Category Archives: Policy

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

Testimony & Briefings, Uncategorized

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

Legislation, Uncategorized, ,

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

Policy, Testimony & Briefings, , ,

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

Statement by Dr. Diana Zuckerman on Sintilimab at FDA Advisory Committee on Oncologic Drugs

Testimony & Briefings, , ,

February 10, 2022

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. Our center is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products.  My expertise is based on post-doc training in epidemiology and public health, and as a faculty member and researcher at Vassar, Yale, and Harvard.  I’ve also worked at HHS and the White House, and I’m on the Board of the nonprofit Alliance for a Stronger FDA, which educates Congress about the need to support the work of the FDA.

On a personal note, I am a cancer survivor, and so I understand the pressure to find new treatments. My goal today is to be as objective as I can in evaluating the evidence regarding Sintilimab.

There are many problems with the data supporting this application, but let’s start with the first mistake:

#1: The sponsor did not consult with the FDA regarding the trial’s design or conduct.  That is almost always a big mistake, and it definitely is in this case. The result is a very inadequate trial design, including a non-representative group of patients.

#2: Most important to me, the study relied on progression-free survival as the primary endpoint.  We agree with FDA scientists that other drugs in the same class have shown highly significant improvement in overall survival. What matters most to cancer patients is how long they will live and the quality of their remaining lives, not whether or not they die of the cancer they are being treated for. So what could possibly be the justification for approving a cancer drug that is not as good as those already available for the same indication?

#3: FDA is sometimes flexible about its usual requirements, especially when there is an unmet need.  We agree with the FDA scientists that this drug does not address an unmet need, since several treatments proven to improve overall survival are already available.  This drug review therefore “does not warrant regulatory flexibility.”

#4: As you know, the data are all based on patients in China.  For the FDA to consider foreign data as the sole basis for marketing approval, the data are supposed to be applicable to the U.S. population and to U.S. medical practice. We agree with the FDA that the data presented today are neither. The population studied is not at all representative of the U.S.’s diverse population.  Equally problematic, the study’s comparative control arm was based on chemotherapy alone, and that is not consistent with the U.S. standard of care. Therefore a different control group would be needed to determine the benefits and risks of Sintilimab.

FDA notes that the studies have NOT been performed by clinical investigators of recognized competence.  And that FDA has not had enough contact with the investigators to be confident of their competence.

#5: The sponsor has proposed an additional study, but their proposed study does not address the serious design issues that have been criticized today. We agree with the FDA reviewers that this additional study does “not address the concerns regarding endpoint selection.”

In conclusion, you’ve been asked to vote on whether additional clinical trials with data applicable to U.S. patients and U.S. standard of care are necessary before a final regulatory decision is made.  I am very concerned about the inadequate informed consent for patients in the study that was conducted.  I hope you will agree that yes, additional trials are needed and they need to address all the major shortcomings of the data submitted so far before the FDA decides whether to approve it.  Overall survival is the essential endpoint, at a level that is meaningful to patients. The patients studied must be representative of U.S. patients in terms of race, age, and other key variables, and the comparison group needs to have the kind of medical care that is the standard of care in the U.S.

FDA notes that they have more than 25 applications whose studies are at least predominantly based on clinical trial data from China. Each should be evaluated on its own merits, but the FDA’s decision regarding Sintilimab should not set a precedent for FDA approval decisions of medical products that are not appropriately studied to determine the risks and benefits of patients in the U.S.

Comments on CMS’s Proposed Decision Memo on Screening for Lung Cancer with Low Dose Computed Tomography (LDCT)

Policy, Testimony & Briefings, , ,

December 17, 2021

We agree that former smokers would benefit from a higher rate of low dose computed tomography (LDCT) lung cancer screening. However, we are concerned with several major aspects of the Proposed Decision Memo’s discussion of Counseling and Shared Decision-Making.

  1. We urge CMS to amend language in the final draft of the Decision Memo to more accurately reflect the science-based evidence. The proposed memo currently reads that “Professional societies and provider groups have noted that providers have gained considerable experience and expertise and believe flexibility will reduce burden.” However, there is no evidence that providers have become better at counseling and shared decision-making regarding LDCT; on the contrary, there is evidence that there is already too much flexibility in how these discussions are framed. For example, research has found that shared decision-making conversations regarding LDCT focus on the advantages and rarely discuss the potential harms.[1] Healthcare providers spent less than a minute explaining the procedure and there was no evidence that decision aids were used. Patients deserve to make informed choices, and this is not possible under the current norms, which are too flexible. Rather than increase flexibility, CMS should provide explicit guidance for shared decision-making discussions on LDCT, such as requiring a checklist of key benefits and risks for the procedure that patients must sign after having read and discussed each point with their healthcare provider. For example, a decision-making tool could include a checklist that explains each benefit and risk in non-technical language, where the patient must initial each section to indicate that they read it, and then the physician must sign it to indicate the conversation took place, in the presence of the patient. In addition, any decision-making tool should highlight beneficiary eligibility criteria to ensure that patients who do not meet these criteria are aware that they are more likely to be harmed by LDCT screening.

 

  1. We urge that CMS maintain the requirement that shared decision-making conversations include a patient’s healthcare provider. Although research indicates that the decision-making conversations with physicians and non-physician practitioners are often inadequate, we believe the solution is to improve training for those conversations, rather than allowing health educators and others who are not healthcare experts to provide counseling and shared decision-making without the inclusion of healthcare professionals. Shared decisions regarding medical options should be made between a patient and a healthcare provider with whom they have an established relationship, which is generally their primary care physician. That is important because if there are any abnormal findings from the LDCT, it is the healthcare provider that the patient will need to follow-up with, not an educator. Shared decision making also provides an important opportunity to discuss smoking cessation options, which primary care physicians are best equipped to do. In summary, when patients engage in shared decision-making with their healthcare provider, that aids in informed decision-making while also helping ensure continuity of care. While health educators and others who are specifically trained to discuss the risks and benefits of LDCT can be an important addition to those doctor-patient conversations, spending more time with patients than physicians do and ensuring that patients clearly understand their options, they should not replace doctor-patient shared decision-making.

 

  1. We also urge that CMS reconsider its proposal to remove the specifications for the components of the shared decision-making tools. The agency justifies this change by stating that “the tools and guidance has matured since the early inception of shared decision-making.” We are not aware of evidence that the tools and guidance have matured, and ask CMS to provide guidance regarding decision-making tools that are based on peer-reviewed research-based articles.

 

  1. CMS also proposes removing the LDCT lung cancer screening registry requirement. We disagree with that proposal, since the ongoing revisions to guidance regarding LDCT screening can best be evaluated using a required registry.

As a final point, we question the assumptions that patients’ current low level of screening is a function of lack of flexibility in shared decision-making and of the criteria for eligibility. We believe it more likely that the major causes are:

  • Former smokers are aware that their smoking put them at risk of lung cancer and they are reluctant to get tested to find out they could have a fatal disease that they were warned about for years.
  • Former smokers who have friends or relatives that died of lung cancer are especially afraid of a diagnosis because they have seen the ravages of lung cancer.
  • Discussions about LDCT that extol the benefits and ignore the risks (which research indicates are typical of these conversations) are likely to be perceived as a sales pitch by skeptical patients. A more balanced conversation about what the procedure is like, the potential risks of screening, and what research says about the benefits is likely to be more effective.

NCHR firmly believes that patients deserve to make informed choices and need access to counseling and evidence-based shared decision-making tools in order to do so. For the reasons outlined above, we urge CMS to reconsider the proposed changes, to better ensure that patients receive accurate, balanced, unbiased information on whether or not they would benefit from LDCT screening.

References

  1. Brenner, A. T., Malo, T. L., Margolis, M., Lafata, J. E., James, S., Vu, M. B., & Reuland, D. S. (2018). Evaluating shared decision making for lung cancer screening. JAMA internal medicine, 178(10), 1311-1316.

Testimony of Diana Zuckerman, PhD, President of the National Center for Health Research at the FDA PDUFA Meeting, September 28, 2021

Policy, Testimony & Briefings,

I’m Dr. Diana Zuckerman, president of the National Center for Health Research, a patient-centered and consumer-oriented public health think tank.  Our Center is very involved in FDA issues pertaining to the safety and efficacy of medical products, and I appreciate the opportunity to share my views today. 

PDUFA performance measures have focused on speed, but in addition PDUFA performance measures should evaluate whether patients are protected from ineffective or unsafe products being approved!  As Commissioner, Peggy Hamburg said innovation needs to mean products are better, not just new.  The performance goals we’ve heard about today fall short, because they emphasize speed and ease of approval, not on the quality of the outcome of FDA reviews or of the outcome for the patients using these products.  

PDUFA have resulted in more and faster approvals, but not all those approvals have helped patients, and some have seriously harmed them.

Premarket performance should also include evaluations of the percentage of applications that were rejected or withdrawn because there was a lack of evidence proving safety or efficacy.  And the specific reasons why they were rejected or withdrawn.

When post-market surveillance works, it should sometimes result in FDA warnings, recalls, or withdrawals.  FDA should provide the percentage of these for 5 years post approval and the reasons for those actions.

Performance should also include the percentage of products approved based on at least two well-designed studies providing solid scientific evidence.  As someone trained in epidemiology, I love big data, but since most applications are for new products not yet on the market, clinical trials will still be the best data available.  We want to know how many approvals were based on at least two phase 3 randomized, controlled trials demonstrating robust evidence of safety and efficacy and favorable benefit-risk profiles.

Performance should also be based on the percentage of approved products for which FDA mandated post-marketing studies and the percentage where those obligations were fulfilled – started and ended on time, conducted as required, and whether they did or did not confirm safety and efficacy.  As you know, FDA recently had a meeting on widely used cancer drugs that were approved for certain indications through accelerated approval but failed to provide data confirming that they worked for those types of cancer.  And yet the indications remained approved for years after it was obvious they did not work.  Those delays are harmful to patients and should be considered a performance goal worthy of user fee support.  

A newly published study indicates that too often a rejected application is subsequently resubmitted and approved when FDA ignores their own criticisms of the original application, even when those criticisms remain valid.  The controversial approval of Aduhelm is just the most salient example of that.

 Specific Changes to Commitment Letter

I have a general concern about the Commitment letter, because it changes policies that should be publicly debated by Congress and should include input from patient, consumer and public health advocates as part of any negotiations. Policies should not be negotiated behind closed doors at meetings that exclude those important perspectives.  

I have time to recommend 5 specific changes to the Commitment letter:

  1.   I was glad to hear about FDA’s new efforts to include patient preferences and involvement. The Commitment letter should specify that these activities should always include harmed patients, not just patients recruited by industry, who are often patients desperate for treatment.  All patient perspectives are important, we all are concerned about patients who urgently need a treatment that works, but harmed patients have too often been excluded from FDA meetings and committees.
  2.   Voluntary REMS strategies are rarely proven to work. The REMS program needs a complete overhaul or REMS should be avoided. Instead, most safety concerns should be resolved before products are approved. A good example is the REMS for prescription opioids, which FDA learned was not working. Few doctors took the voluntary training, fewer finished the voluntary training, and even those who were trained did not learn all the important issues that were included.
  3.   The letter should implement the National Academies’ public health framework for regulatory oversight of opioids.
  4.   In-person manufacturing inspections remain the most effective way to determine problems. We all understand that remote inspections were needed during the pandemic, but the Commitment letter should specify that remote inspections should be the exception.
  5.   User fees should fund independent, objective studies to assess and quantify the harms that resulted or were avoided due to approval decisions.

And I will just add one other issue, since enhancements to the Sentinel program were discussed earlier in this meeting.  I have been a strong supporter of the Sentinel post-market surveillance program, but it has been in place for years and cost an enormous amount of money.  So, it was distressing to hear this morning that the FDA is still trying to figure out how to use those data so that they can provide usable information about safety and efficacy.

In conclusion, those of us who respect and admire the FDA know how important it is as a public health agency. We must make sure that industry user fees do not interfere with that essential mission. When performance goals and the Commitment letter are made behind closed doors, it is difficult for the public to have confidence that the FDA is a public health agency.

NCHR’s Statement to FDA Advisory Committee Meeting on Neurological Devices

Policy, Testimony & Briefings,

June 3, 2021

I’m Dr. Diana Zuckerman, president of the National Center for Health Research.  Our center is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products.  Today I’m speaking from my perspective as a scientist trained in epidemiology and public health who left Harvard more than 30 years ago to come to Washington D.C. to work in the House of Representatives. I worked as a Congressional investigator for the Subcommittee that conducted oversight over all of HHS, and that’s when I first learned about the laws and regulations governing the FDA.  I was responsible for several oversight hearings that attracted enormous media attention, because we found that patients had been harmed when the FDA was not following the law pertaining to FDA regulation of medical devices.

The law states that devices must be reasonably safe and effective.  It’s not exactly clear what reasonably safe or reasonably effective means, and often the FDA states that if they have reason to believe that similar devices are reasonably safe and reasonably effective, that’s good enough.  The special controls for Class II devices that the FDA has suggested for devices you’re reviewing today and tomorrow provide some evidence that the devices will work as intended and will be reasonably safe, but the general controls for Class I devices do not.

Neurological devices are important, and some of these devices are somewhat complex.  Obviously something called a “barf band” is not a complicated device, and it is an example of an acupressure device that costs only about $10, but if the goal is to prevent nausea and vomiting, and the company wants to sell it in the U.S., shouldn’t it be proven to work, like any other neurological device?  And some of those devices cost $20 or $30 or even over $200.   Just because the risks are small should not make it OK for FDA to let companies sell devices that are not effective if used as directed.  The standards for medical devices should be higher than the “let the buyer beware” standards of dietary supplements – which are basically nonexistent standards.

I was reassured that there are randomized controlled trials on many of the devices you’ll be reviewing today and tomorrow, but there are many different companies making many different versions of these devices, so the fact that some are shown to work doesn’t mean that they all work!  For example, when  chemotherapy patients want to reduce nausea and vomiting, they want to know if one of these acupressure devices is more effective than others.  And even when some devices are shown to work in a randomized controlled trial, that definitely doesn’t tell us that a new, similar device made by these same companies or any other companies will be safe and will be effective.  

The FDA has a reputation as the gold standard for safe and effective medical products, but that standard has been tarnished when patients are shown to be harmed in recent documentaries and in TV programs on during prime time this week.

I respectfully urge you to urge the FDA to up their game, by regulating all these neurological devices as Class II, and requiring the kind of meaningful evidence for new devices that we would want for any device that we use as health professionals, as patients, or as consumers.

Thank you for the opportunity to speak today.  I appreciate your service on this panel and look forward to hearing your discussion of these devices.

NCHR Written Statement for North Salem Central School District Board of Education

Policy, , , , , , ,

May 12, 2021

Dear Dr. Freeston and the North Salem Central School District Board of Education:

As president of the National Center for Health Research, I want to share the information we have provided to Members of Congress, state and federal agencies, state and local legislators, parents, and others who want to ensure that our children are not exposed to dangerous chemicals or other substances when they play on artificial turf or playgrounds. Our nonprofit think tank is located in Washington, D.C. Our scientists, physicians, and health experts conduct studies and scrutinize research conducted by other experts in the field. Our goal is to explain scientific and medical information that can be used to improve public health.

Our organization has been testifying and writing about the dangers of synthetic turf and playground surfaces for several years.  Our scientific staff has reviewed all publicly available scientific studies pertaining to the health impact of the lead and chemicals that are in artificial turf and playground surfaces, compared to natural surfaces such as grass and engineered wood fiber.

In the last year, scientists have reported finding potentially dangerous levels of lead in artificial turf fields and playground surfaces.  In addition, plastic grass and synthetic rubber are made with different types of hormone-disrupting chemicals, some of which are known to be particularly harmful to growing children.  Scientists at the National Institute of Environmental Health Sciences, which is an institute of NIH, have concluded that these chemicals can be threats to health even at low levels.

Manufacturers and advocates for synthetic turf often state that artificial turf has been declared safe by federal authorities.  That is completely untrue.  It is essential to understand that there are no federal requirements for safety testing of these synthetic turf products before they are sold. The EPA and the federal Consumer Product Safety Commission are jointly studying the chemicals used in these products, but they have not yet released any data on studies of children exposed to these fields and playgrounds day after day and week after week.

There is a dangerous trend of replacing natural fields and playground surfaces with materials that are dangerous to our children’s health, potentially dangerous to adult fertility and health, and bad for our environment.  In the last year, we’ve learned new information about lead and PFAS in artificial turf, as well as the risks of some of the newer infill materials that turf companies are using to replace tire crumb.

The “plastic grass” itself has dangerous levels of lead, PFAS, and other toxic chemicals.  PFAS are of particular concern because they are “forever chemicals” that get into the human body and are not metabolized, accumulating over the years. As I mentioned in an NPR interview this week1, new research published in the prestigious Journal of the National Cancer Institute found that people with greater exposure to PFAS are significantly more likely to be diagnosed with kidney cancer.2  Previous research suggests that testicular cancer is also associated with PFAS.

Lead

The American Academy of Pediatrics states that no level of lead exposure is safe for children, because lead can cause cognitive damage even at low levels.  Some children are even more vulnerable than others, and that can be difficult or even impossible to predict. You may have been told that lead is only a problem for artificial turf made with tire crumb infill, but that’s not correct. The Centers for Disease Control and Prevention (CDC) warns that the “plastic grass” made with nylon or some other materials also contain lead.  The lead doesn’t just stay on the surface.  With wear, the turf materials turn to dust that is invisible to the eye but that children are inhaling when they play.

Why are Chemicals that are Banned from Children’s Toys Allowed in Artificial Turf and Rubber Playground Surfaces?

There are numerous studies indicating that endocrine-disrupting chemicals found in plastic cause serious health problems. As noted above, scientists at the National Institute of Environmental Health Sciences have concluded that unlike most other chemicals, these hormone-disrupting chemicals can be dangerous at very low levels, and the exposures can also be dangerous when they combine with other exposures in our environment.

That is why the U.S. Consumer Product Safety Commission has banned numerous endocrine-disrupting chemicals from toys and products used by children. The products involved, such as pacifiers and rubber duckies, are banned even though they would result in very short-term exposures compared to artificial turf or playground surfaces.

A report warning about possible harm to people who are exposed to hormone disrupting chemicals at work explains that these chemicals “can mimic or block hormones and disrupt the body’s normal function, resulting in the potential for numerous health effects… Similar to hormones, EDC [endocrine disrupting chemicals] can function at very low doses in a tissue-specific manner and may exert non-traditional dose–response because of the complicated dynamics of hormone receptor occupancy and saturation.”3

Studies are beginning to demonstrate the contribution of skin exposure to the development of respiratory sensitization and altered pulmonary function. Not only does skin exposure have the potential to contribute to total body burden of a chemical, but also the skin is a highly biologically active organ capable of chemical metabolism and the initiation of a cascade of immunological events, potentially leading to adverse outcomes in other organ systems.

Envirofill and Other Alternative Infills

Replacing tire waste with silica, zeolite, and other materials also has substantial risks because the dust from these materials can be inhaled.

Summers in New York can get hot.  Even when the temperature is a pleasant 80 degrees Fahrenheit, artificial turf and playground surfaces can reach 150 degrees or higher.  Obviously, turf and playground surfaces are likely to be even hotter than 150 degrees on a sunny 90 degree day.  That can cause “heat poisoning” as well as burns.

Envirofill artificial turf fields are advertised as “cooler” and “safer,” but our research indicates that these fields are still at least 30-50 degrees hotter than natural grass. Envirofill is composed of materials resembling plastic polymer pellets (similar in appearance to tic tacs) with silica inside. Silica is classified as a hazardous material according to OSHA regulations, and the American Academy of Pediatrics specifically recommends avoiding it on playgrounds. The manufacturers and vendors of these products claim that the silica stays inside the plastic coating.  However, sunlight and the grinding force from playing on the field breaks down the plastic coating. For that reason, even the product warranty admits that only 70% of the silica will remain encapsulated. The other 30% can be very harmful as children are exposed to it in the air.

In addition, the Envirofill pellets have been coated with an antibacterial called triclosan.  Triclosan is registered as a pesticide with the EPA and the FDA has banned triclosan from soaps because manufacturers were not able to prove that it is safe for long-term use.  Research shows a link to liver and inhalation toxicity and hormone disruption.  The manufacturer of Envirofill says that the company no longer uses triclosan, but they provide no scientific evidence that the antibacterial they are now using is any safer than triclosan.  Microscopic particles of this synthetic turf infill will be inhaled by children, and visible and invisible particles come off of the field, ending up in shoes, socks, pockets, and hair.

In response to the concerns of educated parents and government officials, other new materials are now being used instead of tire crumb and other very controversial materials.  However, all the materials being used (such as volcanic ash, corn husks, and Corkonut) have raised concerns and none are proven to be as safe or effective as well-designed grass fields.

Despite claims to the contrary, no independent studies have demonstrated that artificial turf is safe.  Although the Trump Administration’s EPA stated that there was no conclusive evidence that the levels of chemicals in artificial turf was harmful to children, they made it clear that their research was based on assumptions about likely exposures rather than scientific research on children.

Scientific Evidence of Cancer and Other Serious Harm

It is essential to distinguish between evidence of harm and evidence of safety. Like the Trump Administration’s EPA, companies that sell and install artificial turf often claim there is “no evidence children are harmed” or “no evidence that the fields cause cancer.” This is often misunderstood as meaning the products are safe or are proven to not cause harm. Neither is true.

It is true that there is no clear evidence that an artificial turf field has caused specific children to develop cancer. However, that statement is misleading because it is virtually impossible to prove any chemical exposure causes one specific individual to develop cancer. As an epidemiologist, I can also tell you that for decades there was no evidence that smoking or Agent Orange caused cancer.  It took many years to develop that evidence, and the same will be true for artificial turf.

I have testified about the risks of these materials at hearings of the U.S. Consumer Product Safety Commission and state and local agencies.  At these hearings, I am sorry to say that I have repeatedly seen and heard scientists paid by the turf industry and other turf industry lobbyists say things that are absolutely false, most recently at a hearing in a Connecticut community. They claim that these products are proven safe (not true) and that federal agencies have stated there are no health risks (also not true).

On the contrary, we know that the materials being used in artificial turf contain carcinogens, and when children are exposed to those carcinogens day after day, week after week, and year after year, they increase the chances of our children developing cancer, either in the next few years or later as adults.  That should be adequate reason not to install them in your community.  That’s why I have spoken out about the risks of artificial turf in my community and on a national level.  The question must be asked: if they had all the facts, would families choose to spend millions of taxpayer dollars on fields that are unhealthy and unsafe rather than well-designed natural grass fields?

Dangerously Hard Fields and Injuries From Turf

Artificial turf fields get hard over time, and this can cause brain injuries and other injuries.  Turf companies recommend annual tests at 10 locations on each turf field, using something called a Gmax scores.  A Gmax score over 200 is considered extremely dangerous and is considered by industry to pose a death risk.  However, the synthetic turf industry and ASTM (American Society for Testing and Materials), suggest scores should be even lower — below 165 to ensure safety comparable to a grass field.  Do you want to pay to have those tests conducted annually on artificial turf fields, and replace a relatively new field that fails the test?

The hardness of natural grass fields is substantially influenced by maintenance, rain and other weather; if the field gets hard, aeration water will make it safe again.  In contrast, once an artificial turf field has a Gmax score above 165, it needs to be replaced because while the scores can vary somewhat due to weather, the scores will inevitably get higher because the turf will get harder.  Gmax testing involves testing 10 different areas of a playing fields, to make sure all are considered safe.  Some officials average those 10 scores to determine safety; however, experts explain that is not appropriate.  If a child (or adult) falls, it can be at the hardest part of the field, which is why safety is determined based on each area tested.

Any child who plays on artificial turf knows about “turf burns” that can be very painful and can get infected, but other injuries are even more serious. A study of more than 2,000 young female soccer players from 109 teams over the course of a season found that ankle sprains were almost twice as likely on turf compared to natural grass.4 Knee injuries are also much more likely on artificial turf.  A 10-year study of 5 different types of knee injuries on grass compared to artificial turf was conducted across all 3 divisions of NCAA football. They found that posterior cruciate ligament (PCL) tears occurred almost 3 times as often on turf than on grass.5 Athletes playing at lower levels experienced anterior cruciate ligament (ACL) tears 1.6 times more often on turf than they did on the grass.  This issue persists at the professional level as well, which is why the National Football League’s Player Association demanded artificial turf fields be replaced with natural grass, citing the league’s official report regarding increases in injuries on artificial turf surfaces. The report showed non-contact knee injuries happened 32% more often on turf.6

Environmental Issues

In addition to the health risks to school children and athletes, approximately three tons of infill materials migrate off of each synthetic turf field into the community environment each year.  About 2-5 metric tons of infill must be replaced every year for each field, meaning that tons of the infill have migrated off the field into grass, water, and our homes.  The fields also continuously shed microplastics as the plastic blades break down.7,8 These materials may contain additives such as PAHs, flame retardants, UV inhibitors, etc., which can be toxic to marine and aquatic life; and microplastics are known to migrate into the oceans, food chain, and drinking water and can absorb and concentrate other toxins from the environment.9,10,11

Synthetic surfaces also create heat islands.12,13  In contrast, organically managed natural grass saves energy by dissipating heat, cooling the air, and reducing energy to cool nearby buildings.  Natural grass and soil protect groundwater quality, biodegrade polluting chemicals and bacteria, reduce surface water runoff, and abate noise and reduce glare.14

Conclusions

There have never been any safety tests required prior to sale that prove that any artificial turf products are safe for children who play on them regularly.  In many cases, the materials used are not publicly disclosed, making independent research difficult to conduct.  None of these products are proven to be as safe as natural grass in well-constructed fields.

I have cited several relevant scientific articles on artificial turf in this letter, and there are numerous studies and growing evidence of the harm caused by these synthetic materials.  I would be happy to provide additional information upon request (dz@center4research.org).

I am not paid to write this statement.  I am one of the many parents and scientists who are very concerned about the impact of artificial fields on our children.  I’m sure you agree that it is important that decisions are based on scientific evidence, not on sales pitches by individuals with conflicts of interest.

Officials in communities all over the country have been misled by artificial turf salespeople. They were erroneously told that these products are safe.  But on the contrary, there is clear scientific evidence that these materials are harmful.  The only question is how much exposure is likely to be harmful to which children?  We should not be willing to take such a risk.  Our children deserve better.

 

Sincerely,

Diana Zuckerman, Ph.D.

President

 

References

  1. Vega, T., & Zuckerman, D. (May 10, 2021). The Role of Environmental Regulations in the Fight Against Cancer. The Takeaway. New York City, New York; WNYC.
  2. Shearer, JJ et al, Serum Concentrations of Per- and Polyfluoroalkyl Substances and Risk of Renal Cell Carcinoma. 2021; JNCI: Journal of the National Cancer Institute, Volume 113, Issue 5, , Pages 580-587, https://doi.org/10.1093/jnci/djaa143
  3. Anderson SE and Meade BJ. Potential Health Effects Associated with Dermal Exposure to Occupational Chemicals. Environmental Health Insights. 2014; 8(Suppl 1):51–62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270264/
  4. Steffen, K., Andersen, T. E., & Bahr, R. Risk of injury on artificial turf and natural grass in young female football players. British Journal of Sports Medicine. 2007; 41 Suppl 1(Suppl 1), i33–i37. https://doi.org/10.1136/bjsm.2007.036665
  5. Loughran, G. J., Vulpis, C. T., Murphy, J. P., Weiner, D. A., Svoboda, S. J., Hinton, R. Y., & Milzman, D. P. Incidence of Knee Injuries on Artificial Turf Versus Natural Grass in National Collegiate Athletic Association American Football: 2004-2005 Through 2013-2014 Seasons. The American journal of sports medicine.2019;47(6), 1294–1301. https://doi.org/10.1177/0363546519833925
  6. Dulik, Brian. NFLPA asking teams to change all fields to natural grass. AP News. September 20, 2020. https://apnews.com/article/nfl-football-archive-9b34d4402f2f82ae60708605f65aa560
  7. Magnusson K, Eliasson K, Fråne A, et al. Swedish sources and pathways for microplastics to the marine environment, a review of existing data. Stockholm: IVL- Swedish Environmental Research Institute. 2016. https://www.naturvardsverket.se/upload/miljoarbete-i-samhallet/miljoarbete-i-sverige/regeringsuppdrag/utslapp-mikroplaster-havet/RU-mikroplaster-english-5-april-2017.pdf
  8. Kole PJ, Löhr AJ, Van Belleghem FGAJ, Ragas AMJ. Wear and tear of tyres: A stealthy source of microplastics in the environment. International Journal of Environmental Research Public Health. 2017;14(10):pii: E1265. https://www.ncbi.nlm.nih.gov/pubmed/29053641/
  9. Kosuth M, Mason SA, Wattenberg EV. Anthropogenic contamination of tap water, beer, and sea salt. PLoS One. 2018,13(4): e0194970. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895013/
  10. Oehlmann J, Schulte-Oehlmann U, Kloas W et al. A critical analysis of the biological impacts of plasticizers on wildlife. Philosophical Transactions of the Royal Society B. 2009;364:2047–2062. http://rstb.royalsocietypublishing.org/content/364/1526/2047
  11. Thompson RC, Moore CJ, vom Saal FS, Swan SH. Plastics, the environment and human health: Current consensus and future trends. Philosophical Transactions of the Royal Society B. 2009;364:2153–2166. https://royalsocietypublishing.org/doi/full/10.1098/rstb.2009.0053
  12. Thoms AW, Brosnana JT, Zidekb JM, Sorochana JC. Models for predicting surface temperatures on synthetic turf playing surfaces. Procedia Engineering. 2014;72:895-900. http://www.sciencedirect.com/science/article/pii/S1877705814006699
  13. Penn State’s Center for Sports Surface Research. Synthetic turf heat evaluation- progress report. 012. http://plantscience.psu.edu/research/centers/ssrc/documents/heat-progress-report.pdf
  14. Stier JC, Steinke K, Ervin EH, Higginson FR, McMaugh PE. Turfgrass benefits and issues. Turfgrass: Biology, Use, and Management, Agronomy Monograph 56. American Society of Agronomy, Crop Science Society of America, Soil Science Society of America. 2013;105–145. https://dl.sciencesocieties.org/publications/books/tocs/agronomymonogra/turfgrassbiolog

NCHR Statement at FDA Advisory Committee Meeting on Keytruda and Tecentriq for Advanced Urothelial Carcinoma

Policy, Testimony & Briefings

April 28, 2021

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. Our center is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products.  I am trained in statistics, clinical trial design, epidemiology, and public health and was a faculty member and researcher at Yale and Harvard and a Fellow in Bioethics at Penn.  I’ve also worked at HHS. 

The details differ but in both cases our statistical and research analyses support the FDA findings that the data do not confirm the indication.

That’s especially important because both Tecentriq and Keytruda cause substantial adverse events and an alternative treatment has shown clear benefit!

FDA grants accelerated approval with requirements for post-market RCTs to evaluate overall survival to ensure clinically meaningful benefit.  But the randomized clinical trials conducted did NOT show benefit. How could FDA continue to offer accelerated approval for any drugs in the future if post-market RCTs results are ignored?

Most of you are clinicians and you’re used to trying different types of treatment in hopes that something will work. But the rules for FDA approval are different.  Shouldn’t cancer patients be eligible for free treatments in clinical trials instead of paying for treatment that isn’t proven to work – and that has risks?

Can other studies be used to confirm the indication?  FDA explained the problems very clearly.

  • Not appropriate to use studies with data based on patients that aren’t for the same indication:

      #1) PD-L1 high and

      #2) not eligible for cisplatin or other options.

NCHR Statement Regarding Cancer Drugs that Failed to Confirm Efficacy after Accelerated Approval

Policy, Testimony & Briefings, , ,

April 29, 2021

I’m Dr. Diana Zuckerman, president of the National Center for Health Research.  Our center is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products.  Today I’m speaking from my perspective as a scientist who left Harvard more than 30 years ago to come to Washington D.C. to work in the House of Representatives. I worked as a Congressional investigator for the Subcommittee that conducted oversight over all of HHS, and that’s when I first learned about the laws and regulations governing the FDA.  I was responsible for several oversight hearings that attracted enormous media attention, because we found that patients had been harmed when the FDA was not following the law pertaining to FDA approval.

The law is very clear:  Drugs and biologics must be proven safe and effective, and that’s defined as having benefits that outweigh the risks for most patients.  FDA’s memoranda that were provided to this Committee for this meeting and for each of these indications over these last 3 days have made it clear that the data do not support that.  This Advisory Committee has looked at the data, seen reasons for optimism when looking at nonsignificant trends, and recommended that the FDA keep drugs on the market that don’t meet the standard specified by law.  That’s your right to do that, since you are advising the FDA based on your perspectives, experiences, and interpretations of the data.

I want to thank the FDA scientists who carefully analyzed the data and presented their findings.  You did a great job.  I’m here to urge the FDA to follow in your footsteps and follow the law and rescind approval for these indications until the companies complete randomized clinical trials that prove that the benefits outweigh the risks. I especially want to thank Dr. Pazdur for explaining how the FDA’s Expanded Access program can fill in the gaps for patients who need access to these drugs.  The companies agreed to complete confirmatory trials as part of the accelerated approval of their drugs, and I strongly urge the FDA to hold them to it.

All of these companies are leaders in their field and absolutely capable of conducting the research needed to prove whether or not their drugs have benefits that outweigh the risks for the exact specific indications they were previously approved for.  The companies also have the ability to make expanded access quick and easy.  Let’s face it, if they don’t have the expertise and resources to do the studies and help with expanded access, who does?  If the data don’t confirm the initial accelerated approval, the companies should work with the FDA to design trials to narrow the indication to figure out which are the patients most likely to be helped and which are the ones most likely to be harmed.