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What You Need to Know About Breast Implants

Diana Zuckerman, PHD; Elizabeth Naglin-Anderson, MA; and Elizabet Santoro, RN, MPH, National Center for Health Research


In 2020, fewer than 194,000 women and teenagers underwent surgery to have their breasts enlarged with silicone or saline implants, a 33% decrease compared to 2019.  In addition, more than 137,000 breast cancer patients had reconstruction after mastectomy in 2020, often with implants.1 While the popularity of breast augmentation had tripled between 1997, when there were just over 101,000 of these procedure,2  to 2017 when over 300,000 breast augmentations were performed1, recent trends show that fewer women are opting for augmentation.

There were also 59,043 implant removal procedures in 2020, including augmentation and reconstruction patients, compared to 54,539 in 2019 and 48,385 in 20181 . The increasing number of women removing their implants can be attributed to several factors, including news stories highlighting the risks of breast implants, the growing mass media and social media presence of patient advocates, Allergan’s recall of their BIOCELL textured breast implants in 2019 and efforts to notify women of the recall, and several insurance companies expanding their coverage to include women whose textured implants were recalled.

However, debate continues to swirl about the safety of breast implants. Here are the facts about what is known and not known about the risks of breast implants.

History of Implants in the US

Breast implants made with silicone envelopes and filled with silicone gel or saline (salt water) were first sold in the United States in the 1960s, but sales were relatively slow until the 1980s. By 1990, however, almost one million women had undergone breast implant surgery, even though no safety studies had been published. Most of those women had silicone gel breast implants, which the plastic surgeons preferred.

Although most medical products must be proven safe and effective before they can be sold in the U.S., that was not true for implanted medical devices sold before 1976.  The Food and Drug Administration (FDA) did not require that companies selling silicone breast implants prove that their implants were safe until 1991 – after they had been in use for almost three decades. For the first time, the media started to report about women with implant problems, and quoted doctors who were concerned about implant safety. When the studies were provided to the FDA, the safety data were found to be inadequate to warrant FDA approval.

The FDA did not require implant makers to prove that their saline implants were safe until 2000, when, despite high complication rates, the FDA approved saline breast implants for the first time.

Silicone gel breast implants were approved for the first time in November 2006. Between 1992 and 2006, silicone implants were restricted to clinical trials that were primarily for cancer patients and women with broken implants. The FDA required that patients be informed that the implants were not approved by the FDA and to be regularly evaluated by their plastic surgeons as part of the study, in order to provide safety data intended to help all women with gel implants. Unfortunately, there was no enforcement of that requirement and women who were enrolled in these studies to enable them to get breast implants were often not studied after the surgery.

Silicone gel breast implants made by two manufacturers were approved in November 2006, and gel implants made by one/two other manufacturers were approved subsequently.  There are still restrictions, however. For example, they are only approved for women over the age of 22, because younger women are still developing physically and emotionally and probably would not fully understand the risks.

In 2011, the FDA began tracking cases of a cancer of the immune system linked to textured breast implants, known as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Over the next several years, as studies were completed, FDA and medical experts recognized that rather than just being “possibly associated” with ALCL, breast implants caused ALCL, and that the risk was highest among women with textured breast implants. In 2019, Allergan recalled their BIOCELL textured implants worldwide following growing evidence of the greater risk of BIA-ALCL for women with those implants.  At the time of the recall, the FDA reported that 573 cases of BIA-ALCL worldwide had been reported since 2011, and this known total was increased to 1,130 in 2022.

In September 2022, the FDA announced new information about other cancers related to breast implants: various other lymphomas as well as squamous cell carcinoma. At the time of the announcement, the FDA had received 10 reports about breast implant-related SCC and 12 reports about lymphomas other than ALCL. Like BIA-ALCL, these cancer cells all were found in the scar capsule surrounding the breast implant, which is why experts believe the implants are the cause.  The implants involved were saline and silicone, textured and smooth.

What Are the Known Risks?

Reports of complications among women with implants have been published in medical journals and discussed at public FDA meetings. There are a number of short-term and long-term risks that any woman thinking about getting breast implants or about removing or replacing older implants needs to be aware of.

“Local complications” refer to problems that occur in the breast area that are obviously related to the breast implants or the surgery. Common complications include infection and other surgical risks, chronic breast pain, breast or nipple numbness, capsular contracture, breakage and leakage, necrosis (skin death), the need for additional surgery, and “cosmetic” problems (such as dissatisfaction with how the breast looks with the implant).

Studies of saline breast implants and silicone gel breast implants conducted by implant manufacturers have shown that within the first three years, approximately three out of four reconstruction (breast cancer) patients and almost half of first-time augmentation patients experienced at least one local complication – such as pain, infection, hardening, or the need for additional surgery.3

For example, among reconstruction patients:

  • 46% of women with silicone gel implants and 21% with saline implants underwent at least one re-operation within three years;
  • 25% of silicone patients and 8% of saline patients had implants removed; and
  • 6% of silicone patients and 16% of saline patients experienced breast pain.4

Complication rates were lower, but still substantial, for augmentation patients. The FDA has a consumer handbook with descriptions of common complications as well as photographs, available to consumers here.

Among all reported complications related to breast implants, BIA-ALCL has been the most concerning, especially as reported cases continue to rise worldwide.  Since many physicians do not report problems with medical devices, reports to the FDA are considered “the tip of the iceberg.”  Therefore, although rare, it seems that BIA-ALCL is not “very rare.” In Australia, which can track medical problems from any kind of implants better than the tracking of implants in the U.S., they estimate that BIA-ALCL affects one woman per 1,000 with breast implants.5 The estimates were much lower in the U.S., but there is no reason to think BIA-ALCL is less likely to develop in women in the U.S.  Given the dramatic increase in diagnoses in recent years, it is clear that BIA-ALCL was under-diagnosed and under-reported for many years.

In addition to the risks from anesthesia, surgical risks include infection and hematoma (blood collecting around an implant), both of which can range from mild to severe. Surgical risks are highest immediately around the time of surgery, but complications can require additional surgery later, which will have similar risks. A woman may need to face these surgical risks several times if she needs surgery to correct implant problems or has broken or damaged implants replaced with new ones.

Common local complications include loss of nipple sensitivity or painfully sensitive nipples. Some women are dissatisfied with the cosmetic results of breast implants, because their breasts look or feel unnatural or asymmetrical, or they can hear a “sloshing sound” from saline-filled implants. Problems like these can interfere with sexual intimacy.

Scar tissue that forms around any implant or foreign body can become hard or tight around the implant. This common problem is called capsular contracture. The scar tissue is inside the body, but it can cause the breasts to become very hard and misshaped, and it leads to discomfort that ranges from mild to severely painful.

Researchers have shown that bacteria or mold can grow in saline implants, and have expressed concerns about the bacteria or mold being released into the body if the implant breaks.6 What effect that might have on a woman, or a nursing baby, has not been studied.

What Happens When Implants Break?

All breast implants will eventually break, but it is not known how many years the breast implants that are currently on the market will last. Studies of silicone breast implants suggest that most implants last 7-12 years, but some break during the first few months or years, while others last more than 15 years.

In a study conducted by FDA scientists, most women had at least one broken implant within 11 years, and the likelihood of rupture increases every year.7 Silicone migrated outside of the breast capsule for 21% of the women, even though most women were unaware that this had happened.

Implant makers were required to study breakage and provide their studies to the FDA.  Short-term studies of today’s saline implants suggest that between 3-9% break within the first three years, and one implant manufacturer’s study of their silicone gel implants found that between 3-20% break within three years.3,8 A Danish study of ruptured silicone gel implants suggests that most implants last for ten years, but by the time they are 11-20 years old, most will break, and after 20 years the few that are still intact will break.9

Many women with silicone gel implants are unaware that their implants are broken or leaking.  Plastic surgeon Dr. Scott Spear and the former director of FDA’s Office for Women’s Health, Dr. Susan Wood, point out that “magnetic resonance imaging is the most accurate way to detect a rupture…Mammograms are often inaccurate in detecting rupture, and if an implant is already broken, the pressure from a mammogram could cause the silicone gel from the implant to leak outside the capsule.”10

Silicone Migration. Research has shown that silicone gel in implants can break down to liquid silicone at normal body temperatures, and there are reports of silicone leakage and migration from implants to the lymph nodes and other organs.11 What happens if liquid silicone migrates to the lungs, liver, or other organs? A study published by the Royal Academy of Medicine in Scotland found that a woman with a broken silicone gel implant in her calf was coughing up silicone identical to the kind in her implant.12 This has potentially serious implications for women with breast implants, since silicone gel breast implants are considerably larger and closer to the lungs than calf implants.

Do Breast Implants Make Women Sick?

A more controversial question is whether breast implants cause diseases or illnesses, in addition to ALCL and problems in the breast area.

Autoimmune, Connective tissue and Other Painful Diseases and Conditions.  Several reports published since the late 1990’s concluded that there is no evidence that implants cause systemic disease.13,14 These reports, however, often relied on research that focused on painful and autoimmune conditions and diseases in women who had implants for a relatively short time — ranging from a few months to a few years. Since these diseases may take many years to develop and be diagnosed, studies that include women who had implants for such a short time cannot be used to determine whether or not breast implants increase the long-term risks of getting these diseases.

Studies conducted after those initial reports were published indicated that implants might be linked to a number of diseases. For example, FDA scientists conducted a study of women who had silicone gel breast implants for at least seven years and found that those with implants that were leaking outside the scar tissue surrounding the implant were significantly more likely to report a diagnosis of at least one of several painful and debilitating diseases, such as fibromyalgia, polymyositis, Hashimoto’s thyroiditis, mixed connective-tissue disease, or pulmonary fibrosis.15  The risk of these diseases remained even after statistically controlling for patient’s age, implant age, and implant manufacturer.

Do implant patients who have autoimmune symptoms feel better if their implants are removed?  A study of 95 women who had silicone gel-filled breast implants and rheumatologic symptoms such as joint pain, found that the symptoms improved in 97% (42 of 43) of the women who had their breast implants removed. In contrast, rheumatologic symptoms worsened in 96% (50 of 52) of the women who did not have their implants removed.16 In addition, a university researcher has reported that silicone stimulates an immune response, and cellular analyses indicate that these responses are associated with atypical forms of connective tissue disease.17

A study of Danish women who had breast implants for an average of 19 years found that they were significantly more likely to report fatigue, Raynaud-like symptoms (white fingers and toes when exposed to cold), and memory loss and other cognitive symptoms, compared to women of the same age in the general population.18

Despite reporting that women with implants were between two and three times as likely to report those symptoms, the researchers, who were funded by a silicone manufacturer, concluded that long-term exposure to breast implants “does not appear to be associated with” autoimmune “symptoms or diseases.” However, the symptoms they reported can be from autoimmune diseases.

A report summarizing studies of breast implants was conducted by researchers hired by Tufts University and funded by The Plastic Surgery Foundation, which was supported by the 3 U.S. implant manufacturers.  This summary is notable for barely mentioning the studies quoted above.19

A study by MD Anderson Cancer Center researchers that was published in September 2018 in the medical journal Annals of Surgery, concluded that “silicone implants are associated with an increased risk of certain rare harms” and that further study is needed “to inform patient and surgeon decision-making.”20 The study included more than 100,000 women with implants, but is based on data from flawed studies conducted by two implant companies, Mentor and Allergan. Nevertheless, it is important to note that the researchers found that the risks of certain autoimmune diseases increased by 800% (Sjogren syndrome), 700% (scleroderma), and 600% (arthritis) for the women with Mentor silicone gel breast implants compared to the general population of women of the same age and demographics.  Stillbirths increased by 450% in the women who became pregnant.  Other autoimmune and rare diseases were also significantly higher among women with Mentor silicone gel implants.  These diagnoses were also statistically significantly higher for women with Allergan implants compared to the general population of women of similar demographics. Given the large percentage of women who were not in the study for more than 1 year, it is not possible to know how representative these findings are. However, these results raise important questions, especially now that it is known that breast implants can cause cancer of the immune system.

Will Explant Surgery Help Women with Breast Implant Illness Recover?

study published in 2020, conducted by Dr. Lu Jean Feng and her colleagues, also shows the risk of breast implant illness for women with breast implants, by studying the impact of explant surgery on women with breast implant illness symptoms. This study of 750 women focused on 11 symptoms: 1) numbness and tingling in the extremities; 2) joint and/or muscle pain; 3) hair loss; 4) memory loss/cognitive problems; 5) dry eyes and/or blurred vision; 6) chronic fatigue; 7) breast pain; 8) rashes and/or hives; 9) food sensitivity/intolerance; 10) flu-like symptoms and/or low-grade fever; 11) difficulty breathing.  After the women had their implants removed, most reported a significant improvement in their health within 30 days. This was true for women with either silicone gel implants or saline implants21. Not all the women had all the symptoms prior to getting their implants removed, and some reported worse symptoms than others.  After the women had their implants removed, the women reported a statistically significant improvement in their health within 30 days. The highly significant results showed that this was a real difference, that did not happen by chance.  Improvements in symptoms occurred for women with either silicone gel implants or saline implants.21

A study published in 2021 by many of the same physicians and researchers focused only on women who had reported “trouble breathing” prior to having their implants removed.22  There were 53 women in the study, and they had implants for an average of 12 years, including silicone or saline implants.  After their implants were removed, 100% of the women reported improvement in breathing.  Even more important, the physicians used 6 objective measures of “pulmonary function” that were compared before and after their implants were removed.  On half of those 6 measurements, the women showed statistically significant improvement.  In other words, the women reported improvement and those results were consistent with the evaluations conducted by the doctors using medically established objective measures indicating breathing difficulties.22

Do Breast Implants Increase the Chances of Developing Other Types of Cancer?

As mentioned above, breast implants can cause a type of cancer of the immune system called ALCL. There are also unanswered questions about cancer and implants. A study by National Cancer Institute (NCI) scientists found a 21% overall increased risk of cancer for women who had implants for at least seven years, compared with women of the same age in the general population.23 The increase was primarily due to an increase in brain, respiratory tract, cervical, and vulvar cancers. More research is needed to draw any conclusions, however.

There is no research evidence that implants cause breast cancer. However, implants can interfere with detection of breast cancer.

Mammograms have been shown to detect breast cancer earlier, potentially saving lives as well as saving women from needed mastectomies.  There are several ways in which implants have the potential to delay detection of breast cancer:

  • Although mammography can be performed in ways that minimize the interference of the implants, approximately 55 percent of breast tumors will be hidden in women with implants.24
  • FDA scientists report that silicone or saline implants can rupture when women undergo mammograms, and for this reason, women who fear implant rupture may forego mammograms.25
  • The accuracy of mammograms tends to decrease as the size of the implants increase in proportion to the size of the woman’s natural breast.

Patients have reported that their implants delayed their breast cancer diagnosis.24  Research findings have been inconsistent, but a 2013 Canadian systematic review of 12 studies found that women with breast cancer who had breast implants are diagnosed with later-stage cancers than women with breast cancer who did not have implants. This is likely due to delays in breast cancer detection because of implants. 26

A delay in diagnosis could result in the woman needing more radical surgery or the delay could be fatal.  A 2013 Canadian meta-analysis of five studies found that if women who had breast augmentation later developed breast cancer, they were more likely to die from it than women diagnosed with breast cancer who did not have breast augmentation. This increased risk of breast cancer-specific death is likely to be due to the greater inaccuracy of mammography for women with implants.25

An NCI study found that women who had breast implants for at least 12 years were more likely to die from brain tumors, lung cancer, other respiratory diseases, and suicide compared with other plastic surgery patients.27 Augmentation patients were not more likely to smoke than other plastic surgery patients, so the difference in respiratory diseases did not appear to be due to smoking. However, more research is needed to better control for relevant health habits. Three Scandinavian studies have reported that women who had breast implants for augmentation were three times more likely to commit suicide compared to women in the general population.28,29, 30

What Are Other Concerns?

Breastfeeding. According to the Institute of Medicine (IOM), women with any kind of breast surgery, including breast implant surgery, are at least three times as likely to have an inadequate milk supply for breastfeeding.12 Concerns about the safety of breast milk have also been raised, but there has not been enough research to resolve this issue.  A study of a small number of women with silicone gel breast implants found that the offspring born and breastfed after the mother had breast implants had higher levels of a toxic form of platinum in their blood than offspring born before the same women had breast implants.30

Problems with Memory and Concentration. Women with implants have raised concerns about memory loss, difficulties with concentration, and other cognitive problems. FDA’s analysis of studies by implant companies found a significant increase in neurological symptoms, such as poor concentration, for women who had silicone implants for two years compared to their symptoms just prior to getting implants. These differences were maintained even when the women’s ages were statistically controlled.32 Some experts believe these symptoms could be related to the small amounts of platinum that are used to make silicone gel breast implants, since potentially toxic levels of platinum have been found in the blood and urine of women with implants.33

Unfortunately, there is no well-designed published epidemiological research to determine whether there is an association between these complaints and breast implants.

Financial Costs. Breast implant surgery is not a one-time cost. On average, implants last 7-12 years, and each replacement adds to the cost. Even if the implant itself is replaced for free, or if the surgeon offers his or her services for free, the cost of the medical facility, anesthesiology, and other expenses can still cost many thousands of dollars for each surgery.  These expenses are affordable for some women, but not for others, especially if the implant breaks after just a few months or years, or after a woman is divorced or loses her job.

When the FDA approved silicone gel breast implants in November 2006, it stated that women with these implants should have a breast MRI three years after getting silicone implants and every two years after that. 33 However, because of the expense and the reluctance of plastic surgeons to encourage MRIs for silent ruptures, very few women followed the FDA’s advice.  As of October 2020, FDA now recommends an MRI 5-6 years after the initial surgery and every 2-3 years after that. The purpose of the MRIs is to determine if the silicone gel breast implants are ruptured or leaking, because there are often no symptoms.33 Breast MRIs usually cost at least $2,000, and at some facilities they cost more than $5,000. It is important to remove silicone implants if they are ruptured, to avoid the silicone leaking into the breast or lymph nodes. That is an additional expense of at least $5,000, and can be $10,000 or more.

Saline implants do not require MRIs to check for leakage, and do not usually cost more than $5,000 to remove. The cost of MRIs and the additional cost of removing leaking silicone makes silicone implants substantially more expensive than saline.

What about health insurance? Typically, cosmetic surgery is not covered by health insurance, and problems resulting from cosmetic surgery are also not covered.9 Health insurance will not pay for MRIs to check for silicone leakage for augmentation patients. In some states, major health insurance providers do not insure women with breast implants.9 Some insurers will sell health insurance to women with implants, but charge them more, and some insurers will not cover certain kinds of illnesses – or any problems in the breast area – for women with breast implants. Obviously, this can be a terrible problem for women who are diagnosed with breast cancer or any other illnesses that are excluded, whether or not those diseases are related to the implants.

What If I Need to Get My Implants Removed?

Women who have implants sometimes decide to have them removed because of complications, disappointment with how they look or feel, or concern about the long-term health risks. Some surgeons discourage patients from removing their implants. This may be because they don’t share the patient’s concerns, or because they know that some patients will be very unhappy with their appearance after the implant is removed. (See photo #3 here) Women with ruptured silicone implants often lose breast tissue as part of the removal surgery. If silicone has leaked into the breast tissue, the resulting removal surgery may be similar to a mastectomy. (See second photo here).

As noted in the earlier section about safety, many women report symptoms of “breast implant illness.”  After being tested to try to find a cause or treatment, an increasing number of these women are choosing to have their implants removed.  Fortunately, if the entire scar capsule and breast implants are carefully removed, most of these women find that their symptoms disappear or are greatly reduced.21,22

The plastic surgeon who performed the original surgery is not necessarily the best choice for removing the implant. Removal can be much more complicated and expensive than the original surgery, especially after a silicone gel implant has broken. Some plastic surgeons are very experienced at removal and are especially skilled at getting the best possible cosmetic result. Most surgeons who specialize in removal recommend removing the implants “en bloc,” which means that the implant and the intact scar tissue capsule surrounding it are all removed together. This helps remove any silicone that may have leaked from a broken gel implant, and also helps remove silicone or other chemicals that may have “bled” from the silicone outer envelope.

Are There Newer, Safer Implants?

As part of new research studies, plastic surgeons sometimes offer “gummy bear” breast implants, named after gummy bear candies because the implants are a thicker, more cohesive silicone gel. Since the shell and gel in these newer models are thicker than most other silicone gel implants, it is possible that they might be less likely to break or leak into the body.

Despite only 3 years of data provided by Silimed (Sientra) on relatively small numbers of patients, the FDA approved their “gummy bear” implants in 2012.  New implants often have risks that are not immediately obvious, and even after only 5 years of data were available, it was obvious that these gummy bear implants had similar types of complications  to other silicone implants. Only when the cohesive gel implants are in women for more than 10 years will we know whether and how the implant deteriorates or changes when it is in the human body.

Why long-term safety studies matter. In addition to silicone and saline implants, three other kinds of implants were developed and used primarily outside the United States: Trilucent implants (with soybean oil filler), and Novagold and PIP hydrogel implants, which were filled with a plastic gel.  They provide examples of why long-term safety studies are so important.

Although these implants were enthusiastically promoted by plastic surgeons and the media as a “natural” and safer alternative to silicone or saline implants, clinical trials were apparently never conducted on humans with these implants. By 2000, serious safety concerns resulted in the removal of all three from the market.34,35,36 The fact that they had been praised by doctors and patients when they were initially introduced serves as a reminder that the long-term risks of implants are not always obvious during the first few years of use. That is why studies of the risks of long-term use – which are still lacking for silicone implants – are essential to establish the safety of all kinds of implants.

Conclusions

Research clearly shows that implants are associated with significant health, cosmetic, and economic risks within the first few years and these risks increase over time. Unfortunately, long-term risks remain unknown because of a lack of well-designed and carefully conducted scientific studies. When they approved silicone gel breast implants in 2006, the FDA required two implant manufacturers, Allergan and Mentor, to each conduct 10-year studies of at least 40,000 women  to determine why implants break, how long they can be expected to last, and what the longer-term health consequences of broken and leaking breast implants might be. Unfortunately, however, those studies were never completed and the FDA did not require the companies to substitute similarly well designed studies.

Related Articles

Study on Silicone Breast Implants and Unexplained Symptoms

Breast Implants and Cancer of the Immune System (ALCL): A History of Who Knew What When

Why are celebrities removing their breast implants?

For more information about breast implants, see www.breastimplantinfo.org.

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

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  29. Pukkala E, Kulmala I, Sirpa-Liis H, et al. Causes of death among Finnish women with cosmetic breast implants. Annals of Plastic Surgery, 2003; 51: 339-42.], [end Jacobsen PH, Holmich LR, McLaughlin JK. “Mortality and suicide among Danish women with cosmetic breast implants.” Archives of Internal Medicine. 2004; 164: 2450. 
  30. Jacobsen PH, Holmich LR, McLaughlin JK. “Mortality and suicide among Danish women with cosmetic breast implants.” Archives of Internal Medicine. 2004; 164: 2450
  31. Maharaj SVM, & Lykissa ED. Total platinum in urine of women exposed to silicone breast implants and in their children conceived after implantation by ICP-MS. Abstracts of Papers, 230th National Meeting of the American Chemical Society, Washington, DC, United States, Aug. 28-Sept. 1, 2005. American Chemical Society, Washington, DC, 2005; ANYL 510.
  32. Inamed Corporation’s McGhan, Silicone-Filled Breast Implants, October 14-15, 2003, slides #45 and #55, at http://www.fda.gov/ohrms/dockets/ac/03/slides/3989s1.ppt.
  33. Saline, Silicone Gel, and Alternative Breast Implants: Guidance for Industry and
    Food and Drug Administration Staff, https://www.fda.gov/media/71081/download
     (For other identical MRI warnings for Mentor and reconstruction patients, see http://www.fda.gov/cdrh/breastimplants/labeling.htm).
  34. UK Department of Health, Medicines and Healthcare Products Regulatory Agency. “Device Alert – Breast Implants: NovaGold.” UK: Medical Devices Agency. www.medical-devices.gov.uk/.
  35. Laurance J, “Agonizing wait for 5,000 women told that their breast implants might leak and cause cancer.” The Independent, 7 June 2000. www.independent.co.uk/story.jsp?story=5864.
  36. “Statement on the Safety of Trilucent Breast Implants.” UK: Medical Devices Agency. www.medical-devices.gov.uk/.

Dr. Diana Zuckerman’s Testimony on Moderna’s COVID Vaccine Before the FDA Advisory Committee

December 17, 2020.


I’m Dr. Diana Zuckerman, president of the National Center for Health Research.  Thank you for the opportunity to speak today.

Our center scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. My expertise is based on post-doc training in epidemiology and as a previous faculty member and researcher at Vassar, Yale, and Harvard, and a fellow in bioethics at University of Pennsylvania.  I’ve also worked at HHS, the U.S. Congress and the White House.

Today I will focus on 3 major concerns:

#1:  The 2 month median follow-up is too short, so Moderna’s proposal to immediately unblind and offer to vaccinate the entire placebo group should be rejected.

#2:  Moderna made a good effort to include a diverse group of participants, but only 4 COVID cases were in Black patients, and there were even fewer in other racial groups.  We can’t assume that the vaccine was highly effective in demographic groups with so few cases because just 1 Covid case in the vaccinated group would have greatly reduced the efficacy rate.

The data on cases for participants with co-morbidities was slightly more substantial, with 24 placebo cases and only 1 vaccinated case

#3  I’m glad to see that unlike Pfizer, Moderna provided info on the total number of  participants who reported 1 or more adverse events.  That’s important.  Unfortunately, the total of severe systemic adverse events after the 2nd dose was over 17% for vaccinated group compared to 2% for the placebo group.

There are also too few severe cases to draw conclusions:

There were 30 severe cases after the 2nd dose, and none were in the vaccine group.  This is a strong finding.  However, only 9 of the severe cases required hospitalization; 12 involved the questionable criteria of at least slightly low blood oxygen saturation.

Long-term care patients were not included in the study.  About 1300 people ages 75 and older were in the study, almost half of them vaccinated, but only 3 were cases (all of them placebo).  Only 15 cases were in patients over 65.

We want to save their lives, but with no data it’s not possible to provide useful informed consent to nursing home patients.  That puts a tremendous burden on those patients and their family members to decide whether or not to be vaccinated.

We need longer-term data to fully understand the benefits and risks for different types of patients.  The vaccine is clearly effective, but does that last 2 months, 4 months, or a year?  We need to know that, and that’s why it is essential that the blinded randomized controlled trial is continued.

In conclusion, EUA is not approval, and it should have more restrictions than approval would have.  The EUA should be targeted to priority populations, because if the EUA applies to all adults, celebrities and others who are well-connected will cut in line.  We’ve already seen that this week.

Other people could apply for the vaccine under FDA’s Expanded Access program.

We need at least 1 year of blinded, randomized, controlled data.  We agree with Dr. Goodman’s proposal that FDA should delay access to vaccines by members of the placebo group unless they are in priority populations.  Blinded crossover has limitations because it can’t control changes in the community spread of the virus, but it is better than not continuing a blinded controlled study, if continuing the current study is not possible.

FDA Panel Reviewing Pfizer Vaccine Leaves Out Some Experts Who Raised Concerns

David Hilzenrath, Project on Government Oversight: December 9, 2020.


When an FDA advisory committee meets tomorrow to review Pfizer’s coronavirus vaccine, the lineup of committee members will look different from the group that met in October to begin the committee’s discussion of coronavirus vaccines.

Four people who participated in the earlier meeting as temporary committee members, including experts who raised questions and expressed concerns about the testing process, do not appear on the “draft roster” of panelists the FDA has posted for tomorrow’s meeting.

Meanwhile, there will be new faces. The FDA has added 10 temporary committee members who did not participate in the earlier meeting.

The changes in the lineup raise concerns, Diana Zuckerman, president of the National Center for Health Research, said in answer to questions from the Project On Government Oversight (POGO).

Zuckerman said experts might have been excluded to avoid tough questions about Pfizer’s data.

“It is not unusual for temporary members of FDA Advisory Committees to change, but seems surprising since the issues they are considering at the Oct meeting and tomorrow are so similar,” Zuckerman said by email.

Zuckerman’s organization analyzes the safety and effectiveness of pharmaceuticals and other medical products.

POGO asked the FDA whether the disappearance of some people from the advisory committee lineup had anything to do with any questions, concerns, or opinions they have expressed. In response, an FDA spokesperson did not directly answer.

The FDA routinely supplements advisory committees with temporary voting members, including “scientists or medical personnel whose expertise may not be represented by the fixed voting membership,” the FDA spokesperson said by email. “Many times, committees need to invite experts who are unrelated to the knowledge and expertise spelled out in the committee charter if a medical product or topic for discussion calls for a specific need for a particular expert,” the spokesperson added.

That does not seem to explain why the FDA would drop temporary voting members it selected to participate in the October meeting. At that meeting, without evaluating any particular vaccine, the committee advised the FDA on how in general it should approach experimental coronavirus vaccines.

Dr. Luigi Notarangelo, an expert on clinical immunology at the National Institute of Allergy and Infectious Diseases, was not invited to participate in the December 10 FDA advisory committee meeting on Pfizer’s coronavirus vaccine. He served as a temporary committee member when the panel met in October and minced no words then as he expressed general concerns about the testing of coronavirus vaccines.

[….]

POGO recapped his commentary at the October meeting in a November 2 story, “FDA Whitewashes Warnings About Coronavirus Vaccine Trials.”

As POGO reported:

Dr. Luigi Notarangelo, a committee member who is a chief researcher at the National Institutes of Health, minced no words as he articulated several of the critiques.

Notarangelo said measures of vaccine effectiveness included in an FDA document the committee was asked to review have two problems.
“First of all, they really are biased—skewed towards mild disease,” he said. “Mild disease may not mean very much.”
“The other problem with those efficacy measures is that most of them are really subjective,” he said. “And I think that’s a major concern. I mean, we’re relying basically upon reporting from the subjects without any objective validation of what they’re reporting.”

At the time, Notarangelo was not commenting specifically on Pfizer’s data.

Another person who served as a temporary member on October 22 but does not appear on the roster for tomorrow is Kathryn Holmes, a professor emerita in the Department of Immunology & Microbiology at the University of Colorado School of Medicine.

“One of the things I have not heard much about during this conversation is infection,” Holmes said at the October meeting. “I’d like to see how we could actually be measuring infection rather than just mild disease. … We should be looking to see what can prevent infection because that is the rubric which would prevent spread through the community most effectively and that is what would protect our elderly as well.”

Holmes could not be reached for comment for this story.

Another person who participated in the October meeting but is not slated to participate tomorrow is Dr. Michael Nelson, president of the American Board of Allergy and Immunology and a physician at Walter Reed Army National Military Medical Center.

At the October meeting, Nelson said “more real-time data might be needed.”

Nelson also noted that, when the acting chair of the committee summarized members’ comments, he omitted “a lot of concern” about an aspect of how vaccine effectiveness was being measured—whether it was focused inordinately on preventing milder cases.

Read the full article here

What People With Cancer Need to Know about Coronavirus (COVID-19)

Diana Zuckerman, Ph.D., Cancer Prevention and Treatment Fund: updated February 10, 2021.

The coronavirus can infect anyone, young or old, healthy or frail.  But, people diagnosed with cancer during the last year are at higher risk of dying from COVID-19 if they are infected. Here’s what you need to know.

People who are over 60 or who have cancer and other serious health conditions, and their loved ones, need to be especially careful to avoid getting infected.  A study published in December 2020 of more than 2 million cancer patients, found that people diagnosed with cancer during the previous year are much more likely to die of COVID compared to other COVID patients.  All cancer patients were at higher risk, but the ones in most danger had been diagnosed with leukemia, non-Hodgkin’s lymphoma, or lung cancer. The CDC has also updated their list of other health problems that put people at greatest risk, and they include many common health conditions: Anyone who is obese (BMI of 30 or higher) or has a serious heart condition, Type 2 diabetes, a weakened immune system (from cancer or an organ transplant), chronic kidney disease, COPD, or sickle cell disease is especially at risk if they are exposed to the coronavirus.  Smoking also increases the risk of being seriously harmed by the virus, as do many other medical conditions, including high blood pressure, pregnancy, HIV, and liver disease.

If you had scheduled medical appointments, surgery, screening, or other procedures in the past year that were considered not urgent or not immediately life-threatening, those were probably postponed. This was for everyone’s protection.  Many hospital staff, including doctors, nurses, receptionists, and cleaning staff, have been vaccinated against COVID but their facilities may be limiting procedures that are not essential because the doctors are vaccinating others or are treating COVID patients. You don’t want to be exposed to the coronavirus when you go in for surgery or testing procedures for other medical conditions.  And, you don’t want your medical center to be less able to fight the coronavirus at a time when it is spreading throughout your community.

Will the COVID vaccines make it safer to have medical procedures or doctor’s appointments? To visit friends and family members?

Many healthcare workers have been vaccinated, but some nurses and aides have refused the vaccine so far.  You should ask about that when you make an appointment. Pregnant healthcare workers and those with serious allergies may choose not to be vaccinated. Pregnant healthcare workers and those with serious allergies may choose not to be vaccinated.  More important, the vaccines do not prevent infection, even though they usually prevent people from getting obviously sick.  If your healthcare worker is vaccinated, he or she could have asymptomatic COVID without knowing it, and could possibly infect others.  For that reason, healthcare workers and patients need to continue to wear masks and keep their distance.

The coronavirus is still spreading in all 50 states, in urban, suburban, and rural areas, so it is important to listen to health experts who tell you to stay home, limit contact with others, wear a mask, and keep a distance of 6 feet away when you or your family members or caregivers go grocery shopping or other essential activities. It will be months before most people are vaccinated.  Unfortunately, some governors, mayors, and state legislators have reopened businesses for political reasons, even in states where the virus is spiking.  Even if you are staying at home as much as possible, the fact that others in your community are going to bars, parties, restaurants, stores, and hair salons will put you at greater risk when you make essential visits to the supermarket, to work, to the doctor, or spend time outdoors, because you may come into contact with people who are infected because they aren’t being as careful as you are.

What is coronavirus?

Coronaviruses are a large group of viruses that can cause respiratory illness. The new (novel) coronavirus is called SARS-CoV-2 and the illness it causes is called coronavirus disease 2019, which is why it’s abbreviated as COVID-19.

How does COVID-19 spread between people?

The virus usually spreads through close contact with other people, especially through invisible or very tiny droplets when a person coughs, sneezes, sings, exercises – or even when they breathe or talk normally. These droplets can travel through the air and can be inhaled or get into the noses, mouths, or eyes of people nearby.

The virus is thought to be most contagious in the days just before and just after a person develops symptoms, but it is possible to catch the virus from infected people who have no symptoms at all.  Experts still don’t know how contagious the virus is when a person has it but never develops symptoms.  This is crucial information that scientists are trying to find out, especially since experts believe that many young children never develop symptoms, while other children get very sick and some have died from the coronavirus.

What about children?  Unlike the flu, which is riskiest for the youngest children and oldest adults, infants and young children are much less likely to get sick from the coronavirus than adults.  Preliminary studies suggest that children over 10 are as contagious as adults, but that younger children are much less infectious. For example, there are few known examples of the virus spreading in daycare centers that follow coronavirus safety standards. Nevertheless, almost half a million children have been diagnosed with the virus in the U.S. (almost 10% of all cases) and 70,000 children were newly diagnosed in late August, which was 17% more than the weekly number of new cases two weeks earlier.  Fortunately, few children become so sick that they are hospitalized (estimates range from less than 1% to 8.5%), and less than half of 1% of children diagnosed with coronavirus in the U.S. have died.

The tiny droplets from coughing, sneezing, singing, talking, or breathing (as well as fecal matter containing the virus) can result in the virus on surfaces where it can survive for hours or even days. When you touch these surfaces and then touch your face, you can be exposed to the virus. However, there are no documented cases of anyone catching COVID from a surface.  Nevertheless, it’s important to wash your hands regularly.  If you’re concerned about exposure at home, you can wipe down surfaces in your bathroom, kitchen, and other rooms with bleach or rubbing alcohol to help prevent exposure.

What about food or food packaging?  The risk of catching the virus from packaging is extremely low, but it’s a good idea to wash your hands for at least 20 seconds after handling mail, takeout containers, and packaging from groceries. You don’t need to disinfect food packages using a cleaning product that kills viruses, and NEVER use bleach or disinfectants on fruit, vegetables, or any other food.

What about the vaccines?

If you are eligible to be vaccinated with either the Pfizer or Moderna vaccine, that is the best protection available for most people.  Keep in mind, however, that the vaccines were not studied on nursing home patients and not studied on many people with COVID who were ages 65 or older, so it might be less effective for older people.  (Flu vaccines are often less effective for older people, because their immune systems are weaker).  The vaccines were found to be as safe for adults of all ages and races. The vaccines were  studied on few people under 18, pregnant women, people with compromised immune systems, or those with serious allergies, so it will be a while before we have information about safety or effectiveness data for them.

Both of the vaccines have frequent side effects such as fatigue and chills, especially after the second dose.  These are not considered dangerous, but it is important that anyone getting vaccinated is told about those risks, since they could be frightening to patients who don’t understand that those symptoms are not thought to be reason for concern.

What are the symptoms of COVID-19?

Symptoms tend to start between 2 and 14 days after coming into contact with the virus.  Although some people have compared the symptoms to a cold or flu, not everyone with COVID-19 has those types of symptoms.  In fact, some people (especially children, teens, and younger adults) have very mild symptoms or none at all, which is why getting tested is so important before you spend time with others. The CDC says that people with these symptoms or combination of symptoms may have COVID-19:

  • Cough
  • Shortness of breath or difficulty breathing

Or at least two of these symptoms:

  • Fever
  • Repeated shaking with chills
  • Muscle pain
  • Headache
  • Sore throat
  • New loss of taste or smell
  • Congestion or runny nose
  • Nausea or vomiting
  • Diarrhea

Those are the most common symptoms.  However, children or adults can have other symptoms as well, including heart problems and “covid toes” that look like a minor case of frostbite.

Most people who are infected with this coronavirus have mild symptoms and can recover at home in about 2 weeks. However, symptoms can become severe.  These are the ones that require immediate medical attention:

  • difficulty breathing or shortness of breath
  • persistent chest pain or pressure
  • confusion or inability to awaken
  • blueish color in the lips or face

As described above, people who are older than 60 or with other medical conditions are more likely to develop severe illness and complications from COVID-19. The most serious complications include pneumonia, stroke, blood clots, organ failure, and death.

How else can I protect myself and others?

If you are not yet eligible to be vaccinated, the best way to protect yourself is to avoid being exposed to the virus. There are no proven cures, so don’t be fooled by claims, regardless of the source.  Two types of medications have been found to help people who are seriously ill, but are not a cure.  Remdesivir has been found to help very ill patients by reducing the number of days of hospitalization in one study, but was not effective in a WHO study published in October.  It has not been proven to save lives. Two inexpensive steroids, dexamethasone and hydrocortisone, have been found to reduce the chances of dying among COVID-19 patients on ventilators or those requiring oxygen, but not other patients. Regeneron, the experimental antibody drug that President Trump took when he was diagnosed, is not generally available but has been used with good results by some friends of the President.  However, it was found to have a potential safety concern and as of October 30 is no longer being administered experimentally to hospitalized patients receiving mechanical ventilation of intense oxygen.  It is still being studied on less seriously ill COVID-19 patients.

Experts now agree that hydroxychloroquine with or without azithromycin is not a good treatment for COVID-19 because it has been found to increase heart problems and has not been shown to prevent or treat COVID-19.  Another possible treatment is blood plasma from people who recovered from COVID-19.  Research has shown these transfusions are usually safe, but there is no clear evidence that they are beneficial.

Research is continuing to find out which of these treatments are safe and effective and for which patients.

“Social distancing” or “physical distancing” refers to staying away from other people because it is impossible to know who has the virus.  The safest people in your life are the ones you are living with who are not exposed to others who might have the virus (in other words, they are not going to work or spending time close to other people). Staying at home and not seeing your friends and loved ones is not fun, but it is essential for your own safety and for everyone else’s.  If everyone does that now, the spread of this virus will be reduced sooner, and some of these restrictions will no longer be necessary in a few weeks.

Spending time with friends, family, or people at work

In general, the more people you interact with, the more closely you interact with them, and the longer that interaction, the greater your chances of becoming infected or infecting othersThat’s why there have been so many cases after Thanksgiving, and why hospitals are full all over the country. So, think about:

  • How many people will you interact with?  (The fewer the better)
  • Can you keep 6 feet of space between you and others?
  • Will you be outdoors or indoors? (Outdoors is somewhat safer. It can be heated but not if it has walls all around and a ceiling.)
  • What’s the length of time that you will be interacting with people? (Shorter is better)

Research conclusively shows that face masks that cover your mouth and nose help to prevent the spread of the coronavirus.  Some masks are more effective than others:  stretchy “gators” may actually do more harm than good, and bandanas and scarves are too loose to be very helpful.  The paper surgical masks worn in hospitals are effective and so are cloth masks you can make for yourself or buy, if they are made of cotton and at least two layers thick. Masks are important to prevent people from spreading the virus and also to help helps prevent infection or serious symptoms for the person wearing the masks. Experts suggest wearing two masks at the same time for extra protection.

Bottom line: Since most of us haven’t been vaccinated and can’t get coronavirus tests every day, it’s especially important to wear masks whenever you are out in public or with people you don’t live with.  But you should NOT be out in public or with people you don’t live with except when it’s essential.  Depending on your age, health, and who you spend time with, it may not be safe for you to go to all the places that are open.  Especially avoid indoor areas where you are likely to be close to others for more than a very short period of time (15 minutes) or whose workers are close to many other people, such as a tattoo parlor, hair or nail salon, restaurant, concert, party or movie theater.  If you must go to a store, try to go to one that makes appointments with customers or limits the number of customers, and spend less than one hour indoors to reduce exposure to any coronavirus that is in the air.

In summary:

  • Stay at home or go outside in your yard or neighborhood where you can keep at least 6 feet away from others
  • Avoid public spaces where there are other people, especially indoors
  • Avoid public transportation when possible and unnecessary travel
  • Avoid all social gatherings that are indoors or where people are close together
  • Work from home if possible
  • Stay at least 6 feet away from people when out in public (indoors or outdoors). Further away is even better, especially if people are singing or talking, or if there isn’t good air filtration.
  • Avoid physical contact in social situations, such as shaking hands, hugging or kissing

AND

  • Wash your hands using soap and water for at least 20 seconds, especially after being out in public
  • Use alcohol-based hand sanitizer when soap and water aren’t available (or wash your hands as soon as you get home)
  • Avoid touching your face when your hands aren’t clean or you are out in public
  • Avoid contact with people you don’t know very well
  • Put the toilet seat down before flushing in a shared or public bathroom
  • A lower priority would be to clean and disinfect surfaces, and only those in your home or workplace that could expose you frequently to the virus, including doorknobs, light switches, faucet handles, and phones. An antibacterial cleaning agent won’t kill a virus, so try to find one that is effective for killing viruses.

If you have a weakened immune system or other serious health problems, here are extra steps to protect yourself:

  • Make a plan with your doctor to monitor for symptoms
  • Avoid friends and family except those you live with or depend on for essentials.  Otherwise, rely on your phone or computer to maintain contact.
  • Have a plan with your loved ones or caregiver if you or they get sick
  • Have the medications you rely on and order any you need in advance (to be delivered, if possible)
  • Ask a friend or family member to shop for groceries for you
  • Wash your hands (20 seconds with soap and water) even more often if you are exposed to others

What should I do if I develop symptoms?

If you develop more than one of the symptoms listed above, call your doctor.  If you have severe symptoms, such as difficulty breathing, persistent chest pain or pressure, confusion or inability to awaken, or blueish color in the lips or face, you need to call 911. Tell the 911 operator that you think you have COVID-19 so the responders can take the necessary precautions to protect themselves.

People who experience mild symptoms can usually stay home and will recover in about 2 weeks. Do not just show up at the doctor’s office with symptoms:  Call them first so you have tell them about your symptoms and any other health problems so that they can help decide what to do.  If you do become sick, you can take the following steps to protect others:

  • Stay home, unless you need essential medical care
  • Wear a facemask when you are near others.  (People caring for you should also wear a facemask).
  • Stay away from others in your home as much as possible
  • Cover your mouth and nose when you cough or sneeze, properly dispose of tissues, and wash your hands
  • Monitor your symptoms and temperature

If you were not tested for COVID-19, you should follow those steps until at least one or two weeks have passed since you first noticed symptoms or your fever or other symptoms go  away for 3 full days without medicine.  If you have been diagnosed with COVID-19 based on test results, you should follow those same steps until you have 2 negative test results taken 24-hours apart, and your symptoms improve.

What if my other scheduled medical treatment is delayed?

When a person is diagnosed with a serious disease, they are likely to want treatment as soon as possible. If you don’t have COVID-19, you don’t want to be exposed to it during surgery, testing, or follow-up appointments. Treatment or testing may seem more urgent than it really is, but it is definitely more important than going to a restaurant, store, or party.  Some medical centers are overwhelmed with Covid-19 patients, and others are not. Talk to your doctor about what is the best strategy to get the treatment you need when it is safe to do so.

Questions?

We are here to help by answering your questions.  We do not provide medical care.  If you have questions contact info@center4research.org and we’ll get back to you as soon as possible.

CPTF’s Comments on Cyramza for Metastatic Lung Cancer at FDA Oncologic Drugs Advisory Committee Meeting

Cancer Prevention and Treatment Fund: February 26, 2020


Cancer Prevention and Treatment Fund’s Public Comments on Cyramza for Metastatic Lung Cancer at FDA Oncologic Drugs Advisory Committee Meeting

Thank you for the opportunity to share our views today. The Cancer Prevention and Treatment Fund understands the need for effective new treatments for metastatic lung cancer. However, the data provided by the sponsor does not provide evidence that Cyramza improves survival, and it may worsen quality of life.

Although there are not yet enough long-term data to determine how Cyramza affects patients’ survival, the data that are available are not promising. Survival rates are almost identical with the drug or placebo (HR 0.92). It is important to note that the survival rates were never significantly different, but the difference was smaller as longer-term data were analyzed. We agree with the FDA that based on the confidence intervals, the drug could potentially worsen survival by about 30% — or could possibly improve survival by 30%. That risk of shortening overall survival is especially important because of the other risks of the treatment.

Let’s look at the number of deaths that occurred within 30 days of treatment in the RELAY trial. Of the 221 patients taking Cyramza, 6 died from adverse events, compared to none in the placebo arm. FDA specified that one of these was caused by drug treatment, while a second may have been caused by the drug. Although the FDA agrees with Lilly’s assessment that the other deaths are not caused by the drug or drug combination, those data aren’t made available so we can’t draw conclusions. But even if it is only 2 deaths, that’s almost 1% of the patients – not an irrelevant number! Since this shows that Cyramza can be fatal for these patients, and there is no currently no evidence that it significantly increases overall survival on average for lung cancer patients, the FDA expressed a great deal of concern about this indication. If Cyramza benefits any specific types of patients in terms of overall survival, there is no evidence of who those patients are likely to be.

Patients treated with Cyramza had a 7 month improvement in progression-free survival. This may be meaningful to patients if it is also associated with an improvement in quality of life. However, the data from the RELAY trial do not support this.  The sponsor spins these results to conclude that the quality of life of life is not worse in patients taking Cyramza, but in fact, patients in the placebo group had fewer symptoms, such as shortness of breath, pain, and daily activity level, as measured by the Lung Cancer Symptom Scale. Our Center has worked with many seriously ill patients over the years, and we’ve found that
patients care about two outcomes: 1) will they live longer and 2) what will their quality of life be in the days, weeks, months, or years they have left. The only patients that care about progression free survival are the ones that don’t understand what it means. When patients are told a drug is promising based on progression free survival, it is confusing and frankly misleading to most patients. They think it means they will live longer.

The results of the research are also worrisome regarding the FDA’s measures of specific adverse events. 72% of patients treated with Cyramza experienced a grade 3 or higher adverse events compared to only 54% of patients treated with placebo.

  • 29% of patients treated with Cyramza experienced a serious adverse event compared to 21% of placebo-treated patients.
  • Bleeding and hemorrhage occurred twice as often in patients treated with Cyramza,
    compared with placebo.
  • Grade 3 hypertension was roughly 5x more common among those treated with Cyramza compared with placebo. Overall hypertension was roughly 4x as prevalent among the Cyramza group.  I disagree with the sponsor’s assertion that hypertension is no big deal. In fact, heart disease is the #1 killer of men and women in the U.S. and hypertension is called “the silent killer.” Yes, there are medications for it, but they also have side effects that can be debilitating.

Overall, the study’s results suggest that when Cyramza is combined with erlotinib and compared with placebo plus erlotinib, the potential benefits of Cyramza do not outweigh the known risks. Given the data provided, there is no justification for rushing to approve this particular treatment.

We respectfully request that you advise FDA to not approve this indication for Cyramza without evidence that it improves overall survival enough to outweigh the risk for adverse events and reduced quality of life.

After FDA’s Cancer Director Dr. Richard Pazdur instructed the Advisory Committee at length that progression free survival was acceptable evidence for approval even if there was no evidence of overall survival, and even if more effective treatments were already available, the Advisory Committee voted 6 in favor of approval and 5 opposed.

The Cancer Prevention and Treatment Fund can be reached at info@stopcancerfund.org or at (202) 223-4000.

Drugs to Quit Smoking Can Affect Mental and Physical Health: the Truth About Chantix and Zyban


Everyone knows that smoking harms health and that the habit is difficult to quit. Unfortunately, some products that help people stop smoking can also be harmful – perhaps too harmful to consider using.

In June 2011, the U.S. Food and Drug Administration (FDA) announced new concerns about the safety of Chantix. Their announcement came in the months after two reports by independent researchers that there were more reports of deaths and violence from taking Chantix than any other drug.[1]

These reports added to concerns about two stop-smoking drugs, Chantix and Zyban. In July 2009, the FDA had already announced “black box” warning labels on both drugs. A “black box” warning is the FDA’s most serious caution and indicates that a drug carries significant health risks.  The black box warnings for Chantix and Zyban warn of the mental health risks associated with their use, which can include changes in behavior, depressed mood, hostility, and suicidal thoughts.[2]

These warnings were recommended as the result of information gathered from clinical trials, as well as a series of reports to the FDA’s Adverse Event Reporting System. Zheng-Xiong Xi, MD, PhD, a researcher at the National Institute on Drug Abuse, found that Chantix was associated with incredibly dangerous side effects in many individuals, including suicide attempts and seizures, as well as psychosis, depression, and serious injuries resulting from dizziness, loss of consciousness, movement disorders, and visual disturbances.These problems have been noted among individuals with a history of mental illness but also have occurred among individuals with no prior history of mental illness.[3]

Analysis from reports to the FDA’s Adverse Event Reporting System similarly shows that some people who used Chantix and Zyban began experiencing changes in behavior, depressed mood, and suicidal thoughts shortly after starting the medication. The symptoms usually ended shortly after the medication was stopped, but some people still reported symptoms after stopping the medications, while still others did not even begin developing the symptoms until after they stopped taking the drug.

Neither Chantix nor Zyban contains nicotine, unlike other smoking cessation aids such as chewing gum and the patch. Nicotine withdrawal can also cause mental health problems similar to those caused by Chantix and Zyban, such as depression, anxiety, irritability, restlessness, and sleep disturbance. However, the mental health risks of these two drugs far exceed the symptoms suffered by people with nicotine withdrawal.

Zyban is another name for Wellbutrin, an anti-depressant. Its marketing as a smoking-cessation drug came about after researchers noticed that smokers who took Wellbutrin for depression had less desire to smoke. GlaxoSmithKline carried out additional research in order to get approval to sell Wellbutrin under a different name as a medication to quit smoking. However, like most anti-depressants, the pills–whether they are called Wellbutrin or Zyban–can cause an increase in suicidal thoughts.  Antidepressants have carried black box warnings about suicide risks since 2004.

Chantix: News about increased risk of suicide, violent behavior, and other mental health problems

From the approval of Chantix in May 2006 until July 2009, the drug was linked to reports of approximately 100 suicides, 200 suicide attempts, and almost 5,000 serious psychiatric events. Doctors are not required to report deaths or serious complications to the companies that make the medication or the FDA, although drug companies are required to do so.  Because most doctors don’t report, it is assumed that the numbers are much higher and that those problems have continued since 2009.  In fact, in May 2011, the Institute for Safe Medication Practices (ISMP) revealed that hundreds of cases of suicides, psychotic reactions, hostility, aggression and other serious problems tied to Chantix had not been properly reported to the FDA by Pfizer, the drug’s manufacturer. Among the 589 delayed reports of severe problems, there were more than 150 suicides-almost doubling those previously known.  Thomas J. Moore, the ISMP senior scientist who analyzed the data, stated that, based on the FDA’s adverse event reports, Chantix is the riskiest of all drugs sold in the U.S. In the third quarter of 2010, it ranked first in reported deaths, with twice as many fatalities recorded as any other drug.[1]

The discovered reports coincide with a study by Moore released in December 2010 examining all of the most serious adverse drug events reported to the FDA since 1968. Chantix had the largest number of reported cases of violence (408).[1]

A large 2011 study found that Chantix was 8.4 times more likely to lead to suicide or self-injury compared to nicotine replacement products like nicotine gum or patches. There were 1,818 reported cases of suicidal thoughts or behavior for Chantix and only 50 for nicotine replacement products.[4]

Increased risk of heart attack for patients with cardiovascular disease

Research has shown that these stop-smoking drugs affect not only mental health, but can also jeopardize physical health. In June 2011, the FDA warned that Chantix may be associated with an increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease. After reviewing a randomized clinical trial of 700 smokers with stable cardiovascular disease, the FDA found that certain events, including heart attacks, were reported more frequently in patients treated with Chantix than in patients treated with placebo (2.0% vs. 0.9%).[5]

Do the risks outweigh the benefits? NCHR says YES

Quitting smoking is usually a step towards improving one’s health, but doing so at the risk of mental or heart health is not a good compromise.  Instead, there are other, safer ways to quit smoking.

The unreported deaths and serious injuries for people taking Chantix raises questions about whether other information is being withheld. Since most doctors don’t report adverse reactions to the FDA, it is likely that Chantix has caused many more deaths and injuries than reported. For that reason, we believe that Chantix is not a safe choice. At the very least, the mental health of anyone taking Chantix or Zyban should be closely monitored by a healthcare professional. Additionally, if you have a history of cardiovascular disease, consult your doctor before taking Chantix, and if you experience new or worsening symptoms of cardiovascular disease, contact your doctor immediately.

If you or someone you know is trying to quit smoking, be aware of the symptoms associated with quitting, and if symptoms develop, a healthcare professional should be consulted.

Controversy Over Black Box Warning

In 2014, the makers of Chantix lobbied the FDA to remove the black box warning on the drug, citing a meta-analysis, an observational study of hospital records, and reported adverse events to argue that dangerous side-effects were not as common as previously believed. However, we question the results of the meta-analysis, since many studies on Chantix were excluded.

Meta-analysis is a valuable tool, but its accuracy depends on the quality of each study and whether they fit together. The five studies included in the meta-analysis consisted of one study of schizophrenics, one study of depressed patients, and 3 studies of mentally healthy patients. It is important to study schizophrenics and depressed patients, but those data should not be analyzed together with 3 studies that exclude such patients.

To consider the implications of studies that claim to show that Chantix does not have serious psychiatric side effects, it is important to realize that most people with acute psychiatric side effect from medication do not end up in hospitals or the ER. Psychiatric side effects are often not reported in medical records. Because psychiatric commitment laws depend on acts of violence, not threats of violence, many people with dramatic psychiatric symptoms end up in jail, not in hospitals. In fact, some studies show that there are more mentally ill individuals in the criminal justice system than in psychiatric facilities.

Removal of Black Box Warning

After hearing the testimony about these shortcomings from NCHR President Diana Zuckerman and numerous other experts, the FDA decided to keep the black box warning on Chantix in 2015. However, in response to industry pressure, the FDA removed the black box in 2016[6], and the warnings that were in the black box are now part of the label under a heading of “Warnings and Precautions” for both Chantix and Zyban.[7, 8] Thus, although the official black box warning for Chantix has been removed, there are still warnings on their labels about the psychiatric risks of Chantix and Zyban. In addition to the label, which most patients do not read, the Medication Guide listed on the Chantix manufacturer’s website warns of the potential side effects of “New or worse mental health problems, such as changes in behavior or thinking, aggression, hostility, agitation, depressed mood, or suicidal thoughts or actions.”[9] These warnings are also on the home page of Chantix.com. Zyban has a black box warning about suicidal thoughts, and warnings similar to Chantix on the label and medication guide.

Below are the current “Warnings and Precautions” listed for Chantix and Zyban:

Neuropsychiatric Adverse Events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with CHANTIX for the occurrence of such symptoms and instruct them to discontinue CHANTIX and contact a healthcare provider if they experience such adverse events.

Neuropsychiatric adverse events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with ZYBAN for the occurrence of such symptoms and instruct them to discontinue ZYBAN and contact a healthcare provider if they experience such adverse events

Below are the previous black box warnings for both Zyban and Chantix:

ZYBAN:

Serious neuropsychiatric reactions have occurred in patients taking ZYBAN for smoking cessation. The majority of these reactions occurred during bupropion treatment, but some occurred in the context of discontinuing treatment. In many cases, a causal relationship to bupropion treatment is not certain, because depressed mood may be a symptom of nicotine withdrawal. However, some of the cases occurred in patients taking ZYBAN who continued to smoke.

CHANTIX:

Some people have had changes in behavior, hostility, agitation, depressed mood, suicidal thoughts or actions while using CHANTIX to help them quit smoking. Some people had these symptoms when they began taking CHANTIX, and others developed them after several weeks of treatment or after stopping CHANTIX. If you, your family or caregiver notice agitation, hostility, depression or changes in behavior, thinking, or mood that are not typical for you, or you develop suicidal thoughts or actions, anxiety, panic, aggression, anger, mania, abnormal sensations, hallucinations, paranoia or confusion, stop taking CHANTIX and call your doctor right away. Also tell your doctor about any history of depression or other mental health problems before taking CHANTIX, as these symptoms may worsen while taking CHANTIX.

Additional Resources:
Chantix Citizen Petition
Statement of Diana Zuckerman, PhD at FDA Joint Public Advisory Committee Meeting on Chantix
Quitting smoking: women and men may do it differently

All articles on our website have been approved by Dr. Diana Zuckerman and other senior staff.

  1. Moore TJ, Glenmullen J, Furberg CD (2010) Prescription Drugs Associated with Reports of Violence Towards Others. PLoS ONE 5(12): e15337. Retrieved 27 May 2011 at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015337
  2. U.S. Food and Drug Administration. “Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban.” Press release. FDA: Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban. 1 July 2009.
  3. Xi ZX. Preclinical Pharmacology, Efficacy and Safety of Varenicline in Smoking Cessation and Clinical Utility in High Risk Patients. Drug, Healthcare and Patient Safety. 2010;2:39-48. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21278851
  4. Moore TJ, Furberg CD, Glenmullen J, Maltsberger JT, Singh S. (2011) Suicidal behavior and depression in smoking cessation treatments. PLoS ONE 6: e27016.
  5. U.S. Food and Drug Administration. FDA Drug Safety Communication: Chantix (varenicline) may increase the risk of certain cardiovascular adverse events in patients with cardiovascular disease. 6 June 2011. Retrieved 6 July 2011 at http://www.fda.gov/Drugs/DrugSafety/ucm259161.htm
  6. FDA. FDA Drug Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. FDA.gov. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-description-mental-health-side-effects-stop-smoking. December 16, 2016. Updated March 8, 2018.
  7. Chantix. [Package Insert]. New London, CT: PF PRISM CV; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021928s048lbl.pdf
  8. ZYBAN. [Package Insert]. Brentford, United Kingdom: GLAXOSMITHKLINE; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020711s048lbl.pdf
  9. Chantix. [Medication Guide]. New York, NY: Pfizer; 2019. http://labeling.pfizer.com/ShowLabeling.aspx?id=557&section=MedGuide

Report Claims More Women than Men Injured by Medical Devices

The ICIJ used the Food and Drug Administration’s (FDA’s) Manufacturer and User Facility Device Experience (MAUDE) database to conduct the research. This data is publicly available and contains eight million reports which have been filed by doctors, patients and manufacturers when a medical device is suspected of putting someone at risk, causing injury or resulting in death.

Steps had to be taken to identify the gender of those within the database as although the FDA gathers information on the sex of patients, this data is not made publicly available. Therefore, in order to overcome this obstacle, the ICIJ realised that the sex of patients was sometimes disclosed through pronouns and adjectives within the incident reports submitted to the FDA.

The ICIJ group followed four steps to identify the gender of those in the FDA MAUDE database:

1. Generate a set of labels

This stage involved classifying patient sex in 1,000 incident reports from the MAUDE database. Patient sex was classified as female, male or unknown.

2. Assign rules to the computer

The group used rules to train the computer to conduct automatic sex classification on the data.

3. Validate the results from the computer

Humans looked at the results from the computer and implemented additional rules to improve the quality of the results.

4. Run the code against all of the data in the FDA Maude database

Using 1997-2017 (the same time frame as the Implant Files investigation), the computer assigned a gender to 23% of patients with 96% accuracy.

The ICIJ claim that the algorithm created using the above steps was able to positively identify the sex of the patient in more than 340,000 injury and death cases. These findings reported 67% of these people were women and 33% were men.

Talking about the findings, the ICIJ stated: “The trend we noticed is consistent with studies that have shown that women experience higher rates of hip-implant failure than men and have stronger immunological reactions to metal-containing devices.”

Other experts within the industry were keen to voice their opinion over the importance of looking at the effects of medical devices on different genders. Diana Zuckerman, president of the National Center for Health Research commented: “Having information about sex is very important because some products differ in safety between men and women.”

Madris Tomes, founder and CEO of Device Events and a former FDA manager described the ICIJ’s work as critical. Tomes said: “It has long been unclear why the FDA’s device division redacts data elements that are so vital to scientific study…age, sex, and even the outcome of the adverse event are redacted by the device division but not the drug division.”

“But, if we are to look at allergy and autoimmune issues (presented in the FDA Immunology panel’s meeting on Metals in Implants) resulting from the metals and polymers in the hips, this could provide a second reason why the revision rates for women is higher than it is for men. It is an area where more research is necessary, and it shows the need for the FDA to un-redact fields which are so important for patients, physicians and hospitals to evaluate the safety of devices”, she added.

This report is part of the well-known Implant Files, which began from a report on medtech adverse events last year.

Read original story here.

NCHR Testimony on Research Needed on Immunological Responses to Metal in Implants

Diana Zuckerman, PhD, National Center for Health Research, November 13, 2019


Thank you for the opportunity to speak at this Advisory Committee meeting today regarding immunological responses to metal in implants.

The National Center for Health Research is a nonprofit research center that focuses on the quality of medical products and procedures and does not accept funding from medical device companies or pharmaceutical companies. I’m here today to share my perspective as a scientist as well as a patient.  I am trained in epidemiology and served on the faculty at Vassar and Yale and as a researcher at Harvard.  I’ve also worked in the U.S.  Congress on FDA issues and as president of the National Center for Health Research I have  a great deal of experience with FDA regulatory issues.

In addition, I got a hip implant 10 years ago, and I’m glad to say my experience has been a very good one.  But at the time I was deciding on the surgery, neither the surgeons I interviewed nor the research literature provided the kind of information I needed to make an informed choice.  In fact, one surgeon recommended a metal-on-metal hip for me because I was relatively young and active.  Fortunately, I was already aware of metal debris issues so I did not make that choice.  But the lack of information then and now was very clear to me as a patient.  I was not able to obtain scientific data from the surgeons or online, including PubMed.

I want to say that this has been one of the most interesting and informative FDA meetings I’ve attended, and the speakers have provided a great deal of important information.

What Research is Needed?

I’m here to talk about the big picture.  We’ve heard this morning about a great deal of research findings and the need for more and better research.  I want to emphasize that we need much better pre-market studies, not just post-market studies.  Pre-market clinical trials are often lacking because of the 510(k) process, but even when premarket clinical trials are conducted, they are often inadequate to provide the information patients deserve.

We need clinical trials and other well-designed studies of large number of patients, and as one of the speakers said this morning, we need to compare information about patients who have good experiences with their implants with those who do poorly with their implants.  These studies need to include a patient population with sufficient diversity in terms of age, sex, race, BMI, activity levels, allergies, and metal sensitivity, to determine how safe and effective the products are for these subgroups.

We need clinical trials and big data analyses that follow patients for years in order to evaluate the effects of wear and changes in immune responses over time.

We heard this morning that patch testing is inadequate to identify which patients will have a negative reaction to an implant, and that other diagnostic testing also has limitations.

I also want to express our concern with the tendency to extrapolate results from an implant used in one part of the body to implants made of the same materials that are intended to be used in another part of the body.   We know from listening to patients that this can result in terrible problems.

We are also concerned about extrapolating results from an earlier version of an implant to a newer implant, when the newer implant differs in ways that could affect safety and effectiveness.  Those differences might be different metals, changes in size or shape, differences in manufacturing, or numerous other changes typically made in an effort to improve implanted devices.

We encourage the FDA to require that studies specifically look for adverse events that are related to immune reaction or wear.  These adverse events might be local or might be systemic, and some of these events would not necessarily be included in studies asking about all adverse events.

Perhaps most important, we need comparative effectiveness studies that compare clinical effectiveness and patient-centered outcomes.  I know that the FDA rarely requires comparative effectiveness studies, but those are the types of studies that are most likely to provide useful information for patients and their physicians.

If certain implants seem to be causing certain reactions with certain kinds of patients, wouldn’t it be very important to know how that compares to other alternatives of the same kind of implants? We can’t treat all hip implants that are polyethylene and metal as if they’re all the same.  We can’t treat all metal-on-metal implants as if they’re the same. We need to compare different models, different implants made in different ways with different materials by different companies and get the kind of real data that patients and physicians can use to make informed decisions. Until then, it won’t be possible to figure out to what extent negative responses and implant failures are due to patient vulnerabilities or sensitivities and how much is due to the difference between various devices.

For more information about this public meeting, read these articles here or here.

Teens Are Being Hospitalized After Vaping: Here’s What We Know So Far

Parents, Yahoo! Lifestyle: August 27, 2019.


Last month, a 17-year-old from Texas named Tryston Zohfeld‘s lungs suddenly failed. He was rushed to Cook Children’s Hospital in Fort Worth, Texas and put into a medically-induced coma while the situation only worsened. X-rays found that the teen had a total blockage of his lungs. Ruling out diseases like pneumonia, doctors finally concluded that the lung inflammation and inability to exchange oxygen and carbon dioxide Zohfeld was experiencing had been brought on by chemicals the teen had been inhaling from his vape pen, which he had been regularly using since 8th grade.

While Zohfeld was grateful to be released from the hospital after an 18-day stay, his story is just one of several cautionary tales related to vaping and e-cigarettes that are making headlines nationwide. A 20-year-old from Utah named Alexander Mitchell was recently “on death’s door” after his lungs failed. The young man had been using e-cigarettes. Also this summer, 18-year-old Chance Ammirata’s lung collapsed. The Miami student admitted to vaping about one Juul pod every two days (roughly the equivalent of 10 cigarettes-worth of nicotine a day) for a year.

Now, the U.S. Centers for Disease Control and Prevention (CDC) is conducting an ongoing investigation into cases like these. Here’s what you need to know.

[…]

The Dangers of Vaping for Teens

With hope, the ongoing CDC and FDA investigations will offer parents more answers about the link between e-cigarette use and lung disease, but in the meantime, experts are noting that teens are an especially vulnerable group.

Diana Zuckerman, PhD, president of the National Center for Health Research told CBS News, “It seems some kids are having very measurable damage in a very short period of time than what we’ve seen from [cigarette] smoke.” She explained that a young person’s size might be a factor in how they experience the effects of the chemicals, noting, “The same amount of vaping for a child that weighs, say, 100 pounds, is a bigger issue than for somebody who weighs 200 pounds.”

At the same time, e-cigarettes that include nicotine put teens at risk of addiction, which amplifies their risk of illness. Teens who use nicotine can become addicted in just days. Yale Medicine pediatrician Deepa Camenga, M.D., says that nicotine affects teens differently than adults because “teens are just more vulnerable than adults are to developing an addiction to nicotine. As a result, it may be harder for teens to stop because their brain is still growing and developing.”

Potential Lung Damage Symptoms from Vaping

The CDC notes that “in many cases, patients reported a gradual start of symptoms” including:

  • breathing difficulty
  • shortness of breath
  • and/or chest pain before hospitalization
  • in some cases, mild to moderate gastrointestinal illness including vomiting and diarrhea and fatigue

People who experience illnesses after vaping are encouraged to report the incident to the FDA here.

 

Read the original article here.