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Are PIP rubber playgrounds safe for Kingston?

We're In the News

Dr. Diana Zuckerman, PH.D, Kingston Wire, October 23, 2023

When I first saw rubber playground surfaces under swings, slides, and children’s climbing equipment, I was impressed.  They seemed very attractive and safe for active young children. I was wrong. As a scientist I learned that children all over the country are being exposed to unsafe chemicals without their parents’ knowledge or consent.  That’s why I recently wrote to Kingston’s mayor, superintendent of schools, members of the Board of Education, and numerous principals to share scientific information about the lead and dangerous chemicals in artificial turf and playground surfaces, hoping it will help them make the right decisions about what is best for Kingston’s children.  I want to share that information with you.

As president of the National Center for Health Research, I have testified about these products to local, state and federal agencies and legislators and met with parents and community leaders from coast to coast. Our nonprofit think tank includes scientists, physicians and health experts who conduct studies and scrutinize research conducted by others. We explain scientific and medical information that can be used to improve policies, programs, services and products.

What’s in those rubber playground surfaces?

In recent years, scientists have learned about the lead, cadmium, PFAS, and other chemicals that are in the rubber playground surfaces called PIP (Poured in Place) and recycled tire mulch (also called recycled rubber, since that sounds even more environmentally friendly).  We now know that the rubber pieces made from recycled tires contain lead and heavy metals, as well as chemicals that increase the chances of developing obesity; early puberty; attention problems such as ADHD; exacerbate asthma; and eventually cause cancer. Although I’m focusing on playground surfaces, recycled rubber is also used as “infill” for many artificial turf fields and also the rubber mulch sold for your lawn at Home Depot and many other stores.  (The plastic grass that makes up artificial turf also has dangerous levels of lead, PFAS, and other toxic chemicals.)

Pediatricians tell us that no level of lead exposure is safe. The solid rubber surface used on playgrounds looks safe, but whether or not the top is made from recycled tires, underneath is recycled tire crumb that causes lead dust on top of the surface. Children breathe that lead dust as they play.  And, after a few months or years, the solid rubber surface wears off or cracks, revealing small pieces of recycled tires that young children (like those at George Washington Elementary School’s Children’s House) may be tempted to put in their mouths, exposing them to even more lead. Blood lead levels for Kingston residents are already higher than in most communities. That makes it especially essential to avoid additional exposures.

The PFAS in tire mulch are also dangerous because they enter the body and the environment as “forever chemicals.” PFAS are not metabolized and won’t deteriorate, accumulating over the years. PFAS can cause liver damage and other serious health problems. That’s why Governor Kathy Hochul signed a law this year banning PFAS from clothing and carpeting (they are used to make them stain resistant), including the plastic grass carpet used in artificial turf fields, such as the one at Dietz Stadium. Unfortunately, PFAS is not banned from rubber playgrounds, such as PIP.

There are also environmental risks from these materials. They retain heat, so that on a warm sunny day when the temperature above the grass is 85 degrees, it is often over 150 degrees for anyone on PIP and artificial turf fields. And, during heavy rains, the tire mulch washes off, contaminating nearby areas and your water supply.

Evidence of Harm vs. Evidence of Safety

Scientists at the National Institute of Environmental Health Sciences (which is part of NIH) have concluded that unlike most other chemicals, hormone-disrupting chemicals (found in tire mulch and artificial turf) can be dangerous at very low levels, and also when they combine with other exposures in our environment.  That is why the U.S. Consumer Product Safety Commission has banned these chemicals from toys, pacifiers, teething toys and other products used by young children.

Companies that sell and install artificial turf and rubber playground surfaces often claim that there is “no evidence children are harmed” or that their products 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 tell you that for many years there was no evidence that smoking or 9/11 exposures caused cancer. It took many years to develop that evidence, and the same will be true for products made from recycled tires.

We know that these materials contain carcinogens. When children are exposed to those carcinogens day after day, week after week, and year after year, it increases 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.

What Should Kingston Do? 

There have never been any safety tests required prior to sale that prove that any of these 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 engineered wood fiber or natural grass in well-constructed fields.

Officials in communities all over the country have been misled by salespeople and scientists hired to lobby them to purchase these fields and playgrounds. They were erroneously told that these products are safe. In fact, there is clear scientific evidence that these materials are harmful. How much exposure is likely to be harmful to which children? Do you want to take that risk with your children? Don’t our children deserve better?

I am not paid to write this or speak up on this issue. I do so because I care about the health of my family and yours.

This oped is posted on the Kingston Wire website at https://kingstonwire.com/opinions/2023/10/23/opinion-are-pip-rubber-playgrounds-safe-for-kingston/361KUj and you can read a pdf version of the article here.

We Comment to FDA on the Draft Guidance Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act

Legislation

September 12, 2023

Docket No. FDA-2023-D-0559

We appreciate the opportunity to comment on the Food and Drug Administration (FDA) proposed guidance: Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act Guidance for Industry.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which 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.

Noncompliance with required post-market studies (PMRs) is a serious problem that undermines FDA’s authority and the public trust in FDA decision-making. We support FDA’s efforts to ensure clarity and transparency regarding situations when noncompliance with postmarket requirements is acceptable.  These situations should be rare; the more exceptions that are made, the more noncompliance becomes harmful to patients and unfair to companies that comply.

The PMRs that are the focus of this draft guidance are typically required following adverse events that have been reported to the FDA resulting in a serious enough event to warrant further examination into the safety and effectiveness of the drug. Any delay in this process places patients at undue risk and it is FDA’s responsibility to ensure that applicants avoid delays.

We understand this guidance document is specifically referencing non-compliance of PMRs which are not required as a condition of accelerated approval. However, we strongly recommend issuing similar guidance for applicants using this pathway.

We agree that applicants should continue to report regular updates to the FDA throughout the completion of the PMRs. The timelines and milestones established are agreed to by both the applicant and the FDA and should be adhered to. We appreciate the detail provided by FDA in the draft guidance stressing the importance of maintaining regular updates and providing multiple opportunities for applicants to inform the agency of missed milestones. These details, along with specific examples of what would or would not be considered good cause for non-compliance, should minimize overall non-compliance with the regulations. Documentation of delays is not sufficient to justify noncompliance, especially if the delays were foreseeable and avoidable and could suggest inadequate efforts to complete the study as was agreed to.

We support the process described in the guidance for applicants to correct circumstances that led to non-compliance with the agreed upon PMRs; however, we urge that the description of the actions taken by the applicant to address these issues be more explicit and less subjective. The guidance document states that the “FDA considers an applicant to have undertaken appropriate action if the applicant promptly develops and implements a reasonable plan to correct the underlying circumstance(s) leading to the PMR noncompliance” (emphasis added). The guidance document describes the term “promptly” as something the FDA will determine on a case-by-case basis. This is too vague; the FDA should clearly define the agency’s standards by providing examples of what could be considered inappropriate delays that will warrant escalation of actions taken by the agency. We also strongly urge that the FDA take into consideration if a company has a track record of delays in satisfying PMRs, regardless of whether the company’s justifications for those delays seem reasonable. The FDA should scrutinize the reasons given to determine if a company’s track record of delays show a pattern of making commitments to the FDA that the company has shown it is unlikely to meet. This would indicate that what might individually seem like justifiable delays may instead be based on a pattern of foreseeable and preventable delays.

As noted above PMRs which are required as a condition of accelerated approval warrant similar guidance. There have been unacceptable delays in postmarket trials for drugs granted accelerated approval status. More than 280 drug applications have been awarded accelerated approval since the program began; at least 100 of those applications still have incomplete confirmatory trials.1 Approximately 35 percent have at least one trial past its original planned completion date.1 A recently published journal article pointed out that Exondys 51, for Duchenne Muscular Dystrophy, was granted accelerated approval in 2016 with the PMR results required in 2020. Instead, that post-market study was not started until 2020 and FDA granted an extension until 2024, while also granting accelerated approval to 3 other drugs made by the same company, none of which have yet submitted their post-market studies.2 As a result of these delays, patients, insurance companies, and the Medicaid program have paid billions of dollars for treatments that have never been proven to work. This is unfair to patients and their families and threatens the financial integrity of Medicaid programs in States that have been subject to these expenses. We strongly urge that the FDA issue guidance about compliance with PMR for drugs granted accelerated approval before the end of 2023.

1.U.S. Department of Health and Human Services: Office of Inspector General. (2022). Delays in Confirmatory Trials for Drug Applications Granted FDA’s Accelerated Approval Raise Concerns. https://oig.hhs.gov/oei/reports/OEI-01-21-00401.asp#:~:text=WHAT%20WE%20FOUND,104%20have%20incomplete%20confirmatory%20trials.

2. Liam Bendicksen, Diana M. Zuckerman, Jerry Avorn, et al. (2023). The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence. Ann Intern Med. doi:10.7326/M23-1073

Our Comments on Insanitary Conditions in the Preparation, Packing, and Holding of Tattoo Inks and the Risk of Microbial Contamination FDA Draft Guidance

Environmental Exposures, Policy

September 11, 2023

We appreciate the opportunity to comment and support FDA’s proposed rule regarding: “Insanitary Conditions in the Preparation, Packing, and Holding of Tattoo Inks and the Risk of Microbial Contamination: Guidance for Industry Draft Guidance.”

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which 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.

Due to the growing rate of Americans getting tattoos and increased reports of infections related to contaminated tattoo ink, we agree this is an important public health issue that needs to be addressed. Microbial contamination of tattoo inks can occur in nearly 50% of inks on the market in the United States, which can include organisms that are known to cause serious infection and are highly resistant to antibiotics.1  We support the FDA’s objectives of ensuring that ink products are unadulterated and holding manufacturers accountable for contaminated products.

While the act of tattooing is primarily regulated by state, local, and tribal public health authorities, the FDA has the authority to regulate tattoo ink. In addition to microbial contamination, pigments have been found to contain potentially toxic chemicals, heavy metals, degradants, printer toner, car paint, and other substances that were not intended to be used on the human body.2  We agree that the FDA needs to provide guidance that will better support state, local, and tribal public health agencies to help address the growing public health burden of unsafe tattoo ink. This is especially relevant as many local tattooing regulations have recently been found to be outdated as well as inconsistent.

Accordingly, we recommend that the FDA provides explicit guidance regarding the labeling of tattoo inks. While tattoo ink manufacturers are required to include ingredient and safety risks as part of the labeling requirements under the Fair Packaging and Labeling Act, these labels are rarely seen by consumers since the ink is often purchased in bulk by tattoo studios.3 We strongly urges the FDA to require that user-friendly labels for tattoo ink be made available online to consumers prior to getting tattoos; preferably, in a consumer checklist that they must sign, so that they have the information they need to make informed decisions on the risks of tattooing.

We also recommend that the FDA include clear, understandable guidance regarding the water and dilution techniques that should be used to achieve color variation in tattoo studios. This is of particular importance as non-sterile dilution techniques were a primary cause of the nontuberculous mycobacterial skin infection outbreak that was referenced in FDA’s draft guidance. A common practice for tattoo studios is to use distilled or reverse osmosis water for dilution. However, these are non-sterile techniques, and the FDA should prohibit such techniques and instead require and explain the importance of sterile dilution techniques.

We are also concerned about the voluntary reporting system of contaminated ink products, which primarily relies on consumers. This places the burden of contamination identification and reporting on the consumer rather than the manufacturer, and also undermines the responsibility of the manufacturer to ensure that their products are unadulterated. In addition, since consumers are rarely aware of existing reporting mechanisms, the FDA should require that tattoo studios educate consumers on how to report adverse events caused by contaminated ink. We also agree with the FDA’s recommendation that tattoo ink and ink components be tested for microbial contamination and that tattoo establishments be required to discard contaminated products. Although we are concerned that the lack of proposed manufacture accountability and enforcement mechanisms, traceability, and regulatory incentives will lead to noncompliance, having such requirements will increase the risk of lawsuits for noncompliance, and that will serve as an incentive to comply with FDA requirements.

It is estimated that nearly one-third of Americans have a tattoo with reports of microbial contamination at a staggering 49%1,4 Thus, there is a great need to better regulate tattoo ink and raise awareness among the public about the risks of unsafe tattoo ink. We support the objective of the FDA in helping manufacturers to identify and discard adulterated ink to better protect public health. However, we recommend that ink labels be made readily available to consumers and sterile dilution techniques are included in the final guidance. We also strongly recommend that the FDA develop an information toolkit to increase consumer awareness regarding contamination reporting systems in tattoo studios, while working to build robust mechanisms for manufacturer reporting, traceability, and accountability.

As noted above, in addition to microbial contamination, pigments have been found to contain potentially toxic chemicals, heavy metals, degradants, printer toner, car paint, and other substances that were not intended to be used on the human body. The rate of ink contamination with unsafe substances that include but are not limited to microbial contamination has been reported as high as 67%.5 Therefore, we strongly urge the FDA to expand the regulation of all types of dangerous substances in this draft guidance or develop a similar draft guidance specifically to reduce the risks caused by these other dangerous substances.

References:

  1. Nho, SW et al. “Microbiological Survey of Commercial Tattoo and Permanent Makeup Inks Available in the United States.” Journal of Applied Microbiology, 124: 1294-1302 (2018).
  2. “NEHA Response to Request from FDA for Good Manufacturing Practices on Tattooing Inks and Pigments.” 2023.
  3. Association of Food and Drug Officials, Body Art Committee. “Tattoo Ink and Permanent Makeup Labeling Guide.” 2019.
  4. Pew Research Center. “32% of Americans have a tattoo, including 22% who have more than one.” 2023.
  5. Bonadonna, Lucia. “Survey of Studies on Contamination of Marketed Tattoo Inks.” Karger. 2015.

Our Comments on the FDA Proposed Guidance Regarding the Registration and Listing of Cosmetic Product Facilities and Products

Policy

September 7, 2023

We appreciate the opportunity to comment on the Food and Drug Administration proposed guidance: Registration and Listing of Cosmetic Product Facilities and Products; Draft Guidance for Industry.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which 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.

We strongly support the purpose and requirements included in the Modernization of Cosmetics Regulation Act of 2022 (MoCRA), which was part of the Consolidated Appropriations Act, 2023 (Pub. L. 117-328) related to the regulation of cosmetic products. These regulations are long overdue and an essential first step toward protecting public health through the disclosure of the ingredients in these ubiquitous products and the registration of the facilities that make these products. Research has documented scientific concerns about the presence of endocrine disrupting chemicals in cosmetics and their effect on consumers’ health.[1],[2],[3] Some hormone disruptors such as phthalates and parabens are found in a wide range of cosmetic products. Other hormone disrupting substances are used in specific cosmetics, such as triclosan in toothpaste and mouthwash; this chemical ingredient was previously banned from soap products by the FDA in 2016. It is essential that the public be made aware of the potential for cumulative exposure to substances in many different makeups, creams, and other cosmetic products used every day.

We are very supportive of the requirements included in MoCRA, but have four recommendations to improve the proposed guidance:

  • We are concerned that the FDA does not plan to transfer the voluntary cosmetics registration program to this new system. We agree that previous submissions to the voluntary cosmetics registration program fail to satisfy the registration and listing requirements, since that information differs from the information required to be submitted under MoCRA. However, there is likely to be substantial overlap of information. We recommend that these entities should be required to register their facilities and submit product listings even if they voluntarily provided similar information previously. If information is not transferred, where will previously submitted voluntary information be stored? Will it be available to the public?
  • Regarding the requirements set for a product listing, we strongly urge that all fragrance ingredients be required to be listed. Fragrance ingredients in self-care products such as shower gels, shampoos, body lotions, and shaving creams are often labeled “unscented.” This is because manufacturers are not obligated to label the fragrance in the ingredient list if the amount added is just enough to cover the scent of other ingredients versus giving the product a noticeable scent.[4] This is not an appropriate justification. All fragrance ingredients added to the product, no matter how minimal, should be included in the product listing. It is not enough to simply list the product as containing “fragrance” or “flavor” as is required under section 701.3 of title 21, Code of Federal Regulations. A more detailed ingredient list is essential and would not jeopardize trade secrets since according to the guidance document, brand names will not be disclosed publicly.
  • Regarding the requirements set for a facility registration, we support the requirements listed in the guidance but also recommend the disclosure of the amount of the product manufactured or processed in each facility in the year prior to the initial registration. Production levels should also be included in each renewal of registration biennially.
  • According to the guidance, the “FDA requests that individuals submitting registration and listing information to attest to the accuracy and veracity of the information submitted.” The guidance does not specify how violations or inaccuracies in the registrations and product listings will be enforced.  It is essential the manufacturers comply with the requirements in order to ensure transparency, and enforcement is necessary to achieve that goal.

1. Ejaredar, M., Nyanza, E., Eycke, K., Dewey, D. (2015). Phthalate Exposure and Childrens Neurodevelopment: A Systematic Review. Environ Res 142:51-60.

2. Diamanti-Kandarakis, E., Bourquioqnon, J., Giudice, L., et al. (2009). Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocr Rev 30(4):293-342.

3. Harley, K., Kogut, K., Madrigal, D., Cardenas, M., et al. (2016) Reducing Phthalate, Paraben, and Phenol Exposure from Personal Care Products in Adolescent Girls: Findings from the HERMOSA Intervention Study. Environ Health Perspect In Press.

4. Sun, A. (2023) Everything you need to know to choose safe cosmetic products. National Center for Health Research. https://www.center4research.org/cosmetics-safety-regulations-law-tips/

Everything You Need To Know to Choose Safe Cosmetic Products

Environmental Exposures

Andrea Sun, MS, Cancer Prevention and Treatment Fund

Do you know how to pick out the right makeup or skincare products for yourself? Cosmetic products are used by everyone of all ages. They include shampoo, shaving products, and moisturizing creams, as well as make-up, nail polish, and anti-aging products. Promotional videos for cosmetic products are popular among influencers on social media platforms like YouTube and Instagram. Some studies show that the revenue in the U.S. Beauty & Personal Care market will exceed an astonishing $92 billion by the end of 2023.[1]

U.S. consumers use an average of 6 to 12 cosmetic products daily, containing nearly 200 chemicals. With so many choices, and so many potentially risky chemicals, it’s essential to know what to look for when buying these products. Current regulations address some safety concerns for cosmetic products, but many gaps remain.

What are some of the regulations that protect us?

The U.S. has some regulations regarding the manufacturing and selling of cosmetics. Let’s look at what makes cosmetics different from drugs and what might be helpful information when you shop or read the label on a product.

The Federal Food, Drug & Cosmetic Act (FD&C Act) defines cosmetics as articles intended to make the human body more attractive. Lipsticks, nail polishes, perfumes, skin moisturizers, toothpaste, deodorants, and shampoos are especially popular cosmetics. However, there are some topical products that are sold without prescriptions in drug stores that are not considered cosmetics – they are considered drugs. Drugs are defined as products that can cure, mitigate, treat, or prevent diseases or affect the body’s function. For example, products such as hair loss treatment shampoo and acne medications are considered over-the-counter drugs instead of cosmetics. They are regulated by the FDA to make sure that they are safe and effective.

If a product makes you look better and treats your disease or improves your body’s function, it is both a cosmetic and a drug. One example is anti-dandruff shampoos, since they clean your hair and treat dandruff. Other products, such as deodorants containing antiperspirants, moisturizers, and makeup with sun-protection claims, are also drugs and cosmetics. These are also regulated by the FDA to determine if they are safe and effective.

The Modernization of Cosmetics Regulation Act of 2022 (MoCRA) requires manufacturers to list products’ ingredients and manufacturing information, report serious adverse events such as life-threatening reactions, and renew registered facility information at FDA. This law will go into effect on December 29, 2023. Another law, the Fair Packaging and Labeling Act (FPLA), works with MoCRA to ensure consumers receive accurate information. It requires clear labeling of essential information, such as the product’s name and manufacturer and sets standards for quantities and measurements to enable easy comparison across different products. The law also protects consumers from misleading information by prohibiting deceptive packaging or labeling and gives various government agencies the authority to enforce these rules.

The effect of cosmetics on environmental pollution is also limited through regulation. The Microbead-Free Waters Act of 2015 prohibits the manufacturing, packaging, and distributing of rinse-off cosmetics containing plastic microbeads. These tiny plastic particles usually appear in personal care products like facial scrubs, toothpaste, and body washes for their exfoliating properties. However, they pose significant environmental problems, since they could easily pass through water treatment facilities and end up in rivers and oceans. Marine animals could mistake them for food, which would endanger the food chain.

Cosmetic substances that cause health concerns

U.S. regulations require the disclosure of ingredients, but do not set limits on what chemicals can be included in these products. That means that ingredients known or suspected to cause cancer could be in cosmetics that are legally sold in the U.S. This includes chemicals like formaldehyde and formaldehyde-releasers, parabens, phthalates, fragrance, diethanolamine (DEA), and other heavy metals.

● Formaldehyde
Formaldehyde is added to many personal care products to prevent bacteria from growing. Customers sometimes find it in nail polish, shampoo, and body washes. Exposure to low levels can irritate people’s eyes, nose, and throat. However, hair stylists and manicurists who are regularly exposed are more likely to eventually develop nose and throat cancers. A 2019 study in Brazil looked at 23 beauty salons to understand the exposure of hairdressers to formaldehyde and its effects. The result shows that 17% of salons had exceeded the formaldehyde level that is considered safe. Over 65% of the hairdressers reported work-related health issues like eye irritation, skin problems, headaches, limb pain, and breathing difficulties. [8]

● Parabens
Parabens are preservatives commonly used in water-based products. Shampoos, conditioners, face washes, toothpaste, and other cosmetics contain low levels of parabens. Studies on animals indicate that parabens can imitate the actions of the hormone estrogen.[3] that paraben exposure may increase the chances of developing breast cancer in women and disturbances in male reproductive systems. [2]

● Phthalates
Phthalates are chemicals that mimic hormones and are linked to birth defects in animals, especially in the male reproductive system, and are also considered a potential cause for early puberty in boys and girls. They also can increase obesity in children. Personal care product manufacturers started to phase out the direct use of phthalates in 2018 when the U.S. Consumer Product Safety Commission restricted six types of phthalates in children’s toys and child care products after learning about its risks in hormone function and fertility impairment. However, phthalates are still in many products, especially those that smell good.

● Fragrances
Fragrance ingredients are common in self-care products such as shower gels, shampoos, body lotions, and shaving creams. They sometimes are even in products labeled “unscented.” This is because manufacturers are not obligated to label the fragrance in the ingredient list if the amount added is just enough to cover the unpleasant smell of other ingredients versus giving the product a noticeable scent. In the U.S., manufacturers can list fragrance and flavor ingredients as “Fragrance” or “Flavor.” The fragrance is usually a company’s “trade secret,” so they do not need to disclose it. Diethyl phthalate, or DEP, is the phthalate commonly used in fragrance products and is not proven to harm people’s health.

● Diethanolamine
Diethanolamine, also called DEA, is an emulsifier in creamy or foamy products like shampoos and shaving creams. Its reaction with other preservatives in personal care products will form nitrosamines, a human carcinogen according to the International Agency for Research on Cancer and the U.S. National Toxicology Program. Europe and Canada prohibit DEA in cosmetics. Why doesn’t the U.S. FDA?

● Heavy metals
Personal care products such as lipstick, whitening toothpaste, eyeliner, and nail polish often contain heavy metals, including lead, arsenic, mercury, aluminum, zinc, chromium, and iron. Exposure to some of these metals can raise health concerns, particularly affecting the reproductive, immune, and nervous systems. Though “plant-source derived” might sound safe to many customers, several ingredients, such as cottonseed oils and rice derivatives, may contain heavy metals such as lead and mercury, which can harm fertility, cause brain damage, and harm breathing. Sometimes metals are deliberately added to cosmetics; for example chromium is commonly found in eye shadows, blushes, and concealers.

Cosmetics and the Environment

Ingredients from cosmetics can harm our environment. Products such as makeup remover wipes, exfoliating scrubs with microbeads, face sheet masks, skin-whitening creams, and sprays and mists contain non-biodegradable ingredients and chemicals that can harm the environment, waterways, marine life, and even the ozone layer. A 2023 study suggested that microplastics, tiny plastic particles between 100 nm and 5 mm, can move up the food chain from small sea creatures to larger ones, carrying harmful pollutants that could end up in humans.[4]

Additionally, triclosan (TCS), an antimicrobial substance that is often in shampoos, detergents, hand soaps, toothpaste, sunscreen, and deodorants, can also damage the environment. A 2020 study shows that people are more likely to have TCS in their blood, urine, and breast milk if they apply personal care products containing TCS.[5] This can harm human health and our environment, causing an itchy rash, decreased sperm production, and tumors. If TCS is in the environment, it becomes highly poisonous during wastewater treatment, accumulating in animals, plants, and algae, disrupting the ecosystem.

Does consistent exposure to cosmetics harm beauticians’ health?

Hair stylists, manicurists, aestheticians, and other beauticians are constantly exposed to chemicals and heat in their working environments. Do they have a higher risk of some diseases due to these exposures? What can they do to protect themselves from these exposures during work?

A 2021 study examined the chemical and physical conditions in hair salons and assessed the health risks of volatile organic compounds (VOCs) for hairdressers.[6] VOCs are organic chemical components in hair spray that carry substances that can cause heart disease, irritation, insomnia, and nerve damage. This exposure also increases the chances of developing cancer. Installing exhaust ventilation is one of the most effective methods to lower the VOC concentration in the salon. Nail professionals in U.S. salons are also frequently exposed to dangerous chemicals in adhesives, lacquers, removers, moisturizers, and other salon items that can cause breathing problems, rashes, liver complications, reproductive issues, and even cancer. Chemicals found in nail products, such as acetone in nail polish remover, formaldehyde in nail polish and nail hardener, and toluene fingernail glue, can cause headaches, dizziness, allergic reactions, and harm the fetus during pregnancy. For that reason, nail salons should be required to make sure products are 3-free (free from toluene, formaldehyde, and dibutyl phthalate) and free from acid. Nail professionals should always review product labels and instructions when using nail products. [7]

So, what can you do to protect yourself while enjoying personal care products?

1. Read ingredient labels and remember that Ingredients appear in order from highest to lowest concentration. Pay attention to ingredients with higher concentration and avoid those you are allergic to or that can cause environmental problems. See ingredients you want to avoid in cosmetics.
2. When it comes to self-care routine, more is not necessarily better. Skin irritation can occur when layering products. Applying daily makeup without adequately removing it might also disrupt the skin’s protective barrier and cause eye infections and premature aging. Therefore, it is important to build a simple yet effective routine that works well for you and stick with it. Read here for more skin care tips.
3. Choose traditional nail polish over gel polish. Acetone is used to remove gel polish. Traditional nail polish is strong and doesn’t require remover made with acetone. If you use a remover made with acetone, soak a cotton ball in it to remove the polish. Read more here.
4. Cosmetic products that are less dangerous are usually better for the environment as well. Products with sustainable packaging such as refillable and reusable cosmetics can reduce plastic pollution.

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

1. Beauty & Personal Care – United States. Statista. https://www.statista.com/outlook/cmo/beauty-personal-care/united-states
2. Sheikh, Knvul. Many Personal Care Products Contain Harmful Chemicals. Here’s What to Do About It. New York Times. 2023.
3. Hager, E., Chen, J., & Zhao, L. Minireview: Parabens Exposure and Breast Cancer. International journal of environmental research and public health, 19(3), 1873. https://doi.org/10.3390/ijerph19031873
4. Zhou, Yuwen., Ashokkumar, Veeramuthu., & Amobonye, Ayodeji. Current Research Trends on Cosmetic Microplastic Pollution and Its Impacts on the Ecosystem: A Review. Environmental Pollution. Vol. 320. 2023. https://doi.org/10.1016/j.envpol.2023.121106
5. Bilal, Muhammad., Mehmood, Shahid., & Lqbal, Hafiz. The Beast of Beauty: Environmental and Health Concerns of Toxic Components in Cosmetics. Cosmetics. 2020, 7(1), 13. https://doi.org/10.3390/cosmetics7010013
6. Senthong, P., & Wittayasilp, S. Working Conditions and Health Risk Assessment in Hair Salons. Environmental health insights, 15, 11786302211026772. 2021. https://doi.org/10.1177/11786302211026772
7. Health Hazards in Nail Salons. Occupational Safety and Health Administration. n.d. https://www.osha.gov/nail-salons/chemical-hazards
8. Pexe, M. E., Marcante, A., Luz, M. S., Fernandes, P. H. M., Neto, F. C., Sato, A. P. S., & Olympio, K. P. K. Hairdressers are exposed to high concentrations of formaldehyde during the hair straightening procedure. Environmental science and pollution research international, 2019; 26(26), 27319–27329. https://doi.org/10.1007/s11356-019-05402-9

Everything You Need To Know About The New Weight Loss Drugs

Diet, Habits, & Other Behaviors

Jenny Niwa

You have probably heard about several very popular new weight loss drugs, such as Wegovy, Ozempic, Mounjaro, and Zepbound.  Although Ozempic and Mounjaro are specifically approved by FDA for treating diabetes and not for weight loss, all four are being used by people who want to lose weight. Before you decide whether to take these drugs, here are some things you should know.

What are these drugs and how do they work?

The FDA approved Ozempic in 2017 for the treatment of type 2 diabetes and Wegovy in 2021 for weight loss for adults with obesity or who are overweight and have at least one weight-related health condition.  Although these drugs have been on the market for several years, their popularity really exploded in 2023. Mounjaro was approved in the spring of 2022 for Type 2 diabetes and Zepbound was approved in late 2023 for those with obesity or who are overweight with an additional chronic condition such as hypertension. While Ozempic and Mounjaro are not approved specifically for weight loss, doctors may prescribe them anyway – that’s called prescribing it off-label. All four curb hunger and reduce the intake of food. The medications are currently administered by injection once a week, but they may soon be available in pill form.

Both Wegovy and Ozempic  are made of semaglutide. Mounjaro and Zepbound are made of tirzepatide.  Both mimic the GLP-1 hormone, which is made naturally by the body. GLP-1  does 2 things: 1) It One is to slow the passage of food through the stomach, which helps people feel fuller longer; and 2) it promotes insulin release and helping reduce blood sugar.

What do research studies say? 

In August 2023, Wegovy’s maker, Novo Nordisk, claimed in a press release that the drug reduced the risk of serious heart problems. The company described a randomized trial of 17,500 patients with obesity and heart disease, although patients with diabetes were excluded.[2] Half of the participants received regular injections of Wegovy and the other half received a placebo. Rather than publish the results in a peer-reviewed journal, Novo Nordisk publicized their research in a press release that claimed that Wegovy reduced heart attacks, strokes, and deaths by 20% compared to placebo, and this was widely reported in the media. However, this statistic is misleading because it is a relative risk. When the study was finally published in the New England Journal of Medicine on November 11, 2023, the results did not sound as impressive:  8% of the people in the placebo group had had a nonfatal stroke or heart attack or died due to cardiovascular causes, compared to 6.5 percent in the Wegovy group. [3] That decrease from 8% to 6.5% is a 20% decrease, but the difference is only 1.5% for patients considering whether it is a meaningful difference for them.

In August 2023, a study published in the New England Journal of Medicine found that the medication reduced the risk of heart problems for diabetes patients who were at high risk for cardiovascular complications. [4] This study included more than 3,000 patients with type 2 diabetes, who were randomly assigned to receive once-weekly Ozempic or a placebo for 2 years. Results showed that 108 of 1648 patients (6.6%) taking Ozempic either died, had a nonfatal heart attack, or nonfatal stroke, compared to 146 of 1649 patients (8.9%) who took the placebo.  This was statistically significant (which means it did not occur by chance), but is a difference of only 2.3%.

Mounjaro has been found to reduce blood pressure, which could improve health, but no published studies have provided evidence that it reduces heart disease.

What are the side effects?

The most common side effects of these GLP-1 medications include stomach issues such as nausea and diarrhea. Some patients experienced persistent vomiting or cyclic vomiting syndrome and severe gastroparesis. Gastroparesis is stomach paralysis and occurs when there is a delay or stopping in food movement from the stomach to the small intestine.

Warnings about other possible serious side effects that are listed on the companies’ websites include inflammation of the pancreas, gallbladder problems, increased risk of low blood sugar, kidney problems, serious allergic reactions, change in vision for people with type 2 diabetes, increased heart rate, and depression and thoughts of suicide.[5]

In January 2024, a new FDA report listed potential links between the medications and extensive hair loss (called alopecia), a swallowing problem that can occur during surgery called aspiration, and thoughts of suicide.[14]  A few days later, the FDA announced that their preliminary review did not support an increase in thoughts of suicides among patients taking these drugs, but the FDA also said they had drawn no conclusions based on their preliminary findings and would continue to review new data.

An even more serious side effect is the risk of thyroid cancer. According to a study conducted by the European Medicines Agency (EMA, which is the European version of the FDA), researchers found that using GLP-1 medications for 1-3 years may increase the risk for all types of thyroid cancers.[6]

Concerns about aspiration and suicidal thoughts are not new. For example, in 2023 there were media reports about potential complications from anesthesia for people taking these drugs. The American Society of Anesthesiologists advises that people taking these drugs should make sure to stop taking the medication a week before surgery. People who know they are going to have surgery are advised not to eat for 24 hours before surgery, but since these drugs affect how long food stays in the stomach, a 24-hour fast is not enough to prevent regurgitating food during the operation. This is dangerous because vomiting under anesthesia can cause pneumonia and other fatal problems due to the food and stomach acid getting into the lungs.[7]  This risk may be impossible to prevent if someone taking the drug requires emergency surgery.

What Happens if You Lose Weight and Want to Stop Taking the Drug?

Most weight loss strategies work for a limited time; when people stop dieting or exercising, they gain the weight back. Is the same true for the new weight loss drugs such as semaglutide and tirzepatide? Unfortunately, most patients take these drugs for less than 3 months and the number still taking the drug after 1 year is even lower. A study of more than 1,900 patients by researchers at the Cleveland Clinic found that patients’ use of semaglutide and several other weight loss medications dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months.[8]  Regardless of whether they stopped taking the drugs due to side effects, cost, or other reasons, the long-term benefits of these drugs are limited because when they stop taking the drugs, their stomach no longer feels full. A study conducted with almost 2,000 adults without diabetes found that one year after no longer taking Wegovy, participants regained two-thirds of their prior weight loss.[9]  

There is still much that is unknown about these drugs. It is unclear how these drugs affect patients after years of use, whether the drugs are effective at maintaining a certain weight after long-term use, and whether most patients will benefit from taking the drugs for a limited period of time or if they need to stay on for the rest of their lives. Current literature suggests that such medications may need to be taken life-long to experience long-term benefits and prevent any negative consequences that come from discontinuing use. [8]

Other Questions to Consider

In 2022, Novo Nordisk spent a total of $11 million to promote their Ozempic and other weight-loss drugs, including $9 million on meals and $2 million on travel for thousands of doctors to promote their weight-loss drugs.[10] That included more than 457,000 meals; nearly 12,000 prescribers had food paid for by the company more than a dozen times in that one year. Buying meals for doctors is not illegal, but this extreme level of “generosity” raises concerns. If these drugs are so effective, why did the company think it necessary to provide all these free meals?  And since the drugs became much more popular after the company spent all that money providing free meals to doctors, do you wonder if doctors are prescribing these drugs because they have they been unduly influenced to prescribe them?

Is taking these weight loss drugs right for you?

Ozempic is FDA approved for patients with type 2 diabetes and is not approved for weight loss. Due to the risk of thyroid cancer, if you or any family member has ever had a type of thyroid cancer, taking any of these 4 drugs may be dangerous. Similarly, if you have sensitivity to gastrointestinal problems, these drugs may not be right for you.

In January 2024, Eli Lilly, the maker of Mounjaro and Zepbound, warned against their use for cosmetic reasons. The company reminded physicians and patients that GLP-1 drugs are meant for serious diseases (obesity or Type 2 diabetes) and not for cosmetic weight loss. [15]

Another thing to consider is the cost, which is much higher in the U.S. compared to other countries.[11] If insurance does not cover the cost, one monthly dose of Ozempic costs about $900, and the cost for Wegovy is about $1,350 per month.[12],[13] The cost of Mounjaro is similar to Ozempic and Zepbound costs somewhat less than Wegovy. Since they are relatively new, there are no generic versions. You may be able to lower the costs of these drugs through savings programs or through coverage on your health insurance plan. Many private insurance providers cover these drugs to treat Type 2 diabetes. When used for weight-loss purposes, it is much less likely to be covered. Medicare does not cover these drugs, although patients, doctors, and Congress are pressuring Medicare to do so.

The media attention to these 4 drugs makes it seem that they are the only FDA-approved weight loss drugs. They are not. However, all weight loss drugs have unpleasant and potentially serious side effects, and these 4 seem to be more effective.

If you are eligible and interested in taking these drugs, you should first and foremost make sure to talk to your physician and discuss what to expect, the possible side effects, and your medical history. If you are not eligible for these drugs or are not interested in using them, there are other methods available that can help you lose weight and improve your health if you stick with them. These include exercising daily or regularly, developing healthier eating habits, and knowing when to eat.

[1] Hoffman, S. (2023) The Differences between Saxenda and Wegovy. Very Well Health. https://www.verywellhealth.com/the-differences-between-saxenda-and-wegovy-7564310

[2] Chen, E., and Joseph, A. (2023). Novo’s obesity drug Wegovy lowers cardiovascular risk by 20%, landmark trial finds. STAT+. https://www.statnews.com/2023/08/08/novo-nordisk-wegovy-cardiovascular-risk/

[3] Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., Hardt-Lindberg, S., Hovingh, G. K., Kahn, S. E., Kushner, R. F., Lingvay, I., Oral, T. K., Michelsen, M. M., Plutzky, J., Tornøe, C. W., & Ryan, D. H. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2307563

[4] Marso, S., Bain, S., Consoli, A., & Eliaschewitz, F. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/nejmoa1607141

[5] Novo Nordisk. (n.d.). Tips for managing common side effects. https://www.wegovy.com/dashboard/my-library/week-02-tips-for-managing-common-side-effects.html#:~:text=thoughts%20of%20suicide.-,The%20most%20common%20side%20effects%20of%20Wegovy%C2%AE%20may%20include,runny%20nose%20or%20sore%20throat.

[6] Bezin, J., Gouverneur, A., Penichon, M., Mathieu, C., Garrel, R., Hillaire-Buys, D., Pariente, A., & Faillie, J.L. (2022). GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care. https://diabetesjournals.org/care/article-abstract/46/2/384/147888/GLP-1-Receptor-Agonists-and-the-Risk-of-Thyroid?redirectedFrom=fulltext

[7] Goodman, B. (2023). They took blockbuster drugs for weight loss and diabetes. Now their stomachs are paralyzed. CNN. https://www.cnn.com/2023/07/25/health/weight-loss-diabetes-drugs-gastroparesis/index.html

[8] Most Stop Taking Weight Loss Drugs Within 1 Year. (n.d.). Medscape. Retrieved December 12, 2023, from https://www.medscape.com/viewarticle/most-stop-taking-weight-loss-drugs-within-1-year-2023a1000uiq

[9] Wilding, J. P., Batterham, R. L., Davies, M., Van Gaal, L. F., Kandler, K., Konakli, K., Lingvay, I., McGowan, B. M., Oral, T. K., Rosenstock, J., Wadden, T. A., Wharton, S., Yokote, K., &  Kushner, R. F. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity and Metabolism, 24(8), 1553–1564. https://doi.org/10.1111/dom.14725

[10] Florko, N. (2023). Novo Nordisk bought prescribers over 450,000 meals and snacks to promote drugs like Ozempic. STAT+. https://www.statnews.com/2023/07/05/ozempic-rybelsus-novo-nordisk-meals-for-doctors/#:~:text=Novo%20Nordisk%20bought%20prescribers%20over,to%20promote%20drugs%20like%20Ozempic&text=WASHINGTON%20%E2%80%93%20Novo%20Nordisk%20spent,weight%20loss%2Dinducing%20diabetes%20drugs

[11] Amin, K., Telesford. I., Singh, R., & Cox, C. (2023). How do prices of drugs for weight loss in the US compare to peer nations’ prices? Health System Tracker. https://www.healthsystemtracker.org/brief/prices-of-drugs-for-weight-loss-in-the-us-and-peer-nations/?utm_campaign=morning_rounds&utm_medium=email&_hsmi=270760455&_hsenc=p2ANqtz-_P2SZN9DLjS_l7fSn8hrgS8xRf4YvJIonV0X-iRtKF3FtcWbgsMJd-K6tDV2u12XNFMEesDCulwlbdwkw74D1S-2WqXQ&utm_content=270760453&utm_source=hs_email#List%20prices%20of%20drugs%20used%20for%20weight%20loss%20in%20the%20U.S.%20and%20peer%20nations

[12] Wilson, A. (2023). How much does Ozempic cost without insurance?. RO. https://ro.co/weight-loss/ozempic-cost-without-insurance/

[13] Wilson, A. (2023). How much does Wegovy cost? RO. https://ro.co/weight-loss/wegovy-cost/

[14]  FDA Looking Into New Risks With Popular Weight-Loss Drugs. (n.d.). Retrieved January 9, 2024, from https://www.usnews.com/news/health-news/articles/2024-01-04/fda-looking-into-new-risks-with-popular-weight-loss-drugs

[15]  Open Letter Regarding the Use of Mounjaro® (tirzepatide) and ZepboundTM (tirzepatide) | Eli Lilly and Company. (n.d.). Retrieved January 12, 2024, from https://investor.lilly.com/news-releases/news-release-details/open-letter-regarding-use-mounjaror-tirzepatide-and-zepboundtm

Our Comments on the FDA Notice Regarding Changes to Third-Party Vendors for Risk Evaluation and Mitigation Strategies (REMS)

Policy

July 19, 2023

We are pleased to have the opportunity to share our views with the Food and Drug Administration (FDA) on their notice regarding Changes to Third-Party Vendors for Risk Evaluation and Mitigation Strategies (REMS).

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which 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.

Implementing changes in REMS has the potential to cause significant disruptions in the operations of any REMS program, including the ability for prescribers and patients to interact with the tools necessary to fulfill the various REMS requirements. These disruptions can undermine patients’ ability to access a drug in ways that minimize risks. Since the FDA does not approve third-party REMS administrators, or play a major role in the initial development of REMS with elements to assure safe use (ETASU), it is essential that the FDA closely monitors any changes in REMS plans to make sure they are appropriate and yield beneficial outcomes.

We strongly urge that the FDA require drug sponsors and their REMS administrators to test proposed changes to REMS systems prior to implementation with those that actively engage with the system, including but not limited to physicians, patients, and pharmacists. This will ensure that the REMS program will have the intended impact. A less-than-rigorous approach to studying the efficacy of REMS defeats the purpose of REMS and fails to protect patients from predictable harm. The FDA REMS for Transmucosal immediate-release fentanyl (TIRF) drugs and the REMS for Extended Release/Long Acting (ER/LA) opioids provide important examples of how improper implementation of REMS can harm patients. The HHS IG found numerous failures for both these REMS programs, at a time when these REMS were especially important because of the opioid epidemic.1 For example, manufacturers consistently missed the REMS’ targets for training ER/LA prescribers, and the FDA was blamed for not giving manufacturers sufficient time to respond to FDA’s requests for better data before their next assessments were due. As a result, the REMS for ER/LA opioids was changed to primarily measure voluntary prescriber training to educate about risks, a decision that also failed to adequately protect patients.

We also strongly recommend that the sponsor and/or the REMS administrator conduct a Failure Modes and Effects Analysis (FMEA) to identify and plan for system failures. This includes providing for adequate support services in the event that the system fails to work as intended following full implementation of an altered REMS system. Part of the planning should include provisions for an emergency suspension of the REMS or specific parts of the REMS.

Additionally, beyond testing a REMS modification with stakeholders, FDA should require stakeholder input from prescribers in all stages of developing, implementing, and tracking a REMS modification related to changes to third party vendors. This will require greater transparency between drug sponsors, REMS administrators, and stakeholders.

In numerous REMS, the FDA has faced measurement challenges, such as a lack of baseline data and limited surveillance data. These metrics are essential for the sponsor to include when evaluating whether a REMS system was successfully and efficiently implemented. It is also essential to collect data on which types of health professionals are involved in implementing a specific REMS. For REMS that involve training of health professionals, there must be a record of the percentage of prescribers being trained, the percentage who start training who complete it, and what percentage that complete the training will answer training questions correctly.

Finally, we strongly recommend that all future REMS agreements that the FDA enters into with manufacturers and their vendors, require that deidentified REMS data be made available to appropriate outside stakeholders. The availability of this data will reassure the public, patients, and health care providers that each REMS is accomplishing its intended outcomes and promoting the safe use of drugs while minimizing harm, especially serious harm.

  1. U.S. Department of Health and Human Services Office of Inspector General. (2020). FDA’s Risk Evaluation and Mitigation Strategies: Uncertain Effectiveness in Addressing the Opioid Crisis. https://oig.hhs.gov/oei/reports/OEI-01-17-00510.pdf

Our Comments on the FDA’s Use of Generally Accepted Medical Knowledge Draft Guidance

Policy

July 24, 2023

We are pleased to have the opportunity to share our views with the Food and Drug Administration (FDA) on their Guidance: Generally Accepted Scientific Knowledge in Applications for Drug and Biological Products: Nonclinical Information.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which 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.

We support the efforts of the FDA to remain flexible and provide a more open application of scientific and regulatory judgment when conducting nonclinical studies that determine in vitro safety and efficacy. We recognize that this has the potential to streamline product development as well as avoid unnecessary animal testing, decrease costs, and hasten new drug approval time.  However, we predict that this will result in some sponsors providing insufficient data to show the safety, toxicology, and efficacy profile of a drug.

For that reason, we do not recommend using Generally Accepted Scientific Knowledge (GASK) as the sole source of nonclinical data in New Drug Applications (NDAs) or Biologic License Applications (BLAs). Instead, GASK should only be used to support sponsor data and should not replace the vital research that is needed to create a robust safety and efficacious drug profile.

Permitting GASK as the sole or primary evidence would often create a level of ambiguity regarding a drug’s true pharmacologic, distributive, and toxicologic effects. We support sponsor communication that is clear and data that are unequivocal, so that potential harms are minimized. We strongly encourage that the GASK used be: 1) long-standing, 2) uncontroversial, and 3) scientifically robust.  However, we note that even when the generally accepted scientific knowledge being relied upon is uncontroversial, long-standing, and scientifically robust, the external application of that information by the sponsor may be inappropriate. For example, even when a drug’s mechanism of action or the biologic pathway that a drug acts on is well understood, the drug should still be tested to assure that there are no downstream or unanticipated effects when in vitro to the full extent possible, and not solely rely on GASK.

In conclusion, we appreciate the opportunity to comment and support the efforts of the FDA to streamline product development and avoid unnecessary animal testing, decrease costs, and hasten new drug approval time. However, this must be better balanced with the need for sponsors to provide clear, unambiguous data regarding the pharmacologic, safety, and effectiveness profile of new drugs and not use GASK as a means of replacing vital research. To that end, we strongly urge the FDA to revise the proposed GASK guidance to require comprehensive and precise language on when using GASK by the sponsor is appropriate.

Testimony of Diana Zuckerman at the CMS Meeting Regarding Transitional Coverage for Emerging Technologies

Policy

August 1, 2023

I’m Dr. Diana Zuckerman, president of the National Center for Health Research and Cancer Prevention and Treatment Fund.  Our Center is a public health think tank that focuses on policies and programs that increase the safety and effectiveness of medical products.

We support the goals of the TCET program, but we see an enormous disconnect between the types of evidence that FDA requires for breakthrough devices, especially for 510k devices, and the CED standards that CMS requires for coverage.  We hear a lot about flexibility from FDA and industry but not enough about scientific evidence of safety or effectiveness.  Innovation should be defined to require that a device is proven to be better, not just newer.  We urge CMS to work with industry to make it clear that CMS evidence standards of clinical benefit are very different from the standards required by CDRH.  And we urge CMS to urge companies to provide the evidence needed to be worthy of CMS coverage.

Let’s remember that the standards for FDA for devices are not proof of safety or effectiveness, but rather the “reasonable assurance of safety and effectiveness.”  And often that “reasonable assurance” is not so reassuring.

I want to reiterate the previous comment that even when the FDA requires clinical data, many types of Medicare beneficiaries are under-represented:  older patients, people of color, and women.

I want to thank CMS for this effort to improve access to safe and effective medical products and urge CMS to hold firm to its standard for coverage based on scientific evidence that all medical products are proven to be reasonable and necessary for Medicare patients.

Our Comments on FDA Guidance Regarding Decentralized Clinical Trials for Drugs, Biological Products, and Devices

Policy

August 1, 2023

We are pleased to have the opportunity to share our views with the Food and Drug Administration (FDA) on their draft guidance regarding Decentralized Clinical Trials (DCTs) for Drugs, Biological Products, and Devices.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which 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.

DCTs have the potential to increase inclusion of underserved or rural communities and patients who are home-bound. It reduces geographic barriers by enabling patients to participate in clinical trials even if they do not live near a study site. This is much more convenient than traveling to a conventional study for medical interventions, data collection, assessments, and follow-up visits. However, the FDA and those conducting DCTs must also recognize how they could inadvertently reduce the enrollment of diverse populations when relying on digital health technologies (DHTs). The inability to access DHTs or lack of familiarity or comfort with DHTs could limit or prevent enrollment of older adults and children, participants living in rural areas, people who speak a language other than English, and people who have lower literacy skills or lower income. We recommend that FDA revise the guidance to incorporate the following strategies when implementing DCTs, including those that use DHTs:

  1. The guidance should incorporate information on how patients who decide to use their own DHTs during DCTs differ from those individuals who are provided a DHT during the study. Patients who regularly use these tools before study participation may differ in terms of several baseline health characteristics, vary in socioeconomic status, or have different health habits than those who do not have DHTs. Data recorded during a trial should include information on a participant’s prior device experience, as well as reasons for use, and include these variables in study analysis, as prior experience with a device could affect outcomes.
  2. DCTs using DHTs should consider and plan for the consistent availability and use of the same DHTs over time, even if newer versions of a device are introduced, as these updates could affect trial performance. Additionally, DHTs that require software on a participant’s phone or computer could undergo multiple app updates over the course of the study, with the potential to add new features that affect data input. Investigators must plan to follow-up with participants whenever major software updates occur.
  3. The FDA guidance mentions that sponsors should consider syncing information recorded by DHTs across different platforms. Digital health sources such as electronic health record (EHR) portals or portals linking data from personal digital devices, can be disconnected during the course of the DCT and require significant additional effort to reconnect. These disconnections can come from password changes and security issues which can result in the loss of data, which may be temporary or permanent depending on the willingness or ability of the participant to reconnect. Planning for this possibility is essential to ensure comprehensive data capture. Study teams should regularly review the completeness and quality of the DHT data over the course of the study to reduce missing data.
  4. The guidance mentions that, “training should be provided to all parties (e.g., trial personnel, local HCPs, and trial participants)” related to the software used in DCTs. This should apply to all DHTs and, as appropriate, should include caregivers who may assist study participants during DCTs.
  5. Although FDA states that researchers “should attempt” to collect data regarding healthcare services provided outside the study site. This does not adequately provide explicit directions on how to provide information regarding unexpected or routine visits to non-study sites, such as an ER visit for an adverse event that may or may not be obviously related to the clinical trial. The FDA guidance recommended that providers outside of the clinical trial not be included in the task log, which tracks health care providers that perform trial-related activities. However, if that information is not collected and evaluated, then significant information about safety issues would inevitably be missed. FDA should explicitly address how potentially important information should be included in the task log and re-evaluate the need to include these data points.