Category Archives: Policy

NCHR Comments on the USPSTF’s Draft Recommendation Statement, Evidence Review, and Modeling Report on Cervical Cancer Screening

Policy, Testimony & Briefings
National Center for Health Research: October 9, 2017

Thank you for the opportunity to express our views on the U.S. Preventive Services Task Force (USPSTF) draft recommendation statement, evidence review, and modeling report for cervical cancer screening. The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety. We do not accept funding from companies that make products that are the subject of our work.

We agree that this is the right time for the U.S. Preventive Services Task Force to re-evaluate its cervical cancer screening recommendations, due to new research studies and decision modeling analysis. In 2012, the USPSTF recommended starting screening at age 21 and stopping at age 65. Women could get a Pap every 3 years, or starting at age 30, women could get both a Pap and HPV test (co-test) every 5 years. Based on the USPSTF’s review, we agree with maintaining most of the 2012 recommendations, but have significant concerns about changes USPSTF has proposed.

We are very concerned about the proposed grade “A” recommendation to exclusively screen women with the HPV test every 5 years starting at age 30. As the Task Force recognized, clinical trial evidence to support primary HPV screening as a preferred screening strategy is inadequate. There is also a lack of well-designed and implemented clinical trials comparing co-testing and primary HPV screening. The pivotal ATHENA trial, the U.S. prospective study supporting the efficacy of primary HPV screening, had significant shortcomings and does not provide clear and substantial evidence that primary HPV testing reduces cancer incidence or mortality. The Task Force appropriately classified this study as “poor quality” and excluded it from the draft evidence review. However, some medical societies are still quoting it.

Due to lack of available evidence, the Task Force relied heavily on mathematical models to arrive at the grade “A” recommendation. While mathematical models that incorporate real world data help to support available evidence, they are hypothetical, and conclusions must still be weighed against evidence from clinical trials and observational studies. This definitely is well below the standard of an “A” recommendation; in fact, we believe screening based exclusively on HPV tests should not be recommended.

Based on the USPSTF’s decision modeling analysis, primary HPV testing potentially confers a slightly higher mortality benefit (approximately 10 life-years per 1000 women) compared to cytology alone, but it requires significantly more colposcopies to be done for each possible cancer averted (766 vs. 39). Moreover, the models demonstrate that primary HPV testing and co-testing prevent approximately the same amount of deaths, but co-testing would require more total tests (19,806 vs. 12,151). However, models are necessarily based on assumptions that are not necessarily accurate.  The conclusions from these models are not based on research conducted on actual patients.

In addition, while the USPSTF depended on the draft modeling report to conclude that primary HPV screening may provide more benefits than harms, other recent modeling analyses by Felix et al., concluded that screening by co-testing may be superior to screening by HPV test alone. Therefore, the totality of the evidence does not support eliminating co-testing as an acceptable strategy.

We therefore conclude that the Task Force’s grade “A” recommendation assigned to primary HPV screening is inappropriate, because it is primarily based on modeling analysis and not clinical trials or real-world data. This grade “A” would certainly mislead physicians and women to believe that there is incontrovertible evidence to support an HPV testing-only screening strategy rather than co-testing or Pap smear only testing. Since the recommendation is that women can select a Pap smear every 3 years or the HPV test every 5 years, many women will likely choose the less frequent screening option, not realizing that they will be at increased risk of needing additional, more invasive testing with the HPV test only screening.

The seven cited randomized clinical trials are difficult to interpret. First, the studies cannot be assumed to be representative of women in the U.S. since they were conducted primarily in European countries with national screening programs and more standardized triage strategies. Second, the studies were extremely heterogeneous in terms of test technology, screening intervals, and follow-up protocols. Third, the study results were mixed. For instance, the NTCC phase II trial found that hrHPV test alone had a higher CIN3 detection rate only in the first screening round, and actually had a lower rate of detection in the second round. The Task Force’s review contends that the “cumulative rate was still double.” However, it is possible  that detection rates of CIN3 declined in the second screening round because the lesions regressed due to HPV clearance.  Thus, perhaps the colposcopies triggered by HPV positivity in the first screening round were unnecessary. Bottom line: these data are inconclusive. Last, the studies included surrogate endpoints for cancer incidence and mortality, such as CIN2 or CIN3 detection. These endpoints are likely not the most meaningful outcomes for women, since CIN2/3 lesions do not always progress to cervical cancer and sometimes regress instead.  There are several other determinants of disease trajectory that may differ among women in different countries.

While we understand why the USPSTF advises women to “discuss with their provider which testing strategy is best for them” it is obvious that this advice will not necessarily provide excellent guidance for the average patient.  Many providers will not realize that population-based studies and well-conducted clinical trials do not substantially support primary HPV as a preferred testing strategy. Instead, providers are likely to depend on the USPSTF recommendation or those of medical societies, rather than careful scrutiny of the data.  Furthermore, the triage strategy for a positive HPV test is not standardized; it varies from cytology test, HPV genotype test, or direct colposcopy. Such a decision would depend on organized follow-up and would necessitate an informed discussion, which may not be possible in a single office visit. As suggested in the ARTISTIC subsample, a positive HPV test is likely to cause anxiety, and many patients will undergo colposcopy they would not have been needed had they been screened with a Pap smear instead.

In conclusion, we agree with maintaining much of the 2012 recommendations, but we strongly disagree with the proposed “A” rating for HPV testing alone, and urge that the USPSTF reconsider the shortcomings of the evidence and revise their recommendation to give preference to co-testing and Pap smears alone, rather than stand-alone HPV testing.

Thank you for the opportunity to comment on this most important issue which will have an impact on the lives of many adult women on a national level.

For questions or more information, please contact Danielle Shapiro, MD, MPH at ds@center4research.org.

References:

Felix, JC., et. al. The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening: A Modeling Analysis. J Women’s Health. 2016; 25(6):606-16

Draft Recommendation Statement: Cervical Cancer: Screening. U.S. Preventive Services Task Force. October 2017. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2

NCHR Statement on Right To Try Legislation before the House Energy and Commerce Subcommittee on Health

Legislation, Policy
Diana Zuckerman, PhD, National Center for Health Research: October 3, 2017

Chairman Burgess, Ranking Member Pallone, and distinguished Subcommittee Members:  Thank you for the opportunity to submit hearing testimony for the record.  The National Center for Health Research is a non-profit organization which analyzes medical and scientific data and produces original health-related research to inform patients, the general public, and policymakers.  We advocate for patients and consumers to have access to safe, effective, and affordable drugs and medical devices.  We accept no funding from the pharmaceutical or medical device industries.

We all agree that terminally ill patients should receive the best medical treatment as quickly as possible.  Some terminally ill patients are willing to take big risks to have a chance to live longer.  Unfortunately, many of us know desperate patients whose efforts to “try anything” made their remaining days miserable and left their families even more devastated.  What can and should Congress do to make sure that desperate patients won’t be exploited, or suffer even more painful deaths as a result of legislation?  That is the key question before you today.

It is essential that all Members of Congress understand what the various Right to Try bills would do.  A key issue is to understand what it means to give access to any experimental treatment that has been in at least one clinical trial. The earliest clinical trials (known as Phase I) often don’t include even one patient.  Instead Phase I trials can include “healthy volunteers” that are much less likely to be harmed by an experimental drug or device than a terminally ill patient would.

In addition, these first (Phase I) clinical trials study very small numbers of people, and do not study whether or not a product works.  They are designed to determine the immediate risks on just a few healthy volunteers or patients.  Since so few people are studied, even if a treatment is immediately and painfully fatal to 10% of patients, for example, these first clinical trials probably would not be able to provide that crucial information.

The Right to Try bill introduced by Representatives Griffith and Brat do not even require that a first clinical trial be completed – it can have just started.  In other words, there is no way that a patient could be warned about any terrible risks of those treatments.

The Johnson Right to Try bill (S 204) requires that a Phase I clinical trial be completed.  That is an improvement over the Griffith and Brat bill, but it is important to know that 85% of drugs that successfully complete Phase I clinical trials are later found to be unsafe or ineffective and are therefore never approved by the FDA.  So neither version would help most patients.

In contrast, the FDA’s current expanded Access Program requires at least some evidence that an experimental treatment might possibly be helpful.  That’s not a very restrictive safeguard, but it is helps protect many patients. The FDA routinely utilizes what the agency terms “compassionate waivers” for very ill patients when doctors request them, and FDA grants such requests 99% of the time.

Another important issue for Congress to consider is whether these bills would exploit patients financially. The experimental drugs provided through the current FDA Expanded Access program are provided for free most of the time, or “at cost.”  The same is true for clinical trials.  The Johnson bill also protects patients from financial exploitation by limiting what experimental treatments can cost.  The Griffith and Brat bill allows companies to charge whatever they want to dying patients desperate for access to any experimental drug or device – even one that has absolutely no evidence that it is either safe or effective.  That means that desperate patients could be required to pay exorbitant fees for the “Right to Try” to be treated like guinea pigs.  Many families would feel tremendous guilt if they could not afford to do so.

FDA’s compassionate use program could be improved, and improvements are already underway thanks to the Navigator program that the FDA has recently initiated with the Reagan Udall Foundation.  Other access issues are inherent in the situation where patients want drugs that are not yet being manufactured in large numbers or when the companies are reluctant to provide drugs that they fear will be harmful to patients who are too ill to benefit.  The GAO’s July 2017 report was generally supportive, with a few recommendations for improvement. And, GAO pointed out that most experimental drugs distributed under Expanded Access eventually obtain FDA approval.  In other words, the program is doing what was intended – giving patients earlier (usually free) access to experimental drugs that will eventually be proven safe and effective.

In addition to harming individual patients, making unsafe treatments available for sale harms our entire drug development enterprise, by eliminating the incentive for patients to participate in clinical trials that would help millions of patients in the future.  If HR 1020 was to become law, then it is likely that the richest patients will buy access to experimental treatments and only the middle-class and low-income patients will participate in clinical trials.  Reputable companies would continue to study new drugs and devices in clinical trials, but progress would be slowed because of difficulty attracting enough patients to participate in clinical trials.  Meanwhile, scam artists and fly-by-night companies would be motivated to make as much money as possible on dangerous or worthless experimental drugs for as long as they are available, and HR 1020 and would make it impossible to gather information about how dangerous their products are.

Such problems have long been documented regarding unproven treatments sold at outrageously high prices in Mexico and elsewhere, where some patients have been irreparably harmed or killed because they sought unproven treatments that were marketed dishonestly.  Indeed, tragedies arising from the “right to try” unregulated medical sales of the 19th Century and early 20th Century were the reason FDA was created, to protect patients and consumers.

To improve Right to Try legislation, Congress should:

  1. Ensure that experimental treatments cannot be sold at a profit by companies or medical professionals;
  2. Ensure that all experimental treatments have been proven safe in completed Phase I or Phase II trials conducted on a reasonable number of patients (not healthy volunteers);
  3. All experimental drugs and devices available through RTT should be studied as part of FDA’s regulatory process;
  4. Information about harmful side effects and adverse events should be required to be reported to the FDA by the physicians.

We strongly urge this Committee to reject the Right To Try legislation that is currently under consideration, because it would undermine the successful FDA compassionate waiver program already in place to enable patients to have access to experimental drugs for free or at cost.

Thank you for the opportunity to present our views.

NCHR Comments to CPSC on the Organohalogen Flame Retardant Petition

Legislation, Policy
National Center for Health Research: September 14, 2017

Thank you for the opportunity to speak today. The National Center for Health Research is an independent nonprofit organization that conducts research and scrutinizes research conducted by others. We often compare conflicting scientific and medical conclusions to determine which are more scientifically sound. We do not accept funding from chemical companies and pharmaceutical companies, in order to avoid conflicts of interest.

We have been very impressed with the Consumer Product Safety Commission’s careful review of children’s products that contain numerous phthalates and we urge the Commission to play a similarly important role regarding organohalogen flame retardants.

The EPA website clearly states that organohalogens “are highly persistent, bioaccumulative, and cause adverse effects in humans and wildlife. Because of the widespread use of these organohalogens in household items and consumer products, indoor contamination may be a significant source of human exposure, especially for children. One significant concern with regard to health effects associated with exposure to organohalogens is endocrine disruption.”[1]

All organohalogen flame retardants are semi-volatile organic compounds (SVOCs), and when they are in products that are indoors, OFRs migrate into air, dust, and films on surfaces such as walls and fabrics. They will also get on the skin, and although they can be washed off, OFRs in the air and surfaces will once again find their way onto the skin. The bottom line is that once OFRs are indoors, they will stay indoors and that means humans will be exposed day after day.

We were not involved in the petition, but note that it included footnotes of numerous relevant studies that we found persuasive. However, the scientific evidence is even stronger today, indicating that exposure from indoor sources can occur by:

1. Ingestion of dust containing OFRs,
2. Hand-to- mouth transfer of OFR-containing dust on hands or direct hand contact with a OFR-containing product,
3. Skin exposure from air or from clothing exposed to OFRs from indoor air and dust, and
4. Inhalation of OFRs found in indoor air.

Unfortunately, many children’s products contain OFRs and children are also exposed due to common household products such as sofas, mattresses, pillows, and electronics. For example, Dr Julie Herbstman from Columbia has conducted research indicating that pregnant women and children are exposed in their homes to detectable levels of PBDE as well as their halogenated replacements. She points out that children, infants, and fetuses are more vulnerable to health effects resulting from exposure to a variety of environmental chemicals, including halogenated flame retardants.

I hope you will carefully review her footnoted testimony, which clearly documents that OFRs in products are causing OFRs in air and dust: Concentrations of organohalogen flame retardants in dust are higher the closer the dust is to the OFR products;

  • The presence and number of products are statistically significantly associated with contamination levels of OFRs in air or dust; this means the association has at least a 95% probability of being proven, and did NOT occur by chance;
  • When one removes such a product from a room, the level of OFRs in air and dust decreases, and vice versa;
  • Organohalogen flame retardants are directly emitted from products when products are placed in an experimental chamber and the emissions measured. In an actual indoor environment, such emissions would result in flame retardant chemical contamination of the room’s air and dust.

In conclusion, flame retardants used in upholstered furniture, children’s products, mattresses and casings for electronics contribute significantly to the levels of indoor air and dust contamination, and subsequent to human exposures.

We agree with CPSC staff that there are likely to be variations in the impact of specific OFRs on human health. In the ideal world, it would make sense that each specific OFR proposed for use as flame retardants in consumer goods should undergo a risk assessment to determine whether it is safe to use. I understand the desire to be very precise and to determine whether some OFRs are safer than others, but in the meanwhile, we know as scientists that these exposures can be extremely harmful. If we look at all the scientific evidence on the toxicity of organohalogens, the risks are clear. As the Director of the National Institute of Environmental Health Sciences noted, it is not possible to study all OFRs, but so far all of them that have been studied are known to pose risks to human health, and especially prenatally and to children. We also know that the combination of exposures from these various chemicals can be much greater than is demonstrated in the study of just one OFR. In order to keep our children safe, it is essential to regulate OFRs collectively as a class unless and until there is scientific evidence that one or more particular OFRs is proven to be safe, and then treat that specific OFR differently.

Reference

  1. Kodavanti, P.S. and Curras-Collazo M. C. (2010). Neuroendocrine Actions of Organohalogens: Thyroid Hormones, Arginine Vasopressin, and Neuroplasticity. Retrieved from https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=225204.

NCHR Testimony at the FDA on Shingles Vaccine, Shingrix

Policy, Testimony & Briefings
Megan Polanin, PhD, National Center for Health Research: September 13, 2017

Thank you for the opportunity to speak today. My name is Dr. Megan Polanin. I am a Senior Fellow at the National Center for Health Research. Our research center analyzes scientific and medical data and provides objective health information to patients, providers, and policymakers. We do not accept funding from industry, so I have no conflicts of interest.

An effective shingles vaccine is important for public health. As patients get older, they are more likely to develop long-term pain, or post-herpetic neuralgia (PHN), as a complication of shingles. This pain can be severe and chronic. There is no cure, and treatments do not reliably relieve pain for all patients. The only way to reduce the risk of developing shingles and PHN is to get vaccinated.

Like any public health strategy, a vaccine’s benefits must outweigh its risks. Based on available research, Shingrix has displayed significant benefits compared with the current shingles vaccine on the market, Zostavax:

1) Shingrix showed much higher levels of vaccine efficacy (e.g. 97% for 50+ and 90% in 70+) ​ than the current shingles vaccine. Zostavax only reduces the occurrence of shingles by about half for patients 60 and older, and its effectiveness declines as patients age.  For patients 80 and older, Zostavax is only 18% effective.

2) Shingrix has displayed efficacy in preventing ​PHN​ in patients 50 years and older by preventing shingles. Zostavax is less effective in preventing PHN because it is less effective at preventing shingles. For people who were vaccinated and still developed shingles, Zostavax helped to reduce the duration of PHN, but not the severity of pain.

3) Shingrix can potentially be administered to vulnerable patients with ​weakened​ immune systems. Zostavax is a live attenuated vaccine, and therefore is not safe for people with weakened immune systems, such as patients who have had radiation or chemotherapy and those with HIV.

Shingrix requires two doses while Zostavax is a one-time injection. However, that is a small price to pay for a much more effective vaccine.

Post-licensure studies are critical as we need long-term data to evaluate Shingrix’s long-term efficacy for patients 50 years and older. This is especially relevant since Zostavax may no longer be effective 8 to 11 years after vaccination. The company’s proposed long-term follow-up studies will help to determine whether Shingrix is able to protect older adults from contracting shingles as they age. It is essential that those studies be completed in a timely matter and that the company provide adequate incentives to patients to stay in the study.

We do have some concerns about risks. Patients treated with Shingrix had a higher rate of common adverse reactions (e.g. 74% vs. 9% for placebo group), such as pain, swelling, and fatigue. In addition, one serious adverse event, supraventricular tachycardia, was reported more frequently for patients vaccinated with Shingrix compared with patients who had not during the 30-day post-vaccination period. We are also concerned about optic ischemic neuropathy, which was reported within 30 days by 2 patients, within 2 months by another patient, and not reported at all in the placebo group. These issues warrant further attention.

For that reason, we agree with the company and FDA reviewers that continued pharmacovigilance is critical to evaluate adverse events for patients vaccinated with Shingrix compared to those vaccinated with Zostavax and those with placebo. This should include uncommon adverse events observed soon after vaccination and any other adverse events that may arise with larger sample sizes in longer-term studies.

We concur with the FDA’s requests that the company specifically address risks of inflammation from the vaccine, which can lead to the some of the adverse events reported during pre-licensure studies (e.g. optic ischemic neuropathy, gout).

We urge this Advisory Committee to recommend that the FDA require critical post-approval long-term studies to further evaluate the efficacy and safety of Shingrix. We also strongly recommend that the company conduct subgroup analyses to ensure that the vaccine is safe and effective for both women and men and also people of color.

Thank you for the opportunity to share our perspective.

The Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 11-0, that the available data are adequate to support the efficacy and safety of Shingrix when administered to adults 50 years of age and older. 

Letter from NCHR about Dangerous Playgrounds and Athletic Fields to the Mayor and City Council of Washington, DC

Legislation, Policy
National Center for Health Research: July 19, 2017

Dear Mayor Bowser and Council Members,

I am writing as the president of the National Center for Health Research to express my strong concerns about the safety of the synthetic turf that the DC government has used and is continuing to use across the city, including installation that will soon be underway at Janney Elementary.

As a scientist who has worked on health policy issues for 30 years, I don’t shock easily. However, the fact that school athletic fields and playgrounds are exposing D.C. children on a daily basis to chemicals and materials that are known to increase obesity, cause early puberty, cause ADD and other attention problems, harbor deadly bacteria, and exacerbate asthma is very disturbing. Surely these are exactly the types of health problems that the DC government should be doing its best to reduce, not increase. Federal agencies are investigating the safety of these products – even during the Trump Administration – and yet neither District officials nor parents are being provided with accurate information about the products being used.

Whether natural grass or synthetic materials, all types of turf have risks and benefits. However, some materials are well known to have substantial risks. For example, DCPS is installing synthetic turf with Envirofill at Janney Elementary and possibly other schools, even though the Department of Parks and Recreation has already determined that product to be too unsafe to install at city parks. Envirofill was slated for installation at Friendship (Turtle) Park, but after local parents briefed DC officials about problems with the product on June 9th, the District revised its plans and did not install that material. Since children play on school fields five days a week, under the direction of their teachers, this is a particularly questionable decision on the part of DCPS, for safety reasons and in terms of legal liability. How does it make sense that a product is not safe enough for a public park but is safe enough for a school field or playground?

I don’t know if you are aware of the number of synthetic turf fields across the District that have been condemned because of failing safety tests. Gmax is a score that tests for hardness to determine if a surface is safe for playing. A Gmax over 200 is considered extremely dangerous and is considered by industry to pose a death risk. The synthetic turf industry and ASTM suggest that scores should be below 165 to ensure safety comparable to a grass field. It is my understanding that there are at least six fields in the city that are over the 200 level. That information should be made public to all parents, so that they understand why fields are closed and can protect their children’s safety. Since the Gmax score varies with the weather, synthetic fields should be tested at least quarterly, all scores should be posted publicly, and scores over 165 should have warning signs in order to prevent traumatic brain injuries.

This has not happened. For example, the Gmax score at Janney Elementary tested over 200 in June, and yet that information was not made public and the field was used by camp children all summer. Despite the repeated requests of concerned parents for the last few months, the field wasn’t closed until the day before school started last week. Parents were justifiably upset that the field was closed when school started, and some parents claimed to have been told by school staff that the Mayor’s office stated that the field would be closed all year and perhaps forever. It seems unlikely to me that the Mayor’s office would have said such a thing, but it resulted in ugly and unfair accusations. The many parents who were concerned about the safety of the synthetic field were bullied into silence, and a small number of parents who wanted the field available immediately erroneously claimed that all parents agreed that synthetic field was best.

As a result of that controversy, DC officials have recently stated that Envirofill will be used at Janney. Envirofill is basically a type of infill underneath a plastic carpet. It 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 is contained 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; here’s a screen grab from a November 2016 Patriots vs. Seahawks game, which shows how the silica sand infill is kicked up when players dive on a synthetic surface with silica sand infill.

In addition, the Envirofill pellets are coated with an antibacterial called Microban, which is a trade name for triclosan. Triclosan is registered as a pesticide with the United States Environmental Protection Agency (EPA), and last year the FDA banned triclosan from soaps because manufacturers did not prove that that the ingredients are safe for long-term use, since it is associated with liver and inhalation toxicity and hormone disruption. In addition to microscopic particles of synthetic turf infill being inhaled by children, visible and invisible particles come off of the field, ending up in shoes, socks, pockets, and hair.

I have appreciated the opportunity to meet with several Councilmembers’ staff in the last few weeks, and I commend the Council for banning crumb rubber in FY 2018. Unfortunately, however, Envirofill, “poured in place” rubber (PIP), EPDM, and all the other synthetic materials currently on the market all share some of the same health risks. While the companies that sell these products claim they are safe and meet federal safety standards, the sad truth is that there are currently no federal safety tests required to prove that these products are safe, and as noted earlier, the Gmax safety tests have until recently been ignored by DC officials. Most important, none are proven to be as safe as natural grass in well-constructed fields such as the Maryland Soccerplex. Although a well-respected grass expert offered a free consultation on how to install well-engineered grass designed to withstand rain and play. DGS did not respond to his offer.

I am one of many parents and scientists in DC that are asking DC officials to provide essential safety information about the materials being used for fields and playgrounds. We are offering our expertise on these issues and would welcome the opportunity for public meetings so that parents across the city can be informed.

Sincerely,

Diana Zuckerman, Ph.D.
President
National Center for Health Research
1001 Connecticut Ave, NW, Suite 1100
Washington, DC 20036

NCHR Comments on CPSC Agenda and Priorities for FY2018-2019

Testimony & Briefings
Diana Zuckerman, PhD, National Center for Health Research: July 26, 2017

 

Diana Zuckerman, PhD, President of National Center for Health Research 
Comments on the U.S. Consumer Product Safety Commission 
Agenda and Priorities for FY2018/2019

The National Center for Health Research is a nonprofit research center staffed by scientists, medical professionals, and health experts who analyze and review research on a range of health issues. Thank you for the opportunity to share our views concerning the Consumer Product Safety Commission’s (CPSC) priorities for fiscal year 2018 and 2019. We respect the essential role of the CPSC, as well as the challenges you face in selecting the most important priorities.

Two priorities that are clearly consistent with CPSC priorities are the safety of children’s products. We are very concerned about exposures to phthalates in children’s toys and other products as well as endocrine-disrupting chemicals and other safety concerns related to recycled tire crumb rubber and other artificial turf (including “poured in place” surfaces).

The CPSC has been a champion for children with its careful analysis of phthalates in toys and products for children under 3 years of age. As you know, products specifically for children under 3 are not the only ones that pose risks: we need to also be concerned about phthalates in many products used by pregnant women and children. Through dust and other means, phthalates migrate from many products into our environment and bodies. Phthalate metabolites are detectable in nearly all people in this room and in the U.S.[1] Many phthalates are endocrine disruptors that can have long-term effects on our health and children’s development, including their ability to learn.

Our Center was instrumental in shaping the law resulting in permanent and temporary bans on six phthalates in children’s toys and child care articles.[2] However, these bans need to be expanded. Over 2 years ago, CPSC proposed the rule “Prohibition of Children’s Toys and Child Care Articles Containing Specified Phthalates” following the Chronic Hazard Advisory Panel (CHAP).[3][4] This rule is absolutely essential in providing additional protections for children.

We support the permanent bans on four additional phthalates (DIBP, DPENP, DHEXP, and DCHP) and making permanent the interim ban on DINP.[3] However, the CHAP report also recommended an interim ban on DIOP, which should also be included in the rule. We strongly disagree with the proposal to lift the interim bans on DNOP and DIDP. While they may not affect male hormones, they are associated with organ toxicity and altered development.

The CHAP report also recommended additional studies on three other phthalates (DMP, DPHP, and DEP) and six phthalate alternatives.[4] The final rule should include a timeline for the completion of these studies that reflects the potential damage these phthalates can cause.

It is also important for CPSC to expand its work on phthalates to include products that can cause prenatal exposures as well as those that can harm older children and other vulnerable adults. Phthalate exposure has been found to increase risk for early puberty and problems with reproduction.[5][6][7] This is especially important because a new meta-analysis of 185 studies shows that male sperm counts are less than half what they were just a generation ago.[8]  Phthalate exposure also affects pregnant and breastfeeding women and thus their children, which can affect brain and reproductive system.[4][9] Phthalates in household dust can be extremely harmful regardless of what products it comes from.

Artificial turf made with recycled tire crumb rubber and other products raises similar issues because it is widely used and can release chemicals that affect the health of children of all ages, pregnant women, and other adults. Artificial turf is currently used on more than 12,000 athletic fields and numerous playgrounds in the U.S. and most parents are unaware of the risks it poses.[10]

Scientific evidence suggests that crumb rubber, “poured in place” (PIP) rubber and other artificial turf pose potential safety hazards when used on playground and playing field surfaces. Rubber from recycled tires and even from “virgin tires” and “virgin rubber products” is not comprised only of rubber from a rubber plant.  Instead it includes phthalates, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), heavy metals, and other chemicals known or suspected to harm human health.[11][12][13][14] In addition to disrupting hormones, some PAHs may increase a person’s chance of developing cancer.[15][16] While one time or sporadic exposures are unlikely to cause long-term harm, repeated exposures over years, especially during critical developmental periods clearly raise the likelihood of harm.

Artificial turf made with crumb rubber and poured rubber products can also cause short-term harms. For example, crumb rubber generates dust which may exacerbate asthma for children.[17][18] These products heat up much more than ambient temperature, which can cause heat stress and burns.[19][20][21]
In addition, some studies have indicated increased risk for joint injuries and mild traumatic brain injury.[22][23] In other words, we can conclude that grass is a relatively safe alternative. We can’t say that of artificial turf, whether crumb rubber or other products.

As is often the case when researchers are paid by those with conflicts of interest, some studies suggest that the risk is minimal. However, the studies that are more reassuring do not comprehensively evaluate health risks from exposure to recycled tire crumb material. In addition, many studies of air quality pertaining to crumb rubber and similar products use stationary measures, while particulate matter becomes airborne during activity, so these measurements may not accurately reflect exposures during play activities.[24] Our conclusion from the research is that definitive studies of the harm caused by crumb rubber and other rubber products are difficult to conduct, but there are clear reasons to be concerned about children being harmed by them.

We are encouraged that the CPSC is working with other federal agencies to investigate the safety of crumb rubber on playgrounds and playing fields.[8][25][26]

However, we strongly urge you to broaden your investigation to include other synthetic rubber products and to provide warnings to families and athletes as soon as possible. The public has limited access to information about the chemicals that make up these products, which can affect our health and that of our children. All Americans rely on the CPSC to protect us and our children from unsafe products.

In summary, we strongly urge the CPSC to consider our views as it finalizes the proposed rule on phthalates in children’s toys and child care articles, and consider how these rules could be expanded to cover other products that expose children and adults to harmful substances.

References

  1. National Health and Nutrition Examination Survey (NHANES). (2016) Phthalates and Plasticizers Metabolites – Urine (PHTHTE_H); years of content 2013-2014. https://wwwn.cdc.gov/Nchs/Nhanes/2013-2014/PHTHTE_H.htm
  2. Federal Register. (2014) Consumer Product Safety Commission. Prohibition of Children’s Toys and Child Care Articles Containing Specified Phthalates. Docket No. CPSC-2014-0033. http://www.gpo.gov/fdsys/pkg/FR-2014-12-30/pdf/2014-29967.pdf
  3. Federal Register. (2014) Consumer Product Safety Commission. Prohibition of Children’s Toys and Child Care Articles Containing Specified Phthalates. Docket No. CPSC-2014-0033. http://www.gpo.gov/fdsys/pkg/FR-2014-12-30/pdf/2014-29967.pdf
  4. Consumer Product Safety Commission. (2014) Chronic Hazard Advisory Panel On Phthalates and Phthalate Alternatives.https://www.cpsc.gov/PageFiles/169876/CHAP-REPORT-FINAL.pdf
  5. Bourguignon JP, Juul A, Franssen D, Fudvoye J, Pinson A, Parent AS. (2016) Contribution of the Endocrine Perspective in the Evaluation of Endocrine Disrupting Chemical Effects: The Case Study of Pubertal Timing. Hormone Research in Paediatrics. 86(4):221-232.
  6. Wang YX, Zeng Q, Sun Y, Yang P, Wang P, Li J, Huang Z, You L, Huang YH, Wang C, Li YF, Lu WQ. (2016) Semen phthalate metabolites, semen quality parameters and serum reproductive hormones: A cross-sectional study in China. Environmental Pollution. 211:173-82.
  7. Hannon PR, Flaws JA. (2015) The effects of phthalates on the ovary. Frontiers in Endocrinology. 6:8.
  8. Levine H, Jøgensen N, Martino-Andrade A, Mediola J, Weksler-Derri D, Mindlis I, Pinotti R, Swan SH. (2017) Temporal trends in sperm count: a systematic review and meta-regression analysis. Human Reproduction Update. 1-14.
  9. Ejar Ejaredar M, Nyanza EC, Ten Eycke K, Dewey D. (2015) Phthalate exposure and childrens neurodevelopment: A systematic review. Environmental Research. 142:51-60.
  10. Synthetic Turf Council. About synthetic turf. https://syntheticturfcouncil.site-ym.com/page/About_Synthetic_Turf
  11. Llompart M, Sanchez-Prado L, Lamas JP, Garcia-Jares C, Roca E, Dagnac T. (2013) Hazardous organic chemicals in rubber recycled tire playgrounds and pavers. Chemosphere. 90(2):423-431.
  12. Marsili L, Coppola D, Bianchi N, Maltese S, Bianchi M, Fossi MC. (2014) Release of polycyclic aromatic hydrocarbons and heavy metals from rubber crumb in synthetic turf fields: Preliminary hazard assessment for athletes. Journal of Environmental and Analytical Toxicology. 5:(2).
  13. California Office of Environmental Health Hazard Assessment (OEHHA). (2007) Evaluation of health effects of recycled waste wires in playground and track products. Prepared for the California Integrated Waste Management Board.http://www.calrecycle.ca.gov/publications/Detail.aspx?PublicationID=1206
  14. Kim S, Yang J-Y, Kim H-H, Yeo I-Y, Shin D-C, Lim Y-W. (2012) health risk assessment of lead ingestion exposure by particle sizes in crumb rubber on artificial turf considering bioavailability. Environmental Health and Toxicology. 27, e2012005.http://doi.org/10.5620/eht.2012.27.e2012005
  15. U.S. National Library of Medicine, National Institutes of Health. (2017) Tox Town (Environmental health concerns and toxic chemicals where you live, work, and play): Polycyclic aromatic hydrocarbons (PAHs). https://toxtown.nlm.nih.gov/text_version/chemicals.php?id=80
  16. Armstrong B, Hutchinson E, Unwin J, Fletcher T. (2004) Lung cancer risk after exposure to polycyclic aromatic hydrocarbons: a review and meta-analysis. Environmental Health Perspectives, 112(9), 970.
  17. Shalat SL. (2011) An evaluation of potential exposures to lead and other metals as the result of aerosolized particulate matter from artificial turf playing fields. Submitted to the New Jersey Department of Environmental Protection. http://www.nj.gov/dep/dsr/publications/artificial-turf-report.pdf
  18. Mount Sinai Children’s Environmental Health Center. (2017) Artificial turf: A health-based consumer guide. http://icahn.mssm.edu/files/ISMMS/Assets/Departments/Environmental%20Medicine%20and%20Public%20Health/CEHC%20Consumer%20Guide%20to%20Artificial%20Turf%20May%202017.pdf
  19. Thoms AW, Brosnana JT, Zidekb JM, Sorochana JC. (2014) Models for predicting surface temperatures on synthetic turf playing surfaces. Procedia Engineering. 72:895-900.
  20. Penn State’s Center for Sports Surface Research. (2012) Synthetic turf heat evaluation- progress report. http://plantscience.psu.edu/research/centers/ssrc/documents/heat-progress-report.pdf
  21. Serensits TJ, McNitt AS, Petrunak DM. (2011) Human health issues on synthetic turf in the USA. Proceedings of the Institution of Mechanical Engineers, Part P: Journal of Sports Engineering and Technology, 225(3), 139-146.
  22. Balazs GC, Pavey GJ, Brelin AM, Pickett A, Keblish DJ, Rue JP. (2015) Risk of anterior cruciate ligament injury in athletes on synthetic playing surfaces: A systematic review. American Journal of Sports Medicine. 43(7):1798-804.
  23. Theobald P, Whitelegg L, Nokes LD, Jones MD. (2010) The predicted risk of head injury from fall-related impacts on to third-generation artificial turf and grass soccer surfaces: a comparative biomechanical analysis. Sports Biomechanics. 9(1):29-37.
  24. U.S. Environmental Protection Agency. (2017) Federal research on recycled tire crumb used on playing fields. https://www.epa.gov/chemical-research/federal-research-recycled-tire-crumb-used-playing-fields
  25. U.S. Consumer Product Safety Commission. Crumb rubber information center.https://www.cpsc.gov/Safety-Education/Safety-Education-Centers/Crumb-Rubber-Safety-Information-Center
  26. U.S. Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (ATSDR). (2016) Federal research action plan on recycled tire crumb used on playing fields and playgrounds. https://www.atsdr.cdc.gov/frap/index.html

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

Policy, Testimony & Briefings
National Center for Health Research: August 10, 2017

Comments on the USPSTF’s Draft Recommendations for Ovarian Cancer Screening

Thank you for the opportunity to express our views on the draft recommendations for ovarian cancer screening. The Cancer Prevention and Treatment Fund is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

We support the efforts of the U.S. Preventive Services Task Force (USPSTF) to re-evaluate its 2012 grade “D” recommendation in light of new results from a large study, the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). This study confirmed that screening for ovarian cancer does not decrease deaths from ovarian cancer in asymptomatic women who are not known to be at high risk for ovarian cancer. Based on the USTSPF’s robust review of the literature, we agree that there is insufficient evidence to support screening for asymptomatic women.

Effective screening is urgently needed to reduce the number of deaths from ovarian cancer, which is estimated to exceed 14,000 in the United States this year. When ovarian cancer is treated before the cancer has spread outside the ovaries and fallopian tubes, the 5-year relative survival rate is 93%. However, the FDA warns that studies in the medical literature do not provide evidence that currently available ovarian cancer screening tests are accurate and reliable, particularly for asymptomatic women.

We agree with the USPSTF that none of the studies indicated that screening significantly reduced ovarian cancer mortality. Additionally, researchers found that the risks of screening for women are significant, including a high number of false-positive results, which can lead to unnecessary surgery and other medical complications. We agree that these significant potential risks outweigh the benefits of early detection for women with no symptoms of ovarian cancer.

In conclusion, we strongly support the USPSTF’s draft recommendation to maintain the “D” grade for ovarian cancer screening, as well as their broader efforts to improve the health of all Americans by making evidence-based recommendations about clinical preventive services. We also appreciate the attention to quality of life as an outcome of interest, as this is an important factor. As more high-quality research becomes available, we encourage the provision of additional recommendations about the benefits and harms of using new screening strategies in asymptomatic women who are not known to be at increased risk for ovarian cancer.

The USPSTF issued its final recommendation statement on February 13, 2018. The Task Force maintained its grade D recommendation, meaning it does not recommend ovarian cancer screenings in asymptomatic women. 

References

Food and Drug Administration (2016, September 7). The FDA recommends against using screening tests for ovarian cancer screening: FDA Safety Communication. Retrieved from https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm519413.htm

National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Cancer of the Ovary: 5-Year Relative Survival by Stage at Diagnosis (2007-2013). Retrieved from https://seer.cancer.gov/csr/1975_2014/browse_csr.php?sectionSEL=21&pageSEL=sect_21_table.08.html#table5

U.S. Preventive Services Task Force (2017, July). Draft Recommendation Statement. Ovarian Cancer: Screening. Retrieved from https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement174/ovarian-cancer-screening1

U.S. Preventive Services Task Force (2018, February). Final Recommendation Statement. Ovarian Cancer: Screening. Retrieved from https://www.uspreventiveservicestaskforce.org/uspstf/document/RecommendationStatementFinal/ovarian-cancer-screening 

 

 

 

 

NCHR Comment on the USPSTF’s Draft Recommendations for Hepatitis B Virus Infection Screening in Pregnant Women

Policy, Testimony & Briefings
National Center for Health Research: August 9, 2017

Comment on the USPSTF’s Draft Recommendations for Hepatitis B Virus Infection Screening in Pregnant Women

Thank you for the opportunity to express our views on the draft research plan regarding screening for the Hepatitis B virus infection in pregnant women. The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

Hepatitis B is a virus infection that is best prevented through vaccination. The risk of infection is especially high for newborns; 90% of infected infants become chronically infected. Chronic Hepatitis B can lead to serious health issues, such as cirrhosis or liver cancer, and in the United States, results in an estimated 1,800 deaths per year. Detecting Hepatitis B infection in pregnant women and preventing transmission to their children would benefit our society greatly by decreasing its disease burden.

Women who are pregnant are at a unique moment in their health care journey, during which they have multiple visits with a provider. Ideally, strong and trusting relationships will develop between women and their doctors. Thus, the capacity for women to acquire knowledge and respond to information regarding screening and potential immunization is greater during pregnancy than at other times and with other providers. This can lead to positive public health outcomes.

The U.S. Preventive Services Task Force (USPSTF) last reviewed the literature in 2009 and reaffirmed their “A” grade for HBV screening for women at their first prenatal visit. We support the efforts of the USPSTF to carefully draft a research plan to guide the systematic review of available evidence for universal screening and case management programs to prevent vertical transmission of the infection as well as reduced rates of morbidity and mortality. We also endorse the efforts of the USPSTF to obtain updated information on the harms and benefits of universal screenings and case management programs for women with Hepatitis B.

We have two recommendations regarding key and contextual questions:

1) While the proposed research questions may intend to refer to both the mother and child, they do not explicitly state the benefits and harms of maternal screening and subsequent immunization or administration of HBIG for children. We believe that explicitly including harms and benefits to children in utero within your proposed questions will improve your research plan.

2) We commend the USPSTF’s inclusion of proposed contextual question #1 to address subgroup analyses. We particularly recommend subgroup analyses by race/ethnicity, mothers’ age, and mothers’ health. Some subgroups of pregnant women may experience different levels of benefits/harms, and this information is critical in making a recommendation for all women. In addition to benefits, we recommend including any harms of repeat screening in the third trimester based on the presence of specific risk factors for different groups of pregnant women.

Universal screening and prevention programs for pregnant women with Hepatitis B can help to identify pregnant women who are at risk for passing the virus to their children. Preventing vertical transmission protects children from a potentially serious disease and other diseases that may develop as a result, such as cancer; protects others who may be infected; and allows children to participate in school and play activities important to their healthy development. Therefore, screening is highly beneficial for these children.

In conclusion, we support the USPSTF’s draft recommendation for Hepatitis B screening in pregnant women as well as their broader efforts to improve the health of all Americans by making evidence-based recommendations about clinical preventive services.

For questions or more information, please contact Megan Polanin, PhD at mp@center4research.org or at (202) 223-4000.

References

Centers for Disease Control and Prevention (2015, May 31). Viral Hepatitis. Retrieved from https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm#overview

U.S. Preventive Services Task Force (2017, July). Draft Research Plan for Hepatitis B Virus Infection in Pregnant Women. Retrieved from https://www.uspreventiveservicestaskforce.org/Page/Document/draft-research-plan/hepatitis-b-virus-infection-in-pregnant-women-screening

CPTF Response to Senate Health bill

Legislation
Jack Mitchell, Director of Health Policy, National Center for Health Research, on behalf of Cancer Prevention and Treatment Fund: July 14, 2017

The Senate’s revised health bill was revealed on July 13, 2017.

Unfortunately, the revised Better Care Reconciliation Act of 2017 will result in much worse, not better, health care for Americans than our current healthcare program.

Tell me more about the bill

In its current form, over time the bill will:

  • Devastate Medicaid and make insurance coverage unaffordable to millions: it would reduce/deny health care to millions of Americans, especially people over 50, those that are working or middle-class, and people with disabilities, including addictions requiring treatment. States would have unsustainable costs passed along to them by the federal government, resulting in tax increases or cuts in education and other services.
  • Change what health services may be provided: States would be permitted to change or determine what qualifies as an essential health benefit. This would be life-threatening to many patients and create confusion and inequality throughout the health care system.
  • Result in higher premiums and co-pays for most Americans: Consumers will pay more because the bill does not include a requirement or any incentives for healthy Americans to buy health insurance.  When healthier people don’t buy insurance, that increases the price of insurance for everyone who does buy it.
  • Who benefits? The cuts in Medicaid would save the federal government billions of dollars, but the GOP has made it clear that they will use those savings to reduce the taxes on the wealthiest Americans.  It’s reverse Robin Hood: reduce healthcare for middle class and poorer Americans and use the savings to cut taxes to corporations and the richest Americans.

This legislation will unleash a slowly unwinding health care catastrophe.

Take Action

Make your voice heard today and call your senators!

You can use this national call-in number: 202-224-3121

Tell them to vote NO because this bill would make healthcare unaffordable for millions of Americans. Also, it was created in secret, behind closed doors, with no hearing, debate or public input.

Here are some tips for calling your senators.

Testimony at FDA Advisory Committee Oncology Meeting on Mylotarg (“GO”)

Testimony & Briefings
Jack Mitchell, National Center for Health Research, July 12, 2017

Thank you for the opportunity to speak today.  I’m Jack Mitchell, Director of Health Policy at the National Center for Health Research (NCHR).  Our research center analyzes medical and scientific data to provide objective health information to patients, providers and policy makers.  We do not accept funding from pharmaceutical or medical device companies, and so I have no conflicts of interest to report.

I’m not a scientist or clinician, but I previously worked in a senior position in FDA’s Office of the Commissioner and we have a number of science and public health PhDs on our staff.  I’m presenting the organization’s views on behalf of the many patients and consumers whom we represent.

While we strongly support the need for more and better treatments for AML (Acute Myeloid Leukemia) patients, we are very concerned about the data used to support the application for GO.  Problems with the trial design raise questions about its validity.

First of all, the only pivotal trial was open label, which increases the risk for bias.  The purpose of blinding in a clinical trial is to control for the placebo effect, since the knowledge that one is taking the newest experimental drug tends to encourage patients and clinicians to have a greater belief in a perceived effectiveness.

Second, all lower grade safety events and some important severe safety events were collected retrospectively, which increases the risk for inaccuracies.  And, which as FDA presenters have noted, limits the analysis of the safety profile.

Third, the trial took place only in France.  This is of note because there are numerous examples of medical products that do not work as well in American patients as they do in patients in other countries.  French patients can have different health habits and health care.  These issues would raise concerns, even if the data supporting approval was strong, which we believe they are not.  Instead, it is not clear that the data support the efficacy or safety of GO.

As I noted previously, the application is based on a single pivotal trial along with a review of the literature.  The pivotal trial does not provide evidence for overall survival, and the previous clinical trial included in the literature review found an inconsistent effect of GO in overall survival.  It is important to remember that this drug was approved based on a single trial and later removed from the market, in part, because the post-market study did not demonstrate effectiveness.

The pivotal trial and literature review do demonstrate improvement in event-free survival.  The trial also shows an improvement in relapse-free survival.  However, the important metric is overall survival, which is not clearly demonstrated.  FDA reviewers and the sponsor’s scientists showed that event-free survival does not correlate well with overall survival.  This especially is a problem in an open label study where the placebo effect can’t be controlled.

Our research center recently published an article in an AMA journal revealing that many cancer drugs have been approved based on surrogate endpoints, such as event-free survival.  But later studies have found that those drugs did not improve overall survival or quality of life.  We found that patients and their insurers were spending $100,000 or more and suffering serious adverse events for treatments that often had no measurable benefit for their health or survival.

The change in dosing does appear to reduce adverse events compared to the earlier version of this medication.  Nevertheless, there were still serious adverse events that can result in death.  The drug was associated with increased bleeding events, including four fatal hemorrhages, and liver disorders, including three fatal cases of VOD (veno occlusive disease).  There were no fatal hemorrhage or VOD events that occurred without exposure to the drug.   However, we acknowledge the sponsor’s efforts to address the ongoing VOD issue and risk profile.

It’s noteworthy that these results were in a clinical trial where patients are carefully monitored.  Patients in the real world are typically monitored less carefully than patients in clinical trials.  As a result, it is possible that more patients could continue on a drug causing serious adverse events because they hope the drug will improve their condition, putting themselves at increased risk.  Well-intentioned doctors who are unaware of the history of the drug may also decide to increase the dose of patients who are not improving, putting patients at greater risk for adverse events without improving the chance for survival.

In summary, surrogate endpoints, such as event-free survival, often do not predict overall survival or other measures of improved health or quality of life.  Given the research design, only one pivotal study, the lack of U.S. patients, and a less than convincing literature review, the data do not support sufficient support for approval.  The studies, in our view, do not provide strong evidence that GO is effective and there are still continuing safety concerns.

We believe that the evidence does not indicate that the benefits outweigh the risks, which is the most single important consideration before you today.  Thank you for providing this opportunity to present our views.