Steps had to be taken to identify the gender of those within the database as although the FDA gathers information on the sex of patients, this data is not made publicly available. Therefore, in order to overcome this obstacle, the ICIJ realised that the sex of patients was sometimes disclosed through pronouns and adjectives within the incident reports submitted to the FDA.
Talking about the findings, the ICIJ stated: “The trend we noticed is consistent with studies that have shown that women experience higher rates of hip-implant failure than men and have stronger immunological reactions to metal-containing devices.”
Other experts within the industry were keen to voice their opinion over the importance of looking at the effects of medical devices on different genders. Diana Zuckerman, president of the National Center for Health Research commented: “Having information about sex is very important because some products differ in safety between men and women.”
Diana Zuckerman, PhD, National Center for Health Research, November 13, 2019
Thank you for the opportunity to speak at this Advisory Committee meeting today regarding immunological responses to metal in implants.
The National Center for Health Research is a nonprofit research center that focuses on the quality of medical products and procedures and does not accept funding from medical device companies or pharmaceutical companies. I’m here today to share my perspective as a scientist as well as a patient. I am trained in epidemiology and served on the faculty at Vassar and Yale and as a researcher at Harvard. I’ve also worked in the U.S. Congress on FDA issues and as president of the National Center for Health Research I have a great deal of experience with FDA regulatory issues.
In addition, I got a hip implant 10 years ago, and I’m glad to say my experience has been a very good one. But at the time I was deciding on the surgery, neither the surgeons I interviewed nor the research literature provided the kind of information I needed to make an informed choice. In fact, one surgeon recommended a metal-on-metal hip for me because I was relatively young and active. Fortunately, I was already aware of metal debris issues so I did not make that choice. But the lack of information then and now was very clear to me as a patient. I was not able to obtain scientific data from the surgeons or online, including PubMed.
I want to say that this has been one of the most interesting and informative FDA meetings I’ve attended, and the speakers have provided a great deal of important information.
What Research is Needed?
I’m here to talk about the big picture. We’ve heard this morning about a great deal of research findings and the need for more and better research. I want to emphasize that we need much better pre-market studies, not just post-market studies. Pre-market clinical trials are often lacking because of the 510(k) process, but even when premarket clinical trials are conducted, they are often inadequate to provide the information patients deserve.
We need clinical trials and other well-designed studies of large number of patients, and as one of the speakers said this morning, we need to compare information about patients who have good experiences with their implants with those who do poorly with their implants. These studies need to include a patient population with sufficient diversity in terms of age, sex, race, BMI, activity levels, allergies, and metal sensitivity, to determine how safe and effective the products are for these subgroups.
We need clinical trials and big data analyses that follow patients for years in order to evaluate the effects of wear and changes in immune responses over time.
We heard this morning that patch testing is inadequate to identify which patients will have a negative reaction to an implant, and that other diagnostic testing also has limitations.
I also want to express our concern with the tendency to extrapolate results from an implant used in one part of the body to implants made of the same materials that are intended to be used in another part of the body. We know from listening to patients that this can result in terrible problems.
We are also concerned about extrapolating results from an earlier version of an implant to a newer implant, when the newer implant differs in ways that could affect safety and effectiveness. Those differences might be different metals, changes in size or shape, differences in manufacturing, or numerous other changes typically made in an effort to improve implanted devices.
We encourage the FDA to require that studies specifically look for adverse events that are related to immune reaction or wear. These adverse events might be local or might be systemic, and some of these events would not necessarily be included in studies asking about all adverse events.
Perhaps most important, we need comparative effectiveness studies that compare clinical effectiveness and patient-centered outcomes. I know that the FDA rarely requires comparative effectiveness studies, but those are the types of studies that are most likely to provide useful information for patients and their physicians.
If certain implants seem to be causing certain reactions with certain kinds of patients, wouldn’t it be very important to know how that compares to other alternatives of the same kind of implants? We can’t treat all hip implants that are polyethylene and metal as if they’re all the same. We can’t treat all metal-on-metal implants as if they’re the same. We need to compare different models, different implants made in different ways with different materials by different companies and get the kind of real data that patients and physicians can use to make informed decisions. Until then, it won’t be possible to figure out to what extent negative responses and implant failures are due to patient vulnerabilities or sensitivities and how much is due to the difference between various devices.
For more information about this public meeting, read these articles here or here.
Last month, a 17-year-old from Texas named Tryston Zohfeld‘s lungs suddenly failed. He was rushed to Cook Children’s Hospital in Fort Worth, Texas and put into a medically-induced coma while the situation only worsened. X-rays found that the teen had a total blockage of his lungs. Ruling out diseases like pneumonia, doctors finally concluded that the lung inflammation and inability to exchange oxygen and carbon dioxide Zohfeld was experiencing had been brought on by chemicals the teen had been inhaling from his vape pen, which he had been regularly using since 8th grade.
While Zohfeld was grateful to be released from the hospital after an 18-day stay, his story is just one of several cautionary tales related to vaping and e-cigarettes that are making headlines nationwide. A 20-year-old from Utah named Alexander Mitchell was recently “on death’s door” after his lungs failed. The young man had been using e-cigarettes. Also this summer, 18-year-old Chance Ammirata’s lung collapsed. The Miami student admitted to vaping about one Juul pod every two days (roughly the equivalent of 10 cigarettes-worth of nicotine a day) for a year.
Now, the U.S. Centers for Disease Control and Prevention (CDC) is conducting an ongoing investigation into cases like these. Here’s what you need to know.
The Dangers of Vaping for Teens
With hope, the ongoing CDC and FDA investigations will offer parents more answers about the link between e-cigarette use and lung disease, but in the meantime, experts are noting that teens are an especially vulnerable group.
Diana Zuckerman, PhD, president of the National Center for Health Research told CBS News, “It seems some kids are having very measurable damage in a very short period of time than what we’ve seen from [cigarette] smoke.” She explained that a young person’s size might be a factor in how they experience the effects of the chemicals, noting, “The same amount of vaping for a child that weighs, say, 100 pounds, is a bigger issue than for somebody who weighs 200 pounds.”
At the same time, e-cigarettes that include nicotine put teens at risk of addiction, which amplifies their risk of illness. Teens who use nicotine can become addicted in just days. Yale Medicine pediatrician Deepa Camenga, M.D., says that nicotine affects teens differently than adults because “teens are just more vulnerable than adults are to developing an addiction to nicotine. As a result, it may be harder for teens to stop because their brain is still growing and developing.”
Potential Lung Damage Symptoms from Vaping
The CDC notes that “in many cases, patients reported a gradual start of symptoms” including:
shortness of breath
and/or chest pain before hospitalization
in some cases, mild to moderate gastrointestinal illness including vomiting and diarrhea and fatigue
People who experience illnesses after vaping are encouraged to report the incident to the FDA here.
If you’re concerned about the epidemic of e-cigarettes and vaping, contact your two U.S. Senators to let them know how you feel! A sample letter is below. Here is a link to find the names and contact info for your senators.
I am very concerned about the dangers of e-cigarettes and I am writing to ask you to require that Congress address this serious epidemic. Action is urgently needed since the Centers for Disease Control and Prevention (CDC) is investigating reports that more than 250 people, including many teenagers and young adults, have suffered harm and in some cases, hospitalization because of lung injuries from vaping.
One man in Illinois has died and vaping is strongly suspected as the cause of his fatal illness.
Scientists are studying whether certain brands of e-cigarettes are most likely to be harmful, and whether the lung damage is caused by the chemicals, contamination or other causes. Meanwhile a range of vaping products are widely sold and teens and adults are being seriously harmed.
In 2016, the Food and Drug Administration’s (FDA’s) Center for Tobacco Products (CTP) issued regulations aimed at restricting access to e-cigarettes and requiring studies of their risk. The regulations were supposed to go into effect in 2018, but were delayed. Meanwhile, the FDA has failed to require the companies to prove that their products are safe.
The industry and the scientists they have hired claim that vaping helps people to quit smoking, but that has not been proven. Meanwhile, we now know that vaping can cause serious lung damage in just a year or two. That’s faster than cigarettes, which generally take decades to cause serious harm.
After initially delaying the regulation of e-cigarettes for 4 years, the former FDA Commissioner, Dr. Scott Gottlieb, modified his views, calling vaping an epidemic, and vowed that the agency would take appropriate action.
Please become a co-sponsor of the SAFE Kids Act (S. 655), which would ban most flavoring from e-cigarettes. These flavors are a major reason why children like to vape. In addition, please contact the FDA and urge the agency to immediately restrict the marketing of e-cigarettes and require that these devices be drastically restricted until the companies submit conclusive safety data through the PMTA process. The current delay is harming unknown numbers of teens and adults.
Following a request from the Food and Drug Administration, Allergan is recalling its textured breast implants worldwide, the company said Wednesday.
The move comes after 38 countries already recalled the implant because of the higher risk of anaplastic large cell lymphoma, or BIA-ALCL, a cancer of the immune system.
The recall is “a very important step” toward reducing this type of lymphoma, women’s health advocate Diana Zuckerman said.
“When women decide to get breast implants for reconstruction after mastectomy or for breast augmentation, they should not be putting their lives at risk for lymphoma,” Zuckerman, president of the National Center for Health Research, said in a statement. “This recall will reduce that risk but it won’t eliminate it, because not all women with BIA-ALCL had these specific types of implants.”
Last November, NBC News, along with its partner, the International Consortium of Investigative Journalists, found that BIA-ALCL is an emerging risk for women with textured implants.
In March, the FDA said BIA-ALCL is most likely caused by textured breast implants, which have a suede-like coating. But the agency stopped short of taking the implants off the market, noting it wanted to continue studying the disease and tracking cases. It’s estimated that of the 400,000 women in the United States who get breast implants each year, about 1 in 10 has textured implants.
Sydney Lupkin and Christina Jewett, KHN; May 30, 2019
The Food and Drug Administration has acknowledged that more than 56,000 never-before-disclosed surgical stapler malfunctions were quietly reported to the agency from 2011 through 2018.
The newly acknowledged reports were detailed in an executive summary for FDA advisers. The agency convened a meeting of experts this week to help it determine whether surgical staplers should be moved out of its lowest-risk category — reserved for simple devices like tongue depressors and bandages — to a higher grade that may require testing and additional oversight. Surgical staplers are used to cut and seal vessels and tissues inside the body.
When the FDA initially announced the meeting in March, it acknowledged in a letter to doctorsthat “many more device malfunction reports” were reported to the agency than it had publicly disclosed. The FDA executive summary published this week shows that the total reports more than doubled when the agency took nonpublic reports into account, totaling nearly 110,000 malfunctions or injuries from 2011 through 2018.
“It shocks the conscience,” said Chad Tuschman, a lawyer representing Mark Levering, 62, of Toledo, Ohio, who suffered a serious brain injury after a stapler malfunction caused massive bleeding in 2018. The surgeon, hospital and device maker Covidien, a division of Medtronic, have all denied allegations of wrongdoing in an ongoing legal case.
Surgical staplers have a unique ability to harm patients if they malfunction. Often used in minimally invasive surgeries, they are meant to both cut tissue and vessels and then quickly seal them. Patients have been gravely harmed when staplers have failed to fire or seal tissue, suffering from massive bleeding or infections if stomachs or intestines aren’t sealed properly.
The nonpublic reports were sent to the FDA as “alternative summary” reports, the topic of a recent Kaiser Health News investigation that focused on the agency accepting millions of hidden reports related to medical devices — including for surgical staplers.
The agency had previously acknowledged that in 2016, even as it posted fewer than 100 stapler-related injuries in a public database called MAUDE, it accepted nearly 10,000 reports into its little-known internal alternative summary reporting database. (The data in the FDA’s executive summary contains reports for staplers and staples, which experts have said were just different names for the same problem.)
Tuschman said he was stunned that there were more hidden reports than public ones in the executive summary. “The first question should be ‘Why?’ Why would they have the right to submit to a hidden database?”
Leading surgical stapler makers include divisions of Medtronic and Johnson & Johnson. Medtronic has said the FDA granted it exemptions for stapler-related malfunctions; Johnson & Johnson said it has not. (Ethicon is the name of its subsidiary medical devices company.)
On Thursday, the advisory panel recommended switching surgical staplers to a higher-risk classification with additional safety requirements, according to meeting attendee Jack Mitchell, director of health policy for the nonprofit National Center for Health Research. FDA spokeswoman Stephanie Caccomo declined to confirm this, citing a media office policy against telling reporters what happens at advisory committee meetings, which are open to the public.
“Every surgeon that I have ever worked with has had stapler failures,” said Dr. Doug Kwazneski, a Michigan surgeon who authored a survey in 2013 about “unacknowledged” stapler problems after searching the FDA’s public database of device incidents and coming up empty-handed.
“Going into something without data is dangerous,” Kwazneski said. “If the information exists, we should have access to it.”
More than 400 deaths have been reported since 2011 in the FDA’s public MAUDE database; fatalities can’t be reported to the alternative summary reporting database. Deaths were associated with Ethicon and Covidien products.
In recent communications about stapler safety to doctors, the FDA has advised against using the staplers on large blood vessels.
Kwazneski said surgical staplers are a time-saving tool, which lessens the risk of anesthesia complications during surgery, for example. But it’s important for physicians to remember they can fail.
Diana Zuckerman, president of the National Center for Health Research, said that alternative summary reports are “a well-kept secret” and that any reports related to their existence were “done in a way that was not understood as a repository for hundreds of thousands of serious adverse event reports.” […]
Late on Nov. 30, the US House of Representatives voted in sweeping favor across both sides of the aisle (392-26) on a $6.8 billion medical research bill. It’s expected to pass in the Senate, and it has support from the Obama administration.
All of this medical research spending, though, came with a regulatory compromise. Tucked in the folds of the bill were a number of new laws that allow the US Food and Drug Administration (FDA) to speed up the approval process for a range of treatments.
For example, the Cures Act allows for the expedited approval of new uses of drugs that had been approved previously for other conditions with just anecdotal case studies providing evidence that they work, instead of the usual randomized clinical trials. On the one hand, this means that treatments could reach patients more quickly, and save more lives. But on the other, it means that patients could be exposed to therapies whose risks aren’t completely understood.
There’s also a section of the Act that “expedite[s] the development and availability of treatments for serious or life-threatening bacterial or fungal infections in patients with unmet needs.” That sounds great in theory, but in practice, these drugs might be approved for use in specific patient populations without ever being tested in those people.
According to NPR, some 1,445 lobbyists from 400 organizations worked to sway lawmakers on this bill. Over 1,300 were from groups in favor of the bill, including deep-pocketed pharmaceutical companies in favor of the expedited approval process.“It really is a David and Goliath issue of where the money is,” Diana Zuckerman, the president of the nonprofit National Center for Health Research (which did not lobby for the bill), told NPR.
The Act will go to the Senate next week, where it is expected to pass. Notably, though, Democratic senators Elizabeth Warren from Massachusetts and Bernie Sanders from Vermont have vocally opposed it because of the softened regulations. On Nov. 28, Warren called the bill “extortion,” implying the benefits to the patients with additional medical research would be greatly outweighed by the risks of diminished regulation. The same week, Sanders said in a statement, “This is a bad bill which should not be passed in its current form. It’s time for Congress to stand up to the world’s biggest pharmaceutical companies, not give them more handouts.”
Is the FDA ’s approval process broken? […] Here are some excerpts of the conversation, edited for clarity.
Let me start off by asking: What do you think needs to be improved in the FDA approval process?
Zuckerman: I am increasingly concerned when the standards and criteria for what’s safe and what’s effective is moving more from the pre-market stage, before approval decisions are made, to the post-market stage. More drugs and devices are being approved on a basis of preliminary data, smaller samples, shorter time frames, and sometimes lacking control groups, as what recently happened with Duchenne muscular dystrophy. When that happens, it has a chilling effect on those who are trying to develop treatments and cures. Why would a company spend all of its energy working to do the best possible research if they can get an approval based on a shorter-term study, less definitive data, as long as they encourage patient groups to advocate and lobby for them?
What about the notion that patients and parents living with the disease are really the only ones who can understand what that’s like, and they should be in a position to assess the benefit and risk?
Zuckerman: I think patient perspectives absolutely should be factored in. And they should be factored in at every level. It’s not just important for patients who are wanting a treatment, it’s also equally important for the patients who get harmed. There are some folks in this room who have been harmed by unsafe medical products. They feel like FDA doesn’t listen to them. It’s really important to listen to patients, both the patients who can talk about the benefits of the drugs, or devices, but also the patients who can talk about the risks and the complications.
Going forward, why wouldn’t we be concerned that other companies won’t be emboldened to try and put an application in, and then force the issue? What we saw with this Duchenne episode is that when you have an effective pressure campaign, that can have an effect. And I’m not saying that’s necessarily a bad thing, that introduces a very human element into the discussion, and it can provide additional information.
Zuckerman: I want to get into the specifics of why this particular decision concerned us so much. The scientists all said this drug isn’t proven to work, we don’t know if it works, and therefore it doesn’t meet the legal standards that FDA is supposed to use to make a drug approval decision.
The company said they didn’t have a control group because it would be unethical to have a control group. That is a very frightening statement. If you think that it is not ethical to have a control group to study a drug that you don’t know whether it works or not, then you will never be able to find out if the drug works. You have to have a control group, particularly if you have a small sample like that.
Another big issue is the company announced the same day of the approval that this drug is going to cost $300,000 a year. This is a drug that has to be taken every year for the rest of these boy’s lives. It’s not a cure, it’s management. Now, these patients who have been getting this drug, presumably, for free as part of a clinical trial will somehow have to come up with $300,000 a year to continue to get the drug. I don’t know if insurance companies are going to pay for it, considering that the data show there’s not evidence that it works.