Published by the New York Times
By BARRY MEIER
Published: June 25, 2011
Kathleen Herlihy-Paoli, above at Marblehead, Mass., received two all-metal artificial hips two years ago.But the promise of innovation can also prove a trap, a situation now playing out with dire consequences for possibly tens of thousands of people who received artificial hips intended to let them remain active.
In a highly unusual move, the Food and Drug Administration last month ordered manufacturers of all metal hips to undertake emergency studies of patients. And lawmakers and others are now calling for a tightening of how the F.D.A. scrutinizes new implants — both before and after they are sold.
A review of the medical world’s embrace of the metal-on-metal hips over the past decade — including interviews with doctors, industry consultants, regulators, medical experts and patients — shows how innovation’s lure led almost everyone to seize on a product promoted as a breakthrough without convincing evidence that it was better or even as good as existing options.
“As a non-American, I don’t completely understand it, but there is a phenomenon in the U.S., the latest and the greatest,” said Dr. Henrik Malchau, who practiced as an orthopedic surgeon in Sweden before going to Massachusetts General Hospital in Boston. “There was a patient demand to get these implants on the misconception that the latest was the best.”
For many manufacturers, the constant churning of new products can be a business necessity, a way to gain an edge on competitors while maintaining or even raising prices. But in recent years, a host of supposed innovations have imploded not long after introduction.
Several heavily promoted artificial spinal disks, claimed by their makers to be major innovations, proved no better than previous ones. After the blockbuster diabetes drug Avandia was linked to heart attacks, a federal study concluded that older drugs were safer and worked better for most patients. And a new heart device component from Medtronic started fracturing after it was implanted in more than 200,000 patients; at least 12 people died in connection with that product.
Some experts, like Dr. Malchau, said they used a special type of metal-on-metal implant known as a resurfacing device in specific patients — mainly taller, middle-age men — because data showed that they worked in that small group. But as with many innovations, metal hips were marketed to all comers. For example, about 65 percent of the implants went to women and older patients, according to an estimate by a consulting firm, Exponent Inc. As it turned out, those two groups appear most prone to failures involving the devices.
“The vast majority of the ‘innovations’ on which we have spent money with respect to orthopedics over the past two decades have not resulted in improved patient outcomes,” said Dr. Kevin J. Bozic, an orthopedic surgeon and professor at the University of California, San Francisco, who has written about artificial joints’ impact on health care costs.
Last year, DePuy, the orthopedics division of Johnson & Johnson, recalled one of its all-metal hips, the ASR, which was failing at a high rate. Another manufacturer, Zimmer Holdings, also briefly halted sales of one of its metal models, the Durom. DePuy, Zimmer and other companies and doctors have said that most patients who received metal hips have done well.
Experts like Dr. Bozic suggest that big gambles on innovation are justified in dealing with diseases, like some cancers, where current treatments are ineffective. But they say that calculus should shift sharply when existing treatments are highly effective, and that doctors need to use better yardsticks before embracing new technologies in those cases or adopt changes slowly.
The modern artificial hip, which was developed by a British surgeon, Dr. John Charnley, in the 1960s, uses a relatively simple design. A metal “ball” made of cobalt and chromium replaces the top of the thigh bone, while a “cup,” typically made of plastic, serves as an artificial hip socket. By the 1990s, the devices were considered highly effective, with studies then finding that implants still worked a decade after surgery in 95 percent of patients.
Metal-on-metal implants, in which the cup is also made of a metal alloy, had been tried during those early decades, but were largely abandoned after tests found that patients had metal particles in their blood or organs, raising concerns about long-term health risks like cancer.
By 1996, Jonathan Black, an industry consultant and professor emeritus of bioengineering at Clemson University, warned in a medical journal article that the metal-on-metal design posed significant risks because little was known about the biological havoc that metallic debris might cause. He also argued that given the high success rate of existing designs, it would be statistically impossible to run enough studies to prove the new implants’ supposed superiority.
Monica Almeida/The New York Times
What happened? In essence, the old technology was repackaged as new and cutting-edge, and warnings like Mr. Black’s were ignored and considered no longer relevant. This new generation of devices was manufactured differently and reflected better designs, advocates argued.
Companies and surgeons began promoting the new implants as the next big step in orthopedics, one that would let patients, particularly middle-age ones, do strenuous physical activities because their mechanics were more natural. And patients, intrigued by ads featuring celebrity athletes, also wanted such devices.
“I was a skier and a hiker,” said Kathleen Herlihy-Paoli, 55, a graphic designer in Missoula, Mont., who had both of her arthritic hips replaced two years ago with all-metal devices. “My doctors said these would last longer and enable more activity.”
For physicians, new products like the all-metal hips have several attractions, experts say. Along with the potential to improve care, new technology gives the doctor offering it a way to market his or her practice as different from that of a competitor.
An orthopedic surgeon in Los Gatos, Calif., Dr. Edward Littlejohn, was one of the hundreds of physicians nationwide who started implanting the all-metal devices soon after they were marketed. Dr. Littlejohn said he had long used implants made by DePuy, and believed the new all-metal devices were safe because they had passed F.D.A. muster. “I was a DePuy guy,” he explained.
Things started out great, he said. But about a year and some 40 implants later, patients started complaining of pain. One woman developed a condition that Dr. Littlejohn had rarely seen before: a buildup of gray-colored fluid around her hip. It was about then, Dr. Littlejohn said, that he realized he had leapt too soon.
“It has not been fun,” he said.
Dr. Lawrence Dorr, a surgeon in Los Angeles who helped popularize all-metal hips, said they also appealed to doctors for a practical reason: they reduced the risk that a new hip would dislocate soon after implantation.
By using a metal cup, which is thinner than a plastic one, a surgeon could implant a bigger ball component, Dr. Dorr explained, which was less likely to dislocate than a smaller one. Recent research, however, suggests that such oversized components may be a part of the reason the devices shed metallic debris.
“I thought this could be a home run,” Dr. Dorr recalled. “Instead, it turned out to be a strikeout.”
There were skeptics along the way, like Nadim J. Hallab, an implants expert at Rush University Medical Center in Chicago. Dr. Hallab worked with surgeons who were disappointed with the earlier generation of all-metal devices, and they remained skeptical about the new ones. “I never thought this was going to fly,” he says.
But it was an about-face by Dr. Dorr in Los Angeles, that first sounded a public alarm. In 2007, he alerted fellow surgeons after some of his patients developed pain and had to have replacement operations. As the number of affected patients nationwide mounted, it emerged that the devices shared a trait with other failed innovations: most of them had been little tested.
UNDER F.D.A. rules, most all-metal hips don’t have to undergo clinical trials before sale. Instead, they are tested in labs on machines that simulate millions of steps to study the forces exerted by years of motion. Such wear is inevitable in an artificial hip; for example, tests showed that the type of plastic used in some plastic-metal hips shed particles that led to bone loss in some patients.
Similar tests of the all-metal implants did not point to problems, testing experts say. But in retrospect, they added, they think they understand why: the simulations were apparently based on idealized conditions, not on what would happen in the real world of doctors and patients. For example, all-metal devices proved less forgiving than metal-and-plastic ones to small variations in how they were implanted, with components sometimes striking together and generating debris.
Harry McKellop, a device testing expert at Los Angeles Orthopaedic Hospital, said it was his understanding that “most of the early metal-on-metal testing was not done under adverse conditions.”
While some metal implants have performed well in certain patients, the devices, as a group, are twice as likely as metal-and-plastic ones to require early replacement, according to data from Australia’s orthopedic registry, one of the most comprehensive databases on implants.
Most troublingly, damage from debris generated by metal implants is proving far more insidious than that caused by plastic particles. In some patients, it has caused crippling tissue and muscle damage, and has produced neurological problems in others.
The innovation cycle involving the hips has now entered a new phase: cleanup. Regulators, researchers and companies must assess the damage caused, and determine how to undo it.
ACCORDING to one estimate, about 500,000 patients in the United States may have gotten an all-metal hip in the past decade, raising the likelihood that tens of thousands will have painful early-replacement procedures. Even if the share of seriously injured patients stays low, as researchers hope, thousands are likely to be affected, experts estimate.
In early May, orthopedic specialists and company officials discussed how best to perform the special studies the F.D.A. is now requiring. Pitfalls may abound, specialists warned. For example, only certain labs are authorized to measure metallic ions in the blood, and diagnostic equipment, unless specifically calibrated, will not detect tissue damage.
There may also be some confusion about the advice coming from the F.D.A. and other authorities. Officials urge patients to contact their doctors if they experience pain, but internal damage may be occurring in some patients who are free of symptoms.
Ms. Herlihy-Paoli, the graphic designer, said her brother-in-law, a lawyer, urged her last year to get a blood test because he had a client with a failed metal hip. She said she thought it unnecessary because she felt fine, but when she did take the test it showed high levels of metallic ions.
Feeling panicked, she sought out Dr. Malchau in Boston, who discovered that debris had already started a reaction around one implant that was producing aberrant tissue growth. “I had a tumor growing there,” Ms. Herlihy-Paoli said. “If I had left the hip in, it would have started damaging the bone and muscle.”
Needless to say, surgeons, testing experts, implant company officials and regulators are all eager to find a way to prevent such problems with other new devices. The proposals include better pre-market testing, consistent product tracking and phased-in introductions of new products.
But many experts also want to ensure that too much second-guessing does not slow real innovation. Ultimately, the resolution of that quandary, some experts believe, may lie as much with the attitudes of doctors and patients as it does with regulation.
Meanwhile, some participants in this long arc of events have also come full circle. For example, Mr. Black, the consultant who warned about use of all-metal hips, was hired not long ago by DePuy to advise it in connection with the scores of patient lawsuits pending against it. Mr. Black said he anticipates that lawsuits against it and other makers of all-metal hips may emerge as the largest product liability cases of this decade.