By Kristin Wartman for Huffington Post

August 14, 2012

Recently, the U.S. Food and Drug Administration (FDA) announced a ban on the use of bisphenol A, or BPA, in baby bottles and children’s cups. BPA is an estrogen-mimicking chemical that has been used in hard plastics, the linings of cans, food packaging, dental fillings and even receipts for years. This move essentially made official a practice that many manufacturers of baby bottles and cups already follow in response to growing pressure from consumers.

Questions of safety remain when it comes to the use of any plastic products that come in contact with our foods. The FDA ban is raising concern and creating headlines about what manufacturers will substitute in place of the BPA. A 2011 study published in Environmental Health Perspectives found that all plastics contain estrogenic activity (EA) and in some cases, those labeled “BPA free” leached more chemicals with EA than did BPA-containing products. The study’s authors write, “Almost all commercially available plastic products we sampled — independent of the type of resin, product, or retail source — leached chemicals having reliably detectable EA, including those advertised as BPA free.”

EA interferes with our endocrine system, a complex signaling network that is made up of glands (the thyroid) as well as glandular tissue and cells within organs (testes, ovaries, pancreas, etc). Our endocrine systems use hormones that send signals to our various organs and tissues that work over minutes, hours, weeks and years. The processes these hormones regulate include metabolism, growth and development, and sexual reproduction. As hormones travel in the blood to reach each body part, the specific molecular shape of each hormone fits like a key-in-a-lock into receptors on target tissues. Endocrine disrupting chemicals may interfere with, block or mimic the action of our hormones. As a result, EA and endocrine disruptors have been linked in hundreds of studies to brain development problems, breast and prostate cancer, birth defects, learning and behavioral problems in children, early onset of puberty, and obesity.

Manufacturers are now flaunting their “BPA-free” versions of products as though they are safe and free of toxins — but it turns out BPA is possibly just the tip of the iceberg. Bisphenol S, or BPS, is another chemical that manufacturers are using to replace BPA and it may be just as harmful. In a study this year in Environmental Science and Technology, researchers wrote,

“As the evidence of the toxic effects of bisphenol A (BPA) grows, its application in commercial products is gradually being replaced with other related compounds, such as bisphenol S (BPS). Nevertheless, very little is known about the occurrence of BPS in the environment.”

In this study, the authors found BPS present in 16 types of paper products, including thermal receipts, paper currencies, flyers, magazines, newspapers, food contact papers, airplane luggage tags, printing paper, paper towels and toilet paper. The thermal receipt paper samples contained concentrations of BPS that were similar to the concentrations of BPA reported earlier and raised alarm for some scientists. BPS was also detected in 87 percent of currency bill samples. The authors write that several other related compounds are also used to replace BPA: bisphenol B, bisphenol F and bisphenol AF. BPA and BPS are found in high concentrations in canned foods, BPF has been found in surface water, sewage sludge, and sediments, and BPB was found in human serum in Italy. “Limited studies have shown that BPS, BPB and BPF possess acute toxicity, genotoxicity, and estrogenic activity, similar to BPA,” the authors write, adding, “The environmental biodegradation rates of BPS and BPB were similar to or less than those of BPA. Although considerable controversy still surrounds the safety of BPA, the potential for human exposure to alternatives to BPA cannot be ignored.” The researchers also note that people may be absorbing BPS in much larger doses — 19 times more than the BPA they absorbed when it was more widely used.

Bruce Blumberg, professor of developmental and cell biology and pharmaceutical sciences at the University of California, Irvine, wrote in an email,

“There are emerging data to show that BPS is an estrogen but relatively less on the other chemicals. Therefore, it is hard to say with certainty at the moment whether the BPA replacements lack estrogenic activity. BPA free means simply that — that the product is stated to be BPA free.”

I asked Diana Zuckerman, president of the National Research Center for Women and Families if she was concerned about the substitutes being used in place of BPA:

“We are very concerned that BPA could be replaced with products that are just as risky, or even more risky. The federal government is not doing what is needed to protect the American public, either in their regulation of BPA or any of these potential substitutes.”

But the FDA continues to insist that BPA is still safe. In a recent New York Times article, Michael Taylor, deputy commissioner for foods, said that the agency “has been looking hard at BPA for a long time, and based on all the evidence, we continue to support its safe use.”

Zuckerman added that part of the problem lies in the heavy influence that industry has on members of Congress and the FDA.

“Whenever the FDA does something to improve patient safeguards, Members of Congress get lobbied by the industry involved and some of those Members pressure [the] FDA to back off,” she wrote in an email. “This has happened for years but the last few years have been even worse than usual.”

At Mother Jones, Tom Philpott points out that the heavily monied interests behind BPA are none other than the chemical giants Dow and Bayer, which produce the bulk of BPA. Frederick S. vom Saal, curators’ professor at the University of Missouri-Columbia and BPA researcher, told me that BPA represents a $10 billion a year industry. It’s important to note that the recent FDA ban comes at the behest of the American Chemistry Council, an industry trade group that denies any negative health effects from BPA. Why would they have done this?

“[The American Chemistry Council’s] petition to the FDA puts it plainly: ‘All Major Product Manufacturers Have Abandoned the Use of Polycarbonate’ (BPA). In other words: Go ahead and ban it — it’s already been phased out and a ban gives the appearance of strict oversight,” Philpott writes.

By creating the ban, the FDA at least acknowledges that babies and children should lessen their exposure to BPA. But what about the rest of the population?

“BPA remains in millions of food and beverage containers that affect the BPA levels of pregnant women, children of all ages, and all adults,” Zuckerman wrote to me in an email. “The impact on the developing fetus and young children, and on breast cancer patients undergoing chemotherapy, are of particular concern to our Center. One study indicates that BPA may interfere with the effectiveness of chemo for breast cancer patients.”

The FDA should concede that if BPA is a risk for babies and children, it is most likely a risk to all of us. And what about the various substitutes that will be used for BPA and the numerous other toxins lurking in the plastics and other containers that package our foods and drinks? “FDA’s decision is a step in the right direction, but it is a baby step,” Zuckerman said. “They have done the minimum.”

Blumberg added that the answers to all of these questions are complex. “We do not know nearly as much as we need to know,” he said. “I think that it is prudent to reduce our consumption of packaged foods of all sorts for a variety of reasons, including reducing exposure to contaminants from the containers.”

A version of this post appeared on Civil Eats

Lena Groeger, ProPublica: May 3, 2012

Each prescription drug you take has a unique code that the government can use to track problems. But artificial hips and pacemakers? They are implanted without identification, along with many other medical devices. In fact, the FDA doesn’t know how many devices are implanted into patients each year – it simply doesn’t track that data.

The past decade has seen numerous high profile cases of malfunctioning medical devices, which have led to injury or even death. Critics say the FDA’s minimal monitoring of devices contributes to these problems.

“If you’re lucky, you might find a sticker on the operating room note that was left over from the product,” said Richard Platt, who runs the Harvard Pilgrim Health Care Institute. Otherwise, there is little way of knowing what device was used.

Right now, the FDA depends mostly on voluntary reports from doctors, patients, manufacturers and hospitals to notify them of problems with devices already on the market. The agency does have some power to require manufacturers to conduct further studies or track a particular device once it is sold. But many devices don’t get that level of surveillance.

“It’s much like a patchwork of streams of information getting to the FDA,” said cardiologist Frederic Resnic of Brigham and Women’s Hospital, who has worked with the FDA on medical device safety monitoring. “The FDA is relying on anecdotal and very variable information about the safety of medical devices.”

If manufacturers get word from a doctor or hospital about a death or injury that occurred as a result of their product, they are legally obligated to investigate the event and report it to the FDA. But the process isn’t straightforward, as has become clear in the recent controversy over the malfunctioning St. Jude’s Riata defibrillator leads (wires that connect a defibrillator to the heart). The FDA said an individual doctor’s report helped alert them to the problem, but it was months before the device was recalled.

According to attorney William Vodra, a regulatory law expert and member of the Institute of Medicine panel that published a report on medical device safety last year, the number of doctors who actually contact manufacturers is small.

And after being notified of patient harm, manufacturers can minimize their own responsibility if they point the blame elsewhere, said health policy expert Diana Zuckerman, president of the National Research Center for Women & Families.

For example, if someone dies from complications in a surgery to remove an implant, the manufacturer may argue that it was the surgery – not the implant – that killed the patient.

“You have a system that is not rigorous, the standards are not always understood, and they are interpreted differently by different people,” Zuckerman said.

The FDA responds to the criticism by pointing out that while every medical device carries a potential risk, the vast majority of devices perform well and improve patient health. An FDA spokeswoman emphasized that the agency must evaluate thousands of medical devices each year, and is constantly looking for ways to better and more quickly identify problems.

While the FDA makes the adverse event reports publically available in a searchable database, it doesn’t have a standardized system for reviewing reports once they are sent in, said Vodra, the attorney. A disclaimer on the site specifically states that the data is “not intended to be used either to evaluate rates of adverse events or to compare adverse event occurrence rates across devices.”

“What you would normally consider the simplest kind of data analysis is not done,” said Zuckerman. Often, doctors catch a malfunctioning device before the FDA ever notices.

In one case, a group of Pennsylvania doctors noticed that several patients were showing severe complications a few years after getting an IVC filter – a device designed to capture blood clots. Bits of the filter were breaking off, causing chest pain and a dangerous build-up of fluid and pressure around the heart. In 2010 the doctors conducted their own study and found that the filter broke in a quarter of all patients who used it.

On the day that study was published, the FDA issued a warning saying it had received over 900 reports of problems with IVC filters since 2006, and that the device was meant to be removed after a few months, not left in permanently.

There have been numerous attempts at reform. Five years ago Congress ordered the FDA to set up a post-market surveillance system to track the safety of all medical projects, but a system hasn’t yet been set up for medical devices.

A year later the FDA announced the Sentinel Initiative, which would combine existing data from electronic health records and medicalclaims to track drugs, vaccines, and devices. Some groups of hospitals or other organizations have voluntarily set up registries to collect information about the make and model of devices.

While the FDA has made significant progress on tracking drugs, it’s not yet in a position to do the same thing for devices, according to Harvard’s Platt, who is the principal investigator of Mini-Sentinel, the FDA’s pilot program for the national system. The data isn’t there.

The FDA has long acknowledged the need for a unique device identifier system, and got permission from Congress to set one up five years ago. No such system of ID-tags exists yet, but after several recent high profile medical device failures, the issue getting some attention from Congress. A proposed Senate bill, which cleared the Health, Education, Labor and Pensions Committee last week, sets a timeframe for implementing a unique identification system, among other reforms.

“If UDI’s were used in a consistent way, we could use the same kinds of techniques we’ve developed for drugs for devices,” said Platt. “It would be a huge breakthrough.”

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.