Category Archives: We’re In the News

Medical company may be falling short of its patient safety ideals

News Stories & Editorials
by Marshall Allen and Annie Waldman, NPR
October 6, 2014

When medical device entrepreneur Joe Kiani announced his commitment to eliminating medical mistakes, he did it with panache. His medical device company, Masimo Corporation, funded the launch of a nonprofit called the Patient Safety Movement Foundation. And at its flashy inaugural summit in 2013 – featuring former President Bill Clinton as the keynote speaker – Kiani pledged to galvanize the medical industry to reduce the number of deaths from medical errors across the country from hundreds of thousands a year to zero.

“Of all the dreams I’ve had none seem as important as this dream: The dream of no more preventable patient death,” Kiani said to the gathering of health care leaders.

Now people will see whether Kiani, and his company, Masimo, walk the talk. Keeping patients safe requires device makers to respond appropriately to complaints. But an inspection by the Food and Drug Administration last year found Masimo didn’t adequately investigate dozens of reports that its devices may have malfunctioned.

The FDA didn’t find that Masimo’s devices were defective, but rather that the company wasn’t sufficiently looking into that possibility. The inspection report was obtained by ProPublica via public records request.

With over $500 million in annual sales, Masimo is one of the leading makers of noninvasive pulse oximeters — patient monitoring devices that track pulse and blood oxygen, often clipped gently onto fingers or toes. Doctors in emergency rooms and intensive care units rely on the monitors to alert them when a patient has abnormal readings. If the devices give inaccurate readings or fail to alert doctors to drastic changes in a patient’s vital signs, doctors could misdiagnose or fail to recognize the severity of a patient’s condition, which could lead to injury or death.

The complaints identified in the FDA inspection varied. In one case a patient suffered a burned toe, and in another there was a question about whether an alarm properly sounded before a patient died.

If a patient or health care provider sees a problem with one of Masimo’s products they can report the problem to the company, which is then required by law to investigate. If the device malfunctioned or was implicated in a patient injury or death, the company must in turn disclose that to the FDA.

After the agency’s inspection last year, Masimo disputed the FDA conclusions, saying the agency had misunderstood the circumstances surrounding each complaint. But after nearly a year of review, the FDA stuck to its findings. It reprimanded the company with an official warning letter this August, stating that Masimo was still not adequately responding to complaints about its devices.

FDA warning letters aren’t common – it’s the first Masimo has received in its 25-year history. They are generally reserved for significant violations that could result in an enforcement action, such as fines or a recall. The agency declined to offer further comment.

Diana Zuckerman, an expert on medical devices and president of the National Center for Health Research, reviewed the FDA’s findings and Masimo’s response at ProPublica’s request. She said it appears that Masimo is “not taking the care to investigate their own possible malfunctions.”

Since patients or doctors often don’t report problems with products, Zuckerman said, complaints that are filed are “always the tip of the iceberg.” Zuckerman added that she found it striking that Masimo disputed most of the complaints and “particularly troublesome” that the company challenged a complaint that involved questions about whether a Masimo device properly set off an alarm before a patient died.

“It may well be that it’s a user error,” Zuckerman said. “But you have to investigate that and show that it’s a user error and not a device error.”

Zuckerman found it striking that the company refused to admit any wrongdoing to the FDA. “When a company refuses to respond in any way to the FDA other than to say that the FDA is wrong on every issue, that’s not very credible,” Zuckerman said. “Especially when users made complaints that the company’s product put patients at risk,” she said.

In an interview with ProPublica, Kiani again disputed the FDA’s findings, saying Masimo has always followed up on complaints. He said the company is cooperating with the regulator, providing it with information “to show them we did nothing wrong.”

When asked how the FDA findings reflect on the ideals put forth by his nonprofit effort, the Patient Safety Movement Foundation, Kiani said that he never claimed to be perfect. “I’m just trying to do my best and get my other colleagues to do their best, and put processes in place to hopefully minimize preventable death,” he said.

The two-year-old foundation has attracted a who’s who of top health care quality experts to its summits, including decision-makers from Medicare. The second annual conference was in January at the Ritz Carlton Hotel in Laguna Nigel, Calif.

The foundation promotes a “culture of safety” and encourages the early identification of problems that can lead to patients being harmed. “The lack of safety culture results in concealment of errors and therefore a failure to learn from them,” the foundation’s guidelines state.

One member of the foundation’s board said he was disappointed about Masimo’s alleged lack of response. Masimo “has to improve because [companies] are a big part of our ability to get to zero preventable harm,” said the board member, Dr. David Mayer, also a vice president of quality and safety at Medstar Health in Maryland. Mayer said he gets no compensation to sit on the board and pays his own expenses to attend its meetings.

The foundation’s president, Jim Bialick, said the organization is primarily funded by a charitable offshoot of the company, the Masimo Foundation for Ethics, Innovation, and Competition in Healthcare.

In response to a question about whether the FDA’s concerns would be addressed at the upcoming summit, Bialick said that was Masimo’s choice. “I would imagine it would come up. Whether Masimo brings it up, that’s up to them.”

ProPublica is a nonprofit investigative reporting newsroom based in New York.

Read or listen to original article here.

Medical devices lack safety evidence, study finds

News Stories & Editorials
By Thomas M. Burton, The Wall Street Journal
September 29, 2014
Researchers Say Public Data Unavailable on Majority of Newly Approved Devices

The majority of moderate- to high-risk medical devices approved by the U.S. Food and Drug Administration lack publicly available scientific evidence to verify their safety and effectiveness despite requirements in the law, according to a study released Monday.

Researchers reported in JAMA Internal Medicine that 42 of 50 selected medical devices cleared by the FDA over five years lacked such data, despite a 1990 law calling for sufficient detail to justify their FDA clearance. The law calls for public data about studies, which may include clinical studies, involving human patients.

“If wonderful studies are being done, there is no evidence of this, and there’s no way for the public to see it,” said Dr. Diana Zuckerman, a study author and president of the National Center for Health Research, a public health think tank in Washington. “It’s shocking how little information is available despite an FDA leadership that talks about transparency.”

The study’s authors, who were from the health-research center, called for better enforcement of that law.

In response to the findings, the FDA said that it “reviews a significant amount of data—far more than what is publicly available.” The agency said its approach “has served the American public well by balancing the need for robust evidence to assure safety, while expeditiously bringing new technologies” to the market.

At issue is a type of medical-device approval under which about 400 implanted devices annually—the majority of moderate- to high-risk ones—are cleared by the FDA for marketing.

Under that system, called a 510(K) review, the company doesn’t have to conduct studies in human patients, as is generally the case with drug approvals, although it may. Most devices can get FDA clearance simply by showing that they are roughly equivalent to another product, called a predicate device, that is already on the market. The theory is that if the older device has proved safe and effective, the new one should be also.

The 510(K) process has led to cases like metal-on-metal hips, which can leave metal filings in the body.

But the Safe Medical Devices Act of 1990 required companies to make publicly available evidence of why the new product truly is comparable to the old one; the evidence can include studies of patients, known as clinical trials, but it isn’t necessary.

The Institute of Medicine, the research branch of the National Academy of Sciences, in 2011 called for an overhaul of this type of FDA clearance, saying in a report that “reliance on substantial equivalence cannot assure that devices reaching the market are safe and effective.”

“A lot of these are high-risk devices that get on the market with no studies at all,” said Dr. Rita Redberg, medical professor at the University of California, San Francisco, and the chief editor of JAMA Internal Medicine. “When there are studies, they’re not available” for the public to see.

She said that she sees no evidence that the leadership of the FDA under the Obama administration has heightened the level of safety assurance required.

Read original article here.

Lack of publicly available scientific evidence on the safety and effectiveness of implanted medical devices

In the News, News Stories & Editorials
By Diana Zuckerman, PhD; Paul Brown, BA; Aditi Das, PhD

The US Food and Drug Administration (FDA) approves about 400 implanted medical devices each year through an abbreviated process called the 510(k) process, which only rarely requires clinical trials (studies of patients).  These implants include potentially high-risk devices such as heart valves, spinal implants, and hip and knee joint replacements.  In contrast, fewer than 20 implants each year are approved by FDA through the more rigorous Premarket Approval (PMA) process that requires that the impact on the patients’ health be studied in clinical trials

The law requires that all medical implants sold in the U.S. provide a reasonable assurance of safety and effectiveness based on scientific evidence, even if the company doesn’t provide data from studies of patients.  The scientific evidence could include bioengineering studies, for example, to determine if the new implant is expected to be similar to older implants on the market.  This groundbreaking study examined the scientific evidence provided to the FDA and the public for 1155 medical implants.

The study focuses on 50 representative medical implants newly cleared by the FDA 510(k) process from 2008-2012.  Since those implants were required to be substantially equivalent to implants already on the market, called “predicates,” the study also included the 1105 “predicates” for those 50 implants.  The implants included hip implants, surgical mesh, cardiac implants, spinal implants, and dental implants, among others.

By law, every 510(k) medical device application since March 15, 1995 must provide a summary that includes “sufficient evidence” to prove that the new device is substantially equivalent to a device already on the market.  This summary must be available online, linked to a letter on the FDA website granting the company clearance to sell their device in the U.S.  If a company doesn’t provide that summary, the law requires it to provide all the same information within 30 days of a written request from anyone.  This is especially important for implants, since they can cause permanent damage or even be life-threatening if they fail while inside the human body

RESULTS:  Just 3% of the 1155 implants in the study provided scientific evidence that the implant was substantially equivalent to its predicate or that it was safe and effective.   Even when predicates had been permanently recalled because of fatalities or serious injuries, there was no evidence of how the newly cleared implant was similar or different from those predicates.  Since 2009, the FDA leadership has repeatedly focused on the need for transparency at the FDA, but even in 2012, the 3rd year of new leadership at the FDA, only 20% of the implants had any kind of publicly available scientific data.

CONCLUSIONS: For the 1155 implants studied, “sufficient detail to provide an understanding of the basis for a determination of substantial equivalence,” as required by law, was unavailable to physicians, patients, providers, and others who care about patient safety or public health. Numerous newly cleared implants had predicates that had been recalled because of serious risks, calling into question the safety of the newer “substantially equivalent” implants. Regardless of how much effort physicians and providers would make to find out about the safety or effectiveness of new medical implants, they do not have access to such information for approximately 84% of medical implants that have been cleared in recent years, and more than 95% of those cleared in the last 2 decades.

IMPLICATIONS:  Previous criticisms of the FDA medical device approval process by the Institute of Medicine and public health researchers have focused on the lack of clinical trial data proving safety and effectiveness.  The FDA has repeatedly claimed that the agency has other rigorous scientific criteria for approval, such as bioengineering data proving that the new devices are so similar to the ones already on the market that they will be just as safe and effective.  This is the first study to examine the “other scientific data” that the FDA explains that it relies on.  The results indicate that either the companies are not providing solid scientific data proving that the new devices are substantially equivalent to the predicates, or that the companies are not making a sufficiently detailed summary of their scientific evidence publicly available, as required by law.  In cases where an earlier “predicate” was recalled because of serious or possibly fatal risks, the researchers found no publicly available scientific evidence to inform physicians or patients whether the newer implant would have the same potentially fatal flaw.  To safeguard the health of patients, the FDA should enforce the law.

From JAMA Internal Medicine, published online September 29, 2014.  A link to the official abstract of the article is available here. A podcast with Drs. Zuckerman and Sharfstein is available on the JAMA Internal Medicine website and can be found 

Diversity in clinical trials

News Stories & Editorials, Uncategorized

We Need Better Clinical Trials

Our president explained to reporters why drugs have to be tested on all kinds of people to know who they work for and who can be harmed by them. Cancer patients deserve studies that include women and men, people under and over 65, and all major racial/ethnic groups.

 

FDA is Chastised Over its ‘Action Plan’ to Diversify Clinical Trial Participation

By Ed Silverman, The Wall Street Journal
August 28, 2014

In response to a law passed two years ago, the FDA was directed to assess the extent to which women and minorities are represented in clinical trials and also devise a plan to bolster their participation. The requirement was made in response to concerns that drugs and devices may often be used by subsets of the population on whom the products were not actually tested.

Well, the FDA released its plan the other day and it was met with what could best be described as faint praise. In particular, a pair of consumer advocacy groups says the biggest issue is that the so-called Action Plan lacks the sort of teeth needed to generate real change. They also complain the plan fails to require drug and device makers to contain specific demographic information in product labeling.

They acknowledged the plan does contain several constructive steps, such as working with drug and device makers to revise product applications with enhanced information on “demographic subgroups;” strengthening FDA reviewer training so the need for demographic data is communicated; improving FDA systems for collecting and analyzing such data; and updating or finalizing guidance for industry.

“The action plan has a lot of good things,” Diana Zuckerman, the president of the National Center for Health Research, tells us. “The problem is there is no incentive for industry to recruit more diverse groups of patients. As long as they continue to test mostly on white men under 65 [years old] and get drugs and devices approved, then they have no incentives” to diversify the pool of trial participants.

What does she suggest? The FDA ought to consider not approving drugs and devices for use in people on whom these products were not tested. As an example, if a drug is tested predominantly on men, then the agency should not endorse widespread use for women. “They need to put some muscle behind their actions. I think if FDA did this,” she says, “then the companies would find they’re able to miraculously find they can recruit all those groups.”

Read the original article here.

Surgery Studies Rarely Use Females

An analysis of papers published in several surgical journals reveals an overwhelming reliance on male subjects and male-derived cells.

By Kerry Grens, The Scientist

August 28, 2014

Sex biases are evidenced in many areas of science—from clinical trials in humans to basic neuroscience studies on animals. Often, male subjects are overrepresented, compromising the generalizability of findings. In a study published in the September issue of Surgery, researchers from Northwestern University analyzed more than 2,300 papers from five surgical journals, finding an overwhelming skew toward investigations involving male-only subjects and cells derived from males.

“Women make up half the population, but in surgical literature, 80 percent of the studies only use males,” Northwestern Medicine vascular surgeon Melina Kibbe, who led the study, said in a press release.

The studies Kibbe and her colleagues reviewed were published in the Annals of Surgery, the American Journal of Surgery, JAMA Surgery, the Journal of Surgical Research, and Surgery from 2011 to 2012. About a quarter of the studies involved animals or cells. Just 3 percent of the total reported using both male and female subjects or cells, while another 22 percent did not state the sex.

According to the release, “editors of the five major surgical journals reviewed in this study have responded to this finding and will now require authors to state the sex of animals and cells used in their studies. If they use only one sex in their studies, they will be asked to justify why.”

Although sex disparities in clinical trials have received considerable attention, such human studies still suffer from unsatisfactory diversity. Last week, for instance, the US Food and Drug Administration (FDA) released an action plan to address the need for more women and minorities in clinical trials. The Wall Street Journal’s Pharmalot blog pointed out that the plan was met with “faint praise,” lacking “the sort of teeth needed to generate real change.”

Speaking with MedPage Today, Diana Zuckerman, the president of the National Center for Health Research, said: “As long as the FDA is going to approve these products for everyone, when they haven’t been studied on everyone, then the [pharmaceutical] companies really have no incentive to improve.”

Read the original article here.

Johnson & Johnson praised for taking uterine surgery tools off market

In the News, News Stories & Editorials
By Katie Thomas, The New York Times
July 31, 2014

morcellator

Johnson & Johnson, which has come under withering criticism for its response to problems with some of its medical devices, won cautious praise from critics on Thursday for its decision to withdraw three products used in uterine surgery because of a risk of spreading cancerous tissue, only months after the safety issue became widely known.

Some experts continued to debate the medical value of the devices. A handful of other, smaller companies sell similar products.

The Ethicon unit of Johnson & Johnson said Wednesday that it was asking hospitals to return three types of power morcellators, devices that are commonly used in uterine surgery to remove fibroids by cutting the tissue into tiny pieces and extracting them through small incisions. In April, the Food and Drug Administration recommended that doctors stop using the procedure after the agency concluded that the risk of spreading cancer was higher than previously thought. That led Johnson & Johnson to announce that it would suspend sales and marketing of its products while it studied the issue, but it stopped short of withdrawing them from the market.

In a letter sent to health care providers, Ethicon asked that hospitals return three models of power morcellators made by the company: the Gynecare Morcellex and Gynecare X-Tract tissue morcellators, as well as the Morcellex Sigma tissue morcellator system.

About 50,000 operations a year involve power morcellation of tissue containing fibroid tumors, according to the F.D.A.

Some critics said they were pleasantly surprised that Johnson & Johnson acted as quickly as it did. “The company has had a rather abysmal track record on the public health front of ethical breaches in the last few years, so this is good that they’re doing this,” said Diana Zuckerman, president of the National Center for Health Research, a public health advocacy group that has criticized the company in the past over its safety record, especially concerning pelvic mesh implants. Dr. Zuckerman owns stock in Johnson & Johnson and her father, now retired, worked for many years in quality control at the company. Speaking of the decision on the power morcellators, she said, “At least it goes back to an earlier time when the company was seen as doing the right thing.”

The move comes as some in the gynecology field continue to disagree about the usefulness of power morcellators. Although the risk of spreading cancer through this procedure has been previously known, it was long believed that the chances for spreading cancer were lower, ranging from 1 in 10,000 to 1 in 500. In April, the F.D.A. concluded that the risk was closer to 1 in 350.

Still, some doctors cautioned against vilifying the procedure, saying that power morcellation allows minimally invasive surgery that, if carefully done, can be a better choice for some women. Without morcellation, more women will have to undergo serious abdominal surgery, which carries the risk of infection, bleeding, pain and blood clots. “These are things that people also die of,” said Dr. Barbara Goff, director of gynecological oncology at University of Washington. “So my concern is that we aren’t looking at this in balance.”

That medical debate is the reason Prof. Erik Gordon, who teaches business at the University of Michigan and has previously criticized the company for its safety record, said he was surprised that it acted as quickly as it did. “This is one of those things where it’s enough up in the air that you might have expected Johnson & Johnson to say, well, we’re going to keep it on the market because the evidence is inconclusive,” he said. “But that’s not what they did.”

The wrong approach to breast cancer

In the News, News Stories & Editorials
By Peggy Orenstein
New York Times
July 26, 2014

BERKELEY, Calif. — ONE of the nastier aspects of breast cancer is that it doesn’t have the five-year sell-by date of some other malignancies: you’re not considered “cured” until you die of something else. Although it becomes less likely, the disease can come back eight, 10, even 20 years after treatment. I fell on the wrong side of those odds.

I had a tiny, low-grade tumor in 1997; 15 years later, in the summer of 2012, while I was simultaneously watching “Breaking Bad,” chatting with my husband and changing into my pajamas, my finger grazed a hard knot beneath my lumpectomy scar. Just as before, time seemed to stop.

The recurrence appears to have been confined to my breast and was, like the original tumor, a slow-moving form of the disease. Since the lumpectomy and radiation I had in 1997 failed, however, this time the whole breast had to go. My first question to my oncologist (after “Am I going to die?” Answer: yes, someday, but probably not of this) was whether I should have the other breast removed, just to be safe.

It turns out, I’m not alone in that concern. After a decades-long trend toward less invasive surgery, patients’ interest in removing the unaffected breast through a procedure called contralateral prophylactic mastectomy (or C.P.M., as it’s known in the trade) is skyrocketing, and not just among women like me who have been through treatment before.

According to a study published in the Journal of Clinical Oncology in 2009, among those with ductal carcinoma in situ — a non-life-threatening, “stage 0” cancer — the rates of mastectomy with C.P.M. jumped 188 percent between 1998 and 2005. Among those with early-stage invasive disease, the rates went up 150 percent between 1998 and 2003. Most of these women did not carry a genetic mutation, like the actress Angelina Jolie, that predisposes them to the disease.

Researchers I’ve spoken with have called the spike an “epidemic” and “alarming,” driven by patients’ overestimation of their actual chances of contracting a second cancer. In a 2013 study conducted by the Dana-Farber Cancer Institute in Boston, for instance, women under 40 with no increased genetic risk and disease in one breast believed that within five years, 10 out of 100 of them would develop it in the other; the actual risk is about 2 to 4 percent.

Many of those same young women underestimated the potential complications and side effects of C.P.M. Breasts don’t just screw off, like jar lids: Infections can occur, implants can break through the skin or rupture, tissue relocated from elsewhere in the body can fail. Even if all goes well, a reconstructed breast has little sensation. Mine looks swell, and is a remarkably close match to its natural counterpart, but from the inside it feels pretty much like a glued-on tennis ball.

Of course, as any cancer patient will tell you, our fear is not simply of getting cancer, it’s of dying from it. What’s a mere mammary gland when, as Amy Robach, a journalist at ABC News, told People magazine last year after her own C.P.M., “I want to be at my daughters’ graduations. I want to be at their weddings. I want to hold my grandchildren.”

Unfortunately, for most women, C.P.M. is irrelevant to making those milestones. The most comprehensive study yet, published earlier this month in the Journal of the National Cancer Institute, showed virtually no survival benefit from the procedure — less than 1 percent over 20 years.

Researchers used the Surveillance, Epidemiology, and End Results registry and other databases to model survival chances for women who opted for C.P.M. and those who did not. They took into account a woman’s age at diagnosis, the stage and biology of her original tumor, the likelihood of dying from that cancer, the risk of developing cancer in the healthy breast, and the potential of dying from a new cancer. They even tweaked the numbers, nearly doubling the risk of contracting a second cancer and exaggerating the aggressiveness of a new tumor and the effectiveness of C.P.M.

“The story didn’t change,” Todd M. Tuttle, chief of surgical oncology at the University of Minnesota and the study’s senior author, told me. “Even if we used unrealistic figures, the conclusions were still the same. There was no group with a survival benefit of even 1 percent.”

How can that be? Well, first of all, it is extremely rare for a tumor on one side to spread to the other. Cancer doesn’t just leap from breast to breast. In any case, cancer confined to the breast is not deadly. The disease becomes lethal only if it metastasizes, spreading to the bones or other organs. Cutting off the healthy breast won’t prevent the original tumor from doing that. As for developing another cancer, Dr. Tuttle said, when that does happen (and remember, it’s far less common than patients believe), 91 percent will be early-stage lesions, so more readily treatable.

There’s some indication that patients understand that, yet choose C.P.M. anyway. The majority of the young women in the Dana-Farber survey knew the procedure wouldn’t prolong life; even so, they cited enhanced survival as the reason they had undergone it.

Such contradictions aren’t unusual, according to Steven J. Katz, a professor of medicine and health management and policy at the University of Michigan, who studies medical decision making. In exam rooms, all of us — men, women, cardiovascular patients, diabetics, cancer patients — tend to react from the gut rather than the head. “The general response to any diagnosis is, we want to flee it,” Dr. Katz explained. “It’s the kind of fast-flow decision making that we’re wired to perform. And it’s very difficult at that point to put data before a patient.”

I get that. When my cancer was first diagnosed, I felt as if a humongous cockroach had been dropped onto my chest. I could barely contain the urge to bat frantically at my breast screaming, “Get it off! Get it off!” Physicians, according to Dr. Katz, need to better understand how that visceral reaction affects treatment choices. They also need to recognize the power of “anticipated regret”: how people imagine they’d feel if their illness returned and they had not done “everything” to fight it when they’d had the chance. Patients will go to extremes to restore peace of mind, even undergoing surgery that, paradoxically, won’t change the medical basis for their fear.

Mothers inevitably cite their children as motivation for radical treatment; self-sacrifice has, after all, long defined good motherhood. It seems almost primal to offer up a healthy breast — with its connotations of maternal nurturance — to fate, as a symbol of our willingness to give all we have to and for our families. It’s hard to imagine, by contrast, that someone with a basal cell carcinoma on one ear would needlessly remove the other one “just in case” or for the sake of “symmetry.”

Treatment decisions are ultimately up to the individual. But physicians can frame options and educate patients in a way that incorporates psychology as well as statistics. Beyond that, doctors are not obliged to provide treatment that is not truly necessary.

The good news is that treatment to reduce the risk of metastasis has improved over the years. Not enough, but significantly. So those of us who dream of dancing at our children’s weddings? We may yet get there. But if — when — we do, it won’t be because of C.P.M.

Alternative to Pap test is approved by F.D.A.

News Stories & Editorials
ANDREW POLLACK, New York Times

APRIL 24, 2014
The Food and Drug Administration on Thursday approved the first alternative to the long-used Pap test as a primary screening method for cervical cancer, in the face of opposition from some women’s groups and health organizations.

The new test, developed by Roche, detects the DNA of the human papilloma virus, which causes almost all cases of cervical cancer, in a sample taken from the cervix. Pap testing involves examining the cervical sample under a microscope to detect abnormalities.

A committee of outside advisers to the F.D.A. unanimously endorsed the Roche test in a meeting last month.

But a coalition of 17 consumer, women’s and health groups opposed the approval, arguing that the new screening method had not been adequately tested and could upend a practice that has successfully prevented cervical cancer for decades.

“This proposed indication for the HPV test would represent an unprecedented and significant shift in clinical practice that would affect millions of women for the majority of their adult lives,” the coalition said in a letter to the F.D.A. earlier this month.

The letter was organized by the Cancer Prevention and Treatment Fund, a research and patient education organization, and signed by the American Public Health Association, Consumers Union, the National Organization for Women and the women’s health education group Our Bodies Ourselves, among others.

A separate letter making similar arguments was sent to the agency earlier this week by a group of doctors and professors.

The F.D.A. said, however, that the evidence was sufficient.

“Roche Diagnostics conducted a well-designed study that provided the F.D.A. with a reasonable assurance of the safety and effectiveness when used as a primary screening tool for cervical cancer,” Alberto Gutierrez, the agency official who oversees diagnostic testing, said in a statement.

In a letter he sent on Thursday to the coalition of opponents, Dr. Gutierrez noted that the agency merely decided if a test was safe and effective for its intended use. It is up to medical societies and other organizations to decide whether and how to use the test. The approval does not mandate use of the HPV test, just makes it another option.

The Society of Gynecologic Oncology, in a statement on Thursday, said it and other organizations were developing an interim guidance document on incorporating primary HPV testing into cervical cancer screening.

Although the group said HPV testing “will provide doctors one more tool to use in cervical cancer screening,” it also acknowledged that the “approval has raised a number of questions.” It said that it was “extremely unlikely that doctors will stop using the Pap any time soon.”

Roche’s Cobas HPV test and HPV tests sold by other companies have been used until now as a follow-up test to help resolve ambiguous Pap results, or together with Pap testing as a primary screening tool.

The new approval would allow the HPV test to be used alone as an initial screen for women 25 and older. Pap testing would be used only in certain cases as a follow-up test.

Studies have shown that HPV testing can result in detection of more precancerous lesions than Pap testing.

However, the virus test could also conceivably lead to more false alarms because presence of the virus does not necessarily mean cancer. Most young women get infected with HPV after they become sexually active, though in many cases their immune systems can clear the virus.

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That is why HPV testing has generally not been used until now in women younger than 30. Opponents of the F.D.A.’s action said approval of HPV testing for women as young as 25 could lead to more young women being sent for unnecessary cervical examinations and biopsies, which in some cases can lead to preterm births or other problems.

Roche has said that it got around that problem because its test specifically detected the two types of the virus that account for 70 percent of the cancers.

Under its proposal, a women testing positive for one of those two types would then go for a cervical examination known as colposcopy. If a woman tested negative for genotypes 16 and 18 but positive for one or more of the other 12 types the test can detect, she would then get a Pap test to see if a colposcopy was warranted.

HPV tests generally cost $80 to $100 while Pap testing costs only $20 to $40, according to Diana Zuckerman, president of the Cancer Prevention and Treatment Fund. Roche said that Medicare paid only about $48 for an HPV test and that when all factors were considered, the difference in cost between HPV and Pap testing was not significant. Pap testing, begun about 60 years ago, has led to a sharp decline in cervical cancer in the United States. But there are still about 12,000 new cases and 4,000 deaths a year, according to the American Cancer Society.

Letter to the Editor: “FDA’s compassionate-use program offers early access without compromising drug trials”

In the News, News Stories & Editorials
WASHINGTON POST, APRIL 24, 2014

The April 22 front-page article “FDA relents in battle against a cruel disease,” about parents urging the Food and Drug Administration to approve a promising drug for Duchenne muscular dystrophy, pulled on the heartstrings. However, there is a better way to get an experimental drug to patients than lowering approval standards.

If the pharmaceutical company is willing, parents who are understandably desperate to help their children can utilize the FDA’s compassionate-use program, which allows a patient with a life-threatening disease to receive an unapproved drug from the company. This provides patients with early access to drugs. If the patients do well, that early access can help products obtain FDA approval.

Paul Brown, Washington

The writer is government relations manager at the National Center for Health Research, Cancer Prevention and Treatment Fund

FDA OKs first-ever DNA alternative to Pap smear

In the News, News Stories & Editorials
BY MATTHEW PERRONE
AP HEALTH WRITER
April 24, 2014

WASHINGTON (AP) — Federal health regulators have cleared a genetic test from Roche as a first-choice screening option for cervical cancer. It was a role previously reserved for the Pap smear, the decades-old mainstay of women’s health.

The Food and Drug Administration approved Roche’s cobas HPV test to detect the human Papillomavirus, or HPV, in women 25 and up. HPV causes nearly all cases of cervical cancer.

Doctors already use such DNA-based tools as a follow-up to confirm Pap test results. But Thursday’s decision means Roche can now market its test as a first-choice option for cervical cancer screening, ahead of the Pap test.

Currently no major medical guidelines recommend HPV testing alone for cervical cancer screening. Dr. David Chelmow of Virginia Commonwealth University said physicians should hold off on using the test until medical societies can provide guidance on some key questions, including how frequently it should be used. Chelmow spoke on behalf of the American College of Obstetrics and Gynecology at the FDA’s meeting to review the test last month.

Roche supported its bid for expanded marketing with study results suggesting genetic testing is more accurate and objective at identifying cancerous growths than the Pap smear, which requires doctors to examine cervical cells under a microscope for signs of cancer. The test detects 14 high-risk forms of HPV that can lead to cervical cancer.

The FDA approval comes despite pushback from public health advocates, who warned regulators that approving the DNA test as an alternative to Pap could lead to confusion, higher costs and overtreatment. More than a dozen patient groups raised those concerns in a letter to the FDA last week. Specifically, they said HPV-only testing could lead to overtreatment of younger women who carry the virus but have little risk of developing actual cancer. Most sexually active young people contract HPV, though their bodies usually eliminate the virus within a few months. Only yearslong infections develop into cancer.

FDA officials said in a statement Thursday that they approved the test because “Roche Diagnostics conducted a well-designed study that provided the FDA with a reasonable assurance of the safety and effectiveness.” The trial included over 47,000 women who underwent cervical screening using either Pap or HPV screening. The test results were then checked for accuracy against final biopsy results that confirmed whether they actually had cancer.

For decades the Pap test was the only screening option for cervical cancer – and it’s had a remarkably successful track record. The number of cervical cancer cases reported in the U.S. has decreased more than 50 percent in the past 30 years, primarily due to increased Pap screening. Still, an estimated 12,000 cases of cervical cancer are expected to be diagnosed this year, a fact that has spurred development of HPV tests like those from Roche, Qiagen and other test makers. HPV test costs generally cost between $80 and $100, about twice as much as a $40 Pap.

Medical guidelines have been evolving rapidly to try and incorporate both techniques. Under the latest guidelines from the American Cancer Society, a Pap test is recommended every three years for women 21 to 29 years old. Women 30 and older should have both a Pap test and an HPV test every five years, or a Pap test alone every three years. HPV screening is not recommended for women in their 20s because it increases the odds of more invasive testing that can leave the cervix less able to handle pregnancy later in life.

But the FDA approval allows Roche to market its test for women as young as 25. Women who test positive for the most high-risk strains of HPV should be referred for a colposcopy, an invasive test in which doctors view the cervix with a magnifying device and often collect a tissue sample for testing.

Groups including the Cancer Prevention and Treatment Fund, American Medical Women’s Association and Our Bodies Ourselves questioned why the FDA would approve labeling that goes against medical society recommendations.

In its statement approving the test, the FDA staff suggested its decision would not change how doctors use HPV screening.

“It does not change current medical practice guidelines for cervical cancer screening. These guidelines are developed, reviewed and modified by groups other than the FDA,” said Dr. Alberto Gutierrez, who oversees the FDA’s medical testing office.

But patient advocates rejected that reasoning.

“They imply that the FDA approval decision isn’t that important in deciding how this test will be used,” said Diana Zuckerman, president of the Cancer Prevention and Treatment Fund. “By claiming to pass the buck to the experts in the field, FDA is not taking responsibility for the agency’s influential decision to approve the test as a replacement of the Pap smear for women over 25.”

Switzerland-based Roche said in a statement that the FDA approval “is recognition for the value the cobas HPV test provides to physicians and women to make more informed decisions.”

 

DNA alternative to Pap smear sparks medical debate

News Stories & Editorials
Matthew Perrone, AP Health Writer
April 15th, 2014

WASHINGTON (AP) – A high-tech screening tool for cervical cancer is facing pushback from more than a dozen patient groups, who warn that the genetic test could displace a simpler, cheaper and more established mainstay of women’s health: the Pap smear.

The new test from Roche uses DNA to detect the human papillomavirus, or HPV, which causes nearly all cases of cervical cancer. While such technology has been available for years, Roche now wants the FDA to approve its test as a first-choice option for cervical cancer screening, bypassing the decades-old Pap test.

But a number of women’s groups – including the American Medical Women’s Association and Our Bodies Ourselves – warn that moving to a DNA-based testing model would be a “radical shift” in medical practice that could lead to confusion, higher costs and overtreatment.

“It replaces a safe and effective well-established screening tool and regimen that has prevented cervical cancer successfully in the U.S. with a new tool and regimen not proven to work in a large U.S. population,” state the groups in a letter to FDA Commissioner Dr. Margaret Hamburg. The letter, dated Monday, is signed by 17 patient advocacy groups, including Consumers Union, the Cancer Prevention and Treatment Fund and the National Alliance for Hispanic Health.

Chief among the advocates’ concerns is that HPV-only testing could lead to overtreatment of younger women who carry the virus but have little risk of developing actual cancer. Most sexually active young people will contract HPV, though their bodies usually eliminate the virus within a few months. Only years-long infections develop into cancer.

“Unfortunately the HPV test by itself isn’t very useful because so many young women have HPV that will disappear without any treatment,” said Diana Zuckerman of the Cancer Prevention and Treatment Fund. “Having an HPV test without also getting a Pap smear to check for problems is going to scare a lot of women who are not developing cervical cancer.”

An FDA spokeswoman said the agency could not comment on the letter since it deals with a product under review.

For decades the Pap test was the only screening option for cervical cancer – and it’s had a remarkably successful track record. The number of cervical cancer cases reported in the U.S. has decreased more than 50 percent in the past 30 years, primarily due to increased Pap screening. Still, an estimated 12,000 cases of cervical cancer are expected to be diagnosed this year, a fact that has spurred development of genetic tests like the one from Roche and other test makers.

Medical guidelines have been evolving rapidly to try and incorporate both techniques. Under the latest guidelines from the American Cancer Society, a Pap test is recommended every three years for women 21 to 29 years old. Women 30 and older should have both a Pap test and an HPV test every five years, or a Pap test alone every three years. Women who have had an HPV vaccine should still follow screening guidelines.

HPV screening is not recommended for women in their 20s because it increases the odds of more invasive testing that can leave the cervix less able to handle pregnancy later in life.

But Roche is seeking FDA approval to market its test to women age 25 and up.

That approach was endorsed unanimously last month by a panel of FDA advisers who voted 13-0 that Roche’s cobas HPV test appears safe and effective as a first-choice screening tool. The FDA is weighing that recommendation as it considers approval the company’s application.

Despite the overwhelming endorsement, patient advocates say FDA approval would fly in the face of current medical guidelines, none of which recommend testing with HPV alone for younger women. They point out that the U.S. Preventive Services Task Force, which sets federal medical guidelines, gave HPV testing a “D” rating in women under age 30, warning that testing could lead to “unnecessary treatment and the potential for adverse pregnancy outcomes.”

Even physicians who support HPV testing as an important option warn that introducing a DNA-only testing regimen may lead to confusion that disrupts care. The American College of Obstetricians and Gynecologists says many physicians are already confused by the two existing testing options: Pap alone or Pap with HPV testing.

“Introducing a third screening alternative will likely further increase confusion, and the risk to women of getting either over or under screened,” the group said in comments at the FDA meeting last month. The group, which represents 57,000 U.S. obstetricians and gynecologists, did not sign the letter sent to FDA this week.

Finally there is the cost. An HPV test costs between $80 and $100, at least twice as much as a $40 Pap. And under Roche’s proposal, women who test positive for HPV would be referred for colposcopy, a more invasive testing procedure that can cost up to $500.

All these factors have consumer advocates urging the FDA to break from its advisers and deny first-choice status to the Roche test.

“Sometimes the FDA overrules the advisory committee and it’s OK,” said Dr. Susan Wood, a former FDA official who now directors the Jacobs Institute of Women’s Health.

 Article also appears in The Washington Post, ABC News, NBC News, Star Tribune, Business Week, The Washington Times