very nice summary of that meeting.
Katherine Sale and Mary Ann Porucznik
In nearly 23 hours of testimony and deliberations over 2 days in June, the U.S. Food and Drug Administration’s (FDA) Orthopaedic and Rehabilitative Devices Panel (ORDP) considered expert scientific and clinical opinion on the risks and benefits of metal-on-metal (MoM) hip replacement and resurfacing devices. The Panel’s goal was “to better characterize any potential and real safety risks and generate scientifically based recommendations for the clinical and patient communities on how to best communicate and mitigate them.”
William L. Rohr Jr., MD, an orthopaedic surgeon in private practice in northern California, served as temporary chair of the ORDP. Included on the Panel were orthopaedic surgeons, researchers, patients, and industry representatives. Also present were representatives from the FDA as well as from regulatory bodies and professional societies from outside the United States.
Paul A. Manner, MD, FRCSC, associate professor, department of orthopaedics and sports medicine at the University of Washington, led off the presentations on behalf of the AAOS, the American Association of Hip and Knee Surgeons (AAHKS), the Orthopaedic Research Society, and the Hip Society.
According to Dr. Manner, a 2011 survey of AAHKS members found that, since 2009, more than two thirds, have never used or have discontinued their use of MoM hip bearings; nearly one quarter have decreased their use of these devices. “There’s been a strong trend away from MoM these last 2 years,” he noted.
Markus A. Wimmer, PhD, an associate professor in the department of orthopaedic surgery at Rush University Medical Center in Chicago, reviewed ways to make preclinical testing more predictive. These include the adverse conditions observed in clinical practice, such as malpositioning of the implant, lack of joint lubrication, the interaction of wear and corrosion, increased friction, and other mechanical and chemical variables.
“We need a standard for taper wear measurements,” he concluded. “We should look into different testing modalities and include adverse conditions in preclinical testing.”
Young-Min Kwon, MD, PhD, FRCS, FRACS, an assistant professor at Harvard Medical School, explained that biologic reactions to MoM may be systemic or local. Metal ions may lead to the generation of free radicals, which, in turn, can induce DNA cross-linking. “Because the permanent modification of genetic material is a first step in carcinogenesis, this raises questions and concerns about the potential for carcinogenesis in these patients,” he said.
He went on, however, to note that precise prevalence of adverse local and remote tissue responses is unknown and recommended a systematic approach for assessing painful MoM hips. Dr. Kwon presented three such approaches—one from the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA), a diagnostic algorithm published earlier this year in the Journal of Arthroplasty, and one from a scientific exhibit displayed during the 2012 AAOS Annual Meeting.
“In summary,” he concluded, “the systemic adverse biologic reaction to metal-on-metal remains a concern because current studies are limited. This represents an important part of our future research. We also need to further standardize histologic evaluation of periprosthetic tissues in patients with adverse soft-tissue reaction. The various reactions indicate dose dependency as well as patient susceptibility, which point to a complex biologic interplay between the implant and patient, as well as surgical factors. Further research is still required to gain insight and identify the multifactorial etiology of local adverse soft-tissue reaction in patients.”
Hearing from patients
The open public hearing featured comments from seven patients and one patient advocate, all but one of whom had adverse events after MoM hip replacement surgery. Several had multiple revision surgeries; all wanted the FDA to withdraw all MoM devices from the market.
In response to the patient testimony, Barbara Berney, patient representative on the ORDP, asked, “My question as a patient is always ‘What is an acceptable rate of failure?’ When you are the person with the problem, statistics don’t mean anything. Do all systems have the same failure rates? If there’s nothing else that you can use, is it okay to use something that you know may have a high rate of failure?”
Consumer representative Connie Whittington, MSN, RN, called for better patient education materials. “I think patients need very clear, easily understandable information that sets the tone for what they can expect in terms of outcomes and functionality,” she said. “It needs to emphasize the importance of their participation, including follow-up care, taking care of the rest of their health, and asking good questions.”
The panel then heard from industry representatives as well as regulatory bodies and professional societies from outside the United States. Representatives from Biomet, Corin USA, DePuy Orthopaedics, and Smith & Nephew discussed issues such as design considerations, benchmark comparisons with other systems, performance data, and results of clinical trials. Panel members then had the opportunity to question the presenters.
John Skinner, MD, vice president of the British Hip Society and codirector of the London Implant Retrieval Center, discussed the specificity and sensitivity of metal ion testing, the recommendations of the MHRA and the British Hip Society—particularly with regard to use of metal artifact reduction sequence (MARS) MRI and ongoing research.
“This year the British Hip Society advised British surgeons to no longer do large-diameter (36 mm or greater) MoM primary stemmed total hip replacement until more evidence is available,” Dr. Skinner said. “We have good alternatives with much better polyethylene and very good ceramic bearings. We think MARS MRI is the most useful investigating tool; it’s expensive, but it gives the most information. But clinical judgment will always be required in managing these patients because the decision making really is difficult.”
According to Graham Mercer, MBBS, FRACS, president of the Australian Orthopaedic Association, stemmed MoM hip replacement has “all but ceased” in that country and hip resurfacings are on the decline. He also expressed concern that asymptomatic patients with well-functioning implants who are “being significantly spooked by all the media hype” are requesting revision surgery. “I think that that will be associated with increasing morbidity,” he said.
Emil H. Schemitsch, MD, FRCSC, of the Canadian Orthopaedic Association, shared the results of a Canadian hip resurfacing study group. “We believe that this procedure is best indicated for males younger than age 60 with good bone quality, no significant acetabular deformity, with a large femoral head. We also think that it should be performed by surgeons who have an appropriate volume of hip replacement and hip resurfacing, understanding that this is a very technical operation, and have recommended—based on expert opinion—that surgeons performing this procedure should be doing at least 100 hip replacements and 20 resurfacings a year,” he said.
The first day of testimony closed with a question and answer segment. The Panel considered the following two questions:
- What are the key differences, if any, between U.S. practice and practices outside the United States that should be taken into account when reviewing and interpreting the data including differences in patient population, surgeon experience/preference/technique, and the devices themselves?
- What additional data fields would be appropriate and practical to add to existing hip implant registries and include in new registries being developed?
Coverage of the second day of testimony, during which AAOS First Vice-President Joshua J. Jacobs, MD, addressed the panel, is available as on online extra at www.aaosnow.org
- Full list of Panel questions
- Full transcripts of the Panel meeting, background materials, disclosure information on the presenters, the full list of panel members, and the agenda are available on the FDA website.
- The use of MoM hip implant devices has decreased significantly over the past 3 years.
- Better preclinical testing models are needed to identify problems with new devices.
- Metal artifact reduction sequence MRI, although expensive and not widely available, can be an excellent tool for identifying problems in patients with MoM hip implants.
- Determining the prevalence and mechanism(s) of both local and systemic adverse tissue reactions is an important part of future research.
- The results of a Canadian hip resurfacing study group, reported at the meeting, indicate that hip resurfacing is technically challenging and requires training and experience on the part of the surgeon.
- Patients who have had adverse events related to their MoM hip implants are leading the call for the FDA to remove all such implants from the market.
September 2012 Issue