Public Kept in Dark About Hip-Replacement Risks, Says BMJ
Public Kept in Dark About Hip-Replacement Risks, Says BMJ
February 28, 2012 — An article published today in the British Medical Journal (BMJ) charges that hundreds of thousands of patients with metal-on-metal hip implants may have been unwittingly exposed to toxic substances.
A joint effort of the BMJ and BBC Newsnight, the article faults regulators in the United Kingdom and the United States for helping to keep patients in the dark and alleges that hip replacement manufacturer DePuy Orthopaedics, a Johnson & Johnson unit, worried about the potential for patient harm, even as it marketed these products.
The author, BMJ investigations editor Deborah Cohen, MD, writes that the health risk arises from implants in which the pelvic cup and the femoral head are both made with a cobalt-chrome alloy, as opposed to other materials such as ceramic or polyethylene. This metal-on-metal design applies to a total hip replacement system, which replaces the femoral head with a metal ball, as well as hip resurfacing, in which a metal cap is attached to the femoral head.
The wear and tear of metal on metal releases metal ions that can seep into local tissue, destroy muscle and bone, and leave patients with long-term disabilities, Dr. Cohen writes. These metal ions, which may be carcinogenic, also can become blood-borne and spread to the lymph nodes, spleen, liver, and kidneys. The scientific community, she writes, has known about the genotoxic risks of cobalt and chromium ions for decades.
Article Cites Internal DePuy Memo About Risk
Dr. Cohen's article focuses on a metal-on-metal hip replacement technology from DePuy called ASR, which it introduced in Europe in 2003. The technology consisted of 2 different systems: the ASR XL Acetabular System for total hip replacement and the ASR Hip Resurfacing System.
The US Food and Drug Administration (FDA) cleared the ASR XL Acetabular System for use in the United States in 2005, but the ASR Hip Resurfacing System never received FDA approval.
In August 2010, the company voluntarily withdrew its ASR implants on a global basis after learning that the 5-year rate of revision surgery for patients in England and Wales was roughly 1 in 8. At the time, the company attributed the higher-than-expected revision rates to component loosening and misalignment, infection, bone fracture, dislocation, metal sensitivity, and pain.
Dr. Cohen writes that DePuy knew about the potential for 1 implant problem — genotoxicity — long before 2010. She quotes a DePuy internal memo from 2005 stating:
"In addition to inducing potential changes in immune function, there has been concern for some time that wear debris may be carcinogenic. The mechanism is not known and only 24 local malignancies have been reported in patients with joint replacements. Also worrying is the possibility of distant effects. One study suggested a threefold risk of lymphoma and leukaemia 10 years after joint replacement. "
The Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom investigated the issue of metal-on-metal hip implants and genotoxicity, and in 2007, it ruled that patients should sign a consent form in advance of surgery spelling out the risks of metal debris and genotoxic risk.
"But this requirement was not communicated widely — no alert was put out to surgeons or patients," Dr. Cohen writes.
The Saga of "Regulatory Failure"
According to Dr. Cohen, the "regulatory failure" surrounding metal-on-metal hip replacements began in the 1990s, when they were first introduced in Europe and subjected to only simulated mechanical testing, never mind how it might perform inside the human body.
In the United States, the FDA cleared the technology through a "grandfathered" route called 510(k), reasoning that it was basically like other hip replacement devices that were already approved. This process, which is less rigorous than the agency's normal premarketing approval process, did not require any clinical studies, Dr. Cohen writes.
It was not until May 2011, after DePuy had recalled its ASR hip-replacement technology, that the FDA took a harder look. It ordered all manufacturers of metal-on-metal systems to conduct postmarketing surveillance studies on their safety.
Neither European nor US regulators spotted changes in the total hip implant technology and how those changes exacerbated the problem of metal debris, according to Dr. Cohen. About 7 years ago, manufacturers began shortening the portion of the femur implant called the trunnion, or taper that fits into the femoral head, while at the same time enlarging the head, in an attempt to prevent dislocation and increase movement. The design change led to "increased wear, high levels of metal ions in the tissues and blood, and higher rates of joint failure."
Dr. Cohen reports that surgeons were unaware of these changes, which sometimes were not disclosed by manufacturers in marketing materials.
She credits the FDA for finally putting all hip implants into a high-risk category that will prevent new systems from being fast-tracked into the market. Meanwhile, European counterparts have much room for improvement, she writes, quoting a clinical epidemiologist in London as saying, "The methods of device regulation seem to be more from the 1950s than the 21st century."
Commercial Success Trumps Safety, Says Author
Metal-on-metal hip replacements are still on the market, despite their long-known risks. Dr. Cohen attributes that fact to "a drive for commercial success unconcerned with patient safety."
Her account sparked a similar assessment from Fiona Godlee, MD, the editor-in-chief of the BMJ.
"Hip replacements are one of the great successes of modern medicine," Dr. Godlee said in a press release. "But a combination of inadequate regulation and untrammelled commercialism has caused actual and potential harm for large numbers of patients around the world. They should have known about the risks, as the manufacturers and regulators did, but they were not told."
An official with the US watchdog group Public Citizen also laments how the public has been in the dark.
"This is one very large uncontrolled experiment exposing millions of patients to an unknown risk," said Michael Carome, deputy director of Public Citizen's Health Research Group, in a press release. "We will only find out about the safety of these devices after large numbers of people have already been exposed."
Johnson & Johnson did not respond to a request for an interview.
Companion Article Also Criticizes Regulatory Slowness
A companion piece to Dr. Cohen's article in the BMJ also is critical of regulatory agencies' handling of hip implants.
Lead author Carl Heneghan, MB ChB, director of the Centre of Evidence Based Medicine in the United Kingdom, and coauthors fault the FDA's use of the expedited 510(k) process for clearing medical devices, noting that the Institute of Medicine has called for its demise. The regulatory framework in the European Union, they write, is just as lax, because it "allows clinical evaluation of hip replacements to be based on existing technologies rather than the actual device and the clinical data submitted to be based on a literature review alone."
Slow response is another problem. It took the European Commission, the executive body of the European Union, until 2007 to reclassify hip replacement systems as class 3 devices (the highest risk category on its scale) because of their invasive nature, according to the authors. Up until then, the systems were deemed class 2 devices, which "have substantially lower evidence requirements that do not include an assessment of patient safety."
Furthermore, the MHRA knew about the risks of the DePuy metal-on-metal hip replacement technology as early as 2008, but waited until 2010 to issue a safety alert to clinicians, Dr. Heneghan and coauthors write. That alert, among other things, instructed clinicians to monitor patients with metal-on-metal hip replacements for at least 5 years, and to test the patients' blood levels of chromium and cobalt ions.
UK Agency Updates Advice on Day of Article's Release
Today, the MHRA updated its 2010 advice to clinicians on patients with metal-on-metal hip replacements. It stated that clinicians should monitor these patients for the lifetime of their device if its head diameter measures 36 mm or more. "This particular type of hip replacement has a small risk of causing complications in patients," MHRA clinical director Susanne Ludgate, MB ChB, stated in a press release.
Dr. Ludgate noted that although metal-on-metal hip replacements pose a small risk for complications, they have "in most cases completely transformed the lives of patients who in the past were subject to increasingly severe pain and progressive lack of mobility."
In today's press release, the MHRA said that it was the first regulatory agency to issue guidance on metal-on-metal hip replacements, and that it takes its postmarketing surveillance role "very seriously." It encouraged healthcare professionals, industry, and the public at large to alert to it any problematic medicine or medical device.
Dr. Cohen has disclosed no relevant financial relationships. One of the authors of the accompanying article, David Langton, MRCS, is an expert witness in litigation against DePuy for the ASR hip implants. Additional disclosures for the 3 authors of the accompanying article are available at http://www.icmje.org/coi_disclosure.pdf.
BMJ. Published online February 28, 2012. Cohen abstract, Heneghan article
February 28, 2012 — An article published today in the British Medical Journal (BMJ) charges that hundreds of thousands of patients with metal-on-metal hip implants may have been unwittingly exposed to toxic substances.
A joint effort of the BMJ and BBC Newsnight, the article faults regulators in the United Kingdom and the United States for helping to keep patients in the dark and alleges that hip replacement manufacturer DePuy Orthopaedics, a Johnson & Johnson unit, worried about the potential for patient harm, even as it marketed these products.
The author, BMJ investigations editor Deborah Cohen, MD, writes that the health risk arises from implants in which the pelvic cup and the femoral head are both made with a cobalt-chrome alloy, as opposed to other materials such as ceramic or polyethylene. This metal-on-metal design applies to a total hip replacement system, which replaces the femoral head with a metal ball, as well as hip resurfacing, in which a metal cap is attached to the femoral head.
The wear and tear of metal on metal releases metal ions that can seep into local tissue, destroy muscle and bone, and leave patients with long-term disabilities, Dr. Cohen writes. These metal ions, which may be carcinogenic, also can become blood-borne and spread to the lymph nodes, spleen, liver, and kidneys. The scientific community, she writes, has known about the genotoxic risks of cobalt and chromium ions for decades.
Article Cites Internal DePuy Memo About Risk
Dr. Cohen's article focuses on a metal-on-metal hip replacement technology from DePuy called ASR, which it introduced in Europe in 2003. The technology consisted of 2 different systems: the ASR XL Acetabular System for total hip replacement and the ASR Hip Resurfacing System.
The US Food and Drug Administration (FDA) cleared the ASR XL Acetabular System for use in the United States in 2005, but the ASR Hip Resurfacing System never received FDA approval.
In August 2010, the company voluntarily withdrew its ASR implants on a global basis after learning that the 5-year rate of revision surgery for patients in England and Wales was roughly 1 in 8. At the time, the company attributed the higher-than-expected revision rates to component loosening and misalignment, infection, bone fracture, dislocation, metal sensitivity, and pain.
Dr. Cohen writes that DePuy knew about the potential for 1 implant problem — genotoxicity — long before 2010. She quotes a DePuy internal memo from 2005 stating:
"In addition to inducing potential changes in immune function, there has been concern for some time that wear debris may be carcinogenic. The mechanism is not known and only 24 local malignancies have been reported in patients with joint replacements. Also worrying is the possibility of distant effects. One study suggested a threefold risk of lymphoma and leukaemia 10 years after joint replacement. "
The Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom investigated the issue of metal-on-metal hip implants and genotoxicity, and in 2007, it ruled that patients should sign a consent form in advance of surgery spelling out the risks of metal debris and genotoxic risk.
"But this requirement was not communicated widely — no alert was put out to surgeons or patients," Dr. Cohen writes.
The Saga of "Regulatory Failure"
According to Dr. Cohen, the "regulatory failure" surrounding metal-on-metal hip replacements began in the 1990s, when they were first introduced in Europe and subjected to only simulated mechanical testing, never mind how it might perform inside the human body.
In the United States, the FDA cleared the technology through a "grandfathered" route called 510(k), reasoning that it was basically like other hip replacement devices that were already approved. This process, which is less rigorous than the agency's normal premarketing approval process, did not require any clinical studies, Dr. Cohen writes.
It was not until May 2011, after DePuy had recalled its ASR hip-replacement technology, that the FDA took a harder look. It ordered all manufacturers of metal-on-metal systems to conduct postmarketing surveillance studies on their safety.
Neither European nor US regulators spotted changes in the total hip implant technology and how those changes exacerbated the problem of metal debris, according to Dr. Cohen. About 7 years ago, manufacturers began shortening the portion of the femur implant called the trunnion, or taper that fits into the femoral head, while at the same time enlarging the head, in an attempt to prevent dislocation and increase movement. The design change led to "increased wear, high levels of metal ions in the tissues and blood, and higher rates of joint failure."
Dr. Cohen reports that surgeons were unaware of these changes, which sometimes were not disclosed by manufacturers in marketing materials.
She credits the FDA for finally putting all hip implants into a high-risk category that will prevent new systems from being fast-tracked into the market. Meanwhile, European counterparts have much room for improvement, she writes, quoting a clinical epidemiologist in London as saying, "The methods of device regulation seem to be more from the 1950s than the 21st century."
Commercial Success Trumps Safety, Says Author
Metal-on-metal hip replacements are still on the market, despite their long-known risks. Dr. Cohen attributes that fact to "a drive for commercial success unconcerned with patient safety."
Her account sparked a similar assessment from Fiona Godlee, MD, the editor-in-chief of the BMJ.
"Hip replacements are one of the great successes of modern medicine," Dr. Godlee said in a press release. "But a combination of inadequate regulation and untrammelled commercialism has caused actual and potential harm for large numbers of patients around the world. They should have known about the risks, as the manufacturers and regulators did, but they were not told."
An official with the US watchdog group Public Citizen also laments how the public has been in the dark.
"This is one very large uncontrolled experiment exposing millions of patients to an unknown risk," said Michael Carome, deputy director of Public Citizen's Health Research Group, in a press release. "We will only find out about the safety of these devices after large numbers of people have already been exposed."
Johnson & Johnson did not respond to a request for an interview.
Companion Article Also Criticizes Regulatory Slowness
A companion piece to Dr. Cohen's article in the BMJ also is critical of regulatory agencies' handling of hip implants.
Lead author Carl Heneghan, MB ChB, director of the Centre of Evidence Based Medicine in the United Kingdom, and coauthors fault the FDA's use of the expedited 510(k) process for clearing medical devices, noting that the Institute of Medicine has called for its demise. The regulatory framework in the European Union, they write, is just as lax, because it "allows clinical evaluation of hip replacements to be based on existing technologies rather than the actual device and the clinical data submitted to be based on a literature review alone."
Slow response is another problem. It took the European Commission, the executive body of the European Union, until 2007 to reclassify hip replacement systems as class 3 devices (the highest risk category on its scale) because of their invasive nature, according to the authors. Up until then, the systems were deemed class 2 devices, which "have substantially lower evidence requirements that do not include an assessment of patient safety."
Furthermore, the MHRA knew about the risks of the DePuy metal-on-metal hip replacement technology as early as 2008, but waited until 2010 to issue a safety alert to clinicians, Dr. Heneghan and coauthors write. That alert, among other things, instructed clinicians to monitor patients with metal-on-metal hip replacements for at least 5 years, and to test the patients' blood levels of chromium and cobalt ions.
UK Agency Updates Advice on Day of Article's Release
Today, the MHRA updated its 2010 advice to clinicians on patients with metal-on-metal hip replacements. It stated that clinicians should monitor these patients for the lifetime of their device if its head diameter measures 36 mm or more. "This particular type of hip replacement has a small risk of causing complications in patients," MHRA clinical director Susanne Ludgate, MB ChB, stated in a press release.
Dr. Ludgate noted that although metal-on-metal hip replacements pose a small risk for complications, they have "in most cases completely transformed the lives of patients who in the past were subject to increasingly severe pain and progressive lack of mobility."
In today's press release, the MHRA said that it was the first regulatory agency to issue guidance on metal-on-metal hip replacements, and that it takes its postmarketing surveillance role "very seriously." It encouraged healthcare professionals, industry, and the public at large to alert to it any problematic medicine or medical device.
Dr. Cohen has disclosed no relevant financial relationships. One of the authors of the accompanying article, David Langton, MRCS, is an expert witness in litigation against DePuy for the ASR hip implants. Additional disclosures for the 3 authors of the accompanying article are available at http://www.icmje.org/coi_disclosure.pdf.
BMJ. Published online February 28, 2012. Cohen abstract, Heneghan article
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