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FDA Proposes Allowing Medical Device Makers to Summarize Malfunctions

In the News, News Stories & Editorials
Jim Spencer, Star Tribune: February 24, 2018

A Food and Drug Administration (FDA) proposal to let medical device makers summarize malfunctions of certain products instead of filing a report for each incident has kicked off a debate over the public’s ability to judge safety.

Regulators and device industry representatives say the proposal is an efficiency measure limited to malfunctions that do not threaten lives or health and only involves the least risky devices on the market. Summaries that bundle “like events” into summary reports as the FDA proposes let the government, businesses and the public pick up on trends sooner, they say.

“I think it will be very good and not just for our members,” said Shaye Mandle, CEO of Medical Alley, the trade group representing Minnesota’s massive medical technology sector. “I think everybody wins.”

Currently, device makers must file individual reports of device problems with detailed narratives. Depending on the severity of the malfunction, those reports are due within five days or 30 days of a company learning about them from any source.

The move to quarterly filings of single report summaries concerns some patient advocates and those seeking more detailed public disclosure of device problems. They base their worry on existing FDA summary reporting programs that they say keep too many details secret.

“FDA already has difficulty keeping up with device reports that would generate corrective action in a timely manner,” said Jack Mitchell, director of health policy at the National Center for Health Research. “When companies have submitted summary reports in the past, it has resulted in less transparency, with neither FDA nor the public able to have access to adequate information about patients who have been seriously harmed by medical devices. This proposal would further weaken the current post-market safety surveillance system for devices, which is already passive and inadequate.”

Star Tribune investigations into current FDA summary reporting practices found that the agency allowed Medtronic to summarize a study that revealed more than 1,000 malfunctions of its Infuse bone graft in three sentences within a single “marker report” more than five years after the law required the company to reveal those adverse events individually. The FDA also redacted the total number of injuries and complications as a “trade secret” until the newspaper appealed the decision.

Medtronic says that it should have filed the data sooner, but says it misplaced the study for several years and reported it as soon as it was found. The company says it then complied with all requests the FDA made for information about the study.

Medtronic declined to comment on the new FDA summary program, deferring to its national trade group, the Advanced Medical Technology Association (AdvaMed).

In addition to letting Medtronic summarize overdue malfunction reports, the Star Tribune investigation discovered that the FDA has allowed other companies to offer limited, consolidated and sometimes redacted data on thousands of late individual malfunction reports through an informal process called “retrospective summary reporting.”

An FDA spokeswoman did not respond to a question about redactions. She said she could not speculate on whether individual products such as Infuse would qualify for the new summary reporting program, which lets companies that make products with certain device codes file quarterly reports in a summary format. Nor would she say how or if malfunctions resulting from non-FDA-approved uses of devices would be cataloged. Off-label use can be an issue. For instance, research has estimated that Infuse is used off-label 85 percent of the time. […]

Read the original article here.

NCHR Letter to House Energy and Commerce Committee on Right To Try Legislation

Legislation, Policy
National Center for Health Research, February 22, 2018

Dear Members of the House Energy and Commerce Committee,

As a research center that advocates for the best medical treatments for all Americans, we strongly believe that terminally ill patients should have access to potentially life-saving medical treatments.  Some terminally ill patients are willing to take big risks to have a chance to live longer, and if they want access to experimental treatments that are undergoing clinical trials, they should be able to do so as long as they are well informed of the risks as well as the possible benefits.

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 as you consider Right to Try legislation.

A key issue for Congress to consider is whether legislation should provide access to experimental treatments that have been in only one or two preliminary clinical trials. The earliest clinical trials (known as Phase I) often don’t include even one patient.  Instead Phase I trials can include “healthy volunteers,” such as college students, who 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 medical 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 5-10% of patients, for example, these first clinical trials probably would not be able to provide that crucial information.

There are several Right to Try bills under consideration.  For example, the Right to Try bill introduced by Representatives Griffith and Brat (HR 1020) does not even require that a first (Phase 1) clinical trial be completed – it can have just started.  In other words, the experimental treatment could be fatal to many patients and it would be impossible to know that, or to warn patients about it.  That bill also completely restricts any oversight by FDA, and prohibits the agency from requiring the collection or disclosure of any information generated by the experimental drug therapy.  This lack of disclosure is especially problematic since the bill would protect manufacturers and suppliers of such drugs from liability except in cases of “gross negligence or willful misconduct.”

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 85% of drugs that successfully complete Phase I clinical trials are later found to be unsafe or ineffective and are therefore never sold in the U.S. or other countries.  So neither of these Right to Try bills would help most patients, and could potentially be fatal to many patients.  The Senate bill also restricts liability to any participant, except instances of “reckless or willful misconduct, gross negligence, or an intentional tort under any applicable State law.”  The bill directs that an annual summary of the use of any such experimental drug be provided to the HSS Secretary’s Office for later posting on the FDA web site.

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 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.”  Clinical trials also usually provide experimental treatments for free.  The Johnson Senate bill also protects patients from financial exploitation by limiting what experimental treatments can cost.

The Griffith and Brat bill does not allow restrictions on the cost of experimental drugs, thus by such omission allowing 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.  That is unfair to families that do pay for these experimental treatments and it is also likely to induce tremendous guilt for families that 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 Congressionally- created Reagan Udall Foundation.  However, with or without Right to Try legislation, access to experimental drugs will also be limited if patients want drugs that are not yet being manufactured in large numbers, or if reputable pharmaceutical 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 on the FDA’s current Compassionate Use/Expanded Access program was generally supportive, with a few recommendations for improvement.  Importantly, GAO pointed out that most experimental drugs that pharmaceutical companies allow to be distributed under FDA’s 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, Right to Try legislation that makes 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 or ineffective the experimental drugs might be unless the sponsoring company volunteers that information.

It is well documented that unproven treatments have been sold to dying patients at outrageously high prices in Mexico and elsewhere, and many patients have been irreparably harmed or killed by unproven treatments that were marketed dishonestly.  Indeed, FDA was created to avoid the tragedies arising from the “right to try” unregulated medical sales of the 19th Century and early 20th Century.

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 also be studied in clinical trials 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’d be glad to provide additional information upon request.  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.

Sincerely,

Diana Zuckerman, Ph.D.

President

NCHR Comments to FDA on Nicotine Replacement Therapy (NRT) Product Uses and Labeling Changes

Policy, Testimony & Briefings
National Center for Health Research, February 15, 2018

February 15, 2018

Dockets Management Staff
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

National Center for Health Research’s Public Comment on NRT

[Docket no.FDA-2017-N-6529]

Thank you for the opportunity to provide comments on FDA’s evaluation of nicotine replacement therapy (NRT) products, including product labeling. The National Center for Health Research (NCHR) is a nonprofit research center focused on research, policies, and programs that affect public health. Our Center analyzes scientific and medical data and provides objective health information to patients, providers, and policymakers. We do not accept funding from companies that make medical products, so we have no conflicts of interest.

According to the National Health Interview Survey (NHIS), our nation’s effort to reduce smoking has reached a plateau of around 15 percent of American adults1.  Based on early data from the the landmark 1994 Lancet meta-analysis, nicotine replacement (NRT) products are about 70% effective at achieving abstinence up to about 12 months2. However, it remains unclear whether individual achievement of abstinence is sustainable over time and whether long-term NRT use is more or less beneficial on an individual or population health level. We commend the FDA for addressing their role in developing strategies to evaluate NRT products and labeling. We agree that urgent action is necessary and the FDA should consider science-based approaches to reduce further harm from combustible tobacco products.

In consideration of the FDA’s request for public comment, we will focus our remarks on two specific questions–question 3 and question 6.

Questions 3: What data would be required to demonstrate health benefits of reduction in consumption of combustible tobacco products?   

According the U.S. Surgeon General3, we know that smoking contributes significantly to the development of cancer, including cancer of the mouth and throat, esophagus, trachea/bronchus/lung, stomach, liver, pancreas, kidney, cervix, bladder, and colon and rectum. Smoking also increases cancer mortality risk and other cause-specific mortality risk in patients with a history of cancer. We also know that smoking is linked to a number of serious chronic diseases including heart disease, stroke, chronic obstructive lung disease and asthma, diabetes, rheumatoid arthritis, blindness, reproductive defects, ectopic pregnancy, and immune dysfunction. Given the magnitude of harms, there is no doubt that reducing the use of combustible tobacco products is beneficial for individual and population health.

Retrospective analysis of the data indicates that reduction in smoking from 1964 to 2012 averted about 8 million premature smoking-related deaths from all causes4.  Modeling analysis of the short term impacts of smoking with respect to cardiovascular events demonstrate that a one-time 1% decrease in smoking prevalence prevents about 1000 heart attacks and about 500 strokes per year5. Since heart attacks are the leading cause of death and strokes cause substantial disability, these reductions are significant. Short-term impact, such as those seen in the cardiovascular modeling study, can be studied prospectively in identified patient populations. For example, smoking cessation is built into the algorithm for perioperative cardiovascular risk reduction, which may represent an ideal population to follow prospectively in order to gather meaningful data on cardiovascular morbidity and mortality.

However, assessing long-term risk reduction may prove more difficult.  For example, there is a substantial lag in the cumulative effect of tobacco exposure and development of cancers. It will likely take decades to see the full health benefits of tobacco reduction and/or cessation. Therefore, prospective studies are limited in their feasibility for answering the question at hand.

Questions 6: …FDA has recommended the labeling on OTC NRT products be modified to include the following: “If you feel you need to use [the NRT product] for a longer period to keep from smoking, talk to your health care provider.” What is the impact of longer term NRT treatment? What is the impact on likelihood of cessation or relapse prevention? What data would support an affirmative recommendation to use approved OTC NRT products for durations that exceed those currently included…or would support a chronic or maintenance drug treatment indication for such products?

Early studies of NRT products estimate that they are about 70% effective at achieving abstinence up to about 12 months. However, it remains unclear whether maintenance use of NRT products provides added benefit, or whether it increases or decreases potential harm. A 2015 study in JAMA6, comparing standard NRT therapy (8 weeks), extended therapy (24 weeks), and maintenance therapy (52 weeks), concluded that maintenance NRT use did not provide additional benefit. While NRT therapy was shown to delay time to relapse, other research indicates that continued use of NRT products after relapse did not predict a return to abstinence7. Additional data from randomized trials are needed to establish effectiveness and safety of long-term NRT use.

Moreover, long-term exposure to nicotine in NRT products may pose serious harms. A 2017 systematic review found that most studies have assessed relatively short-term exposure to NRT (about 12 weeks or fewer)8. However, the systematic review identified a UK epidemiological study which estimated a small, but significant absolute risk of 3 cases of respiratory abnormalities in 1000 live births8,9.  Such a risk must be considered for labeling regarding use by women who are pregnant or could become pregnant. In addition, a historical cohort from the UK10 found that nicotine exposure from NRT was significantly associated with higher risk of heart disease or stroke and decreased survival over a 52-week follow-up period.

Given the insufficient evidence supporting long-term or chronic use and lack of evidence ensuring safe long-term use of NRT products, we strongly oppose the proposed label modification. In addition, healthcare providers have limited experience in the use of NRT. National data indicate that health care providers assess smoking about two-thirds of the time, but recommend drug therapy less than 2% of the time11. Therefore, more data are needed on providers’ knowledge and perceptions of NRT products to determine why they so rarely recommend them and how guidance from healthcare professionals regarding NRT could be improved. In order for healthcare providers to have an educated and informed discussion with patients about long-term use of NRT, more evidence is needed to determine whether the benefits of long-term NRT outweigh potential harms.    

Thank you for the opportunity to share our perspective.

Footnotes:

  1. Jamal A, Phillips E, Gentzke AS, et al. Current Cigarette Smoking Among Adults — United States, 2016. MMWR Morb Mortal Wkly Rep 2018;67:53–59. DOI: http://dx.doi.org/10.15585/mmwr.mm6702a1
  2.    Silagy C. et al. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. The Lancet. 1994; 343:139-142.
  3.    U.S. Surgeon General. The Health Consequences of Smoking—50 Years of Progress. 2014. Available online: www.surgeongeneral.gov/library/reports.
  4.  Honey K. Advances in Tobacco Control. CANCER RESEARCH Catalyst: The Official Blog of the American Association for Cancer Research. November 2017. Available online: http://blog.aacr.org/advances-in-tobacco-control/
  5. James M. Lightwood and Stanton A. Glantz. Short-term Economic and Health Benefits of Smoking Cessation. Circulation. 1997;96:1089-1096, originally published August 19, 1997 https://doi.org/10.1161/01.CIR.96.4.1089
  6. Schnoll RA, Goelz PM, Veluz-Wilkins A, Blazekovic S, Powers L, Leone FT, Gariti P, Wileyto EP, Hitsman B. Long-term Nicotine Replacement Therapy:A Randomized Clinical Trial. JAMA Intern Med. 2015;175(4):504–511. doi:10.1001/jamainternmed.2014.8313
  7.    Hughes JR. et al. Effectiveness of continuing nicotine replacement after a lapse: A randomized trial. Addictive Behaviors. 2018;76: 68-81
  8. Lee, P.N. & Fariss, M.W. A systematic review of possible serious adverse health effects of nicotine replacement therapy. Arch Toxicol. 2017;91: 1565. https://doi.org/10.1007/s00204-016-1856-y
  9. Dhalwani NN. et al. Nicotine replacement therapy in pregnancy and major congenital anomalies in offspring. Pediatrics. 2015;135(5):859-67. doi: 10.1542/peds.2014-2560.
  10.    Dollerup J, Vestbo J, Murray-Thomas T, et al. Cardiovascular risks in smokers treated with nicotine replacement therapy: a historical cohort study. Clinical Epidemiology. 2017;9:231-243. doi:10.2147/CLEP.S127775.
  11.    Thorndike AN. et al. The Treatment of Smoking by US Physicians During Ambulatory Visits: 1994–2003. American Journal of Public Health (AJPH). Published Online: October 10, 2011. Available online: http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2006.092577

Testimony of Dr. Diana Zuckerman Before the Maryland House of Delegates Appropriations Committee on the Health Risks of Artificial Turf

Legislation, Policy
Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund, February 8, 2018

I am Dr. Diana Zuckerman and I am here today as the president of the National Center for Health Research and as a resident of Montgomery County for more than 25 years.  My children grew up in the county and so this is an issue of great importance to me personally as well as professionally.

I congratulate you on introducing HB 505, to prohibit the use of state funds for artificial turf fields and playgrounds, and I strongly support it.  Public funds should not be used for artificial turf and similarly dangerous playground materials.

There is considerable misunderstanding about the safety and cost-effectiveness of recycled tire material, other synthetic rubber, plastics, triclosan, and other synthetic materials on playing fields and playgrounds.  Your focus today is on whether state funding should be used to install and refurbish these artificial fields.  You will hear from others about the fact that these artificial fields are not cost-effective.  Since my training is in epidemiology and public health, I will focus on why investing in artificial turf fields is bad for our children’s health.

Artificial turf is made from synthetic rubber, plastic, and other materials with known health risks.  For example, the widely used material known as crumb rubber or tire crumb includes carcinogens as well as chemicals that disrupt our body’s hormones. These are called endocrine disrupting chemicals, and studies show that they contribute to early puberty, obesity, and attention deficit disorder.  Since breast cancer and several other cancers are fed by estrogen and other hormones, these materials can also cause cancer in the long-term.

Some endocrine disrupting chemicals have been banned by Federal law from toys and other products for young children.  It does not make sense that chemicals banned from rubber duckies, teething toys, and other products used for a relatively short period of time by children are allowed in playing fields and playgrounds where children are exposed day after day, week after week, and year after year.

The artificial turf industry will tell you that there is no clear evidence that their fields caused any child to develop cancer.  That is true.  But as an epidemiologist, I can also tell you that for decades there was no evidence that smoking caused cancer or that Agent Orange caused cancer.  It takes many years to develop that evidence.  And even then, it is usually impossible to prove that the cancer that any individual has developed was specifically caused by smoking or any other one source of exposure.  However, the weight of the evidence can be clear, even when the specific cause and effect can’t be proven.  There is clear evidence that the materials used in synthetic turf can cause cancer, skin irritation, contribute to obesity, and other health issues.

Artificial grass fields are just part of the problem.  Rubber playground materials used to cover the ground near slides, swings, and other playground equipment are attractive and seem safe, but they are made with the same kind of tire crumb and “virgin rubber” as athletic fields and have the same risks.  At a local park I recently saw particles of synthetic rubber and other potentially harmful material break off – it looks like candy and can end up in children’s mouths, as well as up their noses, in their ears, and on their clothes.  A much safer alternative, which is also ADA-compliant, is engineered wood fiber, which is just as effective as softening any falls and has no dangerous chemicals.

What the Scientific Studies Say

The California Office of Environmental Health Hazard Assessment (OEHHA) conducted three laboratory studies to investigate the potential health risks to children from playground surfaces made from recycled tires. One study evaluated the level of chemicals released that could cause harm to children after they have had contact with loose tire shreds, either by eating them or by touching them and then touching their mouth. The other two studies looked at the risk of injury from falls on playground surfaces made from recycled tires compared to wood chips, and whether recycled tire shreds could contaminate air or water.[1]

It would not be ethical to ask children to eat tire shreds, so the researchers created chemical solution that mimicked the conditions of a child’s stomach and placed 10 grams of tire shreds in it for 21 hours at a temperature of 37°C. Researchers then measured the level of released chemicals in the solution and compared them to levels EPA considered risky. The study also mimicked a child touching the tire shreds and then touching her mouth by wiping recycled tire playground surfaces and measuring chemical levels on the wipes. To evaluate skin contact alone, the researchers tested guinea pigs to see if rubber tire playground samples caused any health problems. This study assumed that children would be using the playground from the ages of 1 through 12. Results of the OEHHA studies showed that a single incident of eating or touching tire shreds would probably not harm a child’s health, but repeated or long-term exposure might. Five chemicals, including four PAHs, were found on wipe samples. One of the PAHs, “chrysene,” was higher than the risk level established by the OEHHA, and therefore, could possibly increase the chances of a child developing cancer.[1]

Out of the 32 playgrounds surfaced in recycled tires that the researchers in California looked at, only 10 met that state’s standard for “head impact safety” to reduce brain injury and other serious harm in children who fall while playing. In contrast, all five surfaces made of wood chips met the safety standard.[1]

A 2012 study analyzing rubber mulch taken from children’s playgrounds found harmful chemicals in all of them, often at high levels.[2] Twenty-one samples were collected from 9 playgrounds, and the results showed that all samples contained at least one hazardous chemical, and most contained high concentrations of several PAHs. Several of the identified PAHs can be released into the air by heat, and when that happens children are likely to inhale them. While the heat needed to do this was very high in some cases (140 degrees Fahrenheit), many of the chemicals also became airborne at a much lower temperature of 77 ºF.  And since rubber playgrounds retain much more heat than grass or dirt, a temperature of 140 degrees can happen even on a sunny spring, summer, or fall day when the temperature near grass is only 70 degrees.  The authors concluded that the use of rubber recycled tires on playgrounds “should be restricted or even prohibited in some cases.”[2]

A 2015 report by Yale scientists analyzed the chemicals found in 5 samples of tire crumbs from 5 different companies that install school athletic fields, and 9 different samples taken from 9 different unopened bags of playground rubber mulch. The researchers detected 96 chemicals in the samples. A little under a half have never been studied for their health effects, so their risks are unknown, and the other chemicals have been tested for health effects, but those tests were not thorough. Based on the studies that were done, 20% of the chemicals that had been tested are considered to probably can cause cancer, and 40% are irritants that can cause breathing problems such as asthma, and/or can irritate skin or eyes. [3]

What the EPA Has Done

The EPA created a working group that collected and analyzed data from playgrounds and artificial turf fields that used recycled tire material. Samples were collected at six turf fields and two playgrounds in four study sites (Maryland, North Carolina, Georgia and Ohio). In a report released in 2009, the agency concluded that the level of chemicals monitored in the study and detected in the samples were “below levels of concern.” However, there were limitations to this study because they did not measure the concentration of organic chemicals that are known to vaporize during summer heat, such as PAHs.

Due to the small number of samples and sampling sites used, the EPA stated that it is not possible to know if these findings are typical of other playgrounds or fields until additional studies are conducted.[4]  When announcing the results of the study, EPA joined other organizations in recommending that as a precaution, young children wash their hands frequently after playing outside.[4]

A meeting was then convened by the EPA in 2010, bringing together various state and federal agencies to discuss safe levels of chemical exposure on playgrounds made from recycled tire rubber, and opportunities for additional research.[4] In the case of PAHs, the EPA has concluded that while there are currently no human studies available to determine their effects at various levels, based on laboratory findings, “breathing PAHs and skin contact seem to be associated with cancer in humans.” [5]

In February 2016, the U.S. government announced a new action plan to better understand the likely health risks of recycled tire crumb and similar artificial surfaces. This initiative involves 4 U.S. government agencies: the EPA, Centers for Disease Control and Prevention (CDC), Agency for Toxic Substances and Disease Registry (ATSDR) and Consumer Product and Safety Commission (CPSC).  However, I’m sure many of you are aware that the current EPA is unlikely to complete the analysis in an objective, scientific way.

In summary, it is essential that the State of Maryland stop paying for artificial turf fields and playgrounds that can clearly exacerbate our children’s existing health problems and cause new  health problems. Let’s instead invest in safe, natural playing fields, unless any artificial alternatives are proven to be safer, more effective, and as cost-effective as grass.

References:

  1. State of California-Office of Environmental Health Hazard Assessment (OEHHA), Contractor’s Report to the Board. Evaluation of Health Effects of Recycled Waste Tires in Playground and Track Products. January 2007 http://www.calrecycle.ca.gov/Publications/Documents/1206/62206013.pdf Accessed February 2018.
  2. Llompart M, Sanchez-Prado L, Lamas JP, Garcia-Jares C, et al. Hazardous organic chemicals in rubber recycled tire playgrounds and pavers. Chemosphere. 2013;90(2):423-431. http://www.sciencedirect.com/science/article/pii/S0045653512009848 Accessed February 2018.
  3. Yale Study Reveals Carcinogens and Skin Irritants in Synthetic Turf. http://wtnh.com/2015/09/03/new-yale-study-reveals-carcinogens-and-skin-irritants-in-synthetic-turf/ Accessed February 2018.
  4. US Environmental Protection Agency (EPA). Fact Sheet – The Use of Recycled Tire Materials on Playgrounds & Artificial Turf Fields. http://www.emcmolding.com/uploads/files/file130102132640.pdf http://wtnh.com/2015/09/03/new-yale-study-reveals-carcinogens-and-skin-irritants-in-synthetic-turf/ Accessed February 2018.
  5. US Environmental Protection Agency (EPA). Polycyclic Aromatic Hydrocarbons (PAHs)-Fact Sheet. November 2009. https://www.epa.gov/north-birmingham-project/polycyclic-aromatic-hydrocarbons-pahs-fact-sheetAccessed February 2018.

Ovarian Suppression Therapy for Young, Pre-Menopausal Women with Early-Stage Breast Cancer

Breast Cancer
Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Breast cancer is the most common type of cancer in women around the world, and the second leading cause of cancer deaths among U.S. women.

Women who are diagnosed with early-stage breast cancer almost always undergo surgery to remove the cancer (either lumpectomy/partial mastectomy or mastectomy). Most will also choose at least one other treatment in addition to surgery.

If their cancer is estrogen receptor positive (about 84% of breast cancers), many women will try to take hormonal therapy for at least five years after surgery to lower the chances of cancer coming back in the future.[1]

For pre-menopausal women younger than 35-40 years old who have estrogen receptor-positive cancer, ovarian suppression therapy may be considered. Ovarian suppression can be permanent (surgery) or temporary (medication), and it stops the body from making hormones.

Suppression therapy is sometimes recommended for women with stage 1 or 2 breast cancer who have high chance of the cancer returning, but more often recommended in women with stage 2 or 3 breast cancer who would ordinarily need chemotherapy. Suppression therapy is given in addition to tamoxifen or an aromatase inhibitor, and instead of or after chemotherapy.[2]

How Does Ovarian Suppression Therapy Work?

Ovarian suppression stops the ovaries from making hormones, which stops women from having menstrual cycles. It should only be used in women who are pre-menopausal and at high risk for cancer recurrence.

There are 3 types of ovarian suppression: 1) monthly hormone injections (temporary), 2) surgery to remove the ovaries (which results in irreversible menopause), and 3) radiation ablation therapy to remove the ovaries.[2]

How Effective is Ovarian Suppression Therapy?

A 2016 study found that 13% of women receiving both tamoxifen and ovarian suppression therapy died within 5 years of breast cancer compared to 15% receiving tamoxifen therapy only.  This is a very small difference, but was statistically significant, which means that it did not just happen by chance. For women who also received chemotherapy, 23% of patients receiving tamoxifen only died within 5 years, compared to 19% of women receiving tamoxifen plus ovarian suppression therapy.  Since women who undergo chemotherapy are those who are known to have a higher risk of dying from breast cancer, the researchers concluded that “high risk” women should be considered for ovarian suppression therapy.[2]

Women with stage I breast cancers who do not need chemotherapy and women who have small cancers (1 cm or less) without spread to lymph nodes should not receive ovarian suppression.[2]

Another study found that combining ovarian suppression with an aromatase inhibitor instead of with tamoxifen can decrease the chances of dying from breast cancer within 5 years, from 13% to 9%.[2]

Although women taking ovarian suppression therapy with hormone treatment were slightly less likely to die of breast cancer, they did not live longer than women who took hormone therapy alone.[2] In other words, they died of a different cause.

What Are the Potential Harms?

Ovarian Suppression therapy causes symptoms of menopause, because it stops the ovaries from making hormones. There are risks to removing the ovaries by surgery or radiation, such as the risks of anesthesia, infection, bleeding, and damage to nearby organs and tissues.

Removal of ovaries causes early menopause, so a young woman will no longer have periods or be able to get pregnant. Hormone injections can cause hot flashes or flushing, mood changes, depression, sexual dysfunction, and breast changes.

Serious side effects include blood clots, strokes, heart attacks, high or low blood pressure, and brittle or weak bones (osteoporosis).[3]

The Bottom Line

For young pre-menopausal women with estrogen-positive breast cancer, ovarian suppression therapy slightly reduces the chance of dying of breast cancer, but it doesn’t help women live longer. Because the therapy can be harmful with permanent side effects, young women should decide whether the small benefits outweigh the risks. Talk with your doctor about whether the risks outweigh the benefits for you.   

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

References:

1. American Cancer Society. Cancer Treatment and Survivorship: Facts and Figures 2016-2017. Available online: https://www.cancer.org

2. Burstein HJ. et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. Journal of Clinical Oncology. 2017;34(14): 1689-1701. Doi: 10.1200/JCO.2015.65.9573

3. Medscape. Drugs and Diseases: Gosarelin. Available online: https://reference.medscape.com/drug/zoladex-la-goserelin-342129

Targeted Therapy for Early-Stage Breast Cancer

Breast Cancer
Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Breast cancer is the most common type of cancer in women around the world, and the second leading cause of cancer deaths among U.S. women.

Women who are diagnosed with early-stage breast cancer almost always undergo surgery to remove the cancer (either lumpectomy/partial mastectomy or mastectomy). Most will also choose at least one other treatment in addition to surgery.

About 14% of all breast cancers (at all stages) make a protein called HER2. There are several targeted therapies that specifically stop the growth of these cancer cells. These therapies can be used with chemotherapy or hormonal therapy.[1]

How Does Targeted Therapy Work?

Trastuzumab targets breast cancer cells that make HER2, and stops them from growing.[2,3]

How Effective is Targeted Therapy?

Studies show that women with early-stage “HER2-positive” breast cancer may benefit from targeted therapy. The landmark study (called HERA) of this treatment showed that women taking trastuzumab for 1 year in addition to chemotherapy had a 21% chance of cancer returning compared to 28% for women getting chemotherapy alone.[4]

Overall survival refers to how long a woman lives after a diagnosis. For women diagnosed with early-stage HER2-positive breast cancer, 10.7% taking both trastuzumab and chemotherapy died within 4 years compared to 12.3% of women getting chemotherapy alone.  This is obviously a small benefit that would not help most women, but it could save the life of one or two women for every 100 receiving the targeted treatment.

At a 12-year follow up, the researchers found that taking trastuzumab for 2 years was not more beneficial than taking it for one year.[5,6]

What Are the Potential Harms?

Trastuzumab therapy can cause headaches, nausea, swelling, rash, and flu-like illness. In rare cases (less than 1%) trastuzumab can cause serious side effects including heart failure (a weakened heart), sudden difficulty breathing, low blood pressure, and sudden death. All women should have their hearts tested with a sonogram of the heart before deciding whether to take trastuzumab.  If they decide to take it, they should also have their hearts tested during treatment.[7]

In 2018, the American Heart Association recommended women with breast cancer discuss with their doctors their cardiovascular risks (such as family history, or having a diagnosis of diabetes, high blood pressure, or high cholesterol) and the risks of cancer therapies, including trastuzumab as well as many chemotherapy drugs, which can cause or worsen heart conditions. The damage to the heart continues after women have finished the therapies, and can be permanent. This risk to the heart helps explain why a treatment can help prevent breast cancer recurrence but have little benefit in terms of women living longer.[8]

The Bottom Line

For women with HER2-positive, early-stage breast cancer, targeted therapy may be beneficial. Because the therapy can be harmful to the heart, each woman needs to decide whether the benefits outweigh the risks for her. Talk with your doctor about your medical history and family history to decide which treatment options may be right for you.

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

References:

  1. American Cancer Society. Cancer Treatment and Survivorship: Facts and Figures 2016-2017. Available online: https://www.cancer.org
  2. National Cancer Institute. Breast Cancer Treatment (PDQ). (Nov. 2017). Available online: https://www.cancer.gov/types/breast/patient/breast-treatment-pdq#section/_125
  3. Medscape. Adjuvant Therapy for Breast Cancer. (Aug. 2017). Available online: https://emedicine.medscape.com/article/1946040-overview#showall
  4. Gianni L. et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncology. 2011;12(3): 236-44. doi: https://doi.org/10.1016/S1470-2045(11)70033-X
  5. Cameron D. et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075): 1195-1205. doi: https://doi.org/10.1016/S0140-6736(16)32616-2
  6. Stenger M. ASCO Post: 11-Year Follow-up of Adjuvant Trastuzumab in the HERA Trial. (March 2017). Available online: http://www.ascopost.com/News/48405
  7. Medscape. Drugs and Diseases: Trastuzumab. Available online: https://reference.medscape.com/drug/herceptin-ogivri-trastuzumab-342231#5
  8. Mehta LS. et al. Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association. Circulation. 2018; (originally published February 1, 2018).https://doi.org/10.1161/CIR.0000000000000556

Trump Targets Drug Prices, Right-to-Try in State of the Union

In the News, News Stories & Editorials
Mary Caffrey, The American Journal of Managed Care Newsroom: January 31, 2018

President Donald Trump returned to a popular campaign theme in Tuesday’s State of the Union address when he vowed to bring down the high cost of prescription drugs. But Trump’s only specific solution—calling on Congress to pass a right-to-try law—doesn’t address the broader problem affecting millions of Americans: the annual increases of necessary drugs for chronic conditions, such as insulin for diabetes or anti-inflammatory biologics for rheumatoid arthritis.

“There’s certainly been a gap between rhetoric and reality,” John Rother, president and CEO of the National Coalition on Health Care (NCHC), told The American Journal of Managed Care®in an interview.

Previously, NCHC ran the Campaign for Sustainable Rx Pricing, which did extensive polling during the 2016 election cycle on Americans’ views on prescription drug pricing. Rother agreed with the overnight observation that the president highlighted the issue for a convenient reason: the president’s own poll numbers are not good, and polls still show Americans are frustrated with high drug prices. A poll taken last fall by the Harvard School of Public Health found that 40% of Americans want Congress to bring down prescription drug prices—a higher score than any other issue surveyed, according to POLITICO.

“One of my greatest priorities is to reduce the price of prescription drugs,” Trump said Tuesday night. “In many other countries, these drugs cost far less than what we pay in the United States. That is why I have directed my administration to make fixing the injustice of high drug prices one of our top priorities. Prices will come down.”

He called on Congress to pass so-called right-to-try legislation, which allows patients to bypass FDA’s Expanded Access program and go straight to the pharmaceutical companies to purchase investigational medications if they are facing a terminal disease. Several states have passed their own versions of right-to-try laws. Diana Zuckerman, president of the National Center for Health Research and a board member of the Reagan-Udall Foundation, told attendees at Patient-Centered Oncology Care® in November 2017 that the Right-to-Try bill that has passed the Senate has far fewer requirements than the FDA’s Expanded Access program; and there are concerns that patients taking these drugs will not track adverse effects, which could threaten the current system of drug development. […]

Read the original article here.

Big Pharma Greets Hundreds of Ex-Federal Workers at the ‘Revolving Door’

In the News, News Stories & Editorials
Sydney Lupkin, Kaiser Health News: January 25, 2018

Alex Azar’s job hop from drugmaker Eli Lilly to the Trump administration reflects ever-deepening ties between the pharmaceutical industry and the federal government.

A Kaiser Health News analysis shows that hundreds of people have glided through the “revolving door” that connects the drug industry to Capitol Hill and to the Department of Health and Human Services.

Azar was confirmed Wednesday as  HHS secretary, joining other former drug industry alumni in top positions.

Nearly 340 former congressional staffers now work for pharmaceutical companies or their lobbying firms, according to data analyzed by KHN and provided by Legistorm, a nonpartisan congressional research company. On the flip side, the analysis showed, more than a dozen former drug industry employees now have jobs on Capitol Hill — often on committees that handle health care policy.

“Who do they really work for?” said Jock Friedly, Legistorm’s president and founder, who called that quantity “substantial.” “Are they working for the person who is paying their bills at that moment or are they essentially working on behalf of the interests who have funded them in the past and may fund them in the future?”

In many cases, former congressional staffers who now work for drug companies return to the Hill to lobby former co-workers or employees. The deep ties raise concerns that pharmaceutical companies could wield undue influence over drug-related legislation or government policy.

“You’ll take the call because you’ve got a friendly relationship,” said Diana Zuckerman, president of the nonprofit National Center for Health Research and a former congressional staffer. “You’ll take the call because these people are going to help you in your future career [and] get you a job making three times as much.”

A 2012 Sunlight Foundation investigation found that, on average, a chief of staff on the Hill could increase his or her salary 40 percent by moving to the private sector.

Experts say the cozy relationships don’t necessarily mean congressional staffers do favors for lobbyists they know, but the access doesn’t hurt.

When John Stone left the House Energy and Commerce Committee last fall to join lobbying firm BGR, he told Politico that he had consulted with two lobbyists at BGR “for advice on basically everything that came across my desk.”

KHN’s review of Legistorm data indicates that one of the lobbyists, BGR’s Ryan Long, overlapped with Stone on the House panel. Brent Del Monte preceded them both on the committee and then spent 10 years at the Biotechnology Innovation Organization (BIO), a trade group for the biologic drug industry, before joining BGR in 2015. BGR’s clients include PhRMA, Celgene and other pharmaceutical firms.

Like Stone, Long and Del Monte, many ex-Hill staffers working in some way for the pharmaceutical industry came from key committees, including the Senate Committee on Health, Education, Labor and Pensions (HELP) and the House Energy and Commerce Committee, which in 2016 shepherded the 21st Century Cures Act into law. The law faced criticism from watchdogs who feared it would make drug approval cheaper and easier but could lead to unsafe approvals.

Tim LaPira, a James Madison University associate professor who co-authored a book about the revolving door published in June, said the practice of leaving government service to lobby for industry isn’t as corrupt as it seems. Rather, as congressional staffs have shrunk over time, they’ve been forced to essentially outsource expertise to lobbyists, he said.

“Don’t tell the private sector to stop doing it. Tell Congress to stop relying on the private sector so much,” LaPira said, adding that Congress spends just 0.5 percent of the discretionary budget on itself.

The number of congressional employees declined by more than 7,000 people — about 27 percent — from 1979 to 2015, according to data compiled by the Brookings Institution, a nonprofit research group.

While there’s a fear that lobbyists are slipping industry-friendly language into legislation, LaPira explained, more often they’re monitoring what’s happening inside government.

The reverse-revolving door, in which former pharmaceutical employees enter public service, is not as clearly understood. Neither is the flow of serial revolvers, who go from industry to government and back.

Some of those Hill staffers, according to financial disclosures, maintain drug industry pensions and stock, Kaiser Health News found. They are not required to divest and are required to disclose those connections only if they hold key positions.

Reverse revolvers may not realize they’re doing Big Pharma’s bidding, Friedly said, but they’ve been so exposed to the industry’s point of view that their implicit biases may seep into their legislative work.

The revolving door operates beyond the Hill, however, LaPira said

In addition to Azar, several former drug industry officials have landed key jobs in Trump’s Cabinet and administration, including Food and Drug Administration Commissioner Scott Gottlieb, a former venture capitalist with deep ties to the pharmaceutical industry.

Gottlieb disclosed serving on boards of several pharmaceutical companies, including GlaxoSmithKline and Daiichi Sankyo, prior to returning to government for his third trip through the revolving door.

KHN also reviewed the résumés of more than 100 HHS appointees, obtained via a Freedom of Information Act request by American Oversight, a nonprofit founded to hold government officials accountable. Although only a handful of recent appointees were employed directly by drug companies, more than a dozen had worked as lobbyists, consultants and lawyers on behalf of pharmaceutical firms.

The high-level HHS appointees include: Keagan Lenihan, a former lobbyist for drug distributor McKesson who now serves as senior counselor to the secretary at HHS; former PhRMA lobbyist John O’Brien, now deputy assistant secretary of health policy for the agency’s Planning and Evaluation arm; and former Bristol-Myers Squibb lobbyist Mary-Sumpter Lapinski, an attorney in the HHS secretary’s office.

Sen. Elizabeth Warren expressed concerns about the revolving door during Azar’s confirmation hearing before the HELP committee in November. Not long after telling Azar that his “résumé reads like a how-to manual for profiting from government service,” she asked him whether drug industry CEOs should be held accountable when the companies they run break the law. He did not answer yes or no.

His reply: “I’m satisfied with our discussion.”

METHODOLOGY

Kaiser Health News obtained revolving-door and lobbying disclosure data from Legistorm, a for-profit, nonpartisan congressional research firm based in Washington, D.C.

The revolving-door data include congressional staffers’ jobs on and off Capitol Hill. It is current through August 2017 and dates to 2001. For lobbyists who did not directly work for pharmaceutical firms but worked for lobbying firms on behalf of pharmaceutical companies and their trade groups, Kaiser Health News used lobbying disclosure data to identify individuals registered to lobby on behalf of these clients. Reporters then tracked down these lobbyists in Legistorm’s revolving door data and checked them by hand.

The HHS appointee résumés obtained by American Oversight covered individuals appointed from Jan. 20 to July 12, 2017.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

Read the original article here.

The Problem with Medical Device Approvals

In the News, News Stories & Editorials
Suzanne Robotti, MedShadow: January 16, 2018

MedShadow doesn’t often cover medical devices, but I’ll make an exception to point out this article about Stephen Tower’s experience with an artificial hip. This is a must-read for anyone who has or anticipates getting an artificial hip or knee — or any other body part.

Stephen Tower, MD, is an orthopedic surgeon experienced in performing artificial hip replacements. Yet he found out firsthand that the hip he requested to be put in his body was defective in its design. He then worked for years to bring attention to the harm that the metal-on-metal hip from Johnson & Johnson was causing.

The interesting part of the story is how that device — and almost all medical devices — got approved by the FDA. Essentially, a device manufacturer can file a form claiming that its product is “substantially equivalent” to an existing device. If the FDA agrees, that’s it. There’s no need for testing and no follow-up studies.

In some cases the “substantially equivalent” claim makes logical sense, but doesn’t work in real life — that’s why the clinical trial process exists. The author of the op-ed, Jeanne Lenzer, explored many examples and the history of the FDA in her new book, The Danger Within Us: America’s Untested, Unregulated Medical Device Industry and One Man’s Battle to Save It. […]

I’ll give the last word to Diana Zuckerman, the president of National Center for Health Research (NCHR), an independent nonprofit that scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. NCHR does not accept funding from device or pharmaceutical companies.

I asked Zuckerman for an example of a substantially equivalent approval that had particularly bothered her. She told me that the da Vinci Surgical System was “cleared for market” as substantially equivalent to the surgical tools it uses, such as a scalpel. But a robotic surgery system is more than just the tools it uses. The da Vinci robot was described by then-FDA Commissioner Jane Henney as the first of its kind and a product that “could change the practice of surgery.”

Although based on the 510(k) review process that rarely requires a clinical trial, the FDA required the first version of the da Vinci system to be studied in one clinical trial comparing the results to traditional surgery for gallbladder and reflux disease surgery. However, it and all future da Vinci robotic systems for all other surgeries were cleared for market by the FDA as substantially equivalent to the scalpel and other tools, and those later reviews didn’t require any clinical trials at all.

“How can a device be revolutionizing the practice of surgery and yet be substantially equivalent to tools that scientists tell us have been in use for more than 2,000 years? Does that make sense to any logical person?” […]

Read the original article here.