Joint replacements are the #1 expenditure of Medicare. The process of approving these medical devices is flawed according to the Institute of Medicine. It is time for patients' voices to be heard as stakeholders and for public support for increased medical device industry accountability and heightened protections for patients. Post-market registry. Product warranty. Patient/consumer stakeholder equity. Rescind industry pre-emptions/entitlements. All clinical trials must report all data.
Please share what you have learned!
Twitter: @JjrkCh

Friday, July 24, 2015

Bayer Essure: A Device of Torture with No Remedy


In hindsight, Dr. Shawn Tassone says he and his colleagues were perhaps too eager to implant metal coils in their patients' fallopian tubes.
"We do kind of treat women's health a little bit on the sly here in the United States," says Tassone, who practices at Austin Area Obstetrics, Gynecology and Fertility. "I think if you were to tell men you [were putting] a metal coil in their vas deferens ... men probably wouldn't do it. Like, 'Are you kidding me, you're going to put a piece of metal in my testicle?' But with women, it's just kind of OK."
Like many medical problems that started out as promising breakthroughs, the coils seemed to be a good idea to doctors some 750,000 procedures ago. For years, obstetricians and gynecologists have searched for a way to sterilize women without cutting into them, for a birth control method both permanent and non-surgical. In 2000, a small company called Conceptus said it had the answer: a small coil that looked like the spring in a ballpoint pen, called the STOP-2000. One coil would go in each fallopian tube, causing the tube to react and grow scar tissue, keeping the product in place forever.
The company began testing on women in the United States, England and Australia in 2000. Women who participated in the clinical trials were promised they were taking part in research that would help many others. "At the very least," says an early consent form, "your contribution will benefit the search for a non-incisional way for women to be sterilized."
Several of the women in the trials say they experienced bizarre, painful side effects, but were told they couldn't be caused by the device. Years would pass before they found other women with complaints like theirs, well after the STOP-2000 had been approved by the Food and Drug Administration under a more marketable name: Essure.
Tassone was an early user of the Essure. Initially, doctors were required to test their patients for any allergies to nickel, a component of the coils, but then the company lifted the requirement. "That opened the floodgates; then more doctors were doing it," Tassone says. Conceptus told doctors they could perform Essure in their offices, no hospital visit necessary, making the procedure even more cost-effective. At Tassone's practice, placing an Essure would earn him around $400. The doctors were trained by pharmaceutical sales representatives who are not doctors, a practice health advocates criticize but which the manufacturer defends.
"The sales reps are not required to have any medical degrees, but this is very common in the device industry," says Dr. Edio Zampaglione, an executive and physician at pharmaceutical giant Bayer, which purchased Essure two years ago. "It takes somewhere between six to eight months for these sales reps in the beginning to get internally certified and go out and train physicians."

Tassone volunteered as a consultant for Conceptus, fielding questions from doctors near him, attending conferences and seeking advice from sales people during the procedures. In a span of six years, he implanted the Essure more than 200 times, he estimates. If any women did complain to him afterward, he says he wouldn't have connected it to the Essure.
Then a doctor in Florida called him two years ago. A woman whom Tassone had implanted with Essure had moved there and then got pregnant. The woman's new doctor thought Tassone should know. "I thought the Essure was supposed to be pretty infallible," Tassone says. The call was an eye-opener. He searched the Internet and found Essure Problems, a grassroots Facebook group that for many women has been the only formal recognition of their pain. Every day the group of nearly 20,000 women is piled with new complaints about side effects from the device, many that defy explanation: distended bellies the women developed shortly after getting the Essure, migraines, constant bleeding, pain near their abdomens, skin rashes, lethargy and heavy periods, to name a few.
Some of the complaints women had about their minds and bodies sounded like borderline conspiracy theories to Tassone, but a pattern emerged in many of the reported side effects and medical evidence: Patients have gone so far as to post X-rays in the group, showing Essure devices that had somehow traveled out of their fallopian tubes and into other parts of their bodies, some in their uteri or colons. Spin-off groups were formed for Essure women who got pregnant. Tassone stopped implanting the device and began treating patients who didn't want Essure anymore.
But Essure isn't like other forms of birth control, which all cause side effects for a percentage of unlucky users. Essure is designed to stay stuck in a woman's body forever, embedded in inflamed scar tissue. "There is no good way, from the company, from the manufacturer, to take it out," Tassone says. "You would think that they would devise a way to remove their product that doesn't cause significant damage to a woman."
Or, as the FDA's website explains: "Essure is considered a permanent form of birth control and therefore is not intended to be removed."
So, women who no longer want Essure in their bodies anymore have limited resources beyond a support network of others bitter at the medical system they say failed them.

Dylan Hollingsworth
On the ground floor of the Texas Health Huguley Hospital in Burleson, Dr. Robert Smith advertises his infertility clinic in neon lights. "ESSURE REVERSALS," reads a glowing pink and blue sign on the door. Two paintings hang in his waiting room. In one, a surgeon and his team operate on a patient as Jesus stands behind the surgeon, guiding his hands. The other shows a young, male doctor looking pensively into the distance. Again, Jesus stands behind him.

Smith takes credit for being the first doctor in North Texas to remove Essure from a woman, and, like the doctors in the paintings, he says his hands are guided by something holier than medical science. "To my knowledge, I had, in the DFW area, the first successful removal of the Essure inserts," Smith writes about himself in one of the several books he's self-published about biblical prophecies that Jesus will rise again. "The above is mentioned not for accolades but rather to acknowledge the gifts that God has entrusted to me."
In person, Smith has a friendly manner, less intense than his literature might suggest. He wears a bow-tie and his hair slicked back. A woman's uterus is embroidered above the right breast of his doctor's coat.

Smith isn't ideologically against birth control, he says, nor will he comment on whether Essure is an inherently flawed medical device. His specialty has been reversing tubal ligation, the older, more common and most effective form of female sterilization. He learned how to do Essure reversals more recently, using similar techniques. Before surgery, he asks his patients to pray with him.

Smith is one of the few doctors near Dallas who will operate on women who don't want Essure anymore. On Texas E-sisters, the local spin-off of the national Essure group, the women compiled a list of trustworthy doctors in the state who can take out Essure. The list contains only 15 names. To get doctors and insurance companies to take their complaints seriously, the women advise each other on how to articulate their problems in the physician's office.
"I think there's this sort of underground carrying of information [in the Facebook group] that you're not going to get from looking at your insurance provider directory," says Dr. Eric Sills, an infertility specialist in Carlsbad, California, who has studied the prevalence of pregnancies with the device.
Patients have a litany of horror stories about doctors who unsuccessfully tried to remove Essure: doctors who simply pulled the coils, causing them to break, or doctors who morcellated them, using a tool to grind up the Essure coils that can release metal pieces into the patients' bodies.
"I looked like I had freaking shrapnel in me," says Angie Firmalino, a mail carrier in New York City who founded the Essure Problems group. Many women assume that the only way to get Essure safely out of their bodies is through a hysterectomy, the kind of invasive surgical procedure Essure was supposed to help women avoid. Patients find that many doctors are reluctant to perform the drastic surgery. Woman instead are told to take medication to deal with pain, or are diagnosed with a "hormone imbalance" or other illness.
"The Essure removal by hysterectomy is not a difficult procedure, but what happens is a lot of us get scared, a lot of us don't want to manage patients with the Essure device in place because we've never had to do surgery like that, so we get scared and so we pass the buck to another doctor," says Dr. Julio Novoa, an OBGYN and plastic surgeon in El Paso and one of the 15 doctors whom the Texas E-Sisters recommend. He counsels women for free regularly on Facebook. On his insurance forms, he makes sure to explain the immediate reason for performing a hysterectomy: not the Essure, but the pain in the woman's abdomen.

Dr. Smith, in Burleson, doesn't just offer Essure patients the basic hysterectomy. He also tells women with Essure they could get pregnant again if they undergo a more complicated surgery called the Essure reversal. He is one of only a few doctors in the state to advertise the procedure. It costs $6,000, gets no coverage from insurance providers and must be paid in cash. "I've been burnt by checks, so after a while you just don't take them," he says.
There's no published data that Smith or any other doctor knows of studying the safety or efficacy of Essure reversal surgeries. By Smith's own count, he has performed reversals on 11 women. "My success rate after 12 months of trying is 66 percent," he says of patients who conceived. He acknowledges that Essure patients who do get pregnant face an unknown risk of ectopic pregnancy, a sometimes-lethal type of pregnancy in which an embryo implants itself outside the woman's uterus. In interviews, IVF specialists tend to be more optimistic about the safety of Essure "reversals" than other types of gynecologists. "If the device itself is supposed to cause inflammation and scarring inside the tube, then if you're going to remove the device you're going to have damage inside that tube," Tassone says.
Smith says he closely monitors any patient who does get pregnant, to ensure the fetus is implanted in the right spot. For now, women who pay cash in hope of getting pregnant again must hope Smith's right in his belief he's getting help from above. "I try to represent what Christ has done for me. I try to do that for the patient, and I think by keeping that in focus, that my hands are guided by God," he says. "So I think I have gifted hands and I think that's part of the reason that these reversals have worked."

Dylan Hollingsworth
Maria Rocha stopped by Dr. Smith's office for a consultation, considering the Essure reversal after suffering effects — mainly a huge, bloated belly, bleeding and fatigue — she says the device caused. She also contemplated having children with her fiancĂ©, whom she wasn't with when she got the device two and a half years before. Smith warned her that if she got pregnant, the baby could die unless she underwent a C-section, so she ultimately decided against the surgery.

Rocha was receiving Medicaid benefits when she had the Essure implanted in 2012 and was told by her doctor at a low-income clinic in Waco that he no longer performed tubal ligation. On the day her device was placed, a representative from Conceptus coached her doctor on what to do, she says.
Rocha remembers being surprised by the pain. Later, she ran into a nurse from the clinic, she says, who told Rocha she was one of the first patients her doctor implanted. (His office didn't return messages). She lived with the pain for two and a half years, searching for doctors to help her, until this spring, when, after deciding against the surgery with Smith, she got a hysterectomy from the same doctor who installed the Essure. But he still denies that her health problems are caused by Essure, Rocha says. "He doesn't have an explanation, like why I'm in pain all the time, bloating, why I have periods like twice a month sometimes," Rocha said. Her surgery is in August.
Essure is popular with insurance providers — Medicaid covered about 6,000 Essure procedures in Texas over the last three years, according to data from the Texas Health and Human Services Commission. The ease of getting the procedure can make the patients feel suddenly stranded when they can't get coverage for subsequent complications.
Casey Kummell, an office manager in South Lake, had her Essure procedure in April last year in the same Irving clinic where she gave birth to her children. Kummell was on Medicaid at the time while her husband was unemployed. She wanted to get her tubes tied, but her longtime doctor told her Essure was the better choice.

Kummell read about the backlash to the procedure online and saw that famed but controversial environmental activist Erin Brockovich had started a website against Essure after women in the Facebook group flooded her with mail in a letter-writing campaign. "He said, you know, what a joke all that was, the whole Erin Brockovich stuff, that it's all a joke, all of that can't be caused by this little device," she says, "and so I trusted him."
The procedure was quick and easy, but she developed cramping soon after, a strange pain that felt like being poked with a hot stick. A scan taken by her doctor, which she provided to the Observer, showed that one of the Essure coils had migrated out of her fallopian tube and into her uterus. Her doctor told her he would perform surgery on her for no charge to get the coil out, she says, but the hospital would still charge her $30,000. No longer on Medicaid, she couldn't afford the procedure.
She developed heavy anxiety, fearing she'd need to get a hysterectomy. Finally, nearly a year later, Kummell was able to get on her husband's insurance after he got a new job. The same doctor who installed the Essure performed a complicated surgery to get it out, slicing off a portion of Kummell's uterus but sparing her a hysterectomy. She believes her doctor was genuine when he told her he had never had complications with Essure before.
A pattern of doctors disbelieving patients who complained of side effects began early, back in the clinical trial phase, women say. The Observer interviewed five women who were in post- and pre-market studies of Essure who say they later underwent invasive surgery to get their organs removed. Two provided medical records from their clinical trials.
"We were told it had been passed in the U.S.A. and was new to England. We were in a trial to see if we could get on with our daily lives immediately after," writes Lisa Bennett, a woman in Leeds who says she was part of a clinical trial in 2000, two years before Essure was approved for sale in the United States. Soon afterward, she was in pain and asked for a hysterectomy. Doctors performed the hysterectomy after she demanded it, she writes, but still insisted her pain wasn't caused by the device. Her doctor "was adamant it wasn't Essure related," Bennett says in a message.

The U.S. Food and Drug Administration approved Essure under stringent guidelines called the Class III Premarket Approval process, which is supposed to be so strict that the manufacturers of the device are protected from lawsuits. One attorney in Florida is trying to start a class-action suit anyway. In a petition to the FDA several months ago, his firm includes the medical records of Kim Hudak, one of the clinical trial participants. Several questionnaires in her file show that doctors crossed out answers to her questions and circled new answers. In an interview, Hudak said she recalls filling out the forms herself but with heavy coaching from nurses and researchers, who told her she wasn't suffering any adverse events despite her failing health. Other questionnaires were done over the phone. "I have continued to see doctors of various specialties since 2006, but no one seems to know what is wrong with me," Hudak wrote to her research doctor, Dr. Linda Bradley at the Cleveland Clinic in 2013.
In 2008, eight years after her participation in the trial began, Hudak asked Dr. Bradley for guidance. She was undergoing a removal of one of her ovaries to treat "excessive endometrial growth." She wanted to make sure the surgery was safe to do with the Essure inserts. Bradley counseled Hudak on the phone, she says, and told her to go ahead with surgery.
Shortly after, Hudak received a letter from Cleveland Clinic's Cheryl Williams, clearly indicating the company was no longer interested in hearing from Hudak. "The sponsor has decided to discontinue the study as of December 31, 2008," the letter said. "This means you will not receive any future phone calls or be asked to come in for office visits related to this study." (The Cleveland Clinic says through a media representative: "Our records indicate that the patient voluntarily and actively participated in the STOP-2000 clinical trial from 2000-2008, and both the Cleveland Clinic and the patient complied and completed all study requirements until the study was discontinued by Conceptus in 2008. At that time and with consent, the collected data was submitted to Conceptus for interpretation. Documentation of the patient is consistent with device studies, and the information recorded was provided by the patient.") More recently, Hudak underwent a full hysterectomy.
Dr. Zampaglione, from Bayer, says he reviewed Hudak's records and found nothing wrong. "There were some cross-outs, but those do occur in any kind of medical record, mistakes are made ... what was done was a cross-out and initialing, a cross-out that is 100 percent absolutely allowable and by the book," he says.

Hudak isn't the only participant who believes medical records misrepresented her experience. "A lot of the documents I have were not filled out by me," says Patricia Rhodes, who agreed to join a clinical trial for a free, permanent birth control method in 2000, at the urging of her now ex-husband. She was 24, with one daughter. A security guard then, she had no health insurance, and her then-husband no longer wanted to pay for her hormonal birth control shots. He heard an ad for the clinical trial on the radio. "He's like, 'Hmm ... permanent and free, go check it out,'" Rhodes says.
Rhodes knew she was allergic to nickel, she says, but the doctors told her the coils contained only stainless steel. (The clinic did not return messages seeking comment.)
"I asked them, I don't know, six or seven times, what they were made out of, because I have metal allergies. After six or seven times of bugging the crap out of them trying to find out what [the Essure coils] were made out of, they just told me, 'Oh, they're 100 percent surgical stainless steel,'" Rhodes says. Her clinical trial paperwork similarly shows no mention of any nickel. Essure pamphlets now explicitly warn: "Patients who are allergic to nickel may have an allergic reaction to the inserts."
Her medical consent forms also show no written warnings that the device contained nickel. Zampaglione, the Bayer doctor, said the forms omitted any mention of nickel because patients with nickel allergies were automatically excluded from participation. "If a woman had a nickel allergy, she would have never even made it in the study to sign a consent form,  so that is probably why the consent forms for the very early studies did not have anything about nickel."
Yet during the FDA's meeting in 2002 to approve Essure, representatives from Conceptus told an FDA panelist that nickel coils were safe even for women with nickel allergies. "There was no evidence of local toxicity or local irritancy used with the Essure devices," the representative said to an FDA panelist who asked about nickel allergies. Firmalino, the founder of Essure Problems, obtained footage of the meeting by organizing a fundraiser through Essure Problems and purchasing the copyright from the video company that produced it.
Rhodes says her complications began immediately. She bled for the next six months, felt constant pain in her pelvis and developed urinary tract infections.

"Six months after I got them, I was diagnosed with a hormone imbalance, which I didn't have prior," she says. The clinical trial documents make no reference to any of her ailments. On patient questionnaires from the trial, which Rhodes recently obtained, she is listed as feeling "very satisfied." At the same time, her medical records indicate that over the years she made multiple "unscheduled visits" to the doctor's office for pain in her abdomen. Her health continued to deteriorate, she says. She developed ovarian cysts and new allergies to certain foods and medications. By her late 30s, she says, she felt as though she was going to die. A doctor diagnosed her with porphyria, a rare blood disease.

The investigating doctors studying her told her the problems couldn't be related to the device, Rhodes says. In 2002, another doctor prescribed her 14 different medications to manage the symptoms in her uterus and stomach, her medical records show. That same year, Rhodes' clinical trial documents claim that she found her "comfort wearing the device" to be "excellent." Years later, another woman in the same trial, at that same clinic in Arizona Rhodes visited, would give an interview on a local news station making a similar claim: Her clinical trial questionnaires were wrong — they grossly underestimated how much pain she was in. Rhodes finally found a doctor to perform a hysterectomy in March of this year.
In late June, an FDA representative gave Hudak a surprise call. The agency wanted to invite her personally to attend a public meeting planned about Essure, coming up this September. That same day, on June 25, the agency posted a new, public statement about Essure. People have sent more than 5,093 complaints about the device to the agency's adverse-events database, including reports of pain, fatigue, weight gain, heavy periods and nickel allergies. Worse were four reports of adult women who died, and five reports of fetal deaths. The FDA's announcement came several months after a study from Yale found Essure comes with a 9.6 percent failure rate for women trying to avoid pregnancy — previously, all methods of sterilization for both men and women were thought to have a failure rate of less than 1 percent and Conceptus claimed Essure was over 99 percent effective.
Bayer argues that the adverse events and pregnancies are still low enough for the benefit to outweigh the risk. About 750,000 women have been implanted with Essure, according to figures provided by the company and based on the number of kits sold.
Tassone, the doctor in Austin, recalls implanting Essure in a woman in 2006 and watching her tube spasm without warning. The coil suddenly disappeared inside her body. The sales rep in the room, he says, told him to go ahead and put another coil in. Tassone says he refused, thinking that didn't seem like sound medical device. He monitored the woman, he says, and as far as he knew, she never had side effects.
Now, women will occasionally post to the Essure Problems group post-surgery photos of multiple coils that were retrieved from each tube, rather than the one per tube supposed to be there. "I think I've seen up to five," Tassone says. Zampaglione said he could not comment on Tassone's story but said in some women, it is OK to use more than one coil per tube.
In recent years, Tassone says he has performed about 20 surgeries on women who want the Essure removed. He describes patients with huge, distended bellies that suddenly disappeared after the surgery. Other women have told him they experienced more subtle relief from the removal: more energy, better moods and a clearer mind. Perhaps some of the improvements are a placebo effect, he acknowledges. But he doesn't think that should matter. "The point is, if they say they feel better ... who am I to say that the reason that they feel better is good or bad?"

Email the author at   Twitter   @AmySilstein

Wednesday, July 22, 2015

ProPublica consumer-accessible Surgeon Scorecard for hip & knee surgeons!

We Go Behind the Scenes on Surgeon Scorecard

ProPublica, July 20, 2015
Last week, ProPublica launched Surgeon Scorecard, our new database showcasing the complication rates of nearly 17,000 surgeons nationwide. For the first time, patients can now weigh surgeons’ past performance before going under the knife and doctors themselves can see where they stand relative to their peers.
Our Surgeon Scorecard team – Marshall Allen, Olga Pierce and Sisi Wei – joined ProPublica’s Eric Umansky on the podcast to discuss how they tackled this ambitious, all-hands-on-deck project.
Highlights from their conversation:

  • The lack of incentive for hospitals to track their own surgeons’ complication rates. It’s difficult to do and also very uncomfortable politically, Allen says. Surgeons are powerful, they bring in a lot of revenue to the institution, and there’s the risk that they’ll take their cases to another hospital. (7:38)
  • What makes a compelling data story: “If there are relentless numbers in a story, it's often a sign that your data is not as strong as you think it is,” Pierce says. “The best data stories are ones where you've reached some sort of interesting finding and that is a launching plane for the rest of the story.” (21:15)
  • How all ProPublica apps, including Surgeon Scorecard, have “a near view and a far view,” offering not only a look at broader trends but specific data on specific localities that journalists can use to power their reporting. “There are going to be so many local stories that we can't focus on,” Wei says. “But other journalists can use our app to do that.” (25:06)

You can listen to this podcast on iTunes, SoundCloud or Stitcher, and use our Surgeon Scorecard app to look up your doctor.

Tuesday, July 21, 2015

US Senate Must NOT Pass 21st Century Cures Bill

How Not to Fix the F.D.A.

A bill passed by the House and ostensibly designed to streamline the Food and Drug Administration is loaded with bad provisions and may not even be necessary. The Senate should either eliminate or rewrite the flawed provisions before passing its version of the legislation.
The bill would weaken the F.D.A.’s already flimsy regulation of medical devices, posing a threat to future patients who have devices implanted that cannot easily be removed if found defective. It would allow a drug to be tested on humans based on only limited evidence that it is safe and effective.
It would expedite the use of new antibiotics by providing financial incentives to hospitals to use them — benefiting manufacturers but also driving up costs and encouraging overuse, potentially breeding resistant superbugs. It would extend exclusive rights for manufacturers to market high-priced, brand-name drugs if they gain a new approval to treat a rare condition. And it would open a wide loophole in rules requiring companies to report payments they make to doctors to get them to prescribe their drugs.
While the bill has some valuable provisions — like making experimental drugs available more quickly to patients who have illnesses that cannot be cured, and promoting the development of treatments based on an individual’s genetic data — those elements don’t justify the bill’s passage in its current form.
The F.D.A. was once routinely vilified for sluggishness and timidity, but with the help of industry funding it has made enormous progress in speeding up its reviews and approvals. The agency testified in April that its drug review times are consistently faster than those of all other advanced regulatory agencies around the world, with the result that American patients receive new drugs sooner than people elsewhere. In 2014, the F.D.A. approved the largest number of new drugs in almost 20 years and also reduced the review times for devices.
A big reason the bill won bipartisan support in the House is that it would increase funding for the National Institutes of Health by $8.75 billion over the next five years, ending a decade of mostly stagnant funding. And any improved Senate version should certainly include new money.
Special interest money also played a role, with many of the top supporters of the legislation having received hundreds of thousands of dollars in contributions from the pharmaceutical industry and the medical device industry last year, according to the nonpartisan Center for Responsive Politics.

The Senate will take up a similar bill later this year. When it does, it needs to cure its many flaws, while also providing sufficient funds to the F.D.A. to meet its ever-increasing workload.

Monday, July 20, 2015

Patients and surgeons select implants blind to effectiveness, safety and cost.

DMN reporter got his knees replaced — but was the stiff price a good deal?

Staff Writer
16 July 2015 

Getting your knees replaced can be an education in much of what’s wrong with health care — as I learned last year from personal experience.
My insurer offered guidance on which hospitals were in network, and how much they’d be reimbursed. My doctor referred me to a surgery group that practiced at only one of those hospitals.
I didn’t know which companies make artificial knee joints, or which ones are best.
Luckily, I came out of it with mechanical knees that greatly improve my quality of life. I remember the times I couldn’t run across the street before the light turned red because running meant bone-on-bone pain. I remember the photos my wife took where I was as bow-legged as a cowboy cliche — my knee cartilage was so far gone.
But the choices I made with limited information about surgeons, hospitals and medical devices probably wound up hitting my employer, The Dallas Morning News, with $10,000 in extra insurance charges.
It was a surprise, though, when one of the nation’s top orthopedic surgeons told me he is almost equally in the dark as he tries to determine where to go to replace one of his own knees.
“There should be a process where I can seek information about quality, outcomes and cost,” said Dr. Kevin Bozic, chairman of surgery at the University of Texas at Austin’s Dell Medical Center. “If you’re in D.C. or Dallas and you’re trying to figure out where you can get that, it’s a joke.”
Market peculiarities
Bozic recently came to Austin from San Francisco, where he was part of an orthopedic surgical team and was on the faculty of the University of California at San Francisco. He has a master’s degree in business administration to go along with his medical credentials.
He’s studied and written about the peculiarities of the joint replacement market for several years.
“If you look this up online,” he said, “you’re going to get a bunch of advertisements saying this one uses robots, or this one has the latest technology, and then you’ll find information on Yelp about the surgeon’s bedside manner, and that’s important.
“But the things you really care about — will it improve my health, reduce my pain, will I have a quality outcome — you’re going to find nothing.
“That needs to change,” Bozic said. “The consumer wants the best outcome at the lowest cost.”
He hopes a more rational way of doing business is on the horizon.

The hope, which is beginning to emerge in Dallas and elsewhere, is that medical devices will have a searchable track record of success — or failure.
It’s a hope that consumers can learn which hospitals and surgeons do the best work — and which surgeons are paid huge sums by the device makers. It’s a hope that patients will be out of bed and able to start physical therapy within a day of surgery, rather than two or three or even four days later.
And it’s a hope that insurers will someday pay one bundled price for joint replacements — and hospitals, surgeons, anesthesiologists, physical therapists and medical device makers will have to work within that budget.
Some device manufacturers are taking cost out of their products. Prices have fallen between 8 percent and 13 percent over the last year for key knee and hip replacement components.

The 4-year-old American Joint Replacement Registry (Bozic is its vice chairman) has data on nearly 300,000 joint replacements. The group is watching to see how long the replacements last, which surgery techniques and technologies work best, and which ones don’t.
This month, Medicare announced a bundled payment initiative for joint replacements. And for two years, it has released data on medical device and pharmaceutical company payments to physicians and hospitals.
The big remaining question is: Value for whom? The consumer, or the hospital? In Dallas, at least, the hospitals are the ones coming out ahead.
Oblivious to cost
The way it’s worked until now is pretty strange.
Most orthopedic surgeons are oblivious to the cost of medical devices. They choose what they’ll use based on a buddy system with a sales representative. Many surgeons get consulting fees or design royalties from those device makers.
Hospitals that want the surgeon’s business buy the joint replacements the surgeon wants. They are contractually forbidden from telling the surgeons or anyone else what price they pay. The hospitals bill patients for the device (often including a big, hidden markup), for the operating room and for their care during a typical two-night stay.
“In most places, physicians are not employees of hospitals and don’t care what things cost, and that shifts a lot of power to the manufacturers,” said Pete Allen, executive vice president for sales and marketing with Novation, an Irving-based company that buys supplies for more than 1,500 hospitals across the country.
The sales reps stick with their surgeons. They go to all the surgeon’s operations with suitcases full of tools and parts for artificial joints. They use laser pointers to tell nurses and other members of the operating team what to use.

Sometimes they upsell, Allen said, recommending a new component to the surgeon while the patient is on the operating table.
When a patient has multiple fractures, the operating room can get crowded. “A trauma case may have four or five reps in the operating room,” Allen said. “That’s a lot of expense, and it’s not free.”

Artificial knees are made of cobalt, stainless steel or titanium that covers the ends of the thigh and shin bones. A hard plastic disc absorbs the friction between the metal pieces. A sliding button on the back of the knee cap keeps it moving.
Hips are made from similar materials and ceramics, with a long stem embedded in the femur and a ball-and-socket placed into the pelvis.
Hospitals pay anywhere from $3,300 to nearly $11,000 for the parts in one standard artificial hip or knee, according to the ECRI Institute, a Pennsylvania group that tracks medical supply pricing for hospitals.
U.S. surgeons are expected to replace more than 1.3 million hips and knees this year. By 2020, the number is expected to hit 2 million, with 3 million by 2030.
In 2012, Truven Health Analytics determined that medical devices were the single-biggest driver of hospital inflation between 2001 and 2006.
Medical device prices doubled between 1997 and 2008, and the number of joint replacements grew even faster. Hospitals complained that they were getting squeezed between what Medicare was prepared to reimburse and what device makers were demanding as payment.
A bill was unsuccessfully introduced in Congress to compel device manufacturers to reveal their selling prices.
The gross margins on joint replacement sales are as much as three times greater than the costs of manufacturing. Relatively little of those margins are invested in research and development. Most of it goes back to the sales reps, who account for 40 percent to 45 percent of the price of a joint replacement.
Steve Lichtenthal, vice president of business development with the Orthopaedic Implant Company of Reno, Nev., argues those margins are too big.
“Thirty-five years ago, orthopedic implant sales operated like any other industry. The sales rep would come around every so often with lunch for the staff and to shake the doctor’s hand,” he said. “Then every few years there’d be new technology; anatomically shaped plates, different screws, or a different material used in spacers for a vertebral fusion case, for a few examples. Hospitals couldn’t keep up with the changes, and the industry did a wonderful job embedding their sales reps to manage the entire implant supply chain for the hospital while upselling physicians in the operating room while attending surgical cases.”
“It’s going to be very, very tough to undo that,” he said. “But if you eliminate that sales rep and modify the supply chain, you halve your implant costs. The magnitude of savings is into the billions.

Lichtenthal’s company is just getting started, and specializes in trauma plates rather than joint replacements. But another device maker is experimenting with a lower-cost, “rep-less” approach.
Smith & Nephew, Britain’s largest joint replacement maker and one of the top four sellers in the U.S. market, recently launched a line of hips and knees called Syncera using last year’s components, training software — and no sales reps. The company hasn’t said how well it’s doing, but promises more information later this month.
Other device makers are watching but haven’t followed.
David Floyd, group president for orthopedics with Michigan-based Stryker Corp., was asked by analysts in May what impact Syncera was having on his firm. “None,” he replied.

Bob Marshall, a vice president with Indiana-based Zimmer Holdings, told another group that the competition was healthy.
“If we can’t prove out the value for the premium technology, those prices won’t be held,” he said. But he warned that value-based joint implants could be costly for hospitals if they lead to liability problems.
And yet, the pricing of joint replacements has dropped.
Tim Browne, ECRI Institute’s price guide director, said prices for a key knee component are down 8.3 percent from a year ago. With hips, the key component price has fallen 13.4 percent.
“Of late, hospitals have really gotten engaged with physicians, working collectively, to drive that down,” Browne said.
Some insurers are also pushing back. CalPERS, the California state employee retirement system, notified members in 2011 that their health insurance would cover a hospital’s knee replacement charges up to $30,000.
If the procedure cost more, the consumer would pay the difference.
In response, California hospitals left out by CalPERS’ reference price lowered their prices by 38 percent — from an average of $43,308 to $28,465.
The Blue Cross Blue Shield Association reported in January that joint replacement charges can double or even triple among hospitals within the same metro area. Between 2011 and 2013, hospitals in Dallas got as little as $16,772 and as much as $69,654 for a knee replacement.
The current average knee replacement reimbursement in Dallas, according to insurance claims sifted by the Health Care Cost Institute, is $45,436. The national average is $33,560.
Dallas hospital administrators say they’re squeezed by low Medicare reimbursements and have to recover by charging more to insured patients.
Big markups
Whether needed or not, the markups are big.
Baylor Scott & White Health System hospitals in the Dallas area performed almost 2,400 hip and knee replacements last year. The hospital chain’s supply managers and surgeons meet to discuss which devices to use. They try to limit the number of suppliers as much as they can to drive a better bargain.
A similar approach with cardiologists led to savings of between 18 percent and 20 percent on $40 million worth of stents, pacemakers and other heart surgery devices, said Pam Bryant, Baylor’s supply manager.
Bryant said the hospital chain spends about $30 million a year on knee and hip replacements. She said she pays between $3,800 and $6,900 each for artificial knees.
Insurers and patients never see those bills. Instead, their line-item hospital bills include component pricing that covers both the negotiated device price and the hospital’s markup.
David Toomey, a health care consultant with Dallas-based Compass Professional Health Services, said area insurers are paying between $7,860 and $12,800 for knee replacement components — almost twice as much as the average cost of the device.
Asked about these markups, Baylor responded with this statement: “Our charges for devices utilize a markup on the raw cost of the device, which is in line with industry standards. Baylor Scott & White Health engages a third party to conduct an annual review of our device markup formula, which is proprietary, to ensure its reasonableness and alignment with device pricing by other leading health care providers.
“Baylor is reimbursed less than 100 percent of the actual cost of treating more than half of its patients, as roughly 60 percent of the patient base we serve is uninsured or underinsured.”
My knees
For my knees, my surgeon chose standard components made by DePuy Synthes, an Indiana firm owned by health care conglomerate Johnson & Johnson.j
So far, they’re working fine. The pain is gone. I can stand a little taller these days.
The hospital where I had them replaced charged $16,097.05 for each artificial knee. My insurance paid $10,982.72 each.
When I studied the bill, I thought it meant my surgeon had used some fancier components that provide the knees with rotation.
Not so. They’re fixed, standard knees.
ECRI Institute’s Tim Browne says the current average price paid by U.S. hospitals for the components of a standard knee replacement last year (when I had my surgery) was $5,081 — half the price paid by my health insurance.

“It’s a very inefficient marketplace,” UT’s Bozic said. “Even [for] me, an orthopedic surgeon who needs a knee replaced — I have no information on value.”

Friday, July 17, 2015

The FDA's Medical Device Problem

The F.D.A.’s Medical Device Problem

By RITA F. REDBERG and SANKET S. DHRUVA              JULY 17, 2015
THE Food and Drug Administration has been regulating the approval of medical devices since 1976, but its regulatory oversight has not kept pace with the increasing complexity of this technology. Many high-risk medical devices today are approved on the basis of just one clinical trial (as opposed to new medications, which usually require two trials). And only a small minority of clinical studies of medical devices are randomized, controlled and blinded — the gold standard for reliable evidence (and the benchmark to which studies of drugs are held).
As a result, there have been many warnings about, and recalls and withdrawals of, medical devices that were found to be dangerous only after they were on the market. (In 2009, for example, the Sprint Fidelis defibrillator, which by that time had been implanted in hundreds of thousands of heart patients, was recalled because it frequently malfunctioned, harming many patients and leading to numerous deaths.) And because the F.D.A.’s oversight of medical devices once they are on the market is also weak, it is very likely that many malfunctions and other problems remain undetected.
Incredibly, legislation that the House of Representatives passed last week would severely weaken, not strengthen, the F.D.A.’s already ineffective regulatory scheme for medical devices. The device industry may stand to benefit from this legislation, but the health of the public does not.
The legislation, disingenuously titled the 21st Century Cures Act, would make it possible for companies that produce high-risk medical devices to submit evidence of safety and efficacy based on sources other than clinical trials, including case histories (i.e., the experiences of individual patients). In other words, anecdotal evidence, rather than the scientific studies, could be used to approve devices.
This act would also create a new, faster approval process for “breakthrough technologies” that are believed — but not necessarily proved — to offer significant advantages over existing alternatives. This would allow a device to be approved based on even lower standards of evidence than are currently used, on the theory that the need outweighs the risk. The legislation defines “breakthrough” loosely, creating a perverse incentive for manufacturers to use this term both to take advantage of the faster approval process and as a marketing gimmick.
In general, the proposed law is likely to shift the burden of evidence to clinical studies that are conducted only after the devices have been put on the market. Unfortunately, such studies are often delayed months to years after a device is approved. Many are never completed (and even when they are, their findings are often not publicly available). Although the proposed law alludes to “timely postmarket data collection,” that vague directive needs to be clearly defined — and more important, enforced — by the F.D.A. In fact, according to a 2014 journal article co-written by one of us, the F.D.A. has never issued a warning letter or penalty for a postmarket study delay.

Even if a postmarket clinical study deems a medical device dangerous, it still can be difficult to remove it from the marketplace. In 2005, for example, an intracranial stent called the Wingspan was approved on an expedited basis to prevent recurrent strokes. When a high-quality clinical trial was finally completed, in 2011, it found that patients who had the device implanted were more likely to have another stroke and to die than those just receiving medical management. Despite this evidence, the F.D.A. did not withdraw the device (though it did narrow its recommended uses). The Wingspan continues to be marketed and implanted today, putting patients at unnecessary risk.
Once a medical device is developed and approved, its manufacturer often makes small changes intended as enhancements (such as using a different size wire or new material). Currently, the F.D.A. is the arbiter responsible for ensuring that these changes result in a safe and effective device. But alarmingly, the 21st Century Cures Act would establish a third-party program of nongovernment authorities to assess whether a company is permitted to make such changes. The act would enable the device manufacturer itself to select — and pay — the third party from an approved list. This flagrant conflict of interest would make it impossible for physicians or patients to have trust in the safety or effectiveness of updated medical devices.
The 21st Century Cures Act would subject millions of Americans to unsafe or untested medical devices. We urge the Senate, as it takes up the bill, to avoid these dangerous provisions. Unlike medical drugs, which can readily be discontinued if problems are found, many medical devices are permanently implanted and cannot easily be removed if found to be defective. Stricter evidence standards and increased federal funding of the F.D.A. are needed to ensure that innovative medical devices lead to better health.

Rita F. Redberg is a cardiologist at the University of California, San Francisco, Medical Center. Sanket S. Dhruva, a cardiologist, is a clinical scholar at Yale University.

Thursday, July 16, 2015

U.S. Congress & FDA: Human Guinea Pigs-"So Be It"

This new bill would add $9 billion for medical research. Here are 5 reasons critics are terrified.

Updated by Julia Belluz on July 14, 2015, 1:10 p.m. ET @juliaoftoronto

Last week, the House passed a bill in a 344-77 vote, an overwhelming consensus at a time when relations in Congress are mostly fractured. The bipartisan effort, known as the 21st Century Cures Act, infuses medical research with $8.75 billion over five years and purports to overhaul drug development and innovation to get lifesaving cures to people who need them faster.
The Cures Act has a chance of actually passing the Senate and getting signed into law. But critics say the legislation is trouble. "What we have here is a Trojan horse," Jerry Avorn, a professor at Harvard Medical School, told the New York Times. "The elevator pitch is very appealing ... But it is a vehicle for some regulatory changes that are really very worrisome."
Hidden in the bill's 352 pages is language some observers think will erode the quality of evidence the FDA uses to evaluate new drugs and devices, making it easier for companies to bring substandard or ineffective medicines and devices to market. The bill would also turn back some recent efforts to make relationships between doctors and drug companies more transparent.
I asked some of the concerned researchers to go through the bill's provisions that they found most worrisome. Here are their top five:
The bill encourages the use of anecdotes as evidence that drugs work

There are a few provisions in this bill that change the standards for the quality of evidence the FDA uses in considering drugs for the market. The idea is that in some cases, waiting for big clinical trials on new drugs slows down the regulatory process and keeps potentially useful drugs away from patients. In other cases, it's difficult to find a sufficient number of patients suffering with rare diseases to run a big trial. The bill encourages the use of early and easier-to-gather data to speed the process up.
But as Rita Redberg, editor of the journal JAMA Internal Medicine, wrote in a recent comment, this could amount to a dangerous trade-off: "In our rush to find new effective treatments, we should not harm our patients with ineffective toxic ones."
Take Section 2062, which would make it possible for companies to seek approval for their products based on anecdotes from doctors who have used the drugs in their patients. Because anecdotes can be cherry-picked and unrepresentative, they don't give a good overview of the actual impact of a medication. That's why regulators today generally rely on randomized control trials — experiments that randomly assign patients to a drug or placebo. If a drug works or harms people, it's clear it's the medicine that made the difference.


"This replaces the gold standard of randomized control trials, and basically says this idea is old-fashioned and if we want to get drugs and devices to market more quickly, we have to use different standards," explained Diana Zuckerman, president of the National Center for Health Research (@NC4HR) "But these different standards are the old standards we used to use 50 years ago when we had disastrous recalls of terribly dangerous drugs and devices." 

The bill would also make it easier to get drugs through based on studies that don't yet have data on what researchers call "hard endpoints" (longer-term measures of whether a drug reduces death and the risk of heart disease). Instead, drug companies can use data on "surrogate endpoints" (blood test results, such as cholesterol levels, which may or may not have an impact on the measures that matter to patients — like reducing the risk of death and disease). But many times, surrogate markers turn out to be misleading, and don't tell us much about whether a drug actually works.
The bill allows antibiotics onto the market that have never been tested in people

Right now, the world is facing a crisis in antibiotic-resistant infections — that is, more and more patients are showing up in hospitals with bacterial diseases that don't respond to any of the available antibiotics on the market.
To encourage the development of new antibiotics, Section 2121 would expand the regulatory pathways that drug companies can use for patients who have no other option and are suffering from life-threatening bacterial illnesses.
So antibiotics would be able to get onto the market for the "limited and specific population of patients" who aren't responding to other drugs after only testing them in a limited number of patients (instead of testing and approving the drugs for a broader population, which costs more money and takes more time). 

Drug companies would also be able to submit "preclinical data" as evidence of an antibiotic's efficacy. This could mean animal studies — instead of the human studies that are typically required to prove a drug works. Drugs with promising results in animals only very seldom work in patients. "Do we really want to approve new drugs based on rat studies?" asked Zuckerman.
The bill lowers the quality of evidence required to approve medical devices

Section 2222 of the bill would change the standards of evidence the FDA uses to scrutinize medical devices, like heart valves or surgical lasers. It would amend the Federal Food, Drug, and Cosmetic Act to basically say that device companies can pass off anecdotes as valid scientific evidence that a medical device works. Case histories (or doctors' write-ups about particular patients), under the new language, would become acceptable data.
"This could mean relying on one doctor, paid for by a drug company, who has done an experiment on three patients, all healthy young men," said Zuckerman. "Because the doctor says, 'This worked great on my patients,' it could be considered sufficient evidence to approve it for all men and women of all ages and all health problems." This is an issue because a few doctor observations about his or her patients may not at all represent the true effects of a device and the experience many other people will have.
An accompanying provision — Section 2221: Third Party Quality System Assessment — would allow device companies to make modifications to their products without resubmitting the new models for FDA approval.
Take the example of heart valves, a high-risk device that goes through the most rigorous device approval hurdles (called the Pre-Market Approval Process). Zuckerman explained that these devices usually need one clinical trial to prove that they're safe and effective. Under the current law, if a company has an approved heart valve that it wants to update, it needs to submit those changes to the FDA, which decides if new clinical trials are warranted. 

Under the 21st Century Cures bill, the company would be able to hire a third-party company to apply for a special status. "The device company would have to prove to that third-party that they have good quality control mechanisms in place, in general, that could be used for the heart valves in question and for other devices on a list the device company gives to the third party," said Zuckerman.

If the third party certifies the device company, she added, that company would not have to apply for changes they want to make to any devices on their certified list for the next two years. 

She called this "a bonanza" for large and wealthy device companies and worried that more unsafe or ineffective medical devices could make it onto the market.
Daniel Carpenter, a Harvard professor who wrote a history of the FDA, calls these sections of the bill "the 19th Century Frauds Act." He continued: "The clauses on using purely observational data for drug approval and what amounts to anecdotal evidence for devices are deeply anti-scientific and would undermine the credibility of the American market for drugs and medical devices ... This Act would seriously undermine that credibility, and by extension the market as a whole."
The bill makes the regulation of drug development tools a political process

Drug development tools are methods or materials that are used to aid in the development of drugs. If the provisions in Sections 2021/2022 that deal with these tools are enacted, they could turn a scientific process into a political one, explained Gregg Gonsalves, a researcher at Yale Law School:
What industry is asking for here are adjudications on the use of key drug development tools very early on, with the guidance of outside experts now taking the central role rather than that of scientists at FDA. These decisions [then become] political ones in tete-a-tetes between [the experts] and the Secretary of Health and Human Services, and commitments to an approval pathway using these drug development tools are agreed upon in an almost binding fashion and are difficult to step away from.
So these provisions essentially create a parallel process outside of the one that already exists at the FDA. Expert groups would be able to meet with the Secretary of Health and Human Services and agree on how a new drug will be developed with a new tool — before the drug has been tested on many people. 

For instance, consider the case of irregular heartbeats: a company could make the case that a drug can alter irregular heart beats using an EKG test as a proxy for the effectiveness of a new medicine. They could argue for approval of the drug based on changes in patients' heart beats, as measured by the tool (the EKG).
"All these drug development tools — surrogates for the 'real thing,' that is, extending life and health—are imperfect," Gonsalves warned. "Making decisions about how to use them early on in the drug development process in the absence of any real clinical experience with a new drug is unwise, to say the least."
Once the companies and the Secretary make an agreement, he added, it can be difficult for the Secretary to rescind her permission. "Companies would have the right to a meeting in which they could appeal the decision face-to-face with [the Secretary]," Gonsalves explained. "This group of advisers would be of outsiders, biomedical research consortia, and 'other individuals and entities with expert knowledge and insights that may assist the Secretary,' which to me means companies and corporate entities could be part of this process of adjudication."
The bill reverses part of the transparency push about pharmaceutical companies paying doctors

The Sunshine Act is part of the Affordable Care Act (a.k.a. Obamacare), passed by Congress in 2010. It requires all drug and device companies to report the payments they make to physicians every year. The idea is that shedding light on the money exchanging hands will shame doctors and drug companies into better behavior.
One way drug companies reach doctors is through medical education, such as running biased medical conferences and publishing supplements (like advertorials) in journals, which influence the types of drugs and devices doctors use. This is why education payments were reportable under the Sunshine Act.
The Cures Act would add an exemption for reporting medical education payments, Harvard's Aaron Kesselheim, who has studied the bill, explained. "This increases the amount of things that doctors can be paid for without reporting it to the physician payment Sunshine database," he said.
The bill does little to address the real problem with the lack of drug innovation
The whole premise of the bill is that a clunky regulatory process is delaying cures from getting to patients.
But these critics say it's not clear that this legislation can solve the biggest problem here — the lack of promising treatments in the pipeline. In other words, a faster approval process can't fix a dearth of innovation from labs themselves.
"There's no evidence the FDA blocks innovation or makes innovation harder or makes it more costly," said Kesselheim. "The goal in drug development isn't merely innovation, it is innovation that works to help patients. When drugs are shown to be effective and safe, the FDA is the fastest regulatory agency in terms of approvals of new drugs in the world."

In a June 2015 New England Journal of Medicine article, Kesselheim and Harvard's Jerry Avorn argued that current FDA processes are actually quite efficient, with numerous pathways for drug companies to seek faster approvals. How speeding up the process even further will lead to more cures is unclear.

Wednesday, July 15, 2015

J&J Tylenol product: 38 years of harm-for-profit?

How Much Acetaminophen a Day is Safe? Canada May Decide It’s Less

After an investigation by the Toronto Star, Canada’s top health agency considers whether to lower the maximum recommended daily dose of the active ingredient in Tylenol and other painkillers.
ProPublica, July 15, 2015, 12:08 p.m.

Canada’s top health agency is considering lowering the maximum recommended daily dose of acetaminophen, the active ingredient in Tylenol and other pain relievers.
Citing the risk of liver damage from overdosing on the popular pain medication, Health Canada announced it will review changes to labels, the creation of an educational awareness campaign and possible revisions to dosage recommendations.

Acetaminophen is considered safe when taken at recommended doses. Tens of millions of people use it weekly with no ill effect. But in larger amounts, especially in combination with alcohol, the drug can damage or even destroy the liver. In severe cases, acetaminophen overdose can cause death.
“Our goal is that we will have fewer effects on liver, less hospitalization, less instances of unintentional overdose, and we have more people that are informing themselves about all the products that they use, not just acetaminophen,” Supriya Sharma, senior medical adviser for Health Canada’s Health Product and Food Branch, told the Toronto Star, in an interview.
The announcement comes after the Star published a lengthy investigation last year on the potential dangers of acetaminophen. The Star, which was assisted in its reporting by ProPublica, found that acetaminophen use in Canada had been responsible for hundreds of deaths, tens of thousands of hospitalizations and tens of millions of Canadian dollars in health-care system costs over the last decade.
An earlier ProPublica investigation done in collaboration with This American Life examined the toll of acetaminophen in the United States. The investigation found that 1,500 people in the U.S. had died and tens of thousands more had been hospitalized as a result of overdosing on acetaminophen over the past 10 years.
ProPublica and This American Life also found that the Food and Drug Administration had delayed implementing safety measures for decades. McNeil Consumer Healthcare, the Johnson and Johnson unit that makes Tylenol, had worked to repeatedly block tougher safety warnings on its billion-dollar product.
Both investigations found a common problem known as “double dipping.” Acetaminophen is present in hundreds of over-the-counter medicines. Thus, people may take several medicines containing acetaminophen — say Tylenol and Theraflu — and not realize that they have exceeded the maximum recommended daily dose of acetaminophen, which is four grams, or eight 500-mg pills.
Another problem with acetaminophen: While generally recognized as safe and effective, the drug has a narrow safety margin — the dosage that can help is relatively close to the dosage that can begin to affect liver function. Some studies have suggested that liver damage can result from taking a few additional pills over the recommended daily dose for several days.
Canada and the United States are among the few industrialized nations in the world to allow unlimited access to acetaminophen. Countries such as Britain, France and Germany restrict access to the amount of acetaminophen that can be purchased, as well as the amount of medicine in an individual pill.
In response to the ProPublica story, McNeil said the company has always put consumer health first and that Tylenol is safe as long as it is used as directed.
After a 2009 FDA hearing in which experts raised new concerns about acetaminophen safety, McNeil changed the label on its Tylenol product to recommend no more than 3 grams, or six extra-strength tablets, per day.
The company maintains that acetaminophen’s safety compares favorably with other over-the-counter pain medications. (The FDA recently announced additional warnings about the risk of heart attacks of taking non-steroidal anti-inflammatory drugs, or NSAIDs, found in popular brands such as Advil.)
“McNeil takes acetaminophen overdose very seriously, which is why we have taken significant steps over the years to mitigate the risk,” the company wrote in an emailed statement.
“We will continue to work hard to educate and warn consumers of the dangers of acetaminophen overdose, reminding them to read the labels on all medicines before taking them, to take medicines only as directed and to be aware that any medicine they take has risks.”
The FDA did not respond to a request for comment on Friday. The agency has previously acknowledged that its procedure for regulating over-the-counter drugs, known as the monograph process, is cumbersome and slow. More than 38 years have passed since the FDA first began hearings on acetaminophen, and the FDA has yet to issue final guidelines on the safe use of the drug.
Last year, the agency announced that it would begin to review the monograph process in order to improve it.

It has yet to take any action.