Wright Medical (NSDQ:WMGI) sought to block rival Smith & Nephew (FTSE:SN, NYSE:SNN) from getting its Birmingham metal-on-metal hip implant into the U.S. marketplace, according to filings with the FDA.
As the federal watchdog agency in 2006 was reviewing Smith & Nephew’s pre-market approval application for the device, which was the first metal-on-metal hip implant, Wright filed a citizen’s petition alleging that the study behind the PMA application was inadequate to prove safety and effectiveness.
The FDA granted 2 PMA’s to Smith & Nephew for the device, first in May 2006 and another in October of that year for additional sizes. Wright Medical itself has at least 2 entries in the metal-on-metal class, its Conserve and Lineage implants.
Wright argued that the clinical data behind the PMA was flawed because it covered only a single surgeon’s cases – the inventor of the metal-on-metal hip implant, Dr. Derek McMinn.
“The PMA for the BHR – which rests on a retrospective, uncontrolled case series at a single center by a single physician without any protocol and with incomplete follow-up – is not scientifically valid and does not satisfy the agency’s standards for safety and effectiveness,” according to an FDA filing.
"Smith & Nephew tries to create the impression that this was a multi-center trial. Yet, at the [FDA advisory] panel meeting, the acting panel chairperson stated that the data was ‘an unusual PMA based on a retrospective study designed by a single surgeon based on a British data set.’"
The implants first hit the market in 1997, pioneered in Birmingham, England, by McMinn in a back-yard shed. McMinn believed that the risk of metal ions being introduced into patients’ bodies could be minimized with a design that kept the metal surfaces apart.
Midland Medical Technologies’ Birmingham Hip Resurfacing device – Smith & Nephew acquired MMT for about $117 million in 2004 – was a popular but tightly controlled release. MMT took pains to emphasize good technique and identification of good patient candidates for the device with its hand-picked coterie of surgeons.
Marketed as the latest advance in hip replacement and targeted at younger, active patients who needed a hip that would last a whole lifetime, the implants instead put up 7-year failure rates of 11.8% for resurfacing models and 13.6% for full-hip replacements – compared with rates between 3.3% and 4.9% for implants made of other materials, according to an investigation by the British Medical Journal and BBC Newsnight.
McMinn’s invention kicked off a boomlet for MoM hips, as Smith & Nephew’s competitors rushed their versions onto the market, including Zimmer’s (NYSE:ZMH) Durom and Johnson & Johnson’s (NYSE:JNJ) Pinnacle and DePuy ASR models.
A multi-district lawsuit combining more than 1,100 personal injury lawsuits over DePuy’s Pinnacle implant is underway in the U.S. District Court for the Northern District of Texas. The 1st of the ASR implant lawsuits should begin jury trials later this year.
In June, Smith & Nephew pulled 1 of its metal-on-metal hip components, the R3 acetabular system.
Last month an FDA panel advised orthopedic surgeons to avoid using metal-on-metal hips in the future, but reassured patients already using the devices that a large percentage have successful outcomes.
Here’s a look at the BMJ/BBC timeline on metal-on-metal hip implants:
- 1975: Study describes local tissue reactions caused by cobalt and chromium ions from metal-on-metal hips.
- 1988: Study shows human synoviocytes killed by cobalt in vitro.
- 1989: Metal-on-metal hip resurfacing designs start in Birmingham.
- 1990: WHO International Agency for the Research on Cancer lists trivalent chromium as a potential carcinogen and cobalt ions as a probable carcinogen.
- 1991: First metal-on-metal hip resurfacing device is implanted in Birmingham, England.
- 1994: Study shows dissemination of cobalt and chromium ions into lymph, liver, and spleen.
- 1996: Patients with metal-on-metal hips found to be at increased risk of cancer compared with those with metal-on-plastic hips.
- 1997: Birmingham Hip Resurfacing (BHR) implant comes onto the European market.
- 1998: Particles of cobalt and chromium shown to be toxic to monocytes in culture.
- 2000: NICE guidance on selection of prostheses for primary hip replacement and resurfacing sets a benchmark revision rate for conventional hip replacement of ≤10% at 10 years.
- 2003: Derek McMinn and Ronan Treacy publish paper showing positive results with BHR. This kickstarts the trend for larger heads in total hip replacement.
- 2004: McMinn, designer of the BHR, says, “Caution still needs to be exercised until longer-term results are available.”
- 2004: One of DePuy’s modified stems with a shortened trunnion is cleared by the FDA, which says the modified design “does not raise any new issues of safety or effectiveness.”
- 2005: Internal DePuy memo reflects early concerns about health risks of wear debris from metal on metal hips. “In addition to inducing potential changes in immune function, there has been concern for some time that wear debris may be carcinogenic.”
- 2006: MHRA Committee on Safety of Devices says there’s growing concern over the biological risks of metal wear debris.
- 2006: The Dept. of Health’s Committee on Mutagenicity concludes that “some metal-on-metal (those using cobalt-chromium) hip replacements may be associated with increased DNA-changes, and increased genotoxicity in patients.” It says this “may present a potential risk of carcinogenicity in humans.”
- 2007: Implantation of large-diameter metal-on-metal hips starts to increase rapidly in the U.K., and resurfacing peaks. Metal-on-metal hips accounted for 20% of market that year.
- 2007: U.K. expert advisory group chooses not to contra-indicate metal-on-metal hips in women of child-bearing age – even though metal ions had been detected in the umbilical cord and placental blood.
- 2007: The MHRA’s Committee on Safety of Devices recommends that all patients sign a consent form setting out the risks associated with metal wear debris. But this recommendation is not widely communicated.
- 2008: Study shows 20% of patients with DePuy’s Pinnacle hip system have metal ion levels over the upper limit accepted by occupational health experts.
- 2009: Japanese surgeons raise concerns with the design of DePuy’s large diameter metal-on-metal system. They report seeing “generated metal debris between stem taper and head, and final necrosed tissue” and blame it on the poor connection between the 2.
- 2009: All joint replacement implants are re-classified as Class III devices in the European Union.
- 2010: In an internal email obtained by the BMJ, a senior executive at DePuy writes: “I feel the problem [with large diameter metal on metal] is emerging as more serious than first thought.”
- 2010: DePuy recalls its ASR hip prostheses. Some studies show a failure of the total hip replacement secondary to adverse reactions to metal debris of 50% at 6 years.
- 2010: DePuy promotes Pinnacle – including metal-on-metal – as “an alternative for the majority of patients.”
- 2011: Tony Nargol and his team warn the MHRA of failures with the Pinnacle implants.
- 2011: British Orthopaedic Assn. writes to surgeons to say that large diameter metal-on-metal total hip replacements should be “carefully considered and possibly avoided.”
- 2011: A 2-year follow-up study of 144 patients shows an incremental increase in metal levels over the study period in a range of large-head metal-on-metal implants made by companies including Zimmer, DePuy, and Smith and Nephew.
- 2011: FDA writes to about 20 manufacturers to say that it is requiring post-marketing studies in cases where an implant’s failure could have serious consequences. Companies would be expected to take blood samples from patients to measure metal ions.
- 2011: National Joint Register describes large-diameter metal-on-metal and resurfacing prostheses in some people as a “cause for concern.”
- 2011: Trial comparing large-diameter Birmingham hip replacement with conventional hip is terminated after 2 years. Metal ion levels were raised above the MHRA advised safety level in 20% of the metal-on-metal group and in 1 patient in metal-on-polyethylene group (who had a metal-on-metal implant on the contralateral side).
- 2012: At the annual American Academy of Orthopedic Surgeons conference, manufacturers promote metal-on-metal products to the 40,000 attendees.