All posts by CPTFeditor

Get BPA Out of Our Food!

Uncategorized
Cancer Prevention and Treatment Fund

Every time you drink a can of soda or eat pizza made from canned tomato sauce, you are consuming bisphenol  A (BPA) – a synthetic estrogen! This is because BPA leaks from the lining of the can and into your food and beverages. By March 31 – just days away – the federal Food and Drug Administration will decide whether or not to continue allowing food packaging with BPA in it. Make your voice heard! Act now before the FDA decides.  Email the FDA today and tell them you want BPA out of your canned drinks and other food packaging!

Here is a sample letter, but feel free to make any changes!

Send your email to margaret.hamburg@fda.hhs.gov

Dear Commissioner Hamburg,

Please ban the use of bisphenol A (BPA) in all food and beverage containers.

BPA is a synthetic form of estrogen, and research shows that BPA could increase the risk of breast cancer, prostate cancer, diabetes or miscarriages. It may interfere with chemotherapy if consumed by breast cancer patients.  Even though the level is low in each food package, it adds up!  Studies have shown that BPA is in breast milk, saliva, urine, amniotic fluid and cord blood.

We are grateful that the FDA has finally banned BPA in baby bottles and sippy cups, but that is not enough to protect our children. As Commissioner, your decision about BPA will affect the health of adults and children across the country, for decades to come.  Please ban BPA from food containers.

Thank you.

[YOUR NAME]

Arsenic and Lead in our Juice (and You Thought Poisoned Apples Were only in Fairy Tales!)

Diet, Habits, & Other Behaviors, Other Cancers, Skin Cancer
Langan Denhard and Brandel France de Bravo, MPH, Cancer Prevention and Treatment Fund

Arsenic—it’s a scary word with dangerous connotations.Recent studies show that arsenic is present in many everyday beverages and food.In response, Congressman Frank Pallone and Congresswoman Rosa DeLauro introduced a bill named Arsenic Prevention and Protection from Lead Exposure in Juice (APPLE) in early February 2012. If it becomes law, it would require the FDA to set limits within the next two years on the amount of arsenic and lead allowed in fruit juices and other foods.[1]

What are the Dangers of Chronic Arsenic Exposure?

There are two types of arsenic: organic and inorganic.Organic arsenic is usually non-toxic and harmless when consumed.However, the FDA has identified two strains of organic arsenic that can cause cancer: dimethyl arsenic acid (DMA) and monomethyl arsenic acid (MMA).Recent testing by the FDA found small amounts of these strains in apple juice. Inorganic arsenic has been linked to increases in bladder, skin, and lung cancers when consumed in high quantities.It also increases the risk of cardiovascular disease and type 2 diabetes, and weakens the body’s immune system, making it harder to fight respiratory infections and flu. Exposure to high levels of arsenic can cause diarrhea, fatigue, nausea, skin discoloration, and in rare instances, death. Very little research has examined what happens to children exposed to low levels of inorganic arsenic over a long period.A 2004 study led by Columbia University’s Joseph Graziano, PhD, suggests that children who consumed water with arsenic levels above 5 parts per billion (ppb) showed evidence of lowered IQ.[2]

What are the Current Laws in Place Concerning the Levels of Arsenic in Food and Drink?

 

There is surprisingly little regulation on the levels of arsenic allowed in food and drink.According to Michael Taylor, deputy commissioner of the FDA, 23 ppb is the “level of concern” for arsenic concentration in fruit juices but there is no legal limit. Information on the FDA site states, “[The] FDA is collecting all relevant information to evaluate and determine if setting guidance or other level for inorganic arsenic in apple juice is appropriate.”[3] The FDA and the EPA revised the federal limit for arsenic allowable in public water and bottled water to 10 ppb in 2006, noting that the safest level would be 0 ppb.[4] States have the authority to mandate limits below 10 ppb, and New Jersey has the strictest limits, with a maximum level of 5 ppb. State officials caution against consuming or cooking with water at any higher concentration.[5]

Do my Family Members Consume Arsenic?

In November 2011, Consumer Reports completed a study of 88 samples of apple and grape juice that found that 10% had arsenic levels surpassing the drinking-water standards.Of this, most of the arsenic found was inorganic.A sample Walgreen’s grape juice was found to have an arsenic concentration of 24.7 ppb—more than double than the legal limit for drinking water—and most of it (82.9%) was inorganic.Of the two harmful types of organic arsenic, MMA was found in higher concentrations in apple juice whereas DMA was more likely to be found in grape juice.Consumer Reports also found that 35% of children younger than 5 drink more juice than is recommended by pediatricians.[2]

On February 2012, another study, led by a research group from Dartmouth College, presented troubling new findings.In an effort to cut down on the use of high fructose corn syrup as a sweetener, some manufacturers have been making the transition to organic brown rice syrup (OBRS).Because arsenic-based pesticides were once used in rice production, and rice plants are extremely effective in taking in the leftover arsenic from the soil, using syrup made from organic brown rice has resulted in arsenic in infant formula and other commonly used products.[6]

Currently, the only formula brand using OBRS is Nature’s One, which produces Baby’s Only Organic Dairy Toddler Formula and Baby’s Only Organic Soy Toddler Formula.These products were tested against 15 formulas that did not contain OBRS, and it was found that Nature’s One’s products had more than 20 times as much arsenic as the other brands.In a statement published on its web site, the company says, “An independent, third party testing laboratory completed testing on organic brown rice syrup used in formulas produced in 2011. The testing proved there are no safety concerns using the organic brown rice syrup ingredient.”The company has not released test results to the public, “to protect against inaccurate interpretations.”[7]

Cereal bars and “energy shots” are other possible daily sources of arsenic. A little less than half of all cereal bars contain organic brown rice syrup, and when tested, those with OBRS listed in the top five ingredients had the highest concentration of arsenic. At least half of the arsenic tested was inorganic and any organic arsenic was classified as DMA, one of the two harmful forms of organic arsenic.[6]

The Bottom Line

The drinking water limit on arsenic was set at a low level because water is frequently consumed on a daily basis throughout one’s life.For that reason, higher arsenic levels in foods consumed less often are of less concern.Fortunately, arsenic is usually excreted within 2-3 days of consumption.Nevertheless, some experts believe that the arsenic level allowed in water may be too lax, and additional sources of arsenic can add to those risks, especially for children and pregnant women.We need more research to know whether or not it is safe to consume low-levels of arsenic every day.

Meanwhile, the two things you can do are:

  1. make sure your drinking water meets the federal limit of 10 ppb of arsenic, especially if you have a private well or live in a rural area, and
  2. protect your children, whose bodies are smaller and still developing, from unnecessary exposure to arsenic.

It is especially important to protect infants from arsenic exposure until further research is conducted, so avoid formulas and baby foods containing rice products as a main ingredient.Most pediatricians advise against giving your children juice regularly because even when it has no added sugar, it delivers a lot of calories with little nutrition.The presence of arsenic is another reason to ration the juice!

If you are worried about your water supply, call your local health department for a list of labs certified to test for arsenic.The cost of testing ranges from $20-$35[8] NSF International provides extensive information on how to treat your home water.

References:

  1. Congresswoman Rosa L DeLauro. US House of Representatives. Congressman Frank Pallone (D-NJ) and Congresswoman Rosa DeLauro (D-CT) Fight to Protect Children from Arsenic in Apple Juice.Congresswoman Rosa L DeLauro: Representing the Third District of Connecticut. 8 Feb. 2012. Web. 28 Feb. 2012.
  2. “Arsenic in Your Juice:How Much Is Too Much? Federal Limits Don’t Exist.”ConsumerReports.org. Consumers Union, Jan. 2012. Web. 28 Feb. 2012.
  3. “Questions & Answers: Apple Juice and Arsenic.” FDA: US Food and Drug Administration. US Department of Health and Human Services, 16 Dec. 2011. Web. 21 Feb. 2012. <http://www.fda.gov/Food/ResourcesForYou/Consumers/ucm271595.htm>.
  4. “Basic Information about Arsenic in Drinking Water.” EPA: US Environmental Protection Agency. EPA, 26 Jan. 2012. Web. 01 Mar. 2012. <http://water.epa.gov/drink/contaminants/basicinformation/arsenic.cfm>.
  5. Buchanan, Gary A. “NJDEP New Jersey Department of Environmental Protection.” The Official Web Site for The State of New Jersey. 1 Nov. 2010. Web. 01 Mar. 2012. <http://www.state.nj.us/dep/dsr/arsenic/guide.htm>.
  6. Jackson, Brian P., Vivien F. Taylor, Margaret R. Karagas, and Kathryn L. Cottingham. “Arsenic, Organic Foods, and Brown Rice Syrup.” Environmental Health Perspectives (2012). Web. 21 Feb. 20
  7. “ORGANIC BROWN RICE SYRUP CONCERNS.” Nature’s One . Nature’s One, Inc. Web. 21 Feb. 2012. <http://www.naturesone.com/brown-rice/>.
  8. “Arsenic in Private Drinking-Water Wells.” Division of Toxicology and Environmental Medicine. ATSDR, 6 Aug. 2008. Web. 01 Mar. 2012. <http://www.atsdr.cdc.gov/arsenic/>.

Can Sleeping Pills Cause Cancer?

Colon Cancer, Diet, Habits, & Other Behaviors, Lung Cancer, Medical Treatments with Cancer Risks, Other Cancers, Prostate Cancer
Brandel France de Bravo, MPH, Kousha Mohseni, MS, Cancer Prevention and Treatment Fund

When we hear “sleeping pills,” most of us think of prescription drugs such as Ambien (generic name zolpidem), Restoril (temazepam), and Lunesta (eszopiclone).  While prescription sleep medications are big business — more than $41 billion/year in the U.S. many people with trouble sleeping turn to over-the-counter antihistamines such as Tylenol PM and Benadryl.[1]  However, the use of these drugs may take a nosedive in light of the findings of a study published in the prestigious British Medical Journal. Led by researchers at the Scripps Clinic Viterbi Family Sleep Center in California, the study shows that people who take these drugs are significantly more likely to be diagnosed with cancer or to die within the next two and a half years than people who don’t take them. Author Dr. Daniel Kripke estimates that these popular sleep medications could cause 320,000 to 507,000 deaths in just one year.

The researchers looked at 10,529 primary care patients who were prescribed sleeping pills between 2002 and 2007 and compared the health of each of them to at least two very similar patients without such prescriptions who were the same sex, ethnicity, marital status, smoking status, and had similar health conditions, alcohol use and BMI (which measures if a person is overweight). The patients were followed for 2.5 years on average, and were from a Pennsylvania clinic that serves a mainly low-income population.

Sleeping Pills, Death, and Cancer

Patients who were prescribed sleeping pills were at least three to five times more likely to have died during the study than were the patients not prescribed sleeping pills. Even the patients who were prescribed fewer than 18 pills per year were at higher risk of dying: 3.6 times higher. Patients who were prescribed more than 132 pills a year were more than five times as likely to die.

The researchers were careful to exclude from the study patients who were diagnosed with cancer before the study or very early in the study. Heavy users of sleeping pills (over 132 pills prescribed per year) had a 35% greater risk than those with fewer pills prescribed.  Among those with prescriptions for sleeping pills, the increased risk of their developing lymphoma, lung cancer, colon and prostate cancer was greater than the risk from being a current smoker.

Before this study, there were at least 18 other studies showing an increased risk of death for people taking sleeping pills, and several also showed an increased risk of cancer.  However, this study is especially well-designed and the only one that includes the newer, short-acting class of popular sleeping pills known as nonbenzodiazepines. These were generally believed to be safer than previous generations of sleeping pills because they wear off more quickly. In fact, before this study it was believed that the worst side effect was weight gain due to night time raids on the refrigerator while sleep walking.

Among study participants, the most commonly prescribed sleeping pill was zolpidem (sold as Ambien, Edluar, or Zolpimist), followed by temazepam (a benzodiazepine sold as Restoril). However, prescriptions for the use of any sleep aid was associated with a significant increase in the risk of death, including eszopiclone (”Lunesta”), zaleplon (”Sonata”), barbiturates, as well as antihistamines such as diphenhydramine (the active ingredient in Benadryl), which is also used in many over-the-counter sleep aids. The average age of patients was 54, but the study found harm associated with sleeping pill use in every age group.[2]

All the sleeping pills showed a similar increased risk of death except Lunesta, which showed a more than 500% increased risk compared to any of the other sleeping pills.  However, Lunesta was a relatively new drug at the time of the study, and relatively few people took it. For that reason, it is not possible to say whether the risk of Lunesta is really that high.  Also important to note: This study did not evaluate cancer among patients taking Belsomra, a newer sleeping aid with numerous side effects.[3]

One shortcoming of the study is that getting a prescription for a sleeping pill is not the same as taking sleeping pills.  It is possible that some of the people with prescriptions, especially for small numbers of pills, never took any of them. It is also possible that people who did not have prescriptions for sleeping pills took Benadryl or other over-the-counter antihistamines to help them fall asleep, instead of the prescription version of the same pills.  However, those shortcomings would tend to underestimate the risk of sleeping pills, rather than overestimate the risks.

In addition to the major study cited above, there is other evidence linking sleeping pills to cancer.  For example, a study of Taiwanese patients published in 2012 found that Ambien promoted viral infections, which reflects a weakening of a person’s ability to fight off infections and diseases.[4]  That could explain the increased risk of cancer.

Also, a study published in the Korean Journal of Family Medicine in 2018 found that sleeping pills were strongly associated with esophageal, kidney, prostate, liver, stomach and pancreatic cancers. Of all the sleeping pills in the study, Ambien most strongly predicted a diagnosis of cancer.[5]

But Why?

What could possibly explain these increased risks?  Are people who are prescribed sleeping pills more anxious or stressed out? There is evidence that they are more likely to have car accidents or to fall down, probably because of the residual effects of the drugs during the day.  Other studies show an increase in infections among people taking sleeping pills, and that can also increase the risk of cancer and death from other causes. These other studies all suggest that sleeping pills really do increase the risk of dying and there are no logical explanations to explain away the substantial increased risks found in this study, especially the increased risk of cancer.

While the researchers can’t say for sure that the sleeping pills caused death or cancer, many people who used to take these medications should think about these new research findings and consider other, safer ways to fall asleep.  The sleep specialists who conducted the research suggest that since these sleeping pills have limited benefits, old-fashioned sleep aids like warm milk, as well as cognitive-behavioral approaches that can be taught and used for the rest of your life, would be excellent alternatives.  If you decide to toss your sleeping pills, be sure to see our article Drugs in the Drinking Water for tips on safe medicine disposal.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References:

  1. Consumer Reports. Why Americans Can’t Sleep. ConsumerReports.org. https://www.consumerreports.org/sleep/why-americans-cant-sleep. Updated January 14, 2016. Accessed October 15, 2018.
  2. Kripke DF, Langer RD, Kline LE. Hypnotics’ association with mortality or cancer: a matched cohort study. British Medical Journal. Open 2012;2:e000850 doi:10.1136/bmjopen-2012-000850
  3. Kripke, D. F. (2015). Is suvorexant a better choice than alternative hypnotics? F1000Research, 4, 456. http://doi.org/10.12688/f1000research.6845.1
  4. Kao, C.-H., Sun, L.-M., Liang, J.-A., Chang, S.-N., Sung, F.-C., & Muo, C.-H. (2012). Relationship of Zolpidem and Cancer Risk: A Taiwanese Population-Based Cohort Study. Mayo Clinic Proceedings, 87(5), 430–436. http://doi.org/10.1016/j.mayocp.2012.02.012
  5. Kim, D.-H., Kim, H.-B., Kim, Y.-H., & Kim, J.-Y. (2018). Use of Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies. Korean Journal of Family Medicine, 39(4), 211–218. http://doi.org/10.4082/kjfm.17.0025

Ten Easy Tips to get Your Family Eating Healthy

Diet, Habits, & Other Behaviors
Cancer Prevention and Treatment Fund

Keeping your weight down and avoiding certain foods help prevent cancer from developing, and help prevent it from returning after treatment. Does switching to healthier foods seem like an impossible chore?  It doesn’t have to be! Change your habits gradually with these 10 simple tips.

  1. Cut out trans fats. These fats are the worst for you, because they increase your chances of heart disease by increasing “bad” cholesterol and decreasing “good” cholesterol.  It’s easy to read food labels and eliminate trans fats from your diet.  To reduce other unhealthy dietary fats, try to bake, broil, or grill meats more often and avoid frying.  Also, try using cooking spray (it allows you to use less oil) or olive oil instead of other oils.
  2. Eat more fruits and vegetables. Fruits and vegetables are good for you and also help to fill you up so you won’t feel hungry.  If you fill up your plate with fruits and veggies, you probably won’t need vitamin pills, you’ll have fewer hunger pangs, and you will train your taste buds to crave fewer sweet and salty foods.
  3. Cut back on salt. That doesn’t just mean keep away from the salt shaker. You also have to read food labels because most of our salt comes from foods that the manufacturers have “salted” for us. The USDA recommends less than a teaspoon of salt each day!  A teaspoon of table salt contains 2,300 mg of sodium but 1,500 mg is what is recommended for all children, all African Americans, all people 51 and older, and other adults with certain illnesses.  Food without salt doesn’t taste boring if you use other seasonings, like garlic, pepper (cayenne or chili pepper if you like things spicy!), curry powder, ginger, lemon juice, or fresh herbs to add flavor.  Or, you can try using seasoned salt, which has less sodium per teaspoon than pure salt.
  4. Cut back on refined grains. Eat less “white” rice, pasta, and bread.  Choose whole grain products instead.  At least half of the grains your family eats each day should be whole grains-including whole wheat bread, whole grain pasta, and brown rice.  If you don’t like the taste of whole grain pasta or brown rice, try alternatives such as quinoa, whole wheat couscous, and bulgur for a change.  Some of these can be hard to find or more expensive than rice, but quinoa (pronounced “kin-o-wa”) tastes good and has almost double the protein of brown rice.
  5. Replace meat and poultry in your favorite recipes with beans, lentils, or fish. They have as much protein, and if the sauce or seasoning is good, you will hardly notice the difference.
  6. Try low-fat dairy products. If your family rejects fat-free cheese, try to slowly ease in low-fat or fat-free dairy and see which products pass the taste test.  If you usually use whole milk, try 2%.  If you usually use 2% milk, try 1% or skim milk.  It may be hard to believe, but once they get used to it, your entire family will prefer the milk, yogurt, and cheeses with lower fat.
  7. Cut out sugary drinks. Even if your family loves dessert, you can drastically reduce sugar consumption by switching to 100% juice, different flavored iced teas (it’s usually better for you to brew and sweeten them yourself), and water instead of sugary sodas, punch, or sports drinks.  Some coffee drinks that appeal to our sweet tooth have all the calories of a meal and none of the nutrients. Many have 500 or more calories and some of them top 1,000!
  8. Gradually reduce portion size. If overeating is a problem for your family, consider using smaller plates and bowls.  Family style eating-which  keeps extra food on the table for everyone to help themselves-is less work for parents but almost always results in everyone eating much more.  If you just serve everyone a single portion, they will eat less.  Keep second helpings small and let kids know that if they want a second helping of meat or grains, they must have a second helping of the vegetables as well. And if they are old enough, let them get up from the table to get it themselves.  Those rules can help everyone eat a more balanced diet.
  9. No food with screen time, and more outdoor activities. Don’t let kids or adults snack while watching TV or using the computer.  Eating in front of the TV or computer almost always results in mindless overeating.  Make plans to keep everyone more active, but when they are in front of a screen keep them away from snacks.
  10. Schedule regular mealtimes. If everyone in the family eats at regular times and snacks are available only when meals are far apart, you’ll be surprised by how that will affect everyone’s weight.  Regular mealtimes help people avoid overeating.  Once you start eating, it’s hard to stop, so try to stick to only 3 meals and no more than one snack each day.   And, it’s trite but true: starting the day with a nutritious breakfast is important for doing your best all day.  An easy and  nutritious breakfast can include cereal with yogurt or milk, and don’t forget fruit juice or fruit.

References:

Diana Zuckerman & Brandel France de Bravo, The Survival Guide for Working Moms (and Other Stressed-Out Adults), 2009.

United States Department of Agriculture and Department of Health and Human Services, Dietary Guidelines for Healthy Americans 2010, available at: http://www.health.gov/dietaryguidelines/

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The Cancer Prevention and Treatment Fund Responds to the Silimed Breast Implant Scandal

Press Releases
Cancer Prevention and Treatment Fund, January 30, 2012

The latest breast implant scandal to hit Europe involves polyurethane foam-covered implants that have been sold in Europe for almost a decade, after being banned in the U.S. for over 20 years. While the PIP implant fears in Europe probably affect more women, the Silimed implant story may be even more frightening. Why did German regulators approve these types of breast implants, which were banned in 1991 because of evidence that the foam broke down into a known carcinogen in the woman’s breasts? The company says there is no evidence that their implants cause cancer, but cancer usually takes at least 15-20 years to develop. That’s why men and women who started smoking as teenagers almost never get diagnosed with lung cancer in their 20’s or 30’s.

Cancer is not the only risk of polyurethane foam. The body can have a very bad immune reaction to the polyurethane, and since the woman’s scar tissue grows into the foam, the implants can be almost impossible to remove. When these implants are taken out for any reason, it is not unusual for some of the woman’s own breast tissue to be removed as well, leaving her with smaller breasts than she had before breast implants. Her breasts may also be deformed from the explant surgery.

FDA can be proud that they did not allow Silimed or PIP breast implants to be sold in the U.S. in recent years. Unfortunately, all of Europe was forced to allow Silimed implants on the market after German regulators awarded the CE mark, which indicated they met European quality standards. How did this happen? It’s simple; Europe requires almost no evidence of safety for medical devices, not even for implants. These lower standards have hurt tens of thousands of women with breast implants, and millions of men and women with other types of implants that were not tested in clinical trials.

To learn more about the Silimed implant scandal, please read this article in the Daily Mail.

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.

To view this article in its original form, please click here.

FDA Needs to Provide Breast Implant Patients and Physicians with Unreported Industry Data about Quality of Life, Connective Tissue Symptoms, Rupture Rates per Patient, and Other Complications

Testimony & Briefings
Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund, January 5, 2012

Dr. Jeffrey Shuren, Director
Center for Devices and Radiological Health
Food and Drug Administration
Silver Spring, MD 20993

RE: FDA Needs to Provide Breast Implant Patients and Physicians with Unreported Industry Data about Quality of Life, Connective Tissue Symptoms, Rupture Rates per Patient, and Other Complications

Dear Dr. Shuren:

At the FDA Advisory Panel meetings in 2003 and 2005, FDA provided and presented data from the Breast Implant Core studies regarding connective tissue disorder (CTD) signs and symptoms (S/S) and Quality of Life measures.  The data indicated poorer outcomes for patients after implants.  Neither the previous data nor any follow-up data were presented nor discussed in the FDA’s June 2011 summary nor at the August 2011 meeting of the General and Plastic Surgery Devices Advisory Panel, when those same studies were summarized. Moreover, in direct contradiction to the 2005 FDA scientific summaries of data from the Core Studies, the 2011 FDA summary erroneously stated that there was no evidence of breast implants influencing connective tissue diseases.

We are writing to request that the data reported by FDA in 2005 be included in an updated version of the 2011 summary that is available on the FDA web site, and to ask for an explanation about why these important data were not included in the 8-year and 10-year Core Study data summaries provided to the Advisory Panel or presented in recent summary documents on the FDA web site.

At the August 31, 2011 meeting, Dr. Dana Casciotti asked that question during the public comment period.  Dr. Marinac-Dabic told Dr. Casciotti that FDA would respond later that day (pg. 371 of the transcript), but no response was ever provided at the meeting or subsequently.

At the same FDA Advisory Panel Meeting on August 30, 2011, Dr. Diana Zuckerman pointed out that both Mentor and Allergan had reported higher complication rates at 3- and 4-year follow-up according to the FDA analyses of their data in 2005, compared to their cumulative 8- and 10-year complication rates reported in 2011.  This makes no sense, since cumulative complication rates should be higher in longer-term studies than shorter-term studies.  Dr. Zuckerman also pointed out that rupture rates were mistakenly reported “by implant” rather than by patient in the FDA 2011 summary.  Five months later, that error has not yet been corrected.

In this letter, we provide those previously reported data on Connective Tissue Disease Signs and Symptoms, Quality of Life, rupture rates, and other complications from FDA 2003 and 2005 public documents. Information in quotations and italics are quoted from FDA documents, and all data and summaries are based on FDA documents.  When available, we also provide data from FDA documents presented in 2011, and show how those comparisons indicate inaccurate reporting in 2011.

Connective Tissue Disease Signs and Symptoms

According to the FDA Summary Panel Memorandum from the FDA review team of the Inamed data, dated March 2, 2005, comparing data from before and two years after getting implants, there was an increase in “5 out of 8 of the CTD S/S [connective tissue disease signs and symptoms] categories for augmentation patients, even after adjusting for age.”

The FDA memo pointed out that Inamed claimed that age accounted for these changes, which the memo stated “is incorrect” (see page 57).  That document is on the FDA web site at:  http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4101b1_tab-1_fda-Inamed%20Panel%20Memo.pdf

In the memo summary on page 59, FDA concluded (entire section is directly quoted, with key sections highlighted):

“• In evaluating whether the increases in CTD S/S from baseline were related to age, the increases in the following CTD categories occurred despite age:

o   Augmentation: Other, Skin, General, Muscle, Joint

o   Reconstruction: Other, Skin, General

o   Revision: Other, Muscle, Joint.

• The responses to fatigue questions increased by 3% from baseline; however, the prevalence of FM S/S reporting was within the range reported for the U.S. population.

• No statistical associations were found for CTD S/S reporting and implant rupture or patient satisfaction; however, lack of statistical association could have been due to the sample size rather than the lack of a relationship.

• Patients in the MRI Cohort and patients with unresolved complications tended to report higher frequencies of CTD S/S and FM S/S.

• When compared to the patients having undergone saline-filled breast implants, the increase in CTD S/S were not significantly different for patients having silicone gel-filled breast implants.

• Without a control/comparison group of patients without implants followed for the same duration of follow-up and with similar demographic characteristics, the interpretation of these data is difficult.”

In addition, at the April 2005 meeting, FDA panel member Brent Blumenstein, a statistician, indicated that the Inamed analysis was inadequate to evaluate changes in signs and symptoms when age was controlled.  According to the FDA transcript, Blumenstein stated, “The model was incorrectly fit….The bottom line is that while there exists data addressing this connective tissue disease signs and symptoms there’s no inference possible at this time.  We are still in a state of ignorance with respect to whether there are notable changes in connective tissue disease signs and symptoms following an implant.”

The FDA Summary Panel Memorandum from FDA’s Mentor PMA Review Team, March 2, 2005, is presented in tables and text, as shown below (for original, see http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4101b1_Tab-1_fda-Mentor%20Panel%20Memo.pdf )

On Page 62, the FDA memo states “The tables below summarize the cumulative incidence through 3 years of any individual sign/symptom and the two most commonly reported individual sign/symptoms for each indication.  Joint pain was one of the top two most commonly reported CTD sign/symptoms for all three surgical indications.”

Augmentation Number with sign/symptom reported Cumulative Incidence
Any Sign/Symptom 53 10.3%
Numbness of Hands 13 2.7%
Joint Pain 13 2.6%
Reconstruction Number with sign/symptom reported Cumulative Incidence
Any Sign/Symptom 44 21.5%
Numbness of Hands 17 8.0%
Joint Pain 10 4.5%
Revision Number with sign/symptom reported Cumulative Incidence
Any Sign/Symptom 39 21.3%
Numbness of Hands 14 7.3%
Joint Pain 11 6.0%

Although the tables do not compare pre and post-tests, on page 63 the FDA team discusses how the incidence increased significantly:

“For augmentation patients, the following CTD signs/symptom increases from baseline were statistically significant and, therefore, were due to reasons other than aging: fatigue, exhaustion, joint swelling, frequent muscle cramps, joint pain, combined fatigue, combined pain, and combined fibromyalgia.Generalized aching was nearly statistically significant at p=0.0641.  For reconstruction patients, the GEE analysis yielded no statistically significant results.  Therefore, for the reconstruction population, it can be concluded that the increases noted in CTD signs/symptoms from baseline were due to aging.  The symptom of joint pain, however, was nearly significant at p=0.0579 for reconstruction patients.  For revision patients, the GEE analysis results indicated statistically significant findings for fatigue, generalized aching, and combined fatigue.  Therefore, for this population, the increases from baseline in fatigue and aching were due to reasons other than aging.”

Although the FDA did not mention it in their 2005 memorandum, the lack of statistical significance for the Mentor reconstruction sample may have been related to the smaller sample size.  According to the table on page 51, only 251 reconstruction patients were included in the study, less than half the number of augmentation patients (551 women).

Statistician Brent Blumenstein presented additional analyses on Mentor augmentation patients for the FDA meeting and concluded that the Mentor data were superior to previous CTD studies on breast implants, saying (from the FDA transcript for April 13, 2005) “What we have here is a well-designed study with subjects serving as their own control.  And that these findings are consistent, that is the specific list of signs and symptoms and classes of signs and symptoms are consistent with our a priori expectations, and we have adjusted for age. And also, it is important to remember that these signs and symptoms changes track well with some of the quality of life changes that we have seen.  So, in my opinion, I find these results disquieting.” Dr. Blumenstein suggested FDA require additional studies, advising “Find patients who have these high symptom scores and study these women, plus a sample of women with low scores, in a supplemental study.  You might even think about assaying tissues if you could get that.  Assess their lifestyles….put them under intense follow-up.  Find out what is going on with these women, because there is something going on here.”

It is worth noting that of the several men and women on the published list of 2011 Advisory Panel members who had participated in previous FDA Advisory Panel meetings on breast implants, Dr. Blumenstein was the only member who had consistently recommended against approval at the 2005 meeting.  Despite being listed as a Panel member for the 2011 meeting, however, Blumenstein was apparently excluded from that meeting.  His exclusion may help explain why these issues of missing Signs and Symptoms data and Quality of Life data were not raised at the 2011 Panel meeting.  His exclusion also raises questions about bias in the final roster of 2011 panel members.

Quality of Life

Despite claims that breast implants would improve self-esteem and quality of life, most of the data presented in 2005 FDA summaries do not support those claims.

In summary, for Inamed augmentation patients, 12 quality of life scores differed significantly in the pre-test and post-test.  Nine of the 12 (75%) were worse in the post-test.  For Inamed revision patients, 9 of 9 (100%) that differed significantly were worse in the post-test.  For reconstruction patients, only two scores were significantly different in the post-test, and both showed improvement in physical functioning, which probably reflects the fact that many of these women were being treated for breast cancer at the pre-test and their quality of life was better as cancer survivors two years later.

The FDA summary points out that for both Mentor and Inamed, the patients showed higher scores on quality of life than the general population, in the pre-test and post-test.  This indicates that the women who had breast implant surgery are not generally women suffering from low self-esteem or poor quality of life.

Inamed (Allergan)

Here are the details from the FDA Summary Panel Memorandum from FDA’s Inamed PMA Review Team, March 2, 2005 (http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4101b1_tab-1_fda-Inamed%20Panel%20Memo.pdf)

“With respect to the Health Status Questionnaire (SF-36 and MOS-20), the core augmentation cohort….There were small, statistically significant declines in some subscales of these measures in breast implant recipients over time.  However, the 2-year values for the augmentation cohort were generally numerically higher than normative values for the general female population” (page 71).

Although the FDA summary does not mention it, most of the significant differences showed lower scores on quality of life in the post-test.  Nine of 12 were worse for augmentation patients and nine of 9 were worse for revision patients.

Quality of Life measures include the SF-36, which measures 8 health concepts: physical functioning; role-physical; bodily pain; general health; vitality; social functioning; role-emotional; and mental health.  The 8 scales can then be collapsed into two summary scales with the first 4 scales comprising the Physical, and the last 4 scales comprising the Mental Health.

Inamed Augmentation Patients

All Statistically Significant Changes are as follows:

  • SF-36 Role Emotional:  Significantly worse in post-test
  • SF-36 Role Physical:  Significantly worse in post-test
  • SF-36 General Health:  Significantly worse in post-test
  • SF-36 Social:  Significantly worse in post-test
  • SF-36 Vitality:  Significantly worse in post-test
  • SF-36 Mental Health:  Significantly worse in post-test
  • MOS-20 Health Perceptions:  Significantly worse in post-test
  • MOS-20 Mental Health:  Significantly worse in post-test
  • Tennessee Self-Concept Scale: Physical Self:  Significantly better in post-test
  • Body Esteem-Total Score:  Significantly better in post-test
  • Body Esteem-Sexual Attractiveness:  Significantly better in post-test
  • Body Esteem-Physical Condition:  Significantly worse in post-test
  • Scores on the Rosenberg Self Esteem Scale were worse in the post-test, but the difference was not statistically significant.

Allergan Reconstruction Patients

  • SF-36 Role Physical:  Significantly better in post-test
  • MOS-20 Physical Functioning: Significantly better in post-test

Inamed Revision Patients

  • SF-36 Role Emotional:  Significantly worse in post-test
  • SF-36 General Health:  Significantly worse in post-test
  • SF-36 Social:  Significantly worse in post-test
  • Mental Health: Significantly worse in post-test
  • MOS-20 Health Perceptions: Significantly worse in post-test
  • MOS-20 Mental Health: Significantly worse in post-test
  • Tennessee Self-Concept Scale Physical Self:  Significantly worse in post-test
  • Rosenberg Self-esteem Scale:  Significantly worse in post-test
  • Body Esteem-Physical Condition:  Significantly worse in post-test

Mentor

Below are the data from the FDA Summary Panel Memorandum from FDA’s Mentor PMA Review Team, March 2, 2005 (http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4101b1_Tab-1_fda-Mentor%20Panel%20Memo.pdf)

Similar to the Inamed findings, when there were statistically significant changes from pre-test to post-test for Mentor patients, almost all were worse in the post-test compared to the pre-test.  For augmentation patients, scores on physical health and mental health were significantly worse, scores on the Rosenberg self-esteem scale were better, and there was no change on the Tennessee self-concept scores or body esteem scale.  For revision patients, scores on physical health, mental health, body esteem and Tennessee self-concept scale all were worse in the post-test, and there was no change in the Rosenberg self-esteem scale.  No scores were better in the post-test.  For reconstruction patients, there were no significant changes on any of the scales.

The data below are not as detailed as the Inamed data, because the FDA memo did not provide as much specific information.  However, it includes differences in scores that were provided by the FDA.

Mentor Augmentation Patients

  • Physical Health: Significantly worse in post-test (1.0)
  • Mental Health: Significantly worse in post-test (1.1)
  • Tennessee self-concept scores: No significant change
  • Body Esteem scale: No significant change
  • Rosenberg Self-Esteem Scale: Significantly better in post-test (0.6)

Mentor Reconstruction Patients

  • Physical Health: No significant change
  • Mental Health: No significant change
  • Tennessee Self-Concept Scale: No significant change
  • Body Esteem Scale: No significant change
  • Rosenberg Self-esteem Scale: No significant change

Mentor Revision Patients

  • Physical Health: Significantly worse in post-test (1.8)
  • Mental Health: Significantly worse in post-test (2.5)
  • Tennessee Self-Concept Scale: significantly worse in post-test (6.6)
  • Body Esteem Scale: significantly worse in post-test (5.0)
  • Rosenberg Self-esteem scale: no significant change

FDA also noted the following about the literature review on Quality of Life information (provided by Mentor):

  • Page 70: “…the literature does not provide strong scientific support that breast implants have measurable psychological and psychosocial benefits for women seeking breast augmentation.”
  • Page 73: “Literature that adequately evaluates the short-term or long-term psychological or psychosocial benefits of breast implants as a reconstructive procedure utilizing appropriate control group was not provided by Mentor.”

Cumulative Complication Rates

Allergan Patients at 3 Years and 10 Years

The long-term safety data on breast implants provide data on the cumulative complication rates for a wide range of risks, including health problems and cosmetic complications.  These data provide important information that patients can use to determine if the risks of implants outweigh the benefits.  Either health risks or cosmetic complications can result in additional surgeries to remove and/or replace breast implants.

At the August 2011 FDA Advisory Panel meeting, the FDA presented data on 8-year complication rates for Mentor and 10-year complication rates for Allergan.  Rates at 3 and 4 years had previously been made available at the FDA’s 2005 Advisory Panel meetings, but were not presented in 2011 at the FDA meeting or in the FDA’s summary report.  However, the earlier data are still available on the FDA web site, and when we compared the complication rates, we discovered that numerous reported complication rates decreased over time for both companies’ data. 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.

The 3-year complication rates for Inamed/Allergan were reported in this FDA official memorandum in 2003:http://www.fda.gov/ohrms/dockets/ac/03/briefing/3989b1_clinical-summary-memo.pdf

For Allergan Primary Augmentation Patients, the following complications were reported to be lower at 10 years (N=455) than at 3 years (N=494).  That raises questions about the accuracy of reporting.  The FDA reported that the samples sizes decreased because some patients died and some withdrew from the study.  However, in order to maintain accurate reports of complications, patients who reported problems earlier in the study should not be eliminated from the later sample.  We ask that the FDA explain whether some of the patients with earlier complications were excluded from the 10-year sample, and if so, under what circumstances and how did that affect complication rates? Accuracy problems are more obvious when the reported percentages decreased over time, but even those where the percentages increased may be inaccurate.

Swelling:  23% went down to 9%

Scarring:  8% went down to 4%

Seroma:  3% went down to 2%

Ptosis:  3% went down to 2%

For Allergan Primary Reconstruction Patients, the following complications were reported to be lower at 10 years (N=98) than at 3 years (N=221).  That again raises questions about the accuracy of reporting, and whether patients with complications were excluded from the 10-year sample.

Swelling:  16% went down to 7%

Redness:  6% went down to 2%

Seroma:  5% went down to 2%

Malposition:  5% went down to 2%

Bruising:  4% went down to 1%

Skin Rash:  3% went down to 2%

Ptosis:  1% went down to 0%

Mentor Patients at 3 Years and 8 Years

For Mentor Primary Augmentation Patients, the following complications were not reported at 8 years but had been reported at 3 years, for a sample described as 551 patients in 2005 and in 2011.  Since all complications experienced by 1% or more of the sample were supposed to be reported, the absence of these reported complications at 8 years raises questions about the accuracy of reporting, and whether patients with complications were excluded from the 8-year sample even though the sample sizes reported were identical.

Hypertrophic Scarring: 6% at 3 years, not reported at 8 years

Ptosis:  2% at 3 years and not reported at 8 years

The above 3-year Augmentation Patient data are reported in the 2005 FDA Summary Panel Memorandum on page 52.

http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4101b1_Tab-1_fda-Mentor%20Panel%20Memo.pdf .  The below 3-year Reconstruction Patient data are on page 53.

For Mentor Primary Reconstruction Patients, the following complications were not reported at 8 years (N=251) but had been reported at 3 years (N=251).  That again raises questions about the accuracy of reporting, and whether patients with complications were excluded from the 10-year sample even though the reported sample size is identical.

Hematoma extrusion: 2% at 3 years and not reported at 8 years

Necrosis: 1% at 3 years and not reported at 8 years

Asymmetry: 7% at 3 years and not reported at 8 years

Ptosis: 7% at 3 years and not reported at 8 years

Hypertrophic scarring: 6% at 3 years and not reported at 8 years

Redness and skin rash were reported for Allergan but not for Mentor.

In addition to the clear errors, where the cumulative percentage reporting a complication decreased or disappeared from 3 years to 8 years, these problems raise questions about the accuracy of all the 8-year data, even those where the percentages increased.  For example, while all experts agree that asymmetry increases over time, especially for reconstruction patients, Allergan asymmetry increased from 15% at 3 years to only 23% at 10 years.  Other increases in complications were also rather modest compared to patient reports: Mentor reconstruction patient reoperations increased from 26% at 3 years to 39% at 8 years and removal from 13% to 23%.  Would those numbers have been higher if the reporting was more accurate, or if patients who had problems had not been dropped from the final sample?  For example, the Allergan 10-year sample is less than half the size of the 3-year sample.  Are women who had their implants removed being removed from that sample and therefore biasing the results?  These questions are important for the Inamed and Mentor data.

Rupture Rates

FDA Memorandum June 2011

On page 10 of the FDA memorandum dated June 2011 (linked above), the implant rupture rate is reported per implant.  Those same percentages are included in Table 4 (page 53), where all the complication rates, including rupture data seem to be reported per patient, since the sample sizes are listed as the number of patients not the number of implants.  This is incorrect, since the percentage of women with ruptured implants is much higher – approximately twice as high – as the percentage of ruptured implants.

Based on the MRI cohort in the 2011 summary, the Allergan rupture rate per implant is 10% of augmentation implants and 27% of reconstruction implants.  No rupture rates per patient are reported.  At 4 years, the Allergan rupture rate per patient was almost exactly twice the rupture rate per implant, according to the March 2, 2005 FDA summary of Inamed (see link on page 3 of this document, pages 21-22).  Similarly, the Mentor rupture rate at 8 years was 14% per implant for augmentation patients and 14% for reconstruction patients, but no data per patient were reported.  At 3 years, the Mentor rupture rate per patient was approximately twice that per implant, according to the March 2, 2005 FDA summary of Mentor (see link on page 5 of this document, page 77).

The use of per implant rupture rates is misleading for patients.  When a patient’s implant ruptures, surgery is required to remove it, regardless of whether one implant is ruptured or both are ruptured.  The risks of surgery and costs to the patients are very similar whether one or two implants are involved.  Therefore, patients want to know what the chances are of having a ruptured implant, not the percentage of implants that rupture.  It is certainly important for women considering implants to know if the rupture rate is more than half the primary reconstruction patients and 20% of primary augmentation patients at 10 years.

An accurate rupture rate per patient is especially important in light of the FDA panel’s discussion about how often women with silicone implants should be advised toundergo breast MRIs to check for leakage.  It is widely acknowledged that most women do not undergo regular MRIs to check for breast implant leakage, but one would expect that to change if patients (especially reconstruction and revision patients) realized how likely it was for their implants to rupture within 10 years.

The importance of per patient rates is true for all complications.  Patients care whether they will have breast pain more than they care whether the pain will be in one or both breasts.  If complications occur that require surgery, that is an important piece of information, whether or not one or both implants are involved.  We ask FDA to clarify whether each of the complication rates reported is per implant or per patient.

The somewhat lower rupture rates for Mentor may reflect a better product or may reflect the different time frames for the analysis (3 vs. 4 years, 8 vs. 10 years).  Or, given other problems with the Mentor data, the data differences raise questions about the accuracy and generalizability of the data because of the high drop out rate.

Summary

In conclusion, we are concerned about missing information and inaccurate or misleading data that were provided to the FDA Advisory Panel on breast implants and that are included (or missing) in the June 2011 summary on the FDA web and in other recent FDA materials.

  • Missing information about signs and symptoms of connective tissue disease from 2005 and the most recent follow-up data, and an inaccurate summary of earlier findings
  • Missing information about poor outcome on Quality of Life measures from 2005, and missing follow-up data
  • Inaccurate cumulative complication rates for at least some outcomes
  • Inaccurate and misleading presentation of rupture data, which should be presented per patient rather than per implant.
  • Questions about which complications are presented per implant or per patient and questions about whether women with complications at 3 or 4 years were excluded from the 8- and 10-year follow-up samples.

We expressed concern about these omissions and errors during the FDA Advisory Panel Public Comment Period in August 2011, and are very disappointed that the FDA has not corrected any of these problems in the last 5 months.  We would appreciate a response to this letter in writing, and also ask for a meeting to discuss these issues.

Sincerely,

Diana Zuckerman, Ph.D.
President

Cc:  The Honorable Barbara Boxer

The Honorable Rosa DeLauro

The Honorable Dianne Feinstein

The Honorable Olympia Snowe

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.