Category Archives: Policy

Testimony of Diana Zuckerman at the Meeting of EPA’s National Environmental Justice Advisory Council on September 28, 2022

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical and consumer products, and we don’t accept funding from companies that make those products.  Our largest program is focused on cancer prevention and treatment.  My expertise is based on post-doc training in epidemiology and public health, and my previous positions at HHS and as a faculty member and researcher at Harvard and Yale.

 Thank you all for the important work you’ve been doing and will be doing on this Advisory Council.  As a public health person, I’ve always been surprised at the lack of other public health advocates who are active on environmental issues and environmental justice issues, and I want to offer to be helpful in any way that would be useful to all of you.  We all know that lives are at stake.

I want to comment very briefly on the PFAS recommendations, since that’s an issue we’ve worked on for years.  Let me add that we are very concerned about all endocrine disrupting chemicals not just PFAS.

Everything I heard about PFAS this afternoon was inspiring and important.  I would just suggest that it’s a huge task, and I encourage you to start a little smaller in order to succeed in educating the public and especially environmental justice communities and at the same time focus on actions that are doable, that will inspire others, and that will make change happen.

Testimony of Dr. Diana Zuckerman About COPIKTRA FDA Advisory Committee Meeting on September 23, 2022

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. Our largest program is focused on cancer. My expertise is based on post-doc training in epidemiology and public health, and my previous positions at HHS and as a faculty member and researcher at Harvard and Yale.

In April this same Committee examined 6 randomized trials of Pi3K inhibitors used for hematologic malignancies and found that all reduced overall survival –despite potential benefit for PFS. FDA says that these consistent findings across multiple randomized trials within the same drug class is unprecedented in oncology.
That’s a shocking finding that we need to take seriously. And that’s the context for today’s meeting.

The sponsor did a 5-year randomized controlled post-market study – 3 years longer than the data that resulted in initial approval. They found the median OS was 11 months shorter than the comparison drug. In fact, 50% of the patients died during those 5 years, compared to 44% taking the other treatment – a treatment that is no longer considered effective and so is rarely used.

Then they analyzed patients with 2 or more prior therapies, since that was the indication. Those Copiktra patients lived about 3 months shorter – not as bad as the larger sample, but still worrisome. Especially since 56% died during the 5 years of the study, compared to 49% assigned to the other treatment.

Adverse events caused the deaths of 15% of the Copiktra patients compared to only 3% of the other treatment group. And the percentage of Grade 3 or greater AEs was 91%, and 78% had Serious AEs–about twice as high as the comparison group. This has clear implications for quality of life, in addition to the patients not living as long.

The FDA did the right thing by requesting this post-market study. And the sponsor did the right thing by completing the study. Now is the time to listen to the results. We urge this Advisory Committee and the FDA to make it clear that approvals will be rescinded when evidence indicates that promising short-term results are reversed based on longer term data from post-market studies.

Patients and oncologists want as many treatment options as possible, but we do patients no favors by maintaining approval for a drug that does more harm than good. As was true yesterday for other cancer treatments, the preponderance of evidence is clear today.

As a cancer survivor myself, I understand the need for treatment options. I thank this committee and the FDA for its objective, scientific analysis of the data presented yesterday and today. I hope it will help everyone understand that an individual patient may seem to do well on a specific treatment, but that treatment may not be the REASON the patient did well. There are other individual differences that cause some patients to do better than others, and to live longer than others. As FDA stated, these diseases are often indolent. That’s why large, long-term randomized controlled trials are so important – to help us understand which treatments are better for which patients.

There are so many problems with the data, including the very substantial changes in treatment standards that have occurred since this study was designed, the low number of US patients, and the dearth of nonwhite patients – all these support rescinding approval for this indication.

It takes years for FDA to rescind approval unless the sponsor does the right thing by voluntarily doing so. But your vote today will be very influential.

I hope that the sponsor will conduct new research to determine if a subgroup of patients can benefit from this drug under current treatment standards, and if a lower dose is safer as well as effective, and if so FDA should of course consider approval for a different indication. But that isn’t where we are today.

Testimony of Dr. Diana Zuckerman About PEPAXTO FDA Advisory Committee Meeting on September 22, 2022

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products.  Our largest program is focused on cancer.  My expertise is based on post-doc training in epidemiology and public health, and previous positions at HHS and faculty member and researcher at Yale and Harvard.

All of us want more treatment options for refractory cancers, but we want patients to be able to have confidence that FDA approval means a product is proven safe and effective.  The OCEAN study of 495 multiple myeloma patients has important information that was not available when the drug received accelerated approval. Even if some patients taking Pepaxto do well, it is only with a randomized controlled trial that we can determine if Pepaxto is helpful or if the patients would do better without it.

Our Center’s analyses support the FDA findings that the data do not confirm the indication.  In the randomized trial comparing Pepaxto to another treatment option, median survival was 5.3 months shorter, and the death rate was slightly higher. 

The Sponsor says some patients do better but we agree with FDA that “Results from subgroup analyses cannot be used to conclude benefit in a subset of patients, when the overall patient population has shown a detrimental treatment effect.”

We also agree with the FDA that PFS is not improved and that “An anti-cancer therapy that prolongs PFS is not considered safe and effective if the therapy results in a detrimental effect on OS”

Public trust in the FDA has been weakened in recent years.  FDA standards matter to all of us.  Would you want your loved one to take Pepaxto rather than a superior treatment option?  Not all oncologists will be as knowledgeable about the data as those serving on this panel.

It concerns us that the sponsor continues to ignore FDA concerns, rely on shortcuts instead of better research, and that the company withdrew the drug in October but then rescinded the withdrawal.  Was this just a delaying tactic?  We agree with the FDA that the sponsor did not provide new data, and with Dr. Pazdur that FDA approval relies on solid information about appropriate dosage, which is lacking here.

Maybe Pepaxto would benefit some types of patients and better research is needed to prove that.  As FDA states, the preponderance of evidence from the prespecified analysis and in all other subgroups suggests an increased risk of death in patients and a potential for harm.”

We were pleased that the Committee voted 14-2 that the evidence does not support that the benefits outweigh the risks.

Joint Letter to Support FDA Proposed Rule Reducing Nicotine Levels in Cigarettes

September 12, 2022

Dr. Robert Califf
Commissioner
U.S. Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993

Re: Nicotine Standard

Dear Dr. Califf:

The undersigned public health, medical and professional organizations write in strong support of your recent announcement that FDA will issue a proposed rule to reduce the nicotine level in cigarettes to non-addictive or minimally addictive levels. Such a standard would generate massive public health benefits, preventing millions of young people from smoking and dramatically reducing the number of people who die from tobacco-caused diseases. We urge you to move forward with this proposal as quickly as possible.

Despite great progress in curbing smoking prevalence in recent years, tobacco use – primarily smoking – remains the leading cause of preventable death and disease in the United States, killing more than 480,000 Americans every year.1 Sixteen million Americans are currently living with a tobacco-caused disease.2 Over 30 million Americans currently smoke, and every day over 1,600 kids try their first cigarette.3 Approximately half of people who smoke will die prematurely as a result of their addiction, losing at least a decade of life on average compared to those who do not smoke.4

We applaud the Administration for taking action to reduce tobacco use as part of its Cancer Moonshot initiative.5 Cigarette smoking causes about 30 percent of all cancer deaths in the U.S.6 Reductions in tobacco use have already had an impact on cancer rates. According to CDC, 60 percent of the decrease in cancer death rates among men and 40 percent of the decrease among women from their peak in 1990 to 1991 until 2014 were due to declines in tobacco-related cancer deaths.7 More progress can be made and reducing nicotine levels will have a profound impact.

Nicotine is the primary addictive agent in cigarettes and other tobacco products. According to the U.S. Surgeon General, “the addiction caused by the nicotine in tobacco smoke is critical in the transition of smokers from experimentation to sustained smoking and, subsequently, in the maintenance of smoking for the majority of smokers who want to quit.”8 Thus, reducing the nicotine content in cigarettes to non-addictive or minimally addictive levels will prevent experimentation by the young from becoming a lifetime of addiction and tobacco-caused disease. It also will reduce the level of nicotine dependence in adults who smoke, making it easier for them to quit.

Current evidence establishes the potentially historic lifesaving impact of reducing nicotine content in cigarettes to non-addictive or minimally addictive levels. As you know, FDA estimated in 2018 that approximately 5 million additional adults who smoke could quit smoking within one year of implementation and, by the year 2100, more than 33 million people – mostly youth and young adults – would have avoided becoming regular smokers. Smoking rates could drop to as low as 1.4 percent, resulting in more than 8 million fewer tobacco-caused deaths through the end of the century.9 The dimensions of this public health benefit make timely implementation of this policy a moral imperative.

Reducing nicotine levels in cigarettes to achieve these enormous public health gains is technologically feasible. As FDA noted in its earlier Advance Notice of Proposed Rulemaking (ANPRM), there are a wide range of available technologies to reduce nicotine in cigarettes, including “through tobacco blending and cross-breeding plants, genetic engineering, and chemical extraction.”10 Indeed, the tobacco industry’s own documents show that the industry has a long history of manipulating nicotine levels in cigarettes to make them more addictive. As U.S. District Court Judge Gladys Kessler determined in her landmark opinion finding that the major cigarette companies had violated the federal anti-racketeering statute, “Defendants have designed their cigarettes to precisely control nicotine delivery levels and provide doses of nicotine sufficient to create and sustain addiction.”11 Surely the companies cannot now credibly maintain that they are unable to reduce nicotine levels to no longer sustain addiction. In addition, FDA has noted that recent scientific studies do not support concerns that nicotine reduction would cause people who smoke to compensate by increasing the number of cigarettes smoked or inhaling more deeply to increase nicotine intake. Studies of very low nicotine cigarettes have not found evidence of compensatory smoking but have found demonstrable reductions in cigarettes smoked per day and in exposure to harmful smoking constituents.12

To realize the full potential public health benefits of a nicotine product standard, FDA must extend that standard beyond cigarettes, to other combustible tobacco products. Exempting other combustible products would invite tobacco manufacturers to market existing, or develop new, non-cigarette substitutes, like the small, flavored cigars the industry introduced after flavored cigarettes (except menthol) were removed from the market. It also would make the exempted products a potential vehicle for youth initiation. Thus, we urge FDA to make any nicotine reduction product standard applicable to other combustible tobacco products.

Reducing nicotine in cigarettes and other combusted tobacco products will complement FDA’s proposed rules to prohibit menthol cigarettes and flavored cigars. By addressing flavors and nicotine levels, FDA will be able to target both what attracts youth to these products and what addicts them. FDA should continue its work to promptly finalize and implement the menthol cigarette and flavored cigar proposed rules. Moreover, FDA should continue to address high rates of e-cigarette use by youth by promptly completing statutorily required premarket reviews and removing from the market those products that are not “appropriate for the protection of the public health.”

Reducing the nicotine content in cigarettes and other combustible tobacco products will dramatically reduce addiction, disease, and premature death from tobacco. We applaud FDA for setting forth a bold plan to protect kids and public health and urge the agency to act quickly to complete the rulemaking process. Every day that passes means more kids moving from experimentation to addiction and more adults who want to quit, and try to quit, but remain addicted to a lethal product.

Respectfully submitted,

AASA, The School Superintendents Association
Academy of General Dentistry
Action on Smoking and Health
Allergy & Asthma Network
Alpha-1 Foundation
American Academy of Family Physicians
American Academy of Oral and Maxillofacial Pathology
American Association for Cancer Research
American Association for Dental, Oral, and Craniofacial Research
American Association for Respiratory Care
American Cancer Society Cancer Action Network
American College of Cardiology
American College of Physicians
American Dental Association
American Heart Association
American Public Health Association
American Society of Addiction Medicine
Americans for Nonsmokers’ Rights
Association for Clinical Oncology
Association for the Treatment of Tobacco Use & Dependence
Association of Black Cardiologists
Association of State and Territorial Health Officials
Asthma and Allergy Foundation of America
Campaign for Tobacco-Free Kids
Cancer Prevention and Treatment Fund
Catholic Health Association of the United States
Center For Black Equity
Children’s Health Fund
Commissioned Officers Association of the USPHS
Common Sense Media
Community Anti-Drug Coalitions of America (CADCA)
COPD Foundation
Counter Tools
Dana-Farber Cancer Institute
Emphysema Foundation of America
Family, Career and Community Leaders of America (FCCLA)
First Focus on Children
GLMA: Health Professionals Advancing
LGBTQ+ Equality
GO2 Foundation for Lung Cancer
HealthHIV
International Association for the Study of Lung Cancer
Kaiser Permanente
March of Dimes
National Alliance to Advance Adolescent Health
National Association of Hispanic Nurses
National Association of Pediatric Nurse Practitioners
National Association of School Nurses
National Association of Secondary School Principals
National Black Church Initiative
National Black Nurses Association
National Education Association
National Hispanic Medical Association
National LGBT Cancer Network
National Medical Association
National Native Network
National Network of Public Health Institutes
National Tongan American Society
North American Quitline Consortium
Oncology Nursing Society
Parents Against Vaping e-cigarettes (PAVe)
Preventing Tobacco Addiction
Foundation/Tobacco 21
Preventive Cardiovascular Nurses Association
Respiratory Health Association
SADD
Society for Cardiovascular Angiography & Interventions
The Center for Black Health and Equity
The Society for State Leaders of Health
and Physical Education
The Society of Thoracic Surgeons
Trust for America’s Health
Truth Initiative
US COPD Coalition

CC: Dr. Brian King, Director of the Center for Tobacco Products

1. HHS, The Health Consequences of Smoking – 50 Years of Progress: A Report of the Surgeon General, 2014 (2014 SG Report).
2. Id.
3. CDC, “Tobacco Product Use Among Adults—United States, 2020,” MMWR Morb Mortal Wkly Rep
2022;71:397–405, March 18, 2022, https://www.cdc.gov/mmwr/volumes/71/wr/mm7111a1.htms_cid=mm7111a1_w. Substance Abuse and Mental Health Services Administration (SAMHSA), HHS, Results from the 2019 National Survey on Drug Use and Health, NSDUH: Detailed Tables, Table 4.9A https://www.samhsa.gov/data/report/2019-nsduh-detailed-tables
4. 2014 SG Report
5. The White House, “President Biden Reignites Cancer Moonshot to End Cancer as We Know It,” Fact Sheet. February, 2, 2022, https://www.whitehouse.gov/briefing-room/statements-releases/2022/02/02/fact-sheet-president-
biden-reignites-cancer-moonshot-to-end-cancer-as-we-know-it/
6. American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society, 2022.
https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html
7. CDC, “Vital Signs: Disparities in Tobacco-Related Cancer Incidence and Mortality—United States, 2004-2013,” MMWR 65(44): 1212-1218, https://www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6544a3.pdf/.
8. 2014 SG Report.
9. Apelberg, BJ, et al., “Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States,” New England Journal of Medicine, published online March 15, 2018. See also, “Tobacco Product Standard for Nicotine Level of Combusted Cigarettes,” Advance Notice of Proposed Rulemaking, 83 Fed. Reg. 11818, 11820 (March 16, 2018)(ANPRM)
10. ANPRM, at 11820.
11. U.S. v. Philip Morris, Inc., 449 F.Supp. 2d, 1, 309 (D.D.C. 2006), aff’d in relevant part. 566 F.3d 1095 (D.C. Cir.2009).
12. ANPRM, at 11820.

Diana Zuckerman Statement on the Role of FDA in Health Inequities Meeting of the National Academy of Medicine

July 26, 2022

Thank you for the opportunity to speak today on how current FDA policies contribute to health inequities.

The National Center for Health Research is a nonprofit think tank founded in 1999 that conducts research and scrutinizes research conducted by others to evaluate medical products, procedures, and policies. We do not accept funding from companies whose products we evaluate.

There are many reasons for health inequities in the U.S., but today I will focus on one that usually gets no attention: Federal laws regarding diversity in clinical trials.

The U.S. Department of Health and Human Services requires research studies to include people representing diverse racial and ethnic backgrounds. This is not always enforced, but the requirement is in the law and NIH, CDC, SAMHSA and other agencies make an effort to abide by this law.

The one exception among federal public health agencies is the FDA, which encourages but does not require diversity in clinical trials. They justify this because the agency doesn’t pay for the studies – the companies that make the products pay for the studies. However, taxpayers do pay for FDA staff that regulate these products, and taxpayers also pay for the products themselves.

Our NCHR Study of Racial Diversity

To see the impact of the lack of a requirement for FDA, we examined 22 of the highest risk medical devices reviewed by the FDA Advisory Panels for 4 recent years. We found:

  • The number of nonwhite patients in key trials ranged from 4 (3%) to 6,788 (17%).
  • Of 19 treatment devices, only 7 had analyses for racial groups for effectiveness and only 3 for safety.
  • 69% to 99% of the patients in the studies were White. The number of nonwhites was as low as 4; 1 for Hispanics.
  • There were too few patients in most racial or ethnic groups to draw meaningful conclusions.
  • Even when subgroup analyses were conducted, their conclusions were often discredited by the FDA, blamed on chance differences due to small sample size. If there was a lack of diversity or even when racial or ethnic differences were significant, that information was were often not included on the label, which is the main source of information for physicians and patients.

    Recent Examples from the FDA

    When the FDA reviewed the data on Aduhelm for Alzheimer’s Disease, they focused on 2 studies comparing placebo to high and low dosage:

    Study 301: 8 Black patients (half of 1%) and 37 Hispanic patients (2%)
    Study 302: 11 Black patients (less than 1%) and 67 Hispanic patients (4%)

    When the FDA reviewed data on the Reducer circulatory system device for angina, they found that there were no Black or Hispanic patients, and more than 80% of the patients were White or male, or both. And yet, most patients with angina are not White males.

    Why is Diversity Important in Clinical Trials?

    Response to treatment can vary due to genetics, health habits, metabolism, body part size/shape and other factors. If you exclude certain groups, you don’t know what works best for them. Keep in mind that you need enough patients to study safety and effectiveness for patients in each group.

    Example – Lutonix drug-coated balloon catheter to open blocked arteries

    You can see on this graph that the device seemed effective compared to the control group when men and women were combined. However, you can also see that the device was only effective for men, not for women. In fact, women did better with placebo. This is an example of how evaluating safety and effectiveness for a specific demographic group can provide information that is completely different from an analysis of a diverse group as a whole.

    Shortcomings of Very Small Samples

    When the racial or ethnic group is very small, the results may not be generalizable to the larger population that those patients represent. A few outliers can have an outsized effect on the outcomes – resulting in significant differences where they do not exist. Or, real differences may be apparent but not be statistically significant because the sample lacks statistical power.

    If an analysis is conducted on a small number of patients of a particular ethnic group, any differences could easily be due to chance. For example, the graphic below shows that the new drug seems to be more effective than an older drug (40% effective compared to 30% effective) , but that difference is not statistically significant. However, if the same difference was based on a much larger sample, it would be statistically significant.

    In conclusion, when the FDA approves a medical product that has not been evaluated on a relatively large number of patients in a specific racial or ethnic group, it is not possible to conclude whether the product is safe or effective for members of that group. If the FDA does not require adequate diversity in clinical trials used as the basis for FDA approval, then the agency should only approve those products for the types of individuals studied. That precision in approval decisions would create the incentive needed for companies to improve diversity in their trials and conduct appropriate subgroup analyses.

    Reference
    1. Fox-Rawlings SR, Gottschalk LB, Doamekpor LA & Zuckerman DM. (2018) Diversity in Medical Device Clinical Trials: Do We Know What Works for Which Patients? Milbank Quarterly, Vol 96 (3) 499-529.

    Dr. Diana Zuckerman Statement to CDC Advisory Committee On Breast Cancer in Young Women

    August 23, 2022

    I’m pleased to have the opportunity to provide this statement on behalf of the National Center for Health Research. We are a nonprofit research center, and our largest program is focused on cancer prevention and treatment. I previously worked at the White House office of Science and Technology Policy, the U.S. Department of Health and Human Services, the U.S. House and Senate, Harvard, and Yale. I am also a breast cancer survivor.

    Today I want to mention an issue that hasn’t been talked about: fear. Research shows that many young women are disproportionately afraid of breast cancer and that young breast cancer survivors are more afraid of recurrence than older survivors. I encourage you to think of what we can do together to help reduce that fear so that young women don’t let their fear overwhelm them as they become aware of and educated about their risks as well as their prevention and treatment options.

    Despite their fear, few women of any age know that diet and exercise help prevent breast cancer. You’ve heard today that alcohol increases the risk of breast cancer, but did you know that drinking more than 3 alcoholic beverages per week can raise the risk of breast cancer? We all know young women who drink much more than that. We should also educate young women about the link between cancer and ultra-processed foods – I’m not just talking about the usual culprits, I’m talking about sauces and many other prepared foods that we assume are healthy when we buy them at the supermarket. In addition, being overweight or obese also increases the risk of breast cancer and of recurrence, because fat cells make more estrogen. We should be educating young women about these strategies for reducing their risks, since these are changes they can control.

    Research shows that more women undergo mastectomies and bilateral mastectomies in the U.S. than most comparable countries. And yet, research shows that early-stage breast cancer patients who undergo lumpectomy (BCT) and radiation live longer with better quality of life than early-stage mastectomy patients, and a study of more than 23,000 young women with early-stage breast cancer found that the 10-year survival rate was at least as good for BCT plus radiation as for mastectomy. Research is needed to see how outcomes vary among women with specific demographic traits and risk factors, but the research available thus far is reassuring. On a personal note, as a professional in the field, I was shocked when my breast surgeon repeatedly urged me to consider a bilateral mastectomy for Stage 1 breast cancer. I had heard from many other women who had similar experiences. I am sure women who aren’t experts in the field, and especially young women, are being influenced by that kind of pressure.

    In addition to all the other important issues raised by this committee today, I want to add that we should make sure that young women understand the difference between lifetime risk of breast cancer and their annual risk of developing breast cancer. And the difference between DCIS and invasive breast cancer. Educating young women can help reduce their fear and help enable them to take the time they need to advocate for themselves based on the information needed to make the treatment decisions that are best for them.

    One last suggestion: We’ve heard many great ideas today about the information that primary care physicians, OB/GYNs, and the public need to know about young women and breast cancer, as well as prevention and treatment strategies. Wouldn’t it be great if CDC put together an education campaign on some of these key issues, to be shown on TV so it reaches a large audience?

    Draft Senate Contact Letter for Patients Supporting User Fee legislation With Policy Riders

    [Date]

    Dear [Name of Senator],

    I am writing on behalf of myself as a cancer [patient/advocate] and constituent of the state of [add State] to convey my strong opposition to efforts to strip user fee legislation of important public health protections in favor of a “clean” user fee bill. I urge that as you work to reconcile these bills, you address urgent public health challenges by maintaining critical protections in the FDA Safety and Landmark Advancements Act (FDASLA), S. 4348.

    This legislation must include provisions that will help ensure the safety and efficacy of cancer drugs, as well as accuracy and reliability for cancer-related diagnostic tests. Accelerated approval reform is necessary to protect patients such as [myself/ my relative/other] from harmful and possibly ineffective treatments. Reform to diagnostic tests will provide the FDA with the authority and resources necessary to ensure that the highest-risk diagnostic tests are valid and reliable. Increasing numbers of patients make life-altering decisions based on diagnostic tests, which can be used to predict cancer or fetal abnormalities.

    We urge you not to forgo this key opportunity to advance long-awaited solutions for the American public. While some provisions could be strengthened still further from the Senate version, we express our continued support for the meaningful reforms contained in the bill, and hope that Congressional and committee leadership remain committed to negotiating these protections as you advance this important legislation.

    Thank you,

    [Name]

    [Affiliation if applicable]

    Who Should You Believe? A critique of the Aesthetic Society’s view of Breast Implant Illness

    By Diana Zuckerman, PhD.


    An article entitled “A Practical Guide to Managing Patients With Systemic Symptoms and Breast Implants” was published in the  Aesthetic Surgery Journal, (Volume 42, Issue 4, April 2022, Pages 397–407). This is a journal of the Aesthetic Society, which is the second largest association of plastic surgeons.  The authors are Patricia McGuire, MD, Daniel J Clauw, MD, Jason Hammer, MD, Melinda Haws, MD, and William P Adams, Jr, MD

    There are many outrageous articles denying the existence of breast implant illness, but this may be the worst since it was published after major studies documented that breast implant illness exists.  The authors are prominent plastic surgeons who are members of the Aesthetic Society and/or the American Society of Plastic Surgeons (ASPS), which are the two major associations for plastic surgeons.  All but one of the authors have financial ties to companies that make breast implants.

    The theme of the article is clearly stated in the summary: “Numerous studies have explored the possibility of an association between breast implants and systemic symptoms potentially linked to exposure to silicone. Some studies show no direct association whereas others provide insufficient scientific evidence to prove or disprove an association. Nonetheless, some patients with breast implants remain concerned about the possible role of their implants in systemic symptoms they may be experiencing. This paper provides a practical approach for plastic surgeons in managing patients with breast implants who present with systemic symptoms, including recommendations for patient counseling, clinical and laboratory assessment of symptoms, and/or referral. Integral components of patient counseling include listening attentively, providing unbiased information, and discussing the risks and benefits of options for evaluation and treatment.”

    In reality, there are numerous studies in major medical journals that show a “direct association” between breast implant illness and diagnosed diseases with similar symptoms.  But the plastic surgeons who wrote the article are saying there is no evidence.  They are also saying that since patients mistakenly think BII is real, surgeons should assure them that although BII it is not proven, research is underway to study the issue.  That gaslighting is intended to show the patients that their surgeon is open-minded.

    You might ask what is the evidence that the authors use to conclude that BII is not real?  To me as a researcher, this is the most mind-boggling part.  In addition to misquoting a 22-year old report from the Institute of Medicine – a report that is extremely outdated — and including a few individual case studies that just happen to all illustrate the authors’ view that breast implant illness isn’t real — the authors made several major errors:

    #1.  They state that “In 2019, an FDA advisory panel on breast implant safety determined that there is currently insufficient evidence of a causal relationship between breast implants and the diagnosis of rheumatologic disease or [connective tissue disease].” They footnote this statement with a document that was written by the FDA before the FDA advisory panel met in 2019 and which did not draw any such conclusions.

    #2. They state that “a number of epidemiological studies taken together are felt by many experts in the field to represent convincing evidence that there is no link between SBIs and auto-immune diseases.” The authors support that statement by listing 9 articles that they do not discuss. Almost all of the articles were funded by implant manufacturers and/or plastic surgeons, and 3 were published more than 20 years ago, based on poorly designed studies. One study was described as a study of 55,000 women, but in reality a large percentage of the patients dropped out before the study was completed.  Most outrageous of all, the last 2 studies listed actually concluded the opposite to what the plastic surgeons claimed:  The Israeli study and the Baylor study that both concluded that several autoimmune diseases with symptoms similar to BII are significantly increased after women get breast  implants.

    #3.  They mistakenly conclude that since women with saline breast implants also report BII symptoms, the symptoms are not related to the silicone shell.  This is a ridiculous statement since all breast implants have silicone shells.

    #4.  In contrast to their uncritical acceptance of poorly designed and biased studies funded by implant manufacturers and surgeons with financial ties to those implant makers, when the authors briefly mention studies showing that women with BII symptoms that improve after their implants are removed, they speculate (without evidence) that such improvement might be temporary.  It is notable that they didn’t even mention the 2021 study by Dr. Feng and her colleagues, which showed significant improvement in lung function after explant surgery.  That is no accident, since this Aesthetic Society article was published many months later.

    There are too many other careless errors in the article to list them all.  I can’t help but wonder if the authors read any of the studies they were supposedly quoting.  While urging plastic surgeons to pretend to be open-minded, the authors are anything but.  They repeatedly misrepresent research findings in order to support their biased view that the symptoms of breast implant illness are not caused by breast implants.

    In summary: This article makes it clear that the Aesthetic Society is encouraging their members to “gaslight” patients with BII, rather than help them get explanted.  Women who are seeking well-informed plastic surgeons should avoid the authors and think twice before believing anything they hear from plastic surgeons that belong to the Aesthetic Society, since the journal is published by that medical group.

    NCHR Comments on the MDUFA V Commitment Letter

    April 21, 2022

    The National Center for Health Research (NCHR) appreciates the opportunity to provide public comments on the Medical Device User Fee Amendments (MDUFA) V Commitment letter, and to express our substantial concerns with the overall process as well as the shortcomings of the Commitment letter.

    NCHR is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues and health policies, with particular focus on ensuring that treatments are safe and effective for patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

    The negotiations between the Food and Drug Administration (FDA) and medical device industry are unlike regulatory processes at other federal agencies. The typical process is more transparent and includes meaningful stakeholder engagement and feedback from the public. The fact that the very industries being regulated by the FDA meet behind closed doors with FDA staff to negotiate a Commitment Letter, with no members of the public allowed to be in the room or have access to a transcript or recording, raises important questions about why industry has more say in FDA policies and practices than other Stakeholders. We previously pointed out the lack of transparency and the lack of meeting minutes, which we were told would be publicly available – but weren’t.

    This proposed Commitment letter, although late, has already been delivered to Members of Congress. The House Energy & Commerce Subcommittee on Health held a hearing on March 30, 2022, on the contents of the proposed Commitment Letter. It seems disingenuous to request public feedback, at this week’s meeting or in writing, at this late point in the process.

    In addition to the lack of transparency in the process and lack of public representation in negotiations between FDA and the medical device industry, the Commitment Letter fails to include any performance measures specifically linked to patient safety. Given the lack of safety or effectiveness data prior to clearance or approval of more than 95% of medical devices, post-market surveillance is crucially important. And yet, the Commitment Letter provides no requirement for financial support for post-market monitoring of studies or MAUDE reports, putting patients at risk for years to come.

    Despite our lack of confidence in the FDA’s negotiated agreement with industry, below are our specific recommendations for your consideration as you finalize the MDUFA V Commitment Letter:

    1. Include performance measures tied to device safety, such as total time to recall a device following adverse event reporting.
    2. Direct any additional funds earned by FDA for meeting premarket performance goals to post-market surveillance activities.
    3. The total product life cycle advisory program (TAP) should include post-market activities to truly capture the full life cycle. This is becoming even more important as devices become more complex and technology rapidly changes. User fees should be used to support technology systems to monitor devices. Based on the description in the proposed Commitment Letter, TAP would focus on early communication with industry to troubleshoot potential issues with applications, but not to monitor the devices once they are on the market.
    4. Diversity and accessibility performance measures should be included in the proposed Commitment Letter.
      1. Industry could be provided a discount on fees if certain diversity performance goals are met in a PMA application.
      2. Industry should be required to include a detailed plan on potential device recalls. The plan should include how information will be shared with patients and what steps will be taken to ensure the information is presented in a timely manner and accessible formats.

    When Congress required that stakeholders have the opportunity to participate in the MDUFA V reauthorization process, they intended that our participation would be meaningful. This is the final opportunity for the FDA to fulfill that obligation in MDUFA V.

    Public Comment PDUFA VII Commitment Letter (Docket #FDA-2021-N-0891) From the National Center for Health Research

    October 28, 2021 


    The National Center for Health Research (NCHR) appreciates the opportunity to provide public  comments on the PDUFA VII Commitment letter, and to express our substantial concerns with the overall process, some of the content of the letter, and performance goals that should have  been made in the letter, but were not. 

    The Prescription Drug User Fee Authorization (PDUFA) negotiation between the Food and Drug  Administration (FDA) and pharmaceutical industry is unlike regulatory processes at other federal  agencies. The typical process is more transparent, and includes meaningful stakeholder  engagement and feedback from the public. The fact that the very industries being regulated by  the FDA meet behind closed doors with FDA staff to negotiate a Commitment Letter, with no  members of the public allowed to even be in the room, raises important questions about why  industry has more say in FDA policies and practices than other Stakeholders. 

    The Commitment letter submitted for public comment is even more problematic than usual  because it includes numerous policy/regulatory changes that would normally be determined by  Congress, not by a negotiation between regulated industry and a federal agency. Policy/regulatory changes should be deleted from the Commitment Letter. 

    The remainder of this comment will focus on performance goals. 

    As a public health think tank, NCHR has supported user fees as a way to improve resources for  the FDA. However, we have repeatedly expressed concerns that the performance goals being  negotiated by the FDA and industry are focused largely on the speed of the review and approval  process, as well as industry’s access to FDA staff, with no explicit metrics to measure the safety and effectiveness of the drugs that are being reviewed and approved. We support performance  goals that enable companies to communicate with the FDA early in the drug approval  process. However, the emphasis on speed has resulted in too little attention to whether the drugs  have clinically meaningful benefits for different populations of patients that outweigh the risks to  those patients. 

    One of our concerns pertaining to the performance goals is the lack of FDA oversight regarding  whether commitments to diversity that companies made to the FDA are met in the studies used  as the basis of approval or post-market studies. When there are too few older patients and racial minorities to conduct subgroup analyses, as is often the case, it has been impossible to draw  conclusions about the safety and efficacy of these drugs across the different patient populations. 

    Another major issue missing from performance goals is that the emphasis on various expedited  review pathways has resulted in FDA making approval decisions based on only one pivotal  study, and often based on a surrogate endpoint or biomarker rather than a clinical outcome that is  meaningful to patients, such as overall survival. When post-market confirmatory trials are  required, they are not monitored closely by the FDA; as a result, years pass before the studies are either abandoned or completed, often with much smaller, less diverse study populations and  higher loss to follow-up than was “required.” For example, in 2021, we learned that  several cancer drugs had been found to be ineffective in confirmatory trials, many years after  they had been approved for several specific indications under an accelerated pathway. A study recently published in JAMA Internal Medicine reported that these ineffective indications cost  Medicare more than half a billion dollars.1 Another example of potential harms from a  questionable review is the recent FDA approval of Aduhelm for Alzheimer’s patients.2 This drug  was originally approved for all Alzheimer’s patients based on a questionable biomarker studied  only in patients with mild Alzheimer’s and the FDA allowed the company 9 years to complete a  confirmatory study. Fortunately, the agency responded to public outrage by changing the  approval to only mild Alzheimer’s, since those were the only patients that had been  studied. Unfortunately, the company still has 9 years to confirm that the drug is effective, and, in  the meantime, other pharmaceutical companies are racing to submit applications based on the  same flawed biomarkers. These are just two examples of why enforcement of timely and  comprehensive post-market surveillance requirements should be required as essential  performance goals. The current version of the Commitment Letter does not do so. 

    User fees have been used previously to generously support the Sentinel program’s post-market  surveillance system; however, the impact of that system is not explained to the general  public. FDA should notify Congress and the public about how many drugs have been removed  from the market due to Sentinel data, the number and type of label revisions that resulted, and  how adverse events found through Sentinel did or did not differ for drugs approved under  various review pathways. The number of years that specific products were on the market before  Sentinel reported the need for label revisions or removal from the market should also be  calculated and widely reported as part of the performance goals. 

    User fees should also be used to improve communication with patients and caretakers, including older adults, people with disabilities, people who are not fluent in English, and those  with limited literacy skills. Information provided by the FDA should include different formats  and videos and virtual meetings should have the option for closed-captioning and American Sign  Language translation. 

    In conclusion, we believe that the Commitment Letter should delete policy/regulatory proposals  and do more to ensure the safety of patients and consumers and the scientific integrity of the  drug review process using the types of metrics we have suggested as part of the performance  goals. We appreciate the efforts of the agency to work toward those ends,  but when patients, consumers and other stakeholders are excluded from the PDUFA  negotiations, their priorities are excluded. We urge the Biden Administration to improve the  PDUFA VII Commitment Letter in the ways described in this comment. 

    For more information, please contact Dr. Diana Zuckerman at dz@center4research.org. 

     1 Shahzad M, Naci H, Wagner AK. Estimated Medicare Spending on Cancer Drug Indications with a Confirmed  Lack of Clinical Benefit after US Food and Drug Administration Accelerated Approval. JAMA Intern  Med. Published online October 18, 2021. doi:10.1001/jamainternmed.2021.5989 

    2 FDA Grants Accelerated Approval for Alzheimer’s Drug, June 07, 202. 1https://www.fda.gov/news-events/press announcements/fda-grants-accelerated-approval-alzheimers-drug