Warning Signs No. 2: Metal-on-Metal Hips,
Lung Cancer Death Rates, Ecigarette and Food Safety

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It’s a new year and here’s another segment on warning signs. I am glad to see that this month, the hazards of metal-on-metal hips, covered in the first warning signs issue, are being examined.

40% Failure Rate of Johnson and Johnson’s Metal-on-Metal Hip

People contemplating a joint replacement should take a close look at this story. Barry Meier, reporter at the New York Times, reported on Jan. 22. that Johnson & Johnson , knew about its Articular Surface Replacement hip, or A.S.R.’s 40% failure rate within 5 years of surgery.

“The episode represents one of the biggest medical device failures in recent decades and the forthcoming trial is expected to shed light on what officials of Johnson & Johnson’s DePuy Orthopaedics division knew about the device’s problem before its recall and the actions they took or did not take.” Barry Meier, NYT, Jan. 22, 2013. 

Thousands of patients have brought lawsuits concerning the A.S.R. A trial begins today in California Superior Court in Los Angeles. Will this be the straw that breaks the camel’s back in terms of inadequate patient protection in medical device regulation? Will we see a more vigilant FDA?

Lung Cancer Death Rates for Women On Par with Men’s

You may be thrilled, as I was, earlier this week, when President Obama called attention to our nation being inclusive. One milestone that I wish women were spared is their achieving near parity with men in their risk for lung cancer death:

A study in the Jan. 24 New England Journal of Medicine, reveals that as women’s smoking habits have become more like men’s, namely starting to smoke at a younger age and smoking more cigarettes each day, their risk of lung cancer death has risen to the same as men. Removal of the stigma against smoking for women began after World War II, and women in their fifties and older, who smoked are part of this surge.

A related study, by Prabhat Jha at the Center for Global Health Research in Toronto, underscores the value of quitting in helping prevent early smoking-related deaths. Using the Centers for Disease Control and Prevention National Health Interview Survey (NHIS) data, researchers report  threefold greater risk for lung cancer death in current smokers, compared with people who never smoked.

Questionable Oversight of the Electronic (e)cigarette Business.

You can see the advertising all over: electronic cigarettes are marketed as a safer non-tobacco alternative. Is the data in? I have my doubts.

insert on electronic cigarette safety

Thanks @Dirk57 at The Addiction Inbox, who flags the lack of regulation in the e-cigarette business, in a post this week. Big tobacco is moving into this lucrative business quickly, Dirk points out. But do we have reason to trust industry marketing. Additionally, safety data has been inconsistent. Long-term safety data concerning e-cigarettes is unclear.  Dirk raises some important questions.

FDA Belatedly Ramps Up Food Safety

Last fall, Center for Science in the Public Interest made a compelling case for the FDA failing to put food safety preventive programs in place. I called attention to it here. Could some of the produce safety outbreaks (e.g. cantaloupe, peanut butter) we heard about last year been averted? Probably.

Finally, FDA is requiring the food industry to perform a hazard analysis of their facilities and put control programs in place to prevent food pathogens from getting into produce and other parts of the food supply.

Still wanting: regulations for food produced in other countries, warns CSPI.

Is the Bar High Enough for Screening
Breast Ultrasounds for Dense Breasts?

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In a unanimous decision yesterday, FDA approved the first breast ultrasound imaging system for dense breast tissue “for use in combination with a standard mammography in women with dense breast tissue who have a negative mammogram and no symptoms of breast cancer.” Patients should not interpret FDA’s approval of the somo-v Automated Breast Ultrasound System as an endorsement of the device as necessarily beneficial for this indication and this will be a thorny concept for many patients to appreciate.

If the approval did not take place in the setting of intense pressure to both inform women that they have dense breasts and lobbying to roll out all sorts of imaging studies quickly, no matter how well they have been studied, it would not be worth posting.

Dense breasts are worrisome to women, especially young women (in their 40s particularly) because they have proved a risk factor for developing breast cancer. Doing ultrasound on every woman with dense breasts, though, who has no symptoms, and a normal mammogram potentially encompasses as many as 40% of women undergoing screening mammography who also have dense breasts, according to the FDA’s press release. Dense breast tissue is most common in young women, specifically women in their forties, and breast density declines with age.

The limitations of mammography in seeing through dense breast tissue have been well known for decades and the search has been on for better imaging studies. Government appointed panels have reviewed the issue and mammography for women in their forties has been controversial. What’s new is the “Are You Dense?” patient movement and legislation to inform women that they have dense breasts.

Merits and Pitfalls of Device Approval

The approval of breast ultrasound hinges on a study of 200 women with dense breast evaluated retrospectively at 13 sites across the United States with mammography and ultrasound. The study showed a statistically significant increase in breast cancer detection when ultrasound was used with mammography.

Approval of a device of this nature (noninvasive, already approved in general, but not for this indication) does not require the company to demonstrate that use of the device reduces morbidity or mortality, or that health benefits outweigh risks.

Eitan Amir, MD, PhD, medical oncologist at Princess Margaret Hospital, Toronto, Canada, said: “It’s really not a policy decision. All this is, is notice that if you want to buy the technology, you can.”

That’s clearly an important point, but not one that patients in the US understand. Patients hear “FDA approval” and assume that means a technology most certainly is for them and a necessary add-on. This disconnect in the FDA medical device approval process and in what patients think it means warrants an overhaul or at the minimum, a clarification for the public.

Materials for FDA submission are available on the FDA website, including the study filed with FDA and a PowerPoint presentation, but lots of luck, finding them quickly. “In the submission by Sunnyvale CA uSystems to FDA, the company stated that screening reduces lymph node positive breast cancer,” noted Amir. “There are few data to support this comment.”

Is Cancer Detection A Sufficient Goal?

In the FDA study, more cancers were identified with ultrasound. However, one has to question whether breast cancer detection alone is meaningful in driving use of a technology. In the past year, prostate cancer detection through PSA screening has been attacked because several studies and epidemiologists have found that screening is a poor predictor of who will die from prostate cancer or be bothered by it during their lifetime. We seem to be picking up findings that don’t lead to much to worry about, according to some researchers. Could new imaging studies for breast cancer suffer the same limitation? It is possible.

Another question is whether or not the detected cancers on ultrasound in the FDA study would have been identified shortly thereafter on a routine mammogram. It’s a question that is unclear from the FDA submission, according to Amir.

One of the problems that arises from excess screening is overdiagnosis, overtreatment, and high-cost, unaffordable care. An outcomes analysis of 9,232 women in the US Breast Cancer Surveillance Consortium led by Gretchen L. Gierach, PhD, MPH, at the National Institutes of Health MD, and published online in the August 21 Journal of the National Cancer Institute, revealed: “High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics.” –Gierach et al., 2012

Proposed Breast Cancer Screening Tests

Meanwhile, numerous imaging modalities have been proposed as an adjunct to mammography and as potential replacements for mammography. In 2002, proponents of positron emission tomography (PET) asked Medicare to approve pet scans for imaging dense breast tissue, especially in Asian women. The Medicare Coverage Advisory Commission heard testimony, but in the end, Medicare did not approve it for the dense-breast indication.

PET scans are far less popular today, while magnetic resonance imaging (AKA MR, MRI) and imaging have emerged as as adjuncts to mammography for women with certain risk factors. Like ultrasound, the outcomes data is not in the bag for screening with it.

In an interview with Monica Morrow, MD, Chief of Breast Surgery at Memorial Sloan-Kettering Cancer Center, New York, several months ago concerning the rise in legislation to inform women about dense breasts, which frequently leads to additional imaging studies, she said: “There is no good data that women with dense breasts benefit from additional MR screening.” She is not the only investigator to question potentially deleterious use of MR ahead of data collection and analysis. Many breast researchers have expressed fear that women will opt for double mastectomies, based on MR, that in the end, may have been absolutely unnecessary.

“There is one clear indication for MR screening,” stressed Morrow, explaining that women with BRCA mutations should be screened with MRI. “Outside of that group, there was no evidence that screening women with MR was beneficial.”

At just about every breast cancer meeting in the past two years, the benefits and harms of MR and other proposed screening modalities come up, and there is no consensus in the field.  It  should be noted, though, that plenty of breast physicians are skeptical about broad use of MR– not just generalists outside of the field. In other words, it is not breast and radiology specialists versus the US Preventive Services Task Force – a very important message for patients to understand.

One thing is clear: as these new technologies gain FDA approval, it will be a windfall for industry. If industry is successful and doctors are biased to promoting these tests, many may offer them on the estimated 40% of women with dense breasts who undergo routine mammograms, as well as other women evaluated as having a high lifetime risk.  The tests will be offered in a setting of unclear value and uncertain harms. Even though FDA has not approved breast MRI for screening dense breasts, breast MR is being used off label and it is far more costly than mammography.

When patients raise concerns about the unaffordability of medical care, they should be counseled about the uncertain benefit and potential harms of such a test. That may be a tall bill for most Americans to consider: it’s clear that the more is better philosophy is alive and well. Early detection of something, anything, even something dormant, going nowhere, is preferable to skipping a test, and risking who-knows-what, and that is something, most of us cannot imagine at the outset.

 

NEXT UP: The Dense Breast Lobby Pushes Legislation to Inform, Increase Access to Tests

 

 

 

Metal-on-Metal Hips: A Tale of Harm, Weak
Medical Device-Approval, and Lax Postmarket Scrutiny

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Hip replacement, National Institutes of Health

Nearly 1 million metal-on- metal hips have been implanted in patients in the United States, making the US the world’s largest consumer of the implants. According to a BMJ/BBC Newsnight Investigation released today, the “risks associated with these devices have been known for decades, yet patients have been kept in the dark about their participation in what has effectively been a large uncontrolled experiment.” At issue are “leaky hips,” specifically, “release of metal ions that can seep into local tissue causing reactions that destroy muscle and bone and leaving some patients with long term disability,” writes Deborah Cohen, BMJ’s Investigations Editor. In a companion paper, Carl Heneghan, MD, director of the Centre for Evidence-Based Medicine, University of Oxford, Oxford, UK, and coauthors, point to the litany of safety warnings out on these implants for a decade or more.

Together, these reports point out:

  • internal memos deemed proprietary acknowledging safety issues dating back more than a decade;
  • lack of medium-to-long-term safety and reliability data on these devices;
  • uncertainty about safe levels of metal (cobalt and chromium) ion exposure;
  • design flaws;
  • a weak device regulatory approval process, seemingly more intent on rapid market entry, and not requiring clinical data submission prior to approval;
  • postmarketing databanks in the EU that alone are insufficient for flagging safety;
  • and despite all of this, exhibitors at a February 2012 American Academy of Orthopedic Surgery annual meeting, showcased metal-on-metal hips to thousands of attendees.

This story is hardly new, but what’s alarming is that the metal-on-metal hip story is emblematic of how thousands of medical devices like hip implants get out to market. FDA does not require clinical data submissions, but merely proof that the implants are “substantially similar” to other devices already out there through FDA’s 510(k) program.

Richard Deyo, MD, Professor of Evidence-Based Family Medicine, Oregon Health and Science University, Portland, OR, reviewed the report. In an email, Deyo wrote: “I think implanted medical devices should have much closer pre-approval scrutiny than they currently receive, and there is a need for much better post-marketing surveillance. The latter might uncover problems of this sort before too many patients are affected.”

As far as patients are concerned, Deyo wrote: “Patients may want to inquire as to the length of the track record for any implantable device. This is a situation where it’s not safe to assume that the latest is the greatest. It often takes years to learn about the durability of implants, and some new devices prove to be worse than older ones.”

Rita F. Redberg, MD, Professor of Medicine at the University of California San Francisco, told Patient POV:  ““We are dependent on foreign registries for data on hip implants and currently,there is no provision that would require collection and reporting of such data.” Redberg says we need more data in the  FDA premarket process, as well as more consistent and complete postmarketing surveillance. “A  US hip and knee registry would help,” Redberg said, adding that plans for such are moving very slowly.

Hip and knee replacement registries are further along outside of the United States. In 1999, Australia launched a mandatory, confidential hip and knee registry that generates detailed information on outcomes, implant performance, patient deaths, and revisions. Proponents say that it has been helpful in real-time quality control, in weeding out poorly performing implants, as well as pushing orthopods with less-than-optimal outcomes to improve their technique or stop doing implants. New Zealand similarly launched its registry in 1999.

In both Australia and New Zealand, individual surgeon data has not been discoverable, but this has been a sticking point for the US-based Association of Health Care Journalists and ProPublica, who have been fighting in the US to have the HHS National Practitioner Databank accessible at the provider level.

Patients need to think through who they should lobby to improve their odds of getting a safe, new hip, pacemaker, or new knee, should they need them. Thousands of devices become FDA approved through the 510(k) process, without clinical data submission. Sadly, I doubt most of us, including me, have tools available to make the best choice on where to go for a hip implant with a good track record and an orthopod with good outcomes. I haven’t found the websites of orthopedists very helpful.

A mandatory, real-time patient registry with uniform requirements would be a step in the right direction, but headway in this area has been slow. Putting safety first and insisting that industry submit clinical data before the FDA approves new devices is paramount. The 510(k) process needs to be abandoned and supplanted with clinical data reviewed by FDA. Postmarketing surveillance needs to be ramped up so that safety problems are flagged as early as possible. Comparative effectiveness research could also go a long way in evaluating the safety of implanted devices. Even though cost effectiveness research provisions are in place through the Accountable Care Act, orthopods have yet to contribute to the process.

An earlier version of this article misquoted Dr. Redberg. The corrected quote appears above.