All posts by CPTFeditor

Remarks to the FDA Science Board on Patient Engagement

Testimony & Briefings
Jack Mitchell, National Center for Health Research: May 9, 2017

Good afternoon.  I appreciate the opportunity to address this distinguished panel and our FDA participants.  I’m Jack Mitchell, director of government relations for the National Center for Health Research (NCHR).   We conduct research, use research data to inform public policy, and advocate for safe and effective medical products.  NCHR accepts no pharmaceutical or medical device industry money, and therefore I have no conflicts to report.

We strongly support FDA efforts to strengthen the role of patients and we urge the agency to define patients as those who use medical products, whether or not they are seriously ill.  The patient-focused meetings with FDA and other patient initiatives mentioned by Dr. Mullins in her presentation are welcome and necessary.  I’d like to speak to broadening those patient perspectives.

We know it is a challenge for FDA to attract patients who are truly independent, since so many patient organizations are funded by industry, and many patients are trained and recruited to participate in FDA meetings by industry.  Of course, all patients deserve to be heard, but  industry-supported perspectives should be augmented by independent patient voices.

For example, a recent study by Harvard researchers found that almost all patients who spoke at FDA public meetings had ties to companies that could benefit from their remarks.  Another study, of an FDA advisory committee meeting on a drug for Duchenne’s muscular dystrophy, reported that of the fifty-one public speakers, all but one had financial ties to the company that makes the drug.  That one public speaker was from our research center.

There are patient organizations that are not funded by industry and can offer a more independent voice.  We suggest that FDA needs to do more to reach out to them and include them.  For example, the USA Patient Network is a new national organization consisting of patients who have received training to help them understand clinical trial research design and analysis, so they can serve as confident, well-informed patient representatives on FDA and NIH advisory committees.

In addition, the Patient, Consumer and Public Health Coalition is an informal coalition of about two dozen non-profit patient, consumer, physician, and public health organizations.  They work together to prepare public comments for the FDA and other health agencies, and to educate Congress about important health policy issues.

Patients from these organizations have made presentations before FDA advisory panels and public forums.  They usually pay their own way to FDA meetings.  Not surprisingly, they are dramatically outnumbered by patients whose travel, meals and other expenses are reimbursed by industry.

We respectfully ask the Science Board to ensure that FDA enhances efforts aimed at including these independent patient voices, not only for new drug development, but also on the wide range of public health initiatives in which the agency is engaged.

Your focus today is on innovation initiatives mandated by the 21st Century Cures Act.  We are concerned that the new law does not guarantee sufficient resources to implement all its FDA-related provisions.  For instance, it encourages the FDA to rely more often on preliminary data such as biomarkers, and allow third party review to replace FDA’s premarket scrutiny.

The law has already resulted in the FDA deregulating more than one thousand moderate risk devices that will no longer be required to submit 510(k) applications.  To better ensure safety, FDA needs to expend more resources to improve post-market surveillance, especially of medical devices.

Unfortunately, neither 21st Century Cures nor the user fees that FDA has negotiated provides sufficient resources for effective post-market surveillance, particularly for medical devices.  Patients from the USA Network and other independent patient organizations have provided documented evidence to FDA of serious, irreversible harm caused by fast-tracked device approvals and inadequate post-market surveillance.  They tell us that FDA often is not sufficiently responsive to their requests to strengthen patient safeguards.

We respectfully urge the Board to carefully address these patient recruitment and safety issues as you advise FDA about implementing the 21st Century Cures Act.  Engagement perspectives should include patients who have been harmed by medical products that were not as safe as the research indicated, or had risks about which the patients were not adequately warned.  While FDA is appropriately and routinely hearing from patients desperate for new treatments, those are not the only patients who have important perspectives from which the agency can learn.  Thank you.

NCHR Comment on the USPSTF’s Draft Recommendations for Prostate Cancer Screening

Policy
National Center for Health Research: May 8, 2017

 

National Center for Health Research’s Comments on
the U.S. Preventive Services Task Force’s Draft Recommendation Statement
on Prostate Cancer Screening

Thank you for the opportunity to express our views on the draft recommendations for prostate cancer screening.

The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety. We do not accept funding from companies that make products that are the subject of our work.

We support the efforts of the U.S. Preventive Services Task Force (USPSTF) to re-evaluate its recommendations in light of new research regarding prostate cancer screening that provides new insights into its benefits and risks. The issue of screening for prostate cancer is complex, because the benefits and risks vary in unknown ways for individuals. For a subset of men, the benefits may outweigh the risks, but for others the situation is reversed. Therefore, a recommendation that, for men aged 55-69 years, the decision is best determined by a patient and their doctor with a rating of “C” may be warranted. However, we have strong concerns about the basis for this change in recommendations and its likely impact on screening. We agree with the USPSTF that the risks outweigh benefits for men who are 70 years old and older.

Changing the grade and recommendation for men aged 55-69 from a “D” to a “C” and from “risks outweigh benefits” to “talk with your doctor” may make patients and practitioners believe that the data supporting screening is now stronger than it was previous.  Unfortunately, most doctors have neither the time nor the communication skills to do convey the ambiguities of risks and benefits to their patients.  As a result, the proposed change would be likely to increase screening for most men.

When the USPSTF changes a recommendation, the scientific data should strongly support that change.  It should indicate a difference in overall survival, not just a change in deaths from the specific disease being screened.

The review lists the benefits of screening for men 55-69 years as preventing 1.3 death from prostate cancer and 3 cases of metastatic prostate cancer for every 1,000 men screened over a 13-year period. The data supporting the 2012 “D” recommendation predicted that screening would prevent 0.7 deaths per 1000 men screened and did not include information about metastatic cancer. This is a small increase, but more importantly, prostate cancer screening has not been shown to improve overall survival.  Experts agree that the vast majority of men with prostate cancer will die with prostate cancer, rather than die of prostate cancer.  Instead, the vast majority will die of another cause.  And yet, the complications of prostate cancer treatment often substantially harm quality of life. Out of these same 1,000 men, 273 would have a positive PSA test, and 35 would get a cancer diagnosis. If these 35 men were treated with radical prostatectomy, 24 would not benefit from treatment, 7 would have long-term erectile dysfunction, and 2 would have long-term problems with urinary incontinence requiring a diaper.

The data on quality of life are definitely confusing.  While the surgical patients have the worst adverse events – primarily erectile dysfunction and incontinence, they tend to score well on general quality of life.  In contrast, the radiation patients are less likely to have these adverse events, but more likely to score poorly on various quality of life measures. Hormone therapy tends to have negative impact on adverse reactions and on general quality of life.

It seems clear that the general quality of life measures that were used in these studies are not measuring quality of life related to the adverse events that are assumed to be most severe – erectile dysfunction and incontinence – but in the case of radiation and hormone treatment, are measuring some significant problems.  And, perhaps active surveillance is also taking a toll on quality of life, because the knowledge that a man has prostate cancer has a negative impact when he doesn’t treat it.

Looking dispassionately at these numbers, it seems clear that patients’ decisions regarding treatment for prostate cancer should be carefully discussed with one’s doctor.  But the question here is screening, not treatment.  The data clearly indicate that screening is having a negative impact, because once a man has a high PSA and is found to have prostate cancer, he seems likely to feel worse than he felt before screening whether he seeks treatment or active surveillance.  Given that there is no evidence that any of these treatments improve overall survival, how can one justify recommending prostate screening for men with no symptoms?  If the USPSTF believes that it is important to reduce overtreatment and unnecessary harm, data on overall survival is crucial to determine if screening should or should not be recommended.

Even when screening tests accurately detect cancer, they cannot accurately predict whether a tumor will become life threatening within the man’s lifetime. There is a high rate of overdiagnosis and subsequent overtreatment. Longer-term studies and studies designed to distinguish between higher and lower risk populations (for unproblematic vs. concerning cancers) may help address these issues in the future. However, these data will not help men and their doctors with the issue now. On the other hand, the use of active surveillance as opposed to other treatments could help reduce harms, but only if it is considered a real option by doctors and patients.

If men decide to undergo screening for prostate cancer, it is important that they are educated about the risks and benefits of specific screening tests. Prostate-specific antigen (PSA) tests have a high rate of false positives, between 20% and 50%. This leads to unnecessary stress and anxiety, as well as increased follow-up testing. The PSA test alone is insufficient for diagnosis because it also detects other changes in the prostate and even urinary tract infections, making follow-up tests are necessary. One of the most common follow-up test is a biopsy, which has its own risks, including injury requiring hospitalization.

Changing the grade and recommendation for men 55-69 years of age testing from a “D” to a “C” and from “risks outweigh benefits” to “talk with doctor” will likely increase the use of screening. If done properly, this may help a small number of men. However, if discussions between doctors and patients are not effective at sharing information to help patients weight the risks, benefits, and the patient’s personal values, then there will be an increase in overdiagnosis, overtreatment, and medical complications.

The Cancer Prevention and Treatment Fund is the major program of the National Center for Health Research. For questions or more information, please contact Stephanie Fox-Rawlings at sfr@center4research.org.

References:

Draft Recommendation Statement: Prostate Cancer: Screening. U.S. Preventive Services Task Force. April 2017.
https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/prostate-cancer-screening1

Draft Evidence Review: Prostate Cancer: Screening. U.S. Preventive Services Task Force. April 2017.
https://www.uspreventiveservicestaskforce.org/Page/Document/draft-evidence-review/prostate-cancer-screening1

Final Recommendation Statement: Prostate Cancer: Screening. U.S. Preventive Services Task Force. May 2012.
https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostatecancerscreening

Lin K, Croswell JM, Koenig H, et al. Prostate-Specific Antigen-Based Screening for Prostate Cancer: An Evidence Update for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Oct. (Evidence Syntheses, No. 90.) https://www.ncbi.nlm.nih.gov/books/NBK82303/

 

NCHR Comment on the USPSTF’s Draft Recommendations for BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing

Policy, Testimony & Briefings
National Center for Health Research: April 12, 2017

Thank you for the opportunity to express our views on the draft research plan for Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-related cancer risk.[1]

The National Center for Health Research is a nonprofit research center staffed by scientists, medical professionals, and health experts who analyze and review research on a range of health issues.

Based on its previous review, the USPSTF recommended risk assessment, genetic testing, and counseling for women with a family history of clinically important mutations in BRCA1 or BRCA2 genes.[2] However, as noted in the recommendations, there were a limited number of good quality studies that looked at long-term risks and consequences of testing for BRCA1/2 gene mutations. Additionally, only poor evidence was available to determine the risks and benefits for women without a family history.

We appreciate and support the USPSTF’s efforts to review and update recommendations based on evolving research. The current draft research plan has the potential to identify relevant research for the review and subsequent recommendations. We want to emphasize some points that we consider particularly pertinent.

The evidence regarding the likelihood of developing cancer for women with BRCA1 or BRCA2 mutations continues to evolve.  Shortly after mutations were discovered to increase risk for cancer, women were told that their cumulative risk of developing breast cancer or ovarian cancer was close to 100% for BRCA1 mutations and only slightly lower for BRCA2 mutations. Those estimates have decreased substantially since then, and according to the most recent estimates, around 55% to 65% of women who inherit BRCA1 mutations and around 45% of women who inherit BRCA2 mutations will develop breast cancer by age 70.[3] In addition, 39% of women who inherit the BRCA1 mutation and 11% to 17% of women who inherit the BRCA2 mutation will develop ovarian cancer by age 70. Despite these statistics, women who have lower chances of developing BRCA-related cancer due to the type of mutation and/or their age, still tend to believe that their lives are in immediate danger, with prophylactic surgery being the only real option. To make meaningful recommendations concerning screening, testing, and counseling around BRCA-related cancers, it is important to determine which BRCA1/2 mutations are clinically relevant, how they affect the likelihood of developing BRCA-related cancer and by what age they are likely to develop cancer, preferably 50, 60 and 70.

If a woman is diagnosed with clinically significant BRCA1/2 mutations, the major options are prophylactic medications, bilateral mastectomy or oophorectomy, or active surveillance.  All come with serious health risks, which means that the potential harm from screening, testing, counseling, and interventions can be serious.  The risks range from false security (and less vigilance) to unnecessary anxiety due to false positives resulting from inaccurate testing or poor counseling.

Poor or limited counseling, confounded by the lack of accurate, up-to-date information about the risks of treatment and management options, also may harm women who choose prophylactic treatments or surgery. Prophylactic surgery causes hormonal changes and self-image issues.  For women choosing mastectomy with reconstruction with breast implants, for example, there are known and unknown risks, including the possible development of ALCL, a type of lymphoma.  ALCL was thought to be extremely rare, but research now indicates that it is less rare than expected and can be caused by breast implants.[4]

The benefits and harms of testing, detection, and early intervention can differ for women of different age groups, socioeconomic status, ethnic origin and insurance status, in addition to family history of BRCA1/2 mutations. The research review and subsequent recommendations will be more beneficial if they are based on diverse populations, with subgroup analyses whenever possible to enable the USPSTF to determine if there are some demographic groups for which recommendations should be different.

In conclusion, we support The USPSTF’s efforts to provide updated recommendations on risk assessment, genetic counseling, and genetic testing on BRCA-related cancer, based on quality, up-to-date scientific studies. We hope the review will quantify the benefits and harms of each step starting with screening, in order to help USPSTF to make meaningful recommendations for appropriate subpopulations of women.

The Cancer Prevention and Treatment Fund is the major program of the National Center for Health Research. For questions or more information, please contact Stephanie Fox-Rawlings at sfr@center4research.org.

References

  1. USPSTF Draft Research Plan Draft Research Plan for BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing, March 2017.
  2. USPSTF Final Recommendation Statement BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing, December 2013.
  3. “BRCA1 and BRCA2: Cancer Risk and Genetic Testing.” National Cancer Institute, National Institute of Health, April 2015
  4. Safety Alerts for Human Medical Products- Breast Implants: Update- Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), March 2017

 

NCHR Comment on the USPSTF’s Draft Recommendations for Breast Cancer: Medications for Risk Reduction

Policy, Testimony & Briefings
National Center for Health Research: April 19, 2017

Thank you for the opportunity to express our views on the draft research plan for Breast Cancer: Medications for Risk Reductions. The National Center for Health Research is a nonprofit research center staffed by scientists, medical professionals, and health experts who analyze and review research on a range of health issues.

In their previous recommendation, USPSTF found that treatment with tamoxifen or raloxifene was beneficial for a subpopulation of women at increased risk. However, these treatments only slightly reduced the occurrence of invasive breast cancer in these women and came with serious risks.

We appreciate and support the USPSTF’s efforts to review and update recommendations based on evolving research. The current draft research plan should identify relevant research for the review and subsequent recommendations. We want to emphasize some points that we consider particularly pertinent.

When considering the harms and benefits of medications to reduce the risk for invasive breast cancer, it would be beneficial to also compare the effect size to other options, such as lifestyle changes. Behaviors such as maintaining a healthy diet, exercising, abstaining from smoking, and low levels of alcohol consumption have been shown to be protective against several types of cancer, including breast cancer. In other words, the risk of developing breast cancer may be reduced by changes in lifestyle that have many other advantages and no risks. That context is important for women as they consider drug therapy that may help prevent breast cancer but that also increases the risk of other types of cancer as well as very unpleasant side effects.

We greatly support the inclusion of key question 4 to look at the difference between population subgroups for outcome measures. Studies that target understudied populations and/ or that include subgroup analyses for racially and socioeconomically diverse populations will enable the reviewers to understand the prevalence of breast cancer risk across demographic groups but also enable them to evaluate the effectiveness and risks of drug therapy for these subpopulations. This will enable the USPSTF to determine if recommendations should be different for some demographic groups.

We also support the inclusion of quality of life as an outcome measurement, as this is an important dimension in assessing the harms and benefits of using drug therapy to reduce breast cancer risk. Quality of life outcomes are important for the decision to undergo treatment and to continue after adverse effects become apparent. Considering how drug therapies affect quality of life will provide doctors and patients with important information for making an informed decision about prophylactic medication.

It is important that the review evaluate the long-term health outcomes in terms of benefit and harms extending beyond when treatment stops. Several studies evaluated for the previous USPSTF review suggested that reduced breast cancer risk continued for at least 3 to 5 years and the risks of some harms returned to baseline after cessation of treatment. However, it was unclear how long the benefit might continue or to what extent any or all risks diminished.

These studies showed only a small benefit of treatment (5 to 9 fewer invasive cancers per 1000 people treated). This was not very different from the increased risk for harm (4 to 7 more thromboembolic events, 4 to 5 more cases of endometrial cancer, and up to 15 more cases of cataracts per 1000 people treated). If these numbers change over longer time frames, then it could shift the risk/benefit ratio. This is especially important because, as the previous recommendation noted, women are already cautious of treatment due to the small benefit and potentially serious harms. It is also important to determine which women will most likely benefit from treatment, to increase cases of reduced risk and limit the chance of harms.

Most important, the studies used for the previous USPSTF review were not sufficiently long-term to determine if there was an effect on mortality. Given the similar statistics for benefits and serious harms noted above, the impact on mortality could be a deciding factor for many women considering these drugs.

In conclusion, we support the USPSTF’s efforts to re-evaluate recommendations as the scientific evidence expands and improves. The proposed draft review should facilitate this process and includes questions and outcomes that we agree are important. In addition, we strongly urge the USPSTF to consider how the apparently modest benefits of medications compare to specific lifestyle changes for reducing breast cancer risk.

The Cancer Prevention and Treatment Fund is the major program of the National Center for Health Research. For questions or more information, please contact Stephanie Fox-Rawlings at sfr@center4research.org.

 

References:

USPSTF Final Recommendation Statement: Breast Cancer: Medications for Risk Reduction. U.S. Preventive Services Task Force. December 2016.

USPSTF Draft Research Plan: Breast Cancer: Medications for Risk Reduction. U.S. Preventive Services Task Force. April 2017.

Breast Implants Linked to Rare Cancer

News Stories & Editorials
Diana Zuckerman, PhD, National Center for Health Research, on behalf of Cancer Prevention & Treatment Fund, in Our Bodies Ourselves:  March 24, 2017

breast implants

 

Last week the media discovered that breast implants can cause cancer. Rather than causing breast cancer, experts now say that breast implants can cause a type of lymphoma (cancer of the immune system) called anaplastic large cell lymphoma (ALCL).

You’ll be excused for thinking this is news. The truth is that experts have known that breast implants cause ALCL since at least 2013, and some of the foremost plastic surgeons in the country were discussing it behind closed doors since at least 2010.

The U.S. Food and Drug Administration (FDA), which is responsible for making public information about the risks of medical devices, including breast implants, first published a report on its website about ALCL and breast implants in 2011. At that time, they said there was evidence that implants might possibly cause ALCL. The FDA’s report came months after anarticle published in Allure magazine stated that plastic surgeons and their medical societies were studying the possible link between breast implants and ALCL.

Articles subsequently published in medical journals concluded that breast implants cause ALCL. But despite the growing evidence, the FDA didn’t update its website to officially report that breast implants really can cause ALCL until last week. That’s when the media realized it was a real story.

If you think women should have been told this sooner, here’s what you need to know:

In May 2016, the World Health Organization published a report that included the term breast implant associated ALCL (BIA-ALCL). A few months later, the National Comprehensive Cancer Network (NCCN) released the first worldwide oncology standard for the disease. The guidelines (you need to sign up for a free account to see them) include a guided algorithm for surgeons and oncologists to test for and diagnose the disease. The authors conclude that any abnormal accumulation of fluid or a mass that develops near the breasts months after breast implants are  implanted must be evaluated.

They also state that even if the BIA-ALCL is confined to the scar capsule that surrounds the implant and even if that capsule is totally removed through proper explant surgery, the patient must be followed for 2 years to make sure the ALCL is eliminated.

Why didn’t plastic surgeons or the FDA make that information more widely available? I’m sure there are women and their doctors who would have benefited from that information in the last few months.

In 2015, plastic surgeons who had denied any link between breast implants and cancer for more than two decades published an article in a plastic surgery journal about 173 women with ALCL that was caused by their breast implants.

However, plastic surgeons across the country focused on reassuring women that BIA-ALCL is “very rare” and the FDA echoed that mantra.  But, 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., the Australian Department of Health estimates that BIA-ALCL affects as many as one in 1,000 women with breast implants.

The estimates of plastic surgeons and the FDA are 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. than in Australia. Given the dramatic increase in BIA-ALCL diagnoses in recent years, it is clear that BIA-ALCL was under-diagnosed and under-reported for many years.

For women with ALCL, it doesn’t matter how rare it is. The sooner it is diagnosed, the more likely it can be cured easily by removing the implants and scar capsule surrounding it. At later stages, women will need chemotherapy and are less likely to survive, according to research conducted at the MD Anderson Cancer Center that was published in 2013.

The study followed women for 5 years and found that ALCL related to breast implants sometimes requires chemotherapy, and approximately 25% of the implant patients with the more serious type of ALCL died during the 5 years following their diagnosis. You can read more about the study here.

ALCL caused by breast implants can result in swelling, which is often mistaken for an infection and treated with antibiotics. Antibiotics are ineffective against ALCL and the delay in timely and appropriate treatment for ALCL is dangerous.

A published response in the same medical journal urged physicians to respond quickly and to check patients who have swelling near their implants for ALCL. This would require cytology testing rather than testing for bacteria.

This news is especially important to women who undergo mastectomies to prevent cancer or for DCIS or very early breast cancer, either of which is equally likely to be cured with a lumpectomy instead. Women trying to beat cancer by undergoing a radical surgery they don’t need are unlikely to do so if breast implants will put them at risk of developing a different type of cancer.

The news is equally frightening to cosmetic surgery patients. Many health insurance companies refuse to cover the cost of medical tests or treatment for women with breast problems related to cosmetic breast implants. We now know this can result in undetected ALCL, which can be fatal. In addition, delays in treatment for ALCL can be extremely expensive for patients and their insurance companies; the companies would be required to pay for treatment for ALCL when it is eventually diagnosed at a later stage.

Women deserve to know the facts.  And they deserved to know them years ago.

Read the full article here. 

FDA Proposal Would Lower Requirements for Some Moderate-Risk Devices

In the News
Bronwyn Mixter, Bloomberg BNA: March 24, 2017

Over three-hundred class II medical devices made the list of those that might become exempt from premarket notification requirements once the FDA takes final action.

The Food and Drug Administration March 14 published a proposed list of class II devices that will be exempt from the requirements, also called 510(k)s, when the list is made final (82 Fed. Reg. 13,609). Class II devices are moderate-risk devices. A 510(k) clearance demonstrates that a device is substantially equivalent to another (or predicate) device already on the market. Clinical data typically aren’t generated for a 510(k).

The 21st Century Cures Act (Pub. L. No. 114-255), a 2016 law to speed new drugs and devices to market, required the FDA to publish the list. The FDA said the final list will decrease regulatory burdens on the industry by eliminating time and resources needed to submit 510(k) notifications. The devices include dentures, umbilical clamps, obstetrical forceps and surgical clamps. […]

Safety Concerns

The National Center for Health Research, a nonprofit that encourages new and more effective medical treatments, is concerned these devices won’t be reviewed by the FDA.

“We are very concerned about this huge list of devices that will no longer go through any kind of FDA review,” Diana Zuckerman, president of the nonprofit, told Bloomberg BNA in a March 20 email. “The FDA’s faulty justification is that the FDA already knows quite a bit about these devices, but that ignores the fact that when a new company starts making a device, or when any company makes changes to a device, the device can become substantially less safe or substantially less effective, or both.”

Zuckerman said “it is very disturbing that the FDA’s Center for Devices is so focused on relieving device companies of the burden of providing evidence of safety and effectiveness, but not at all concerned that now doctors and patients have an impossible burden of trying to figure out which devices they can rely on and which they can’t. And if we are ever going to have a value-based reimbursement system for medical care, increasingly devices will not be covered because so often there is no scientific evidence that a specific device will benefit patients.” […]

 

Read original article here.

Are breast implants safe? What is FDA’s Track Record?

Breast Cancer
Diana Zuckerman, PhD, Cancer Prevention & Treatment Fund

In 2013, a study showed that a rare cancer of the immune system, ALCL, which had previously been linked to saline breast implants and silicone breast implants, was caused by breast implants and could be fatal.  The latest research indicates that this cancer is sometimes cured by removing the breast implants, but at other times also requires radiation and chemotherapy; in some cases, the patients died despite treatment. Although the FDA had reported in 2011 that ALCL might be caused by breast implants, the agency didn’t update its website when the 2013 study was published.  It took the FDA more than 3 more years to revise articles on its website indicating that breast implants caused ALCL ( to conclude that breast implants could cause ALCL. The FDA reported that they have received 359 reports of ALCL among women with breast implants through February 2017. It’s likely there are still numerous unreported cases; for example, Australia’s medical agency estimates that one in 1,000women with breast implants develops ALCL.  There is no reason to think American women would be less likely to develop ALCL, and that would result in several thousand U.S. women developing ALCL

This is just the latest bad news for women with breast implants, and for the government agencies that have allowed them on the market with inadequate studies or warnings.  For example, in 2011, tens of thousands of defective breast implants made by PIP were recalled in Europe. An article in the December 2012 issue of the British medical journal Reproductive Health Matters explains how these developments illustrate the strengths and weaknesses of the safeguards intended to protect patients in different countries from unsafe breast implants and other medical devices.  In the U.S., breast implants are regulated as high-risk medical devices that must be proven reasonably safe and effective in clinical trials and subject to government inspection before they can be sold. This standard is higher than the FDA requires for hip joints, numerous cardiac devices, and many other medical implants. In contrast, clinical trials and inspections have not been required for breast implants or other implanted devices in Europe. As a result of these differing standards, the PIP breast implants that were recalled across Europe had already been removed from the U.S. market years earlier. The FDA was justifiably proud that they had done a better job of protecting breast cancer patients and cosmetic augmentation patients than the EU regulatory system. Nevertheless, the FDA track record on breast implants shows how limited those safeguards can be. The FDA required two breast implant companies to conduct enormous 10-year studies of breast implants, but has done little to ensure that the studies are providing useful information to patients.

The authors conclude that neither the European Union nor the U.S. has used their regulatory authority to ensure the long-term safety of breast implants. However, in 2012 the EU announced regulatory changes that could improve that situation. In addition, the CEO of PIP was sentenced to 4 years in prison by a French Court, and in January 2017, a French court demanded that the German regulatory company that had certified PIP implants as safe pay $60 million euros to women harmed by PIP implants. This is only 3,000 euros each to 20,000 women, however.

Meanwhile, the FDA shows no indication that they will improve their safeguards on breast implants or other medical implants; in fact, those safeguards have weakened since 2012.

For more information about ALCL caused by breast implants, see:

Miranda RN, Aladily TN, Prince HM, et al: Breast implant–associated anaplastic large-cell lymphoma: Long-term follow-up of 60 patients. J Clin Oncol 32:114-120, 2014.

Mazzucco, AE.  Next Steps for Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol, 2014.  Early Release publication. June 16, 2014.

FDA Agrees With WHO, Links Breast Implants To Rare Cancer. How Worried Should Women Be?

In the News
Rita Ruben, Forbes: March 22, 2017

The Food and Drug Administration has received nine reports of women dying of a rare blood cancer years after getting breast implants, according to information the agency released Tuesday.

The FDA says it now agrees with the World Health Organization that such cases are linked to the breast implants and not some unfortunate coincidence. As of Feb. 1, the FDA says, it had received a total of 359 reports of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

The FDA reports suggest that implants with a textured surface are more likely to be associated with the cancer than smooth implants—of the 231 reports that contained information about the implant’s surface, 203 were reported to be textured implants, while 28 were reported to be smooth. The Australian Therapeutic Goods Administration (TGA) analyzed 46 confirmed cases of BIA-ALCL, including three deaths, and none of the cases occurred in women with smooth implants.

BIA-ALCL on average is diagnosed about a decade after implant surgery, according to the WHO. The first reported case of a woman with breast implants developing ALCL was published in a 1997 letter to the journal Plastic & Reconstructive Surgery. While that case was a woman with saline-filled implants, the FDA says the filling, be it saline (salt water) or silicone, doesn’t seem to make much of a difference, although no well-designed studies have yet been conducted to settle that issue.

BIA-ALCL is rare, but just how rare isn’t clear. As the FDA notes, it medical device reports can’t answer that question, because they don’t represent all cases, and the denominator—the total number of women who’ve received breast implants—isn’t known.

ALCL is more common in the breasts of women who’ve had implants than in those who don’t have implants, in whom the cancer almost never develops in the breast. A U.S. studypublished in January concluded that over their lifetime, 3.3 women out of every 100,000 with textured breast implants will develop BIA-ALCL. But the TGA estimates that the disease is more common, affecting 1 in 10,000 to 1 in 1,000 women with breast implants (that agency says it has received no reports of BIA-ALCL in women with smooth implants).

“There is no reason to think it is less likely to develop in women in the U.S., and given the dramatic increase in diagnoses in recent years, it is clear that it was under-diagnosed and under-reported for many years,” Diana Zuckerman, a health advocate who has long questioned the safety of breast implants, told me.  Zuckerman serves as president of both the National Center for Health Research and the Cancer Prevention and Treatment Fund, nonprofits based in Washington, D.C. […]

Read the full article here.

ALCL and Breast Implants: 2017 Update

Other Cancers, Other Cancers
Anna E. Mazzucco, PhD and Diana Zuckerman, PhD, Cancer Prevention & Treatment Fund

In March, 2017, the U.S. Food and Drug Administration (FDA) updated its website to officially report that breast implants could cause a type of cancer of the immune system called anaplastic large cell lymphoma (ALCL).  They stated they have received 359 reports of ALCL among women with breast implants.

The FDA’s announcement came 10 months after the disease was named breast implant associated ALCL (BIA-ALCL) in a  World Health Organization publication in 2016, and a few months after the and the National Comprehensive Cancer Network (NCCN) released the first worldwide oncology standard for the disease.  NCCN includes a guided algorithm for surgeons and oncologists to test for and diagnose the disease.  They concluded that any abnormal accumulation of fluid or a mass that develops near the breasts months after breast implants were implanted must be evaluated.

The oncologists also state that even if the BIA-ALCL is confined to the scar capsule that surrounds the implant and even if that capsule is totally removed through proper explant surgery, the patient must be followed for 2 years.  Here is the link to their guidelines: https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf#page17

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.  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.

The sooner ALCL is diagnosed, the more likely it can be treated easily and effectively by removing the implants and capsule.  At later stages, treatment includes chemo and is less likely to be successful, as specified by researchers at the well-respected MD Anderson Cancer Center in a medical journal in 2013. Their study followed women for 5 years and found that ALCL related to breast implants sometimes requires chemotherapy, and approximately 25% of the implant patients with the more serious type of ALCL died during the 5 years following their diagnosis.[1] Dr. Anna Mazzucco published a response to this study,[2] urging physicians to respond quickly and to check patients who have swelling near their implants for ALCL. This would require cytology testing rather than testing for bacteria. The authors of the original study also published a response to Dr. Mazzucco’s article, expressing similar concerns.[3]

For more information, see our summary of that study here.

ALCL caused by breast implants can result in swelling, which is often mistaken for an infection and treated with antibiotics. Antibiotics are ineffective against ALCL and the delay in timely and appropriate treatment for ALCL is dangerous.

Unfortunately, some health insurance companies have traditionally not covered the cost of medical tests or treatment for women with breast problems related to cosmetic breast implants. The published articles on ALCL clearly indicate that this can result in undetected cancer of the immune system (ALCL), which can be fatal. In addition, delays in treatment for ALCL can be extremely expensive for patients and their insurance companies; the companies would be required to pay for treatment for ALCL when it is eventually diagnosed at a later stage.

References

  1. Miranda RN, Aladily TN, Prince HM, et al: Breast implant–associated anaplastic large-cell lymphoma: Long-term follow-up of 60 patients. J Clin Oncol 32:114-120, 2014.
  2. Mazzucco, AE. Next Steps for Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol, 2014.
  3. Miranda RN. Reply to AE Mazzucco. J Clin Oncol, 2014. Early Release publication. June 16, 2014.

Right to Try National Law Would Exploit False Hope

In the News, News Stories & Editorials
Diana Zuckerman, PhD, Cancer Prevention & Treatment Fund
Published in 19 newspapers including, Chicago (IL) Tribune, Sacramento (CA) Bee, McAllen (TX) Valley Voice, Bellingham (WA) Herald, Cambridge (OH) Sunday Jeffersonian, Lawton (OK) Constitution, Mason City (IA) Sunday Globe Gazette, Willimantic (CT) Sunday Chronicle, New Bedford (MA) Standard Times, Frederick (MD) News Post, and others from March 16-20, 2017

right-to-tryIf you or a loved one were dying of a terminal illness and your doctor told you there were no proven treatments, would you take the risk of trying an experimental, unproven drug?

Many patients would say yes. But as with most medical decisions, the more you know, the more you realize the answer is not so simple.

As has been clearly shown, Congress is not very good at making complicated and nuanced decisions about medical care.

That’s reason enough to question the new federal Right to Try Act dozens of senators and representatives are pushing this spring.

The most important thing to know is that all terminally ill patients already have a right to try experimental drugs in this country.

The proposed new law, however, is much more dangerous to all patients, and not just those facing fatal illness.

Here’s why:

The current national expanded access program enables doctors to request experimental drugs for their patients. If the company that makes the treatment agrees, the patient will get the treatment for free or at cost; companies are not allowed to sell experimental drugs for a profit.

Many patients get access to experimental drugs through this existing program, and improvements are underway to further streamline the process.

In contrast, under the proposed new law, a drug company could charge desperate patients as much as they want to get access to an experimental drug.

Since insurance companies do not pay for experimental treatments, many patients would wind up with the right, but not the money, to try such regimens. Out of desperation, some would surely go into debilitating debt to try a drug that might harm rather than help them.

The current national program makes sure patients understand the risks of taking an experimental treatment and requires that the drug has been studied enough to know that the patient might possibly benefit from it.

Under the proposed new law, drugs that were only studied at a low dose on a small number of healthy volunteers could be sold to patients, and unethical doctors could receive kickbacks for persuading patients to try treatments that will not help them.

It’s easy to understand why every patient wants to have hope of a cure, and that’s the power of right-to-try laws.

So far, hype and false hope have convinced 33 states to pass right-to-try laws that provide no real advantage over the current national program. But rather than learning from the mistakes at the state level, patient activists and others are pushing Congress to pass a much more dangerous federal law.

In addition to encouraging the sale of unproven treatments at sky-high prices to desperate patients, the 2017 federal Right to Try Act would do the following:

  • Allow the sale of almost all experimental drugs, even those never tested on patients before.
  • Prevent patients and family members from suing the company if the treatment harms or even kills them.
  • Prohibit doctors and scientists from evaluating the benefit or harm of the experimental drugs.

Desperate patients are lobbying for the bill, but do they realize what they are lobbying for?

Instead of getting access to free experimental drugs that have some evidence of benefit and are being tested to help all patients, this law would allow naive and desperate patients to be exploited by greedy companies and unethical doctors.

The right-to-try movement opposes the FDA for what’s described as “interfering” with the doctor-patient relationship. They do not understand that unbiased scientific evidence is needed to help physicians and patients make informed decisions – whether to save a life or make a patient’s last months as enjoyable as possible.

Patients already have a right to try through the FDA’s humanitarian expanded access program, which gives them hope while protecting them from greedy exploitation. The proposed federal Right to Try Act would not.

Read original article here.

On the other side of the debate, Naomi Lopez Bauman of the anti-FDA Goldwater Institute wrote a misleading article about why they support a national Right to Try law. 

Let’s set the record straight on at least a few of her misstatements::

  • She claims that companies are prohibited by law from charging more for the investigational treatments than their “actual cost.”  That is true of current law.  However, the national Right to Try Acts that are being considered in Congress specifically allow companies to determine what they will charge for their experimental drugs.
  • She states that in 2015, FDA only allowed 1,300 patients to have access to experimental drugs through their Expanded Access program.  That is true but very misleading, because the FDA is approving 99% of the applications to participate in the program.  The reason the number is low is that when doctors request access for their patients, the companies that are being asked to make their drugs available are not always willing or able to do so.  In some cases, they don’t have enough of the experimental drug available.  In other cases, they believe that the specific patient requesting the drug could be harmed and would not be helped by taking the drug.
  • She states and implies that the national law would not change FDA safeguards and would do no more than make the current state laws national.  That is not true.  On the contrary, the national law would eliminate the role of the FDA from these decisions and the protections that current law provide to prevent patients from being exploited by greedy companies or doctors.
  • She states that “promising new treatments” take more than a decade to be approved by FDA.  We don’t know where that inaccurate statistic comes from, but we do know that the average drug is approved about a year after it is submitted to the FDA, and an article in Cancer World concluded that the FDA approves drugs an average of 6 months faster than the European medical agency
  • She expresses concern that “FDA would retaliate” against those utilizing Right To Try laws.  There is zero evidence to back up that statement.  That is just anti-FDA rhetoric.
  • She states that “most” of the 78 patients treated by an “oncologist” under the Texas Right to Try law “are doing very well,” according to his testimony before a U.S. Senate committee.  If you watch the video of his statement online, you can see the doctor who testified (Ebrahim Delpassand, who is a radiologist, not an oncologist) never said “most are doing very well.” He said that the treatment “has helped many” of the patients, but he doesn’t say how many or to what extent the treatment helped, nor does he say how many were hurt by the treatment.
  • She says something is wrong because “fewer than one-tenth of 1 percent of terminal patients can take advantage of the FDA’s compassionate use exception.”  But the truth is that experimental drugs are just that: experimental and not proven to work or be safe.  Patients can die sooner and in agony from experimental drugs, especially those that have only gone through tiny, preliminary studies of a few healthy volunteers or patients (as the proposed national law would allow).  She neglects to mention that only about 15% of the drugs that complete those preliminary trials are eventually proven to be safe or effective.  The other 85% are either not safe, not effective, or both. That is a very important reason why most patients (and their doctors) do not seek experimental treatments even when they know they can.