Tuesday, May 31, 2011

My final appointment with the ortho surgeon

We will be selecting a date for revision. That surgery is an 8 week wait.    I asked him to contact my ortho consult to review the new choice of implant first, the need for allergy testing prior to surgery and requested any systemic tests we can perform prior to surgery.

The ceramic ball with poly liner is the new prosthesis he is considering now.

In terms of the explant, they are being stored at the hospital or sent for analysis via an attorney.  I have not hired an attorney yet however.

My surgeon is very confident that the outcome will be good.

No major new news.

connie

Monday, May 30, 2011

My final visit with my Ortho Surgeon Tomorrow

I finally collected all of the recommendations from the consults and will be reviewing them tomorrow with my Ortho. Surgeon (This appointment was postponed for two months due the need for written opinions from the consults.)  

My agenda:
  • Review the consults opinions (one ion expert, one ortho surgeon, one MRI, one toxicologist, one nephrologist.
    • especially interested in his opinion of the MRI results
  • Reach agreement on the next step following my investigation and his prior recommendation.
  • Review the replacement he would like to use on revision
  • Discuss whether I should have an allergy test (to the metals) prior to the revision.
  • What is the plan with explant?
  • Are there any tests I can get re measuring the systemic levels in the Kidney, spleen and lymph nodes
  • Will be handing him 3 articles:
    • Silent soft tissue pathology (mainly for his other patients)
    • Instructional review of the evidence thus far for MoM implants- I will be publishing something on this soon.  Excellent summary.
    • Out of Joint which is the summary of what did depuy know and when did they know it.
  • I will be handing him 3 abstracts:
    • Nine year Incidence of Kidney Disease in Patients who have had total hip Artroplasty- just published by Dept of Ortho Surgery at Stanford.
    • March paper on the Pragmatic clinical work up of patients with allergic disease to MoM implants by the Cleveland clinic and others.
    • Abstract on several assays that might be used to look at allergies to MoM.
  • What kind of dates are available for the surgery?
I will be asking him to phone one the ion consult for 3 reasons:
  • Are we selecting the right replacement?
  • What about the explant-will my consult take it?
  • Testing
    • Is it worth while to consider the allergy test which in fact was recommended by the toxicologist.
    • Are there any tests we can undertake for the systemic issues?
connie

Sunday, May 29, 2011

Surprising statement from older (2004) Journal Article

I was reading some journal articles from 2004 and found something suprising.  There are risks to replacement surgery but had not heard this risk highlighted in the abstract below:
 
While all components can be associated with the distant spread of particles and metal ions, it is the environment of revision arthroplasty that provides the greatest potential for the generation and systemic dissemination of wear debris.
 
 
J Arthroplasty. 2004 Dec;19(8 Suppl 3):94-101.

Accumulation in liver and spleen of metal particles generated at nonbearing surfaces in hip arthroplasty.

Source

Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois 60612, USA.

Abstract

Systemic migration of metal particles generated at nonbearing surfaces rather than the intended primary bearing was studied in postmortem specimens from 30 patients with total hip arthroplasty. Using light and electron microscopy with x-ray microanalysis, submicrometer metal particles were identified within macrophages in the liver and/or the spleen in 11 of 15 patients with a revised arthroplasty and in 2 of 15 patients with primary hip arthroplasty. The macrophages formed focal aggregates in the organs without apparent toxicity. Fretting at ancillary fixation devices, loose components, and modular connections can generate a substantial volume of debris. These particles are in addition to those generated at the bearing surfaces, further increasing both the local and systemic particulate burdens. While all components can be associated with the distant spread of particles and metal ions, it is the environment of revision arthroplasty that provides the greatest potential for the generation and systemic dissemination of wear debris. The long-term effects of accumulated wear particles in the liver and spleen are unknown.

Interesting X rays of hip issues with Artheroplasty

I thought these radiograph  were interesting and show the issues with these implants if they fail. They look like radiographs from the Hospital of Special Surgery in NYC.  They were published on Parker Waichman's site.
 
Wear of hip implant with pieces of broken material in tissue. Broken head of hip implant (upper left) and pieces of broken ceramic material embedded into tissue (lower right) due to wearing of hip implant which may lead to Osteolysis and bone breakage.
Wear of hip implant with pieces of broken material in tissue.
 
 
Failed total hip replacement with revision. 1. Patient with a failed total hip replacement with considerable proximal femoral bone loss, proximal migration of the greater trochanter and breakage of multiple screws distally from the previous interlocking device.
2. Surgeons revised the hip implant with a constrained acetabular component and cemented a proximal femoral replacement into the distal femur.
Failed total hip replacement with revision.
 
 
Wear of the acetabular liner of hip implant. 1. A radiograph of the pelvis demonstrates area of wear of the acetabular liner, with superolateral displacement of the femoral head (red arrow). Large radiolucent area superior to the acetabular companent (yellow arrow), and bony resorption of the proximal medial femur adjacent to the insertion site of the femoral prosthetic companent (green arrow).
2. Changes not seen in first film.
Wear of the acetabular liner of hip implant.

Hip Implant Revision
1. Loose total hip replacement
2. Right hip revision hip replacement to correct loosened hip implant.

Hip implant revision. Loose total hip replacement


Osteolysis bone loss disease 
1. Osteolysis involves wear particles (worn off the contact surface of the artificial ball and socket joint). As the body attempts to clean up these wear particles (typically consisting of plastic or metal) it triggers an autoimmune reaction which causes resorption of living bone tissue. Osteolysis has been reported to occur as early as 12 months after implantation and is usually progressive. This may require a revision surgery (replacement of the prosthesis).
2. Aseptic loosening of a hip implant. Note the radiolucencies next to the implant, a result of osteolytic bone loss.

Osteolysis bone loss disease

 

DePuy Pinnacle Hip Lawsuits Consolidated in Texas

exerpts from News Infirno story
http://www.newsinferno.com/defective-medical-devices/depuy/depuy-pinnacle-hip-lawsuits-consolidated-in-texas/

The DePuy Pinnacle is a metal-on-metal hip implant similar in design to the DePuy ASR hip implant, the headline-making device that was recalled last August over unusually high early failure rates. Like the DePuy ASR device, the Pinnacle hip implant is the subject of numerous lawsuits. This week, a federal panel of judges decided to consolidate DePuy Pinnacle hip implant lawsuits in a multidistrict litigation and transfer them to federal court in Texas.

An increasing number of lawsuits involving the DePuy Pinnacle hip implant have been filed in recent months, many alleging problems that sound familiar to anyone following DePuy ASR hip implant recalls. Many lawsuits contend the DePuy Pinnacle should have been subject to a recall, much like the one DePuy issued for its ASR hip implant devices last August.

Recently, a motion was filed with the U.S. Judicial Panel on Multidistrict Litigation to consolidate all pending and future federal DePuy Pinnacle hip implant lawsuits in a multidistrict litigation (MDL), and possibly make them a part of the DePuy ASR hip implant litigation that has already been consolidated in the U.S. District Court for the Northern District of Ohio. The DePuy Pinnacle hip implant litigation has the potential to become just as large as that surrounding the DePuy ASR device.
Now, about 57 product liability lawsuits filed against DePuy Orthopaedics over its Pinnacle device have been consolidated in the U.S. District Court for Northern Texas for a single MDL. The U.S. Judicial Panel on Multidistrict Litigation consolidated the cases on the grounds that the grouping involves similar claims

The Pinnacle device was on the market for years prior to DePuy’s ASR implant and the lawsuits allege the increased risk for adverse reactions and that these issues make the Pinnacle likelier to undergo premature failure.

Thursday, May 26, 2011

Senator Kohl's FDA's Post Market Reivew of Hip Implants Welcome But More Scrutiny Needed.


Today, U.S. Senator Herb Kohl, Chairman of the Special Committee on Aging, wrote Dr. Margaret Hamburg, Commissioner of the Food and Drug Administration (FDA) commending her Agency's recent decision to require medical device manufacturers to conduct post-market surveillance for high-risk, metal-on-metal hip implants. In his letter to Hamburg, Kohl suggests that more surveillance of high-risk devices is still necessary, particularly for devices that were approved through the FDA's fast-track review process.

Last month Kohl held a hearing examining the FDA's role in protecting patient safety as part of the medical device approval process. The hearing featured testimony from Ms. Katie Korgaokar, a Denver resident who received a DePuy ASR hip implant to treat a congenital condition called Perthes disease. In 2010, the DePuy hip was recalled and Korgaokar endured a second hip-replacement surgery in early 2011. Korgaokar was one of 96,000 patients affected by the DePuy hip recall.

Kohl writes: "As stated in the hearing, it is unacceptable that so many high risk, Class III devices continue to be approved through the 510(k) process.

"However, it is encouraging that, during our hearing, FDA pledged to finish either reclassifying the devices or requiring Premarket Approvals (PMAs) for Class III devices currently considered through the 510(k) process. Completing this review is essential to protect the public health."

The April 13th Aging Committee hearing is archived online here.

Full text of the letter copied below.

May 24, 2011

Dr. Margaret Hamburg
Commissioner
The Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993

Dear Commissioner Hamburg:

I applaud your decision to require medical device manufacturers to conduct post-market surveillance for high-risk, metal-on-metal hip implants. The Food and Drug Administration's (FDA) use of its 522 regulatory authority will help improve our understanding of the health risks metal-on-metal implants pose to patients. FDA should continue to advance its surveillance of high-risk devices, especially those that have been approved through the fast-track, 510(k) process.

As you know, last month, the Special Committee on Aging held a hearing entitled, "A Delicate Balance: FDA and the Reform of the Medical Device Approval Process," in which Dr. William Maisel of FDA participated. The hearing highlighted the problems with metal-on-metal hip implants. A victim of the DePuy ASR hip implant recall, Katie Korgaokar, testified to the distress she experienced with revision hip surgery as a result of the faulty hip implant.

As stated in the hearing, it is unacceptable that so many high risk, Class III devices continue to be approved through the 510(k) process. However, it is encouraging that, during our hearing, FDA pledged to finish either reclassifying the devices or requiring Premarket Approvals (PMAs) for Class III devices currently considered through the 510(k) process. Completing this review is essential to protect the public health.

Metal-on-metal hip implants are an example of these Class III devices being cleared through 510(k). It is imperative for patient safety that Class III devices like metal-on-metal hip implants have appropriate review before being marketed to patients, and rigorous oversight once the devices are marketed.

Again, I applaud and support FDA's efforts to protect the public health through more vigorous post-market surveillance. I look forward to continue working with FDA to improve post-market device oversight, specifically to ensure that there is adequate post-market surveillance of high-risk devices, like the metal-on-metal hip implants.

Sincerely,

Herb Kohl
United States Senator

Source:
U.S. Senator Herb Kohl

Wednesday, May 25, 2011

Metal Artificial Hips May Need A Hip Check

Nice article in the NPR morning edition.  Reprinted in full below

by Patti Neighmond

May 23, 2011
The Food and Drug Administration has told companies that make "metal on metal" artificial hips to take a closer look at how patients fare after their hip replacement surgery. The request involves about 20 manufacturers.

The request comes in response to an increasing number of consumer complaints about the implants, along with last year's voluntary recall of an all-metal model made by DePuy Orthopaedics, a division of Johnson & Johnson. Company officials say the company is paying for "reasonable and customary costs of monitoring" the recalled product, including the cost of surgery, if needed, to replace damaged artificial hips.

There are many varieties of hip implants, and numerous materials are used in their construction, including ceramics, plastics and metals. In the case of all metal implants, both the ball and socket of the artificial joint are made of metal. When those two parts rub together during normal wear and tear, minuscule particles of metal can shed and be released into surrounding tissue and even into the bloodstream. This can cause severe damage to local tissue, including necrosis, infection and allergic reactions.

A diagram of a total hip replacement.
Courtesy of the American Academy of Orthopaedic Surgeons A diagram of a total hip replacement.

FDA officials say there have also been rare reports of enough metal released into the bloodstream to cause problems with a patient's heart and neurological system.

Dr. William Maisel, chief scientist at the FDA Center for Devices and Radiological Health, which regulates hip implants, says there is no consensus in the scientific community about how much metal in the bloodstream is harmful.

He hopes the follow-up studies by hip-device manufacturers will help answer that question, along with a number of other queries. Specifically, the agency has asked companies to answer the following: How long do the hips last? What types of problems are patients having with the hips?

The FDA is also asking companies to collect blood samples from patients with all-metal hip implants in order to better understand exactly how much metal may be released into the bloodstream.

Dr. Joshua Jacobs, chairman of Rush University Medical Center's orthopedic surgery department and an official with the American Academy of Orthopaedic Surgeons, says it's important to remember that artificial hips are the single biggest advance of the century in the treatment of debilitating arthritis.

Prior to hip replacement, Jacobs says, patients had limited options and were often "condemned to a life of pain, immobility and lack of function." They couldn't work, he says, and couldn't participate in society.

Orthopedic surgeon Joshua Jacobs examines patient Ali Hussein who recently received an artificial hip with a plastic lining between a metal ball and socket.
Enlarge Jennifer Brandel for NPR Orthopedic surgeon Joshua Jacobs examines patient Ali Hussein who recently received an artificial hip with a plastic lining between a metal ball and socket.
 
Even amid concerns about certain models of artificial hips, Jacobs says most patients have no problems and are doing extremely well with their new artificial hips.

"The majority of patients who have these implants do not need to have them removed," he says. "They just need to make sure they have periodic follow-up with their physician."

And, Jacobs adds, they should be "mindful" of any changes like pain, numbness or swelling. If these occur, Jacobs suggests that patients visit their doctor, who will likely do an exam and take X-rays or ultrasounds of the hip and some blood samples.

Today, Jacobs says, researchers are working to develop sturdier implants that won't be vulnerable to wear and tear and will last longer than 15 years, possibly as long as 20 or 30 years.

Tuesday, May 24, 2011

Great discussion on video in 2005 re the issues surrounding the the Depuy hip and issues hip early on

I highly recommend looking at these videos if you are interested in the key issues and allegations surrounding the Depuy hip.

Short overview:

In search of more durable hips, surgeons began using the MOM devices.  A new hip prosthesis called the Birmingham Hip Resurfacing had entered the market in Europe in 1997 and was gaining tremendous market traction.  That prosthesis was purchased by Smith and Nephew.   Depuy had to design a better product so that it didn’t loose market share.  Competition between manufacturers spurred Depuy to develop its ASR in 2003.  A successful marketing campaign would be crucial to persuading surgeons to change from the BHR to the ASR in Europe.

There are two tapes:

·         The first tape is what I would consider to be  a pro Depuy pitch. 

·         The second tape is a detailed account of all of the issues regarding the Depuy prosthesis. 

This is the URL to the presentations: http://www.mcminncentre.co.uk/research-lectures-debate.html    


·         Click on the “case for ASR” which is the case FOR the Depuy hip.


o    Maximum bone preservation


o    Lower wear


o    Precise tissue sparing during surgery


o    Better range of motion


o    Reduction in wear due to increased fluid lubrication


  Once you listen to that,


·          Click on the “case for BHR” which is a clearly articulated case against Depuy and for the BHR.


o    Dupuy has the following issues:


§  Design issues


§  Material issues (as in materials used in the hip)


§  Instrumentation issues


§  Acetabular component is too thin


§  Clearance is dangerously small


§  Heat treated metal increases wear


§  Femoral component cement risks loosening


§  Primitive instrumentation risks component malpositioning.


§  4x the revision rate of BHR


§  “critical redesign is urgently required”


Remember, these discussions took place in 2005!

Monday, May 23, 2011

Additional study done post mortem illustrating Asymptomatic Osteolysis after Death

Bottom line of this study: The patients reviewed in this study died between three and ten years after arthroplasty, and six of the seven were asymptomatic at the time of death. The postmortem findings however showed osteolysis and/or lymphocytic infiltration associated with eight clinically well-functioning, low wear devices....yet another illustration of the "Silent Pathology" involved with these MOM hip replacements.


J Bone Joint Surg Am. 2010 Jul 21;92(8):1720-31.
Postmortem study of femoral osteolysis associated with metal-on-metal articulation in total hip replacement: an analysis of nine cases.

Source

Institute of Pathology and Bacteriology, SMZ Otto Wagner Spital, Baumgartner Hoehe 1, 1145 Vienna, Austria. Monika.Huber@wienkav.at

Abstract

BACKGROUND:


Improved metal-on-metal articulations were reintroduced in total hip replacement to avoid the osteolysis sometimes seen with conventional ultra-high molecular weight polyethylene bearings. Osteolysis and local lymphocytic infiltration have been reported at revision of some metal-on-metal devices. We report similar and additional results in a study of second-generation metal-on-metal hip implants retrieved post mortem.

METHODS:


Components and surrounding tissues were collected post mortem from seven patients with nine total hip replacements (Zweymüller SL stem with an Alloclassic cup) with Metasul metal-on-metal articulations. All available patient information was recorded. Radiographs of the hips were evaluated for osteolysis. Sections of joint capsule as well as of the femoral implant with surrounding bone were reviewed, and energy-dispersive x-ray analysis was used to evaluate the composition of wear products. The amount of wear was measured for each component (nine femoral heads and eight cup inserts), when possible, by a coordinate measurement machine with use of the dimensional method.

RESULTS:


The patients died between three and ten years after arthroplasty, and six of the seven were asymptomatic at the time of death. One patient, with the highest rate of total wear (i.e., wear of femoral head and acetabular cup; 7.6 microm/yr), had increasing hip pain for one year, and histological analysis confirmed the radiographic findings of osteolysis. For two other patients, histological analysis confirmed the radiographic findings of asymptomatic osteolysis. For three patients, histological analysis revealed osteolysis that had escaped conventional radiographic analysis. Joint capsule tissue showed evidence of metallosis in all hips and local lymphocytic infiltration in eight hips. Energy-dispersive x-ray analysis revealed elements attributable to CoCrMo alloy in all hips and traces of corrosion products in three hips.

CONCLUSIONS:


The postmortem findings of osteolysis and/or lymphocytic infiltration associated with eight clinically well-functioning, low wear devices (a total wear rate of <4 microm/yr) suggest there may be frequent, unappreciated femoral bone loss and local immunological response in patients with second-generation metal-on-metal hip implants. Compared with previous postmortem studies, our findings showed the extent of osteolysis was similar to that with metal-on-polyethylene articulations.

Saturday, May 21, 2011

Induction of apoptosis and necrosis by metal ions in vitro.

I have been reviewing the past articles re the immunology issues associated with the high ions in the blood. This journal article was published back in 2004.  So, its now 2011 and the research is still looking at the same issues in vitro.  the article I published yesterday is one example of that. Still talking about cell death observed when the ion exposure and ion concentration is prolonged.  Still talking about ion toxicity with these metals and still it appears that little progress has been made between this study published in 2004 and the one I published yesterday in 2011....7 years later.  What am I missing here?

Perhaps this Depuy suit will spur increased research in this area?

Source

Division of Orthopaedic Surgery, McGill University, Lady Davis Institute for Medical Research, The Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.

Abstract


There has been a renewed interest in the use of the metal-on-metal (MOM) implants for total hip arthroplasty (THA). It is well known, however, that the MOM articulation generates both metal particles and ions. The physiologic effects of these ions are poorly understood and their potential toxicity remains a cause for concern. In the present study, murine J774 macrophages were incubated with Co2+ and Cr3+ ions and the mode of cell death (apoptosis/necrosis) was evaluated in vitro by transmission electron microscopy and cell death ELISA. Overall, results demonstrated that the mode of cell death was dependent on the ion concentration and the incubation time. Indeed, at short incubation times (24 h), the noninflammatory process of apoptosis was predominant. At longer incubation times (48 h), however, necrosis was predominant at higher ion concentrations.

Friday, May 20, 2011

Interesting research re the MOM hip issues: Chromium 3 vs Chromium 6?

I have blogged extensively on the confusion surrounding Chromium 6 (the toxic form of Chromium) and Chromium 3, purportedly the non toxic form of Chromium found in the Depuy hip.  As mentioned previously, Chromium seems to have the ability to oxidize from 3 to 6 and vice versa. Thus far,  reported cases of this  oxidation  have occurred  only under specific industrial conditions.

 I noted two really interesting studies published with one investigator in common; Professor Mary Grant in Glasgow Scotland  m.h.grant@strath.ac.uk.  She resides in the biomedical engineering department and specializes in Cell & Tissue Engineering,and Xenobiotic Metabolism and Toxicity.

My question is why are they studying the effects of Chromium 6 in metal implants when the metal in these implants is suppose to be chromium 3 (the non toxic type?)

In 2009 she published a study Response to chronic exposure to hexavalent chromium in human monocytes. 

 The question she reviewed was depletion of lymphocytes has been reported in vivo in patients with metallic prostheses, and correlated with elevated chromium and cobalt concentrations in blood. However, the implications for immune function were unclear. [Important because lymphocytes fight infection.  Prolonged inflammation from infection can result in long term  issues. ]

She assessed the in vitro responses of human monocytes to chronic exposure (4 weeks) to Cr (VI) ions at concentrations which have been measured in patients with metal artificial hip implants (0.05-0.5 microM).  She found that chronic exposure to these low clinically relevant concentrations of Cr (VI) induced a potent adaptive response on a cellular level and concluded that such direct toxicity of Cr ions may contribute to the effects of metal implants on lymphocyte populations in vivo.

In May of 2011, she was a co author of another journal article; Effect of chromium and cobalt ions on primary human lymphocytes in vitro.

The exposure of resting lymphocytes to 100 µM Co(2+) resulted in significant decrease in  cell viability accompanied by a significant increase in apoptosis (cell death.)  The results indicate that exposure to high concentrations of metal ions initiate apoptosis that results in decreased lymphocyte proliferation (can’t fight infection/compromised immune system.)

 Her conclusion: metal ion concentrations not directly cytotoxic to lymphocytes may affect events at a molecular level, thereby impeding lymphocyte proliferation. Hence, this may contribute to altered immune system function in patients with Co-Cr implants.

You would think that studying Cr 6 is a non issue for orthopedic implants.  Guess not!

Wednesday, May 18, 2011

What did Depuy know and when did they know it?

There are many questions to address in the litigation with Depuy.  One of the questions is "What did Depuy know and when did they know it?  I ran across an article that was just published in the British Medical Journal which  addresses this question  by an investigative reporter for the BMJ.  Its a pretty good article and would suggest you read it below.  It surely provides quite a bit of insight into the question as to when Depuy became aware of this issue with their hip.

http://www.bmj.com/content/342/bmj.d2905.full  You can go directly to the URL if you wish as the videos in the article may not copy well into this format.

BMJ 2011; 342:d2905 doi: 10.1136/bmj.d2905 (Published 14 May 2011)
Cite this as: BMJ 2011; 342:d2905                                                              
                              

Out of joint: The story of the ASR

                             
Deborah Cohen, investigations editor   dcohen@bmj.com
    1BMJ, London WC1H 9JR, UK  
                                                                       
    Why did it take so long to recall from the market a hip implant after it became apparent that it was causing pain and disability in patients. In an investigation for the BMJ, Deborah Cohen describes how companies dictate the fate of their own devices and exert an unduly strong hold over surgeons.
    It is one of the biggest disasters in orthopaedic history, according to one senior surgeon. On 24 August 2010, DePuy, a subsidiary of American giant Johnson and Johnson, recalled its ASR (articular surface replacement) hip prostheses from the market. The recall followed years of denial by the company that the ASR implants had caused pain and disability in patients. In a statement to the BMJ, DePuy claim that “given the available information, we believe we made the appropriate decision to recall at the appropriate time.”

    Pathologically, the failing prosthesis had several effects. Metal debris from wear of the implant led to a reaction that destroyed the soft tissues surrounding the joint, leaving some patients with long term disability. Ions of cobalt and chromium—the metals from which the implant was made—were also released into the blood and cerebral spinal fluid in some patients.1

    The long term effects are uncertain. But the US Food and Drug Administration recommends that patients should be monitored for systemic effects, particularly cardiovascular, neurological, renal, and thyroid signs and symptoms.1

    With more than 93 000 ASR implants sold and ongoing litigation in many countries, the situation may prove costly for DePuy. And if lessons are not learnt from this latest episode in the chequered history of hip implant failures, it may also prove costly for the reputations of the regulators and the orthopaedic community.

    The ASR is not the first hip implant to be recalled—there have been many others. One such recall in the late 1990s—the 3M Capital Hip—prompted questions about European device regulation2 and a parliamentary investigation by then health minister, Lord Hunt.3 But nor may it be the last—concerns are now being raised about the failure rates of other metal on metal hip implants.4

    Metal on metal

    The ASR is a “metal on metal” hip—the head at the top and the lining of the cup it fits into are made of cobalt chrome metal rather than ceramic or polyethylene. The devices come in different sizes according to the existing anatomy and there are forms for both total hip replacement (ASR XL) and hip resurfacing (ASR resurfacing).

    Hip surgery

    • Total hip replacement surgery—The femoral head is removed and replaced with a prosthetic ball made of metal or ceramic, and the acetabulum is replaced with a prosthetic cup. The cup consists of one or two components made of metal, ceramic, or plastic. A stem is also placed in the femur to support the femoral head
    • Hip resurfacing surgery—The femoral head is trimmed and capped with a metal covering. Any damaged bone and cartilage within the acetabulum are removed and replaced with a metal cup 
    The conventional total hip replacement consists of a metal head with a polyethylene cup. But these joints don’t last forever. Over time the plastic cup wears away against the hard metal head. Younger, more active people are especially likely to require early revision surgery to replace the worn out joint. 5

    In search of a more durable option, surgeons turned their attention to the development of joints using a metal head against a metal cup. Not only would metal be much harder wearing, but advancements in manufacturing meant that the metal could be produced with incredibly smooth surfaces. Complicated physical phenomena dictate that these smooth bearing surfaces trap a layer of fluid between them. So in perfect circumstances, the metal surfaces do not touch and the surfaces wear very little. And, in theory, the quicker the patient moves the thicker this fluid layer becomes, ensuring even less wear.6 7
    Competition between manufacturers spurred DePuy to develop the ASR. A new hip prosthesis called the Birmingham Hip Resurfacing (BHR), designed by UK surgeon Derek McMinn, had entered the European market in 1997 (the FDA approved it in 2006), and was proving popular. Smith and Nephew acquired it, and DePuy had to design a better product so that it didn’t lose market share. The attempt to prise surgeons away from the BHR led to fractious competition between the companies, which was reflected in their marketing campaigns.
    (go directly to the link to see the video.)
    Jennifer is a patient who has received an ASR replacement hip. (Channel 4, Dispatches)

    Simulator testing

    Both forms of the DePuy ASRIIb device, which meant they didn’t need to be tested in patients before entering the EU market.

    DePuy followed and met the European standards. These provide guidance on how to conduct simulator studies to test how well the implant wears. According to DePuy, it conducted laboratory testing “including tests on simulators that evaluate how the device wears over time, the materials used in the device and device strength.”

    But exactly what information the company submitted is not open to public scrutiny—the scientific rationale is held by the company and by the notified body—one of several private organisations that do the premarket approval on behalf of EU governments.8 In this case the notified body was the British company BSI.9

    The UK Medicines and Healthcare Products Regulatory Agency (MHRA) says that clinical studies may be too small and short to detect problems for premarket approval purposes. But clinical tests with relatively short follow-up may have picked up problems with the ASR. According to David Langton, a surgical researcher at the University Hospital of North Tees and Newcastle University who has been studying the ASR, problems in some patients first emerged about two years after implantation.10
    The absence of any clinical studies of implants in patients before approval remains a cause for concern—much like it was over 10 years ago with the 3M Capital hip.2

    “The reason they get on to the market is that they look and smell like a joint replacement,” says Stephen Graves, orthopaedic surgeon and director of the Australian National Joint Replacement Registry. Professor Graves thinks that simulator testing should not be relied on entirely to see if a device will function well when you use it in a person. Indeed, a recent Smith and Nephew backed paper suggests that simulators do not really represent the biological environment.11

    “Before a hip or knee replacement is placed onto the market it should have been used in a limited number of people who had been monitored very carefully for a number of years,” Professor Graves says, adding “the outcome of that monitoring would indicate that the device is actually working very satisfactorily in that small group of patients.”

    Professor Graves thinks this would not only protect patients but also the company. “They [clinical studies] may well prevent a situation where they have a device that is not performing anywhere near as well as they would have hoped,” he says.

    ( go directly to link to see the video)
                                       
    Deborah Cohen interviews Stephen Graves, orthopaedic surgeon and director of the Australian National Joint Replacement Registry (Dispatches, Films of Record.)

    Problems emerge

    Although the ASR resurfacing made it onto the European market, it was not approved in the US. Resurfacing was a new technique and so the implant had to go through the FDA’s more rigorous premarket approval process. This requires manufacturers to submit their product to clinical testing to prove it is both safe and—unlike the European process—effective for its intended use. The FDA asked DePuy to perform a clinical study called an investigational device exemption (IDE).

    Tony Nargol, an orthopaedic surgeon at the University Hospital of North Tees, was one of the surgeons involved in the studies for the American market. But not everything was going to plan. As internal DePuy emails show, he reported problems with fractures in some of his patients. The FDA sent detailed questions to the company.

    “You have not provided any explanation why this experienced investigator may have had a higher femoral neck fracture rate in this IDE study. It is concerning that an experienced surgeon who is familiar with patient selection criteria and surgical technique would have the highest neck fracture rate,” it said.

    So problems were being picked up in the premarket clinical study—despite some insisting that these studies are too small for this purpose. Surgeons experienced in the resurfacing technique should not have a fracture rate of more than 1% a year.12 Yet according to a June 2008 document from the French health agency Haute Autorité de Santé, this two year follow-up study had a 4.9% fracture rate in the ASR resurfacing arm. And the two year survival of the implant was 95.9% (95% confidence interval 93.5% to 99.9%) when only 25.6% of people in the group were women—who typically fared worse with the prosthesis.9 The French agency concluded in 2008 that given the data and the alternatives it would not fund the ASR resurfacing. But it was still being used in the NHS.

    DePuy’s response to the FDA questions shows its close relationship with the surgeons it chooses to participate in its regulatory studies and the hold it believes it has over them. The company assigned the list of questions to one of its marketing representatives with experience in regulatory affairs. It asked the representative to formulate the answers and ask Mr Nargol to sign the document if needed. In the end the company withdrew its application and the ASR resurfacing was never approved by the FDA.
    But this did not stop US surgeons from using it “off label.” Rita Redberg, editor of Archives in Internal Medicine and a cardiologist, has studied the US device regulatory system and testified to recent Congressional hearings.

    “Patients have a right to know what the risks and benefits of any procedure are for them. If a device is used off label, it generally means there are not good data to support its use for that indication. That is information that should be discussed in the informed consent process. These discussions are particularly important for an implanted device, which cannot easily be removed,” she says.

    Similar equivalence—a flawed approach

    Although the FDA’s premarketing approval process requiring a clinical study may have protected patients from the widespread uptake of the failing ASR resurfacing prosthesis, the same could not be said about ASR XL, the total hip replacement. This passed through the FDA’s 510(k) clearance process via the “similar equivalence” route, whereby companies need only to show that their product is similar to something else on the market. Even a small change in design can have a substantial effect on long term outcome.13

    Critics say that the similar equivalence route is not nearly stringent enough.14 Yet this is how 90% of devices gain US approval.15 Companies say that toughening up the approval process will be bad for patients—they will be denied access to new improved technologies that are available elsewhere. But can this be true in a market saturated with hip prostheses? Isn’t there an argument that the bar for market entry should be raised? According to data from the 2010 Australian Joint Registry report, there are more than 1539 stem and acetabular combinations for total hip replacement, but only 72 are commonly used (defined as having been used in more than 400 recorded procedures).16
    Yet, companies scarcely let a year go by without introducing a “new improved” joint replacement which “offers undreamt of (and unproved) advantages over the older designs.”17

    The same is true in other fields. Alan Fraser, an interventional cardiologist at Cardiff University, says: “I think any doctor who is treating patients is keen to try to stay up to date and use the most recent advances. And indeed, I think there is a tendency for doctors to want to use whatever the latest new technology is, and perhaps not always to be critical as to whether or not it’s really been thoroughly evaluated.”

    The desire to use something newer, smaller, and shinier might well trump the evidence base. And nearly 20 years ago an editorial in the BMJ warned that this “fashion trade” in joint replacements is costing the health service many millions of pounds each year and, even more important, is causing patients unnecessary pain and distress through early failure of unproved implants.17 And judging from the recent history of joint failures, it seems not much has changed.

    Surgeons and the company

    Surgeons involved in the design of a device can make large sums of money. One of the surgeons involved in the design of the ASR, Thomas Schmalzried, medical director of the Joint Replacement Institute in Los Angeles, received just under $3m (£1.9m; €2.1m) in royalties during 2009-10 alone. In the same period, another of the designers, Thomas Vail, University of California San Francisco professor, received just over $500 000. Figures are not available for the other designers—their respective countries do not have the same legislation about transparency of company payments as the US.
    Royalties are legal, as are consultancies, research fees, and stock options. But some companies have been in trouble for providing other kinds of payment.

    Four years ago, four of the major orthopaedic companies in the US were fined about $311m for paying doctors to use their products.18 And last month, DePuy was ordered by the UK court to pay almost £5m for similar unlawful payments in Greece between 1998 and2006,19 while Johnson and Johnson was fined $21.4m by the US court for making “improper payments to publicly employed health care providers in Greece, Poland and Romania in order to induce the purchase of medical devices and pharmaceuticals” made by their subsidiaries—including DePuy.20

    Charles Rosen, professor of orthopaedic surgery at University of California, Irvine, School of Medicine, says companies try to find a relationship to keep you using that product. “It could be in the form of maybe having you as a consultant with the company for a certain amount per year and then you feel obligated to continue using that product. Or have you lead courses in how to use that drug or that device and reimburse you for that and tie you up to become an advocate as well as a user of that product,” he says.

    At the time of the launch of the ASR, DePuy was behind in the sales stakes and it would have to turn to its design surgeons. The ASR’s design surgeons located in several different countries acted as key opinion leaders, promoting the new device. They led educational programmes, published papers in journals, spoke at company dinners, and presented at conferences promoting the ASR.

    Marketing campaign

    A successful marketing campaign would be crucial to persuading surgeons to change from the BHR to the ASR resurfacing in Europe. Among its many strategies, DePuy ran simulator tests on its prosthesis and its competitor. The pictures appeared to show that the ASR produced less metal wear debris than the BHR—the ASR fluid was clear whereas the BHR was sitting in a dark metallic stained fluid. An accompanying journal article indicated that the ASR fluid had been changed and the pictures of the two devices had been taken at different time points.21 22 Yet these pictures were used by sales representatives for marketing purposes divorced from the accompanying article and might have been misleading.23 When we put this to DePuy, it said that it would not respond to “speculation.”
    But in the absence of publicly available data and no independent assessment of study summaries in Europe, manufacturers are able to interpret and promote their studies as they wish. This is in stark contrast to the US, where devices can only be marketed for a clinical claim that is included in labelling that has been reviewed by the FDA. Even the MHRA does not routinely collect any premarket clinical data. This means that clinical claims are difficult to verify.

    Tony Nargol was one of the surgeons who was persuaded to change from the Birmingham hip after being shown the pictures by DePuy in 2004. As internal emails show, the company targeted him because he was known to be a big user of the BHR.

    “They said the ASR would last considerably longer than a Birmingham [Hip Resurfacing],” Mr Nargol said. He described the simulator test he was shown. “After a while the BHR went all black. It looked like metal had come off the bearing and it looked abnormal. And there’s a clear difference between the two and it was very persuasive. And I know a lot of surgeons round the world were very persuaded by this.”

    Device failure or surgical technique?

    A few years later, Mr Nargol started to notice problems with the ASR. In early 2007, some of his patients reported groin pain and difficulty walking. He got a shock when he opened them up to revise their prostheses. “The soft tissues and muscles around the hip were destroyed.” He noticed a pus-like fluid coming from the capsule. Initially he put it down to infection. But cultures were negative. “And then we went on to find cases where the bone was starting to get destroyed as well,” Mr Nargol said.
    Other surgeons also mentioned problems with the device. But according to Mr Nargol, some of those with ties to DePuy declined to report what they were seeing and simply stopped using the device.
    He raised his concerns with the company, and asked whether anyone else was having problems. As internal emails show, company managers hoped to pass this off as a failure of surgical technique—even though he was an experienced resurfacing surgeon. “I’m sure that the complications that Tony has experienced are wholly related to interoperative surgical technique compromises and I’m sure if managed effectively we can ensure that the published presented data from North Tees draws this conclusion and more critically clearly illustrates that it is not a device related complication,” an email said.

    Professor Graves says this response is not wholly surprising. “There’s a natural tendency for companies [to think] it’s probably factors other than a device, because they have invested a lot of time in it . . . It does take some time on occasions to convince a company that there may be problems with the device.”

    The high revision rate of the ASR should not have come as a surprise to the company or to the regulators. In 2005, Mr McMinn—designer of the Birmingham Hip Resurfacing—participated in a debate in Helsinki pitching the prosthesis he had created against the ASR. While Mr McMinn’s arguments primarily focused on his prosthesis, he described in detail what he perceived to be the ASR’s design flaws that would later lead to its demise.11 24 25 26 27 28 29

    He criticised the shallowness and the rim on the inside of the cup and the manufacturing processes used, all of which, he said, could lead to increased wear. The design changes, he said, would mean the prosthesis would be less forgiving of surgeon technique—something which, some argue, should be factored into the design of a successful device.30

    Mr McMinn says DePuy were “certainly aware of this lecture” and the “president wrote to me in a non-friendly tone ‘advising’ me to remove this talk from my website.” He declined to remove it and it’s been there ever since. DePuy chose not to comment on this allegation.

    The company was also aware of raised blood levels of metal ions. At a conference in Dallas in 2007 one of DePuy’s engineers gave a presentation, seen by this investigation, of two year follow-up data that showed 30% of women and 7.5% of men had markedly raised metal ion concentrations in their blood. Even though the procedures in the study had been performed by the design surgeons—who would be expected to position the device with the most precision—the presentation concluded that surgical technique was to blame.

    The following year, in 2008, Mr Langton, who had been analysing both the ASR and the BHR, gave a presentation at the British Orthopaedic Association conference in Liverpool describing the problems caused by the shallowness of the ASR cup. This, he said, was leading to increased wear as the edge of the cup rubbed against the head. DePuy representatives were at the meeting.

    Registry data also dismissed

    By 2007, individual surgeons were not the only people noticing problems. The Australian National Joint Replacement Registry reported that the ASR had a high revision rate. The registry was set up to spot “outliers”—prostheses that have twice the rate of revision of others in their class. All hip prostheses fail in some patients, but it is expected that the rate will be about 1% a year. The Australian data showed a 5.16% (95% confidence interval 3.50% to 7.56%) revision rate at two years.31
    The registry uses revision as the primary outcome to identify implants that aren’t performing as well as they should. Of course, it’s only one measure of how well a joint performs, but according to Professor Graves, it’s an “unambiguous end point—nobody can argue about [it].”
    But that’s precisely what DePuy did. According to Professor Graves, when the registry first notified DePuy about the high revision rate, the company released a safety warning to surgeons saying that positioning was important.
    Over the next three years, DePuy used a range of techniques and arguments to try to assuage fears arising from the evidence generated repeatedly by the Australian registry and surgeons themselves.16 31 32
    According to a presentation Professor Graves gave at a meeting in Glasgow, the Australian joint registry warned the Australian regulators and DePuy 17 times about problems with the ASR between 2007 and 2009.

    But, according to internal company documents, concerns were explained away and sales representatives were instructed to keep on marketing the product. To counter the Australian registry’s findings, internal documents show that DePuy sent out a “white paper” by one of the ASR design surgeons, Professor Vail, explaining how to interpret the Australian data.

    It said that the Australian data did not account for the surgeons’ learning curve with resurfacing. The Australian rates were almost double those of the “international surgeon design team at two years,” it added. In order to “set the record straight” the sales representatives were told to tell surgeons about a paper detailing the American experience with the BHR, which reported an adverse event rate of 4.9%, which they claimed was higher than for the ASR.33 Their marketing team also quibbled with the exact definition of the term “revision” used by the Australian registry.

    Surgeons carrying out a lot of operations had the same failure rates as those doing only a few, Professor Graves says. So their findings totally contradicted DePuy’s assertion that surgical experience and patient selection were to blame. “We were quite strong in our conclusion,” says Professor Graves, “We thought it was the device.”

    Meanwhile the North Tees team—including Mr Nargol and Mr Langton—were keeping DePuy updated about the problems they were finding and their data, as internal emails show. At a meeting in Norwich in 2008, they gave a presentation reporting the cases of 10 women with soft tissue reactions who had significantly increased metal ion concentrations in their blood and high joint fluid metal ions. Representatives of both DePuy and the MHRA attended.

    Before presenting the data, Mr Langton had sought advice from a senior surgeon—who, according to internal emails, had instructed DePuy on promoting the ASR. He advised Mr Langton to keep quiet. “He told me, ‘you have great data which will allow you to travel the world. But my advice would be not to present it at the Hip Society. I would go to DePuy and suggest a consultancy role with them. You can earn a lot of money just for doing nothing. I have done this a couple of times in the past with previous research,’” Mr Langton said he didn’t take the advice.

    Targeting women

    One paper—published in mid-2008 and seen by DePuy before submission—showed that several of the ASR patients had raised chromium and cobalt concentrations in their blood. In some patients, these concentrations were 100 times greater than normal physiological values.34
    It was also clear from these data that patients implanted with smaller ASRs, used mainly in women, were more likely to develop higher metal ion concentrations—as DePuy’s own presentation in Dallas the year before had shown.

    Yet this was the group of patients targeted by DePuy in an “advertorial” in the Daily Telegraph on 21 February 2008. Featuring quotes from the UK design surgeon Andrew Cobb and a young woman, Penny Brown, who said her life had been changed by the ASR, the advertorial “aimed to educate patients on their treatment options and demonstrate the unique advantages that the DePuy ASR can provide to the right patients.” Unlike prescription drugs, there is no European legislation preventing direct to consumer advertising of devices.

    According to John Nolan, orthopaedic surgeon at Norfolk and Norwich Hospital, patients were keen to have resurfacing. They would see adverts for it on the internet. “The emergence of resurfacing hip surgery coincided with the increased use of the internet to advertise hip replacement surgery on websites that were not peer reviewed. As a result, patients would request resurfacing surgery when it was not appropriate. I believe the surgeon has a professional responsibility to advise the patient accordingly and to decline the procedure when the correct indications are not present,” he said.
    And rather than advise surgeons not to use the ASR in women—DePuy merely instructed surgeons to be careful how they put the cup part of the implant in— again refusing to believe that it might be the device that was giving rise to the large increases in chromium and cobalt concentrations. Mr Langton was even told by a DePuy sales representative that good sources had told them that an illegal chromium ship unloaded its cargo in the river Tees a couple of years earlier and that was the reason for the raised chromium and cobalt levels he was finding in patients’ blood. DePuy declined to comment on this allegation.

    But it was the threat of losing a valued surgeon to their rival that made DePuy really start to take note. Panic started to set in in early 2009. In an email written in capitals, a local sales representative wrote: “Tony Nargol has said he will no longer use ASR at Hartlepool and instead will use BHR.” The company had calculated the value of his custom—over a quarter of a million pounds in 2008. The representative said they would “work as closely as possible with Tony and to move him to Silent [another DePuy implant] as soon as possible to brickwall the account against competitors.”
    Later that year, DePuy was still in denial about the extent of the problems and was providing a counter argument to any concerning data. An internal email from March 2009 reported on outreach to surgeons. “All major XL users have been seen over recent weeks and are happy with their results.”

    Reporting adverse events

    But not all surgeons were happy, and their revision rates were far higher than they ought to be. Shouldn’t the regulators have stepped in to remove the product from the market and stop those who were purportedly happy to continue to implant the ASR?

    In the UK, the onus is on manufacturers, doctors, and patients to report problems directly to the MHRA—and the MHRA itself has been critical of the deficiencies in postmarket clinical follow-up.35 According to the Association of British Healthcare Industries, manufacturers capture and analyse information from a variety of sources—clinical follow-up, registries, published and unpublished literature, expert meetings, and complaints.
     
    The MHRA told the BMJ that it is the “manufacturer’s responsibility to monitor the performance of their devices, for as long as they are in use, and to ensure these devices continue to be safe and suitable for clinical use. If in the light of this evaluation, the manufacturer establishes that products should not be used, the manufacturer should take the necessary steps to ensure patient safety.”
    But, in the case of the ASR, they chose which evidence to believe. And we have no way of knowing if doctors and patients reported adverse events to the regulator or what kind of postmarketing surveillance was required of the company.

    The BMJ and Channel 4 Dispatches filed a Freedom of Information request asking the MHRA for reports of adverse reactions to the ASR. This was declined under medical directive legislation that keeps all device regulatory affairs confidential. Nor could we access documents that would show what kinds of discussions the MHRA or the notified body were having with the company.

    Role of MHRA

    They knew that there were concerns about the risks of metal debris from wear of orthopaedic metal implants. In March 2006, an expert advisory group at the MHRA discussed the issue. “There is evidence to suggest that some metal on metal hip replacements may be associated with increased DNA-changes, which might result in genotoxicity in patients.”36 But it was not known whether there were any clinical implications of the findings. “The benefits of such implants are real. Whereas the discussed risk is theoretical and unquantifiable, but definitely low,” it said.                              
    But the agency knew it was a sensitive topic. Before the paper was presented, the chairman stressed the importance of confidentiality, adding that “anyone who felt they were unable to keep this matter completely confidential was asked to leave the room.”

    Despite the raft of data being published in both the medical literature and as formal registry reports over a number of years, the ASR was left on the market. No one from the MHRA contacted Mr Nargol and Mr Langton to follow-up their data despite the MHRA having a group specifically to look at metal on metal concerns for several years.

    At the end of 2009, DePuy voluntarily recalled the ASR in Australia. But, according to Professor Graves, their registry reports had influenced the practice of the Australian surgeons and the number implanted had already dropped.

    But it remained on the market in the rest of the world. Confused by the apparent inaction by the MHRA, in April 2010 a team from University Hospital of North Tees directly approached the agency to force it to acknowledge the problems associated with the ASR. By this time they were seeing a 15% revision rate at five years and almost all patients had tissue damage to some extent.

    Mr Nargol told the investigation that the MHRA officials stopped the team’s presentation halfway through, saying they believed the team and asking what they wanted. But when Mr Nargol and Mr Langton said the ASR should be banned, the MHRA officials said they couldn’t do that as they would be sued. Instead, the MHRA sent out a medical device alert warning about all metal on metal hip implants. However, a spokesperson for the MHRA said that “the MHRA would never be influenced by the threat or possibility of legal challenge in not taking regulatory action it thought to be appropriate.”
    Shortly after, UK National Joint Registry (NJR) saw a rapid rise in the number of revisions. Up until this point there had been a rate of 7.5%. But this increased and they notified the MHRA. Internal company documents show that DePuy had decided to phase out the ASR globally by the end of 2010 for “commercial performance” reasons. In a statement to the investigationDePuy said that this decision “was not related to any concerns about product safety.”

    “At the time of the decision, data available to DePuy indicated that the revision rate of the ASR Hip System was similar to that reported for other large diameter metal on metal monoblock and resurfacing hip devices, ” the company said. “Because the decision was based on business factors, not safety concerns, the timing to discontinue sales differed from country to country.”

    Recall of the ASR

    But in the end, DePuy “voluntarily recalled” the ASR in August 2010, saying the recall was due to unpublished NJR data showing a 12% revision rate for resurfacing at five years and an ASR XL revision rate of 13%. “Early revision of poorly performing hip replacements that generate metal debris should give a better revision outcome,” it added on the field safety notice—the means by which manufacturers alert people that a product is being recalled.
    But revision of a destroyed joint is not straightforward. Not only are patients put at anaesthetic risk once again, the revisions have a higher risk of failure.37

    And although DePuy state that it is “committed to addressing reasonable and customary costs of testing and treatment” for patients who might need revision after the recall of ASR, “including revision surgery if necessary,” there is a cost to the NHS—in some centres primary hip procedures are being put back to accommodate urgent revisions.

    But the delay in the recall might serve as a lesson to other companies. Not only will DePuy have to pay for the cost of revision in the NHS, there is global litigation that, if successful, may cost the company many billions of dollars. The last major litigation against a hip manufacturer was against Sulzer in 2002, which resulted in a roughly $1bn payout and a major net loss that year for the company.38
    But even while DePuy was offering to pay revision costs, it again used the opportunity to promote its products. An internal presentation the day before the recall went out—seen by the BMJ and Channel 4 Dispatches—said that since the ASR system was no longer available, none of the components should be used for revision. However, it said that “DePuy offers a full line of both revision and primary acetabular and femoral implants and instruments to meet individual patient needs.” For revision of both ASR resurfacing and ASR it recommends a total hip replacement. “DePuy option: Pinnacle,” it said—including the cobalt chrome metal implant. And in a briefing to the sales force it said the “Pinnacle is an alternative for the majority of patients.”

    According to Mr Nolan, this probably wasn’t the wisest thing to do. “I don’t think it is advisable, in the presence of an adverse soft tissue reaction to a cobalt chrome implant, to revise the hip replacement by using another implant made of cobalt chrome. I feel strongly that all cobalt chrome should be removed from the affected joint,” he said.

    But a much more widespread problem may be looming involving a range of other makes and models. And once again it illustrates the delicate trade-off between innovation and safety. Like resurfacing, the use of large head metal on metal total hip implants have followed another surgical trend. Heads have got larger to make them less likely to dislocate. But with this comes associated corrosion problems where the head meets the stem. “Some cemented, stemmed, metal on metal implants have shown marked corrosion of the stem and some large diameter head, stemmed implants have shown corrosion at the taper junction of the head/stem,” Mr Nolan says.

    A two year follow-up study in 144 patients published at the beginning of May this year shows an incremental increase in metal ion levels over the study period in a range of large head metal on metal implants made by manufacturers such as Zimmer, Biomet, DePuy, and Smith and Nephew.39 A letter from the British Orthopaedics Association sent out to members at the end of March says the use of large diameter metal on metal bearings in primary total hip replacement should be “carefully considered and possibly avoided.” Data now show a higher than expected early failure rate, it said. “These range from 21% revision rate at 4 years (potentially rising to 35% if all currently known painful implants progress to revision) to 49% at 6 years for the ASR XL device. Other devices have a revision or impending revision rate of 12-15% at 5 years,” it added.

    And there continues to be debate within the orthopaedic community about what constitutes a large head—one or two centres are seeing problems that others are not. As Mr Langton asked in a presentation to the British Hip Society this year: “Why is the first response not to suspend the implantation [of a device] when legitimate concerns are raised?”

    Lack of regulator power

    The story of the ASR shows the power that companies have in deciding the fate of their devices, their hold over surgeons, and the lack of regulatory power in Europe.

    The failure of the 3M hip over 12 years ago prompted calls for a device regulatory system analogous to that set up for drugs, involving clinical trials, a licensing process, and postmarketing surveillance. Some new products will always have rare and unwanted consequences—it’s an inevitable consequence of innovation. The regulatory imperative is to ensure that these are limited in scale and picked up early. A good regulatory system will benefit everybody by ensuring patients are not exposed unnecessarily to risk and that manufacturers and others are not exposed to undue liabilities.

    But will we learn from the story of the ASR and large head metal on metal prostheses? “I think we have to rethink the whole system of how devices come onto the market and whether we should be doing things a bit differently from what we are now,” Professor Graves says.

    Notes

    Cite this as: BMJ 2011;342:d2905

    Footnotes

    References