly admirable to try to get 40,000 patients [in each study] to come back, that just wasn’t going to happen,” Hammond said.

Perspective of Surgeons

The American Society of Plastic Surgeons (ASPS) agreed, and it urged the FDA to consider other data sources, besides the troubled studies, if the agency still felt the need for continued safety monitoring.

“There has been shown to be no relationship between silicone breast implants and connective tissue disorders, which was the main reason these studies were agreed to on the release of these products,” said Phil Haeck, MD, president of the ASPS, in testimony to the panel. “This issue has been settled with the post-approval study data as it already stands now.”

Haeck said sources like the FDA’s own surveillance system, the Manufacture and User Facility Device Experience (MAUDE), which relies on clinicians to report instances of adverse events associated with devices, case reports, patient registries in the U.S. and Europe, and reviews of medical studies, could be relied on to spot any rare events that might arise.

Consumer advocates, like Dana Casciotti, PhD, the public health research director at the Cancer Prevention and Treatment Fund, said annual, 27-page questionnaires women were asked to complete should be shortened and simplified.

“I’ve seen copies of these questionnaires, and they are much too long” and technical, she said.

Panel members seemed to agree, and some suggested that future questionnaires might yield better data if they focused on symptoms rather than diagnosed diseases, since many connective tissue diseases, like lupus, are difficult to diagnose.

Perspective of Surgeons continued…

Patients who took time off work and paid their way to testify at the meeting urged the FDA to keep trying to answer questions about the long-term and rare complications of breast implants.

“Not everyone gets sick, but those who do, we pay dearly,” said Sharon Schwengler of Phoenix.

 

FDA Affirms Safety of Breast Implants

News Stories & Editorials
Gardiner Harris, New York Times: August 31, 2011

WASHINGTON — After two days of discussion and testimony about silicone breast implants, a top government health official said he had heard nothing to shake his faith in the safety of the widely used implants.

The official, Dr. William Maisel, chief scientist for the Food and Drug Administration’s Center for Devices, said silicone breast implants were safe.

“We felt that way before the meeting, and we continue to feel that way after the presentations and discussions over the past two days,” Dr. Maisel said.

There are risks to the implants, however, Dr. Maisel said, including ruptures, a hardening of the area around the implants, the need to remove the implants, scarring, pain, infection and asymmetry. “Women should feel assured that the F.D.A. continues to believe that currently marketed silicone breast implants are safe,” he said.

Some patients and women’s groups who testified at the meeting disagreed.

Diana Zuckerman, president of the National Research Center for Women and Families, a research and education group, told an expert panel that the two companies that manufacture silicone breast implants — Johnson & Johnson and Allergan — had done a poor job of studying patients who got the implants, as the F.D.A. required them to do.

“And without proper data, we still don’t know how safe or effective they are and whether there are certain patients at risk for extremely negative outcomes,” Ms. Zuckerman said.

Dr. Maisel agreed that the studies conducted by the two companies had failed to follow as many patients as the agency had hoped.

One purpose of this week’s meeting was to ask the expert panel what the agency and the two companies should do about that poor follow-up. Some suggested that patients should be paid for participating; others mentioned that doctors should get some money, too.

There was some criticism of the 27-page research form that patients who participate in the study are required to complete and whether it could be shortened. Nearly all expressed hope that a registry could be created that would follow all breast implant patients, but such registries are expensive to maintain and complicated to create.

The committee also agreed that patients should no longer be told that they should get a magnetic resonance imaging test three years after getting implants and every two years following.

The reason for telling patients to get M.R.I.’s is that silicone breast implants sometimes rupture without women being aware, and an M.R.I. can reveal this unseen problem.

But many patients ignore the requirements because M.R.I.’s are expensive and it is not clear what they should do when an unseen rupture is discovered; the risks associated with ruptured implants may not be greater than the risks of the operation needed to take them out.

“F.D.A. continues to believe, as does the panel, that M.R.I. is the gold standard for evaluating breast implants for silent rupture,” Dr. Maisel said. “But there was consensus among the panel that the requirements for ongoing M.R.I.’s should be removed.”

Dr. Maisel promised that the F.D.A. would study whether to follow this advice.

 

Experts Say Medical Device Review System Flawed

In the News, News Stories & Editorials
The Miami Herald: July 29, 2011

The government should abandon a 35-year-old system for approving most medical devices in the U.S. because it offers little to no assurance of safety for patients, a panel of medical experts concludes in a report Friday.

The surprise recommendation from the Institute of Medicine panel calls for a massive reworking of how the government regulates medical devices, a $350 billion industry that encompasses everything from pacemakers to X-ray scanners to contact lenses.

The 12-member group’s advice, commissioned by the Food and Drug Administration, is not binding. But it could signal a new era of tighter standards for medical device manufacturers, who have long benefited from less safety scrutiny than their peers in the drug industry.

FDA requires that most new prescription drugs go through clinical trials to prove that patients fare better after receiving medication. Most devices only have to show that they are similar to devices already on the market. Truly new devices have to undergo more scrutiny.

In a highly unusual move, the FDA said Thursday evening that it disagreed with the group’s recommendations, but would hold a public meeting to discuss them.

The report arrives as the FDA fends off pointed criticism from manufacturers who say the agency has become too slow and bureaucratic in clearing new devices, driving up costs for companies and forcing some out of business. They point out that some devices reach the market two years earlier in Europe, where safety standards are lower. In the past year, companies have taken their arguments to Capitol Hill, where lawmakers have grilled FDA officials over device reviews.

But the Institute of Medicine panelists, mostly doctors and researchers, appear to overwhelmingly side with public safety advocates who have argued for years that devices used to treat and detect illnesses must undergo real medical testing.

The FDA sought the group’s advice as it updates the system used to clear more than 90 percent of devices in the U.S. The so-called 510(k) system was created by Congress in 1976 to grant speedy approval to devices that are similar to products already on the market. The pathway was originally intended as a temporary method to grandfather in devices that had been used for decades. Instead it has become the standard tool to launch new medical implants.

The IOM generally recommends ways to improve or modify government programs, but in an unexpected move the panel said 510(k) approvals are “flawed” and should be eliminated completely.

“A system was put in place 35 years ago that does not really assess safety and effectiveness,” said panel chair David Challoner, former vice president of health affairs at University of Florida. “We need something different for the next 35 years. We’re dealing with a whole new world: new technology, new materials and new data.”

Challoner and the other panelists recommend the FDA develop a new system based on safety metrics and tracking device failure rates in the real world. He said better tracking of device complications could take the place of premarket testing, which would be financially unfeasible if applied to all new devices.

The group stresses that medical devices cleared through the pathway are not inherently unsafe – most probably are safe – but the system used to clear them provides little assurance to doctors and patients.

The 510(k) system is popular among manufacturers because it is a faster, cheaper path to market than the review process for first-of-a-kind devices, which must undergo rigorous medical testing. Hip replacements, CT scanners and drug pumps are among the devices cleared by 510(k).

As generations of devices have been cleared year after year, FDA critics say dangerous devices that pose real risks to patients have slipped through because they vaguely resemble products approved decades ago.

“Originally there was this idea that the 510k would wither away and over time more and more new devices would go through the more onerous path. But instead there are more devices cleared this way than ever,” Dr. Diana Zuckerman, director of the nonprofit National Research Center for Women & Families, said in an interview Thursday.

Earlier this month Zuckerman and other safety advocates critics seized on new reports of painful complications with pelvic surgical mesh as the latest example of the shortcomings of the abbreviated review system. Reports of pain, bleeding and infection with the implants are up 500 percent since 2008 among women who’ve had surgery to support the pelvic wall. The FDA cleared the device for that use in 2002 via 510(k). Similar safety issues have plagued metal-on-metal hip implants in recent years. […]

 

Most Women with Silicone Breast Implants Need More Surgery

News Stories & Editorials
Rita Rubin, MSNBC: June 22, 2011

More than one in five women who had silicone breast implants for cosmetic purposes and half of those who got the implants after a mastectomy needed surgery to remove the implants within a decade, according to a Food and Drug Administration report out Wednesday.

“Recognize that breast implants are not lifetime devices,” says the FDA report on the longest studies on the implant to date. “The longer you have your implants, the more likely it will be for you to have them removed.”

In 2010, U.S. surgeons performed nearly 400,000 breast implant procedures. About three-quarters were for breast augmentation, while the rest were for breast reconstruction. About half the surgeries used silicone gel implants; the other half used implants filled with saline.

Silicone implants were pulled off the market in 1992, after concerns were raised about lack of safety data and worries that leaking silicone was linked to immune-system disease.

But the FDA returned the implants to the market in November 2006 after clinical trials didn’t find a link to feared diseases. Plastic surgeons and some women were clamoring for the return of the silicone versions because they say they look and feel more real than saline, which can ripple because it’s essentially a sack of salt water.

The approval required implant makers Allergan and Mentor to conduct large 10-year studies following up on patient experiences, and Wednesday’s report is the first glimpse at how the breast implants held up.

The FDA says 20 to 40 percent of patients who get silicone implants for cosmetic reasons will need another operation to modify or remove them within 10 years. For women with implants for breast reconstruction, the number is even higher, at 40 to 70 percent. The biggest issue was scar tissue hardening around the implant.

Other complications include implant rupture, wrinkling, asymmetry, pain and infection, the report said. Women with breast implants are also slightly more likely to be diagnosed with anaplastic large cell lymphoma, a rare form of cancer.

Despite the risk of complications, the FDA believes that silicone implants are reasonably safe, the report said.

But women in the studies had a high dropout rate and so other complications or long-term safety issues might be missed, the agency’s report says.

Mentor has three-year data for only one out of every five women in its study, while Allergan has two-year data for three out of every five, according to the FDA’s safety update.

“Low follow-up rates and other study limitations may limit interpretation of the data and preclude the detection of very rare complications,” the agency concluded.

Without knowing why patients have dropped out of the studies, it’s impossible to reach any conclusions about implant safety, says Diana Zuckerman, president of the nonprofit National Research Center for Women & Families in Washington, D.C.

“Did they stop going to the doctor because their implants were removed?” Zuckerman says. “Did they stop going because they died or got very sick? Or are they so happy with their implants that they skipped follow-up visits?”

The FDA has been working with the companies to improve patients’ participation in the studies and will convene a meeting of outside experts to discuss the issue later this summer, says William Maisel, deputy director for science and chief scientist at the agency’s Center for Devices and Radiological Health.

Most women who get breast implants are in their 20s and 30s, and may mistakenly consider breast implants a one-time investment.

“They need to understand they’re going to need many removals and replacements for the rest of their lives,” Zuckerman says.

Most Recalled Medical Devices Received Speedy FDA Review

News Stories & Editorials
Andrew Zajac, Los Angeles Times: February 15, 2011

A disproportionate number of medical devices recalled because of possible links to serious health problems or deaths — including external defibrillators and insulin infusion pumps — were approved under an abbreviated process that did not require advance testing on patients, according to a five-year study of such recalls.

More than 70% of the 113 recalled devices were cleared for market under a shorter Food and Drug Administration review because they were deemed similar to products already on the market, the study found.

Cardiovascular devices, chiefly external defibrillators, made up nearly a third of the recalled medical products from 2005 through 2009, the time covered by the review. A 2006 study linked defibrillator failure to more than 300 deaths over a 10-year period.

Only 21 of the recalls in the new study involved products approved after clinical trials. Eighty had been approved under the shorter process. Eight were exempt from FDA regulations, and four were counterfeit or categorized as “other.”

The findings, published Monday in the Archives of Internal Medicine, showed that a recent update of the FDA’s abbreviated review process, known as 510(k), was inadequate, said Diana Zuckerman, one of the study’s coauthors.

Medical device companies have stretched the notion of “similar” far beyond regulators’ intention when the law went on the books in 1976, said Zuckerman, president of the National Research Center for Women & Families. “The law has gotten looser and looser over time.”

The FDA should increase the number of devices subject to the stricter review, known as pre-market approval, or devise an intermediate category with more rigor than the 510(k) process, said Steven Nissen, a Cleveland Clinic cardiologist and a study coauthor.

The findings buttress a 2009 Government Accountability Office report that dozens of high-risk devices did not meet the legal standard for abbreviated review, Nissen said.

The FDA is evaluating high-risk products approved through its abbreviated process to see whether they should be subject to more rigorous oversight, agency spokeswoman Karen Riley said in a statement.

The study is the latest chapter in a bitter debate between device makers and public health advocates. In August, the FDA released a draft of new rules that added stricter requirements to the shorter process. […]

 

Zuckerman said she was hopeful the study would influence regulators to tighten standards.

“The process should be more stringent,” she said. “It doesn’t have to be slower.”

Read the original article here.