6:53 p.m.: The FDA panel has adjourned.
6:43 p.m.: An FDA representative has reviewed the previous days proceedings, and is currently reviewing today’s.
6:41 p.m.: Several panel members are expressing final thoughts on the matter, with an FDA summary of the day’s proceedings to follow.
6:34 p.m.: Rohr, trying to summarize the consensus of the panel, said the FDA should explore additional labeling considerations about the technical difficulty of implantation (i.e,., “optimal positioning cannot be guaranteed”), as well as a warning to patients that both pseudotumors and elevated metal ion levels have been reported in symptomatic and asymptomatic patients.
Cheng, to patients: “Orthopedic surgeons remain committed to analyzing [MoM] hip joints and their pros and cons, so those patients: If you have a [MoM] implant within you, take comfort in knowing the vast majority of those implants are succeeding ... the absolute risk remains small.”
6:30 p.m.: “We have to be as transparent with the people getting the devices as we are with the people putting them in,” Whittington said.
6:24 p.m.: Yates: “Rather than making broad, blanket statements ... I think the ‘horse is out of the barn.’ We’re not going to be able to go back, these devices are in hundreds of thousands of patients. It’s time to get those 522s going ... so decisions can be made that are more design-specific. There is potentially a lot to learn about what may be some valuable prosthetics as opposed to ones that aren’t.”
6:22 p.m.: “Some of these people do not know that if they have implants, they’re going to wear out. That should be emphasized to them,” O'Brien said. “Shouldn't that be in the directions?”
6:16 p.m.: Evans noted that he believes females should be included as a risk factor in product labeling, as they demonstrate higher revision rates.
6:14 p.m.: The final question from the FDA concerns what information should be conveyed to physicians and/or patients as part of product labeling. The panel apparently does not have much to say, although Goodman has noted that it should be stressed that MoM devices are extremely sensitive to surgical technique.
6:09 p.m.: The panel does not appear to have any specific opinion as to whether MoM total hip replacements or resurfacings have any place as the secondary device for patients undergoing revision.
6:07 p.m.: The panel is in agreement that information needs to be disseminated more properly to patients in a more accessible fashion.
“It’s an alternative discussion of the risks,” Rao said. “Much like any other discussion of any other procedure, where some of the risks are general and some are more specific for the procedure.”
6:00 p.m.: Rao: Patients and physicians need to be informed of the risks inherent in MoM. Further, surgeons should have to explain why they would want to use MoM. These factors are critical for properly informed consent.
5:57 p.m.: Goodman: “I don’t do metal-on-metal ... but when I have a discussion about any operation with the patient, besides talking to them about the operation ... I talk to them about risks. The question being asked is if there are any additional risks that you would tell a patient getting a [MoM] prosthesis. It does behoove the surgeon to tell the patient about these concerns. There are other potential risks. There has to be a frank discussion between the surgeon and the patient about these risks. There is perhaps less long-term follow-up of [MoM] resurfacings and hips when compared to more traditional resurfacings and hips.”
5:49 p.m.: Rohr said he has heard no consensus for any particular subgroup of patients who should be warned against using a MoM implant aside from those already on the labeled warning. Yates noted that patients with renal insufficiencies, as well as patients who have been through multiple bouts of cancer, and it was pointed out these patients are already labeled.
5:42 p.m.: O’Brien is calling for caution as well, noting that “metal-on-metal” is a broad category when cobalt-chromium appears to be the mix of materials causing problems.
5:37 p.m.: Cheng noted caution still has to be exercised in making any broad declarations, as there are specific implants, populations or situations wherein the potential benefits outweigh the risk.
The consensus appears to be that the decisions should be left to the patients and physicians.
5:33 p.m.: Rohr has reaffirmed he sees no reason to use metal-on-metal.
Yates: “I can’t say any one recommendation is right or wrong at this point because there can be long-term success for some of these patients and implants. I wouldn’t want to be quoted as saying it’s unreasonable. However, the current option of crosslinked polyethylene isn’t having these same questions, and at this point in time I can’t think of any indication where I wouldn’t feel more comfortable using metal-on-crosslinked polyethylene as my first choice.”
5:29 p.m.: “There are a lot of therapies that are potentially toxic to the patient, but we stop using those when a safer treatment comes along,” Lyman said. “I’ve seen no evidence that safer treatments we have are less effective.”
5:27 p.m.: “For resurfacing, I believe in a well-defined, strict population there are some benefits. I would define that population as a young male, skeletally mature, larger head size.”
Rohr answered by saying the early part of his career was dominated by revisions, and he fears he is doing it again. “I do not use metal-on-metal, and I can see no reason to do so,” he said.
5:16 p.m.: “I can imagine one patient characteristic that might result in my recommending either the [MoM] total hip or resurfacing system,” Mayor said, noting this case was a patient who absolutely insisted upon the treatment.
When asked if this situation would change if the patient were female, Mayor said he would refer that patient elsewhere.
Rao: “This has to be a discussion between the patient and the physician ... but I don’t think we should be in the process or game of determining which implant any one patient should get. As far as patient or population characteristics ... I think it goes back to old-fashioned orthopedics. Patients who have minimal disease are less likely to do well, while patients with severe disease are more likely to do well.”
5:15 p.m.: The panel has resumed their deliberations. First up is the discussion of which patients or population characteristics are more likely to achieve the most favorable outcome and for whom the risks most likely outweigh potential benefits with MoM THR system and a MoM resurfacing system.
4:59 p.m.: The panel is taking a 15-minute break, and will resume at 5:15 p.m.
4:56 p.m.: Rohr is currently trying to get a consensus of sorts from the panel in terms of an answer to the question being posed by the FDA.
4:48 p.m.: “Not every patient who is asymptomatic is going to want to have an imaging test,” Potter said. “In that case, do not do it ... what it does provide you, however, is a baseline.”
“I think it’s something to offer,” she added. “I'm not mandating it, but if you want to evaluate the integrity of the soft tissues ... then this is the best means by which to do that.”
4:45 p.m.: “I don’t hear much difference in the asymptomatic patient, except in the frequency of follow-up,” Rohr said, trying to summarize the panel’s point of view.
Barber went back to the MRI point, saying he “can see no reason in the world” to MRI the 750,000 hip implants in use today.
4:42 p.m.: Goodman asked Potter if she means to perform baseline MRIs on the 750,000 implants already in use today. Potter replied in the affirmative, saying it is critical to have a baseline. Goodman remarked the cost would make such an effort essentially impossible.
“The way to suggest a longitudinal study is not by recommending 750,000 patients all get screened at baseline,” Lenchik said. “Why would you subject somebody who has no symptoms to MRI? That makes no sense to me.”
4:41 p.m.: Lenchik disagrees about getting a baseline MRI because he feels it does not apply.
“In this field, most significant collections are large,” he said. “I’m concerned not just with the expense of the baseline MR, but what if you find a collection of someone who is asymptomatic? You may not want to take it out but the patient will go across the street and find someone who does.”
Potter replied by saying “we really don’t know what is ‘significant,’” saying more information is needed.
4:37 p.m.: Rohr said his and Goodman’s strategies are similar, but he said he would still perform yearly follow-ups for at least 5 years based on the information presented this meeting.
He related prior experience with lowering debris load within implants to keep them functioning, noting there may be interventions short of complete revisions that may extend the life of the implants.
4:34 p.m.: Barber stressed there should be a distinction made between small-head MoM and large-head MoM, as the larger ones have displayed more issues and he would be more inclined to get baseline ion levels for larger heads. When asked if he’d change that assessment if the patient were a woman, he said he would not.
4:29 p.m.: Yates: “Given the fact that there is a big part of the ‘iceberg’ we are not seeing because it is still under the water ... I would offer the patient who has no concerns the option of a baseline ion level just so we would have one if he had any symptoms in the future. If it came back elevated, [then] I would offer a repeat of that in 6 months to a year. If he came back abnormal twice, [then] I would press for the MARS, or even the first time.”
Yates also expressed concern for offering a patient a revision they may never need, noting he wouldn’t necessarily write it off if a patient did not seem worried.
4:25 p.m.: Goodman said he is seeing more patients who want to know their metal ion levels. He said he lets them know that the levels are just one piece of the puzzle, but if they really want it done, then he does it.
Cheng: “I probably will come down a little bit more on the aggressive side than some of my colleagues here, in the belief that baseline studies should be performed ... over time, it may change the management of the patient. I would do metal ions and the baseline MR because if you’re going to show any change over time you’re going to need the baseline study.”
“I say this with a little bit of caution,” he noted, “because I see the possibility for patients to act on poor test results with no real reason to do so.”
4:24 p.m.: The FDA’s next question focuses on an asymptomatic hip.
“We’re increasingly faced with a situation where the [physician/patient] interaction is suboptimal,” Mayor said, with the physician interrupting the patient frequently and not paying much attention.
“The patient needs to be given the opportunity to fully express his- or herself based on what they are experiencing,” he added.
“At the same time, suggestibility is a very real concern,” he said. “It’s not just the patient’s attorney — it could also be the physician accidentally.”
4:20 p.m.: Rohr, summarizing the panel’s answer, noted there were not many differences between a resurfacing case and the way the panel would handle the previous case.
4:17 p.m.: The FDA is satisfied with the answer. The panel has moved onto the next question, which uses many of the same criteria but focuses on a surface replacement.
4:15 p.m.: “I didn’t hear anyone say they wouldn’t do metal ion levels ... I heard some controversy over what levels would actually make you do something,” Barber said.
Rao: “I think we felt a trend may be indicative of something, so I think Tom may be right ... we’re going to watch the trend.”
Rohr modified the summary to note metal ion testing was agreed upon if a patient had gone through other workups and the physician was still unsure as to whether there was a failed implant.
4:09 p.m.: The panel is still discussing how they would handle a symptomatic patient displaying specific symptoms. Rohr is summarizing the section. “What I hear is ... general agreement every patient should start with a history and physical performed by an orthopedic surgeon. That patient should have general X-rays,” he said.
With abnormalities on X-ray, a patient should have further imaging performed, Rohr added. He noted he did not see a consensus from the panel on ion testing. Head size, female patients and bilateral implants were listed as risk factors that would lead a panel physician to perform further testing.
4:01 p.m.: Goodman: “If you take care of these patients, one has to realize these patients often don’t sleep during the interim. They’re very disturbed by these things, and they want answers quickly. If it’s a symptomatic patient, [then] I think a lot of these tests should be done swiftly.”
Barber: “Where we have issues with metal ion levels, where they are high and the MRI is normal, that would precipitate me bringing them back in 3 months to repeat that."
3:57 p.m.: Rao: “We’re talking about a patient who is significantly symptomatic ... the frequency of follow-up in such a patient, I agree that it should be 6 months unless testing suggests a more acute course of events.”
“The question is, in a patient who has a metal-on-metal hip, should we get an MRI if the X-ray shows obvious problems?” he added. “I’m not in favor of routine imaging mandates, such as an MRI for patients who have problem hips. I think there’s unforeseen downstream consequences of mandating a specific modality for imaging. We need to see if there’s some type of soft-tissue lesion.”
“With regards to specific patient or implant characteristics, I think the only one we’ve seen specific evidence for is acetabular cup position,” he noted.
3:50 p.m.: Potter went back to a earlier presentation wherein it was stated there are no clinically significant fluid collections, noting “we really don’t know what would be clinically significant.”
3:44 p.m.: Rohr is talking about the increasing frequency with which patients present without having gone through proper examinations in the past.
“I don't know what’s happened where we’ve allowed our peers to degenerate to this level of clinical care,” he said. “In my office, I examine every patient personally ... every patient I see, I see them well before their surgery. I do their history and physical. I see them as often as I have to see them ... they’re then required to see me at 3 months, 6 months and a year ... it seems we’ve gotten out of that.”
3:42 p.m.: Yates: “I would go with a MARS MRI plus ions on top of the regular radiograph for a patient with this presentation. If those were normal, [then] I would follow-up in 6 months and consider running those tests again.”
3:36 p.m.: Goodman: “I think I would do both imaging and metal ion levels, and I think there has been a lot of debate on which imaging is best. But I think since this would be done throughout the U.S., it should be discussed with a radiologist at that institution or be referred to a center that has sophisticated imaging techniques.”
3:31 p.m.: The FDA has requested the panel discuss optimal follow-up regimens for patients who have received a MoM THR but are symptomatic.
3:27 p.m.: This portion of the panel has closed. The panel members have moved on to answering specific questions posed by the FDA.
3:21 p.m.: “I’m trying to get a grasp on the few case reports there are in the medical literature and the thousands of patients with one of these implants, if many of these symptoms are as common as the patients may say,” Goodman said.
“There is a very small number of case reports,” Jacobs replied. “Given the nature of my practice, I commonly get referrals for this issue ... what I’ve done is I’ve now partnered with a clinical toxicologist. They’re more used to dealing with heavy metal toxicity.”
“In working with [the toxicologist], I’ve identified maybe one or two of the dozens and dozens of cases that have been referred ... having said that, we’re talking about clinical symptoms,” he added. “I would say this does fall under the rubric of being a rare event.”
3:20 p.m.: “[Corrosion] is not a trivial issue, and it is not limited purely to cobalt chrome,” Mayor said. “It doesn’t require the participation of a cobalt chromium source.”
3:14 p.m.: “If we just see titanium-on-titanium corrosion, [then] we’re not seeing the same type of corrosion responses we’re seeing with cobalt chromium,” Jacobs said.
3:09 p.m.: The discussion of local systemic effects and immune response continues.
“I’m now surprised if I see a metal-on-metal head made of cobalt chrome ... that doesn’t have easily identifiable scratches on the surface,” Mayor said. “If that’s the case, we have ... layers being scraped off of these implants.”
3:00 p.m.: The panel has reconvened after lunch. Rohr has announced a few changes in schedule. Deliberations over what was heard in the previous session will commence.
2:00 p.m.: The panel has broken for a one-hour lunch, and will reconvene at 3:00 p.m.
1:57 p.m.: “We do have one other material, as well as stainless steel, and that is copper,” McMinn said. “With copper, there was the most massive sharing of materials into the wound ... I know that in the UK, a lot of hospitals still have wretched copper hammers, and I wonder if we’re setting up a problem of copper being embedded into the local tissue.”
1:49 p.m.: “I think whole blood would give you a better measure of the total amount of chromium released into the blood and give you a measure of that exposure,” Squibb said.
1:43 p.m.: “My sense is in a well performing bearing that is not metal-on-metal, the rate of clinically important metal hypersensitivity is vanishingly low,” Jacobs said. “You’re not going to get it if you have a well performing bearing.”
1:36 p.m.: The panel is now asking questions of the FDA guest speakers.
“The local effects of metal-on-metal debris are the most commonly seen effects," Kudrna said. "Ion levels of cobalt and chromium are measures of wear and not toxicity since toxic levels generated by these hips remain unknown."
1:33 p.m.: James C. Kudrna, MD, PhD, Clinical Associate Profesor of Orthopaedic Surgey, Pritzker School of Medicine at the University of Chicago, is now speaking on the systemic and local effects of MoM THAs.
“We have no real reliable measurements of metal sensitivity of patients, but we are likely coming closer,” he said.
“It’s the adverse local tissue reactions that have been a problem,” he added.
Kudrna also said he doesn’t consider metal sensitivity to be related to the degree of bearing wear. He said that most information regarding the systemic effects of metals is related to occupational exposure and may not be representative of prosthetic wear. Close monitoring of patients with MoM hip implants for local as well as systemic effects of metals should continue to better understand these processes, he said.
1:28 p.m.: McGinn is speaking now on the topic of various complications, displaying a large list of issues. “For all of these things, the average [MoM] patient has no cause for concern,” he said.
1:12 p.m.: Squibb’s currently discussing the toxicity and carcinogenicity of chromium, noting there are a number of factors that need to be understood better in terms of the responses from the body.
1:05 p.m.: “One important thing about metals is they can be stored in cells in non-toxic forms,” Squibb said. “So the metallothionein levels can establish the threshold value before metals are introduced.”
1:03 p.m.: “Valence states are very important,” Squibb said.
1:00 p.m.: Katherine S. Squibb, PhD, Professor of Medicine, Department of Medicine at the University of Maryland School of Medicine, is now delivering an overview of the toxicity of cobalt and chromium as it applies to MoM hips.
12:56 p.m.: “There are numerous factors affecting debris burden in metal-on-metal bearings,” Jacobs said.
He listed clinical risk factors for adverse local tissue reactions as hip pain, poor implant track record, suboptimal component position and elevated cobalt and chromium levels.
Jacobs said that there are increasing clinical reports of osteolysis and soft tissue masses in patients with MoM THR and surface replacement is associated with signs of metal hypersensitivity and/or tissue necrosis.
“The occurrence of soft tissue masses are associated with elevations in serum metal concentrations likely reflecting accelerated wear and/or corrosion,” he said. “Optimization of metal-on-metal bearings to further diminish wear and corrosion — which I think is possible — is highly desirable.”
He also said that adaptive immunity may play an important role in the pathogenesis of adverse soft tissue reactions, but current diagnostic tools have yet to be clinically valiated.
12:50 p.m.: Jacobs: “I think there is no doubt that the phenomena of metal allergy exists; I think the only question is the prevalence.”
“How prevalent might this be?” he added. “They were grappling with this issue back in the ‘70s ... and here we are 40 years later, grappling with the same issue.”
“There is an interesting association between patch test sensitivity and implant performance,” he said.
12:47 p.m.: Jacobs is going over the impacts of metal toxicity and how it is incumbent upon physicians to check to symptoms of toxicity as part of basic patient testing.
12:41 p.m.: “This is problematic," Jacobs said of analysis variability. "I think you might want to reconsider your decision about whole blood, and I think serum might be even better.”
12:37 p.m.: Jacobs: “Corrosion products in and of themselves can lead to osteolysis.”
12:32 p.m.: Joshua J. Jacobs, MD, Professor and Chiarman, Department of Orthopedic Surgery, Rush University Medical Center, and First Vice President of the AAOS, is now speaking on the local and systemic effects of metal-on-metal bearings.
“To understand the context of this, we all have to realize ... there’s a tendency to lump all [MoM] devices together, but that's a problem because there is a lot of heterogeneity between devices,” he said.
"The reality is that a large majority of patients with metal-on-metal bearings are functioning well clinically," he added.
12:28 p.m.: Lavernia: "We need data. Registries are going to give it to us, but we need data now ... we need standardized labs and testing."
"Do not have advisory panels with nonconflicted folks. It is a bad idea," he added. "These minds do have a bias, but they've been thinking about this issue longer than anyone ... include some conflicted folks. Just be transparent. That's where we've erred in the past. Don’t let them lead the panel.”
12:23 p.m.: “In my opinion, a lot of these metal-on-metal failures have more to do with how they are put in than the fact that they are metal-on-metal," Lavernia said.
12:20 p.m.: “There’s an issue of unrealistic expectations,” Lavernia said. “I’m also really careful of patients who have depression, sleep disorders, chronic fatigue syndrome or fibromyalgia.”
"If I have a painful MoM, I will actually do a full review of systems of these patients," he added. "I do a little bit more work on these patients."
12:17 p.m.: “One of the first things they taught me in medical school is that it is extremely difficult to make an asymptomatic patient better,” Lavernia said.
12:09 p.m.: The first FDA guest speaker, Carlos J. Lavernia, MD, FAAOS, Medical Director of the Orthopaedic Institute at Mercy Hospital in Miami, is the first presenter in this session. He is speaking about the evaluation of a painful MoM implant.
“We have fixed one of the initial and most horrible problems we had with regards to fixation through trial-and-error," Lavernia said.
12:05 p.m.: The panel has resumed. The upcoming FDA guest speakers will talk about outcomes, including local and systemic complications.
11:53 a.m.: The panel has taken a break and will resume at 12:05 p.m.
11:48 a.m.: Berney: “The whole issue of what consumers call ‘unnecessary testing’ comes to mind, but I am sure if I had a metal-on-metal implant, I would want to make absolutely sure it does not fail.”
11:46 a.m.: Li: “Right now, if we go down the path of doing whatever is good for the patient, that’s great for the patient, but 1,000 patients later, we may have no more basic knowledge than we do now. If we mix the two, where we give the patients proper care but you have a study where you know you're going to have some kind of answer at the end, that may be best.”
11:44 a.m.: Evans: “We keep coming back to a need for some prospective studies to answer these questions. If you want to know whether a screening or monitoring strategy is effective, you need to compare the clinical outcomes of patients who are using the screening strategy for intervention decision making versus people who don't have that information. We haven’t seen the results of any studies comparing if you know this information and can direct intervention based on that information, what the outcomes are compared to when you don’t have that information. It’s a common theme, and it re-emphasizes the need for some prospective longitudinal studies ... I think we have the same problem when we’re trying to compare risks for options, whether it’s metal-on-metal or alternatives. If you’re going to get contrasts between these alternatives, [then] you need studies that contrast these alternatives.
Li was in agreement with Evans’ statement.
11:40 a.m.: Rao: “I favor an approach put forward earlier today, where asymptomatic patients will not benefit substantially from any blood or urine testing, and I'm not sure there's much role for testing in patients with obvious failure. I think it is the patients in the middle who will benefit most.”
11:37 a.m.: Barber says cobalt chromium testing is a valuable adjunct, but he does not know if it is a viable screening tool.
“The screening of these folks may lead to more problems than not,” he said, adding he is not sure if it is the right tool for asymptomatic hips.
11:35 a.m.: Yates has reported more of his patients have been put at ease by normal metal ion levels than those who have experienced concern because of higher levels. He added he is more concerned with getting levels of symptomatic patients, “because I think you have to have it to take them through a comprehensive evaluation of the painful hip.”
11:27 a.m.: Goodman: “Ion testing is an adjunct in addition to history and physical examination, as well as imaging of some type. What's more important than one absolute value are multiple values sequentially done over some time period by the same laboratory according to the same methodology. Would that be an acceptable summary or conclusion for Dr. Stulberg and the others who have spoken?”
Stulberg: “Yes, that is what I would be most comfortable with.”
This portion of the meeting is closed. The panel is now being asked to consider cobalt and/or chromium testing.
11:26 a.m.: Skinner: “There’s no doubt that even if we don’t have a specific number that will trigger a reaction, it is extremely valuable to have the cobalt and chromium levels of these patients.”
11:17 a.m.: Li: “It strikes me, if I take a step back, that this whole issue of measuring metal ions and what to do with those measurements is more a research project ... given all these variables, this seems more a research project than it is something we truly know much about.”
Jones: “We are involved in collaborating with researchers on different projects looking at human health endpoints, so we cannot comment on the specific utility of these methods. We can only provide the best data possible.”
11:12 a.m.: Panel member Michael L. Dourson, PhD, DABT, ATS, President of the Toxicology Excellence for Risk Assessment, is asking about the measurement of chromium in the blood, referencing the talk of valence states from yesterday’s panel session.
11:07 a.m.: More on metal ion level evaluation with a presentation from Daniel. The panel is now asking questions of the presenters.
“Yesterday it was implied there are dietary supplements and herbal compounds” that can interfere or confound findings, Yates said. “Can either speaker address what those compounds might be? Are there particular dietary supplements I should screen my patients for?”
Daniel said that although the potential for contamination is there, the risk is very low.
10:55 a.m.: Bernard N. Stulberg, MD, Professor of Orthopaedic Surgery at the Cleveland Clinic, is currently sharing his 30-year perspective on metal ion level evaluation.
He said the metal ion measurement can be useful in the current climate of MoM THA and hip resurfacing both as a clinical tool to monitor patients with concerns of failure and symptoms without signs of impending clinical compromise. It can also be useful as a research tool to monitor the effects on patient populations over time to confirm the absence of adverse consequences. Metal ion mesurement is most meaningful when used in a repeated fashion with the patient as the control, and historically it has been abnormal only when associated with clinical failure or impending failure.
10:50 a.m.: Jones talked about the criteria that should be necessary in selecting a clinical laboratory — including the current analysis for the analyte of concern in the matrix of choice, CLIA certification, a proper LOD/LOQ for reporting, laboratory-provided prescreening materials, turnaround time and cost.
“These things need to be considered because they can influence,” Jones said. “The machines that do this testing are primarily made of metal. There's always a potential for contamination.”
10:40 a.m.: Jones is currently discussing limits of detection and quantification.
“The bottom line is: What is the uncertainty required for the decisions being made?” he said.
10:34 a.m.: Robert L. Jones, PhD, Inorganiz and Radiation Analytical Toxicology Branch for the Centers for Disease Control and Prevention (CDC), is now speaking on the topic of CDC’s metals measurements for public health.
10:25 a.m.: The panel has resumed after the break. Paula Caposino, PhD, a biologist in the Division of Chemistry and Toxicology Devices, Office of In Vitro Diagnostic Device Evaluation and Safety, is now introducing the topic of metal ion testing methodology. She said that the panel will be asked to consider if cobalt and/or chromium testing should be incorporated in the management of patients with MoM hip systems. The panel will be asked to consider the appropriate patient population for the testing, the most appropriate clinical use of the tests, and the most appropriate sample types to evaluate.
10:09 a.m.: Cheng has agreed that allergy testing may be beneficial, especially in groups with joint pain that can’t be explained.
The open public portion of the hearing has been officially closed. The panel is currently taking a 15-minute break and will resume the meeting at 10:25 a.m.
10:04 a.m.: “Most of the data on patch testing I and others in my group have reviewed is very equivocal,” Goodman said, noting there are very few — if any — reports of allergic reactions.
Barker replied that she is aware she is talking about a very small cohort.
10:02 a.m.: The public presentations have concluded. The panel is now asking questions of presenters.
9:54 a.m.: The current speaker is Joshua P. Rising, MD, MPH, Project Director of the Medical Device Initiative. He is questioning why the 522 studies are not being finalized in a proper time span.
“We don’t know why, specifically, these findings have not been finalized,” he said. “Fortunately, Congress has taken steps to prevent this issue.”
“The FDA and manufacturers should finalize the protocols for all of the 522 studies ordered more than a year ago,” he added.
9:49 a.m.: Al Alonzo is currently speaking on behalf of the Orthopedic Surgical Manufacturers Association (OSMA), discussing the organization’s history of working with the FDA to provide appropriate regulation for orthopedic devices. He is detailing the efforts made to work with the FDA on gathering information regarding MoM hips.
“OSMA will continue its work to develop consensus standards and appropriate controls to assure reasonable assurance of the safe and effective use of metal-on-metal hips,” Alonzo said.
9:46 a.m.: Lisa McGiffert, Director of Consumers Union’s Safe Patient Project, calls for greater transparency — “act like you want this information to get out there.”
“Ensure there is full disclosure to doctors of the limitations of the processes that bring these products to market,” McGiffert said. “They should be required to pass that disclosure on to their patients.”
She also advocated that the FDA immediately put out an alert advising women should not get MoM hips, partiulary women of childbearing age, and to direct to women with MoM to get monitored. “Don’t count on doctors and hospitals to give you informed consent up front,” she said.
McGiffert added her group strongly supports a comprehensive, neutral national registry that is not run by manufacturers who produce the devices.
9:42 a.m.: Lisa Barker, BS, MS, of the National Jewish Health, presented metal allergy as a potential cause of hip replacement failure, noting that these allergies may be diagnosed by patches or blood tests — and patients should be screened prior to surgery for reactions to jewelry, belt buckles, jean snaps, etc.
9:36 a.m.: “Incidence is low, but it is concerning and varies depending on multiple factors,” Barrett said.
“Most [MoM] total hip replacements function well,” he added. “There is a low percentage, class specific, device-related adverse reaction to metal ions, which warrants increased scrutiny of [MoM] THAs.”
Barrett noted physicians should be “cautious.”
9:34 a.m.: William P. Barrett, MD, of Valley Orthopedic Assocites, presents next on his experience with adverse tissue reactions in MoM THA modular implant systems. Barrett's team evaluated a series of large-diameter (36 mm or greater) MoM modular bearings.
Eight revisions in the series were associated with adverse tissue reaction, Barrett noted. This included two cases of metallosis and four cases of pseudotumor.
9:30 a.m.: John S. Rogerson, MD, of Madison, Wisc., presented next — also on the top of hip resurfacing.
“We’ve had no avascular necrosis, no cup loosening and no head loosening,” Rogerson said of his 300-patient cohort with a 3-year follow-up.
9:24 a.m.: “Not all of these implants are created equal,” Brooks said. “There are differences between metallurgy, roundness, clearance and socket design. These differences account for the different outcomes.”
Brooks concluded by asserting hip resurfacing has significant advantages, particularly in younger, active patients and male patients. He noted the need for the right patient, a properly designed implant and proper surgical technique.
9:21 a.m.: The next speaker is Peter J. Brooks, MD, FRCS(C), of the Department of Orthopaedic Surgery at the Cleveland Clinic, who is speaking on hip resurfacing.
“I think the panel should be made aware that resurfacing can actually last longer than total hip replacement, particularly in young, active patients,” Brooks said.
9:20 a.m.: Bernasek’s study involved 318 patients with 5 years or more of follow-up (mean: 6.8 years). His group found significantly improved Harris hip scores. Nine patients underwent revision: three for infection, three for dislocation, two for periprosthetic fracture and one for unexplained pain.
“We had a 2.3% raw revision rate ... consistent with the Australian Hip Registry,” Bernasek said. “We did see significant improvement in the majority of patients.”
“We did have satisfactory results,” Bernasek said. “Metal-on-metal workup for painful hips is recommended.”
He also added that more research is required to determine the etiology and to predict MoM sensitivity.
9:16 a.m.: The first speaker is Thomas L. Bernasek, MD, of the Florida Orthopaedic Institute, with a presentation on his multicenter midterm study using a modular metal-on-metal total hip arthroplasty.
9:13 a.m.: The open public hearing portion has started.
908 a.m.: Potter is discussing the use of ultrasound in histological diagnoses.
“I think what you’re suggesting is using ultrasound as a screen for MRI,” Lenchik said. “The problem with that approach as I see it is ultrasound doesn’t give you as much coverage anatomically as MR, and ultrasound is not as good as MR at detecting small collections ... you’d potentially be screening out patients with clinically significant collections, because those collections you miss with ultrasound may be significant clinically.”
9:03 a.m.: “Some of these symptoms are really pretty subtle,” Mayor said, discussing the importance of clinicians lending their experience to any FDA imaging guidelines.
“I do think that some specificity as far as the time frame in terms of follow-up is important,” Barber said. “I would think having follow-up studies between 2 [years] and 10 years would be of the best utility, with maybe an average of 5 years.”
Lenchik: “I am a strong proponent of including MRI in the FDA’s surveillance. My issue today is what protocol would you choose? Would we take the HHS protocol and adapt it? Or would you wait until these three vendors come up with a new protocol? I’m not necessarily on board with how you’d standardize the image acquisition.”
8:55 a.m.: Rao and Lenchik have noted that there is too much variability between centers, machines, physicists and specialists to get good, basic MRI scans consistently.
“I’m quite convinced it will be impossible to get good quality MARS MRI scans across the country,” Rao said. “Plus, we have patients with pacemakers, we have patients with claustrophobia ... my preference would be to have some kind of option available.”
8:52 a.m.: Li: “If the panel or anybody else should determine we should use MARS MRI on these patients, is that practical?
Potter: “I think it is, yes.”
Leon Lenchik, MD, of the Department of Radiology at Wake Forest University School of Medicine, said, “I would be more cautious than Dr. Potter. I would be concerned about how much is done in the community.”
8:42 a.m.: Mayor has asked about baseline imaging.
“The value of baseline is seeing the significance after the operation, but what’s probably more important is for us to follow these patients longitudinally,” Kwon said. “There are those patients that are very obvious, we know what to do with those. But there is a portion of abnormality that we don’t know how much clinical significance to attach to it.”
“Getting a baseline would be useful, but following these patients longitudinally would be useful as well,” he added.
Daniel noted that baseline imaging would be the ideal.
8:37 a.m.: Barber is asking about the timing of pseudotumors. He noted pseudotumor peaks seem to be around 3 years to 7 years, but Daniel’s findings were from the 10-year mark — and so the question focused on whether there seems to be a sort of progression.
“In our experience ... the time of development of pseudotumors after the operation varied from 3 years to about 11 years with a mean of about 9 years,” Daniel said. “There are reports of pseudotumors at 1 year ... there seems to be a threshold limited response.”
“Component positioning, wear and all of these things come into play,” he added. “In a scenario with high wear, you might see more pseudotumors ... there is also the issue of sensitivity, which is individualized.”
8:31 a.m.: Kwon said the necrosis seen with MoM bearings appears more significant, but it is hard to make a distinction.
8:24 a.m.: “I do agree [MoM] failures ... are a real nightmare, and we should do everything we can to avoid it happening,” Daniel said. “We cannot ignore that other bearings also have these problems ... we have to act quickly and early.”
8:23 a.m.: Potter, on imaging: “Where we need to go, we’re getting there — it’s just unpublished.”
8:20 a.m.: “The abnormalities, these soft tissue reactions, do exist in other devices,” Kwon said. “Prevalence is something we still need to know.”
8:15 a.m.: “All patients who required revision were identified based on clinical symptoms, examination and routine radiography,” Daniel said, noting that further investigations followed.
“No asymptomatic patient with normal radiographs needed to be revised based on their metal ions or CT scan findings in this series,” he added, citing his experience.
The presentations have ended. The panel is now asking questions of the two presenters.
8:10 a.m.: Daniel reports good experiences with multislice CT scans, as it provides good osseous details and can make assessments of component positions. He is moving on to discussion about pseudotumors.
8:05 a.m.: Kwon's presentation has come to an end. Joseph Daniel, MBBS, FRCS, of Smith & Nephew, is now presenting his experience with MoMl implant imaging. He hopes to answer questions about which imaging technique should be used, add his own experience with MARS CT scanning, and determine whether all patients need to be screened.
8:03 a.m.: After discussing “what we know” and “what we do not know,” Kwon is now moving on to “what we need to know.” This includes a maximization of the clinical utility of MRI (optimization of imaging, standardization of protocols and standardization of reporting), quantification of sensitivity and specificity, validation of MRI findings and any MRI features which are predictive of progression of lesions or symptoms.
‘It would also be helpful for us to get insight into the prevalence of adverse soft tissue reactions in other bearings,” he added. “It is important to have a comprehensive, systematic approach in evaluation of these patients.”
The cross-sectional imaging modalities play an integral role in the evaulation of MoM failure, he said.
“However, we should avoid an over-reliance on a single diagnostic tool with these patients.”
He noted that MARS MRI has the potential for early and accurate detection of adverse soft tissue reactions and will play an increasing role in the clinical decision-making process.
7:58 a.m.: Kwon’s now illustrating the use of MARS MRI in detecting adverse local tissue reactions. He's showing numerous slides of patient scans and citing a "high prevalence of abnormal findings."
"However, MRI does not correlate to hip function," he said. "No correlation has been found between lesions and clinical symptoms. We also know solid consistency increases the likelihood of revision surgery."
7:56 a.m.: Kwon discusses MARS MRI and that it has been shown to be accurate in detecting wear induced adverse synovial response predating osteolysis on radiographs.
7:50 a.m.: Kwon has discussed CT’s advantages and limitations, and is now discussing the utility of ultrasound.
“Ultrasound has the potential to be a quite useful screening tool,” he said, citing its relatively low cost and lack of ionizing radiation. Ultrasound does have limitations, he added, including the evaluation of deep lesions, the definition of anatomical extension and the evaluation of the surrounding soft tissue envelope.
7:46 a.m.: Kwon is now presenting on the topic of soft tissue imaging in metal-on-metal total hip arthroplasty.
“The important point here is that the information obtained from plain X-rays is often enough to indicate the need for revision surgery,” he said.
7:44 a.m.: Today's topics will include soft tissue imaging of the hip, metal ion testing methodology, and outcomes (local and systemic complications). There will also be another open public hearing, and panel deliberations.
7:41 a.m.: The FDA recap of day one has begun. Christina Savisaar, PhD, is presenting the recap on behalf of the FDA.
7:30 a.m.: Rohr has called the meeting to order. The panel is foregoing panel introductions. Conflicts of interest are currently being read.
6:31 p.m.: “At this point we do not have clear evidence that [MoM] is superior to other systems,” Rao said. He noted, however, that the data observed today was largely registry-based. One of the purposes of moving to MoM hips was range of motion, he said, and thus range of motion data should be included in these analyses.
“There is no generalizability to the data,” Rao said of the registries presented. “There may be disproportionate representation of some of the devices in some of the registries.”
“In terms of the testing of metal ions, there seems to be a fair amount of uncertainty as to how reliable the results of this testing will be,” he said.
“I think ... I’d also like some clarity on whether we’re able to actually test the valence of the ions being leeched out because the research suggests a fair amount of the variability in the toxicity,” he added.
6:29 p.m.: Band: As a manufacturer, we use extensive control to reduce variability in the final device.
6:22 p.m.: Barber: “Do you really want to go back in to do a revision because of pain and not replace the acetabulum? I would say ‘no.’ Others may disagree with me on that, but that’s my own personal clinical opinion.”
6:17 p.m.: Barber has noted that he has seen a lack of evidence of MoM being more beneficial to any patient subset, enough evidence that MoM hip failure is more catastrophic to the patient and enough evidence that revision or resurfacing of these hips is no easier than that of standard hips.
6:09 p.m.: The panel has reconvened with more discussion of the day’s presentations.
“Microseparation is a bad thing for unforgiving surfaces,” Mayor said, noting that if these materials are allowed they will re-dock and produce edge-to-head contact. He claims these result in gouges or other deformities on the head, creating raised elements on the previously smooth surfaces and scratching the head.
5:55 p.m.: The panel is now taking a 10-minute break. They will resume at 6:05 p.m.
5:51 p.m.: “I didn’t hear anybody comment on the presence of other joint implants, which could have an impact on outcomes,” Cheng said.
5:46 p.m.: “I think we need to differentiate between a hospital database and a registry,” Goodman said. “We have to be economic in terms of what data we gather, because otherwise it becomes unmanageable.”
Goodman also said that hormonal differences must be taken into account when judging the performance of an implant in male and female patients. “Hormonal status is something we must definitely collect,” he said.
According to panel member Scott Evans, PhD, of Harvard University, patient outcomes other than just revision — such as function — should also be taken into account. Further, information must be gathered as to why patients are being lost over time.
“That could be differential, and if you're only analyzing what you have left you could have a very distorted view of what is actually going on,” he said.
5:43 p.m.: The panel is now discussing how differences between males and females (including musculoskeletal differences, osteoporosis occurrence, etc.) may impact the prevalence of MoM issues and how these differences may be accounted for via registry development.
5:38 p.m.: “I would add activity level and pain,” Barber said. “One thing we don't have is a patient-reported outcome measure that works well ... that would be a marvelous thing to have.”
Panel member Barbara Crouch, PharmD, of the Utah Poison Control Center and the University of Utah, College of Pharmacy, suggested a more specific definition of metal sensitivity would be beneficial.
5:34 p.m.: The panel is now discussing what additional data fields would be appropriate or practical to add to existing hip implant registries — or include in new registries being developed.
“Before I added more fields, I would devote more time to splitting the data in the existing registries to see what you can and can’t find,” Li said. “You may find something startling ... there are ethnic differences possibly hidden in there, but if we never split the data we will never know.”
5:29 p.m.: “The threshold of revision may vary among countries and among surgeon, and this may impact the way these data are analyzed,” Cheng said. “The completeness of the database is an issue, there are different levels of training, different access to implants. There are also different styles of practice in the United States.”
5:26 p.m.: Goodman suggested perhaps revision cases in other countries are “shuttled” to surgeons and centers with more expertise, while that is not the case in the United States.
“There may be geographical differences,” he said.
5:23 p.m.: “Surgical technique has become so universal worldwide ... it is amazing how little difference there is, how similar the surgical procedure and technique,” Rohr said, adding that patients in various may have to be more severely impacted by disease or other issues before actually receiving an operation, thus giving the surgeon a more difficult mountain to climb — and potentially impacting data.
5:09 p.m.: “It is with great appreciation, awe and frustration that I listen to the data from these registries,” Li said. “Again, I go back to specificity.”
“At the end of the day, you always seem to end up saying [MoM] does ‘this’ and everything else does ‘that,’” he added. “The problem for me is, when confronted with another device, there is no way for me to take your data and predict its performance. Is it going to be a gender issue? Is it going to be an age issue?”
“It is always really interesting reading, but I have no idea what to do with the information. Is there a plan, now that you have all of this information, to actually sort it all out?”
5:03 p.m.: “It seems like although the results are excellent, they’re slightly less excellent than for other diagnoses,” Goodman said to McMinn, referring to patients with osteonecrosis. “Have you separated out the patients who are on ongoing steroids vs. no steroids at the time of hip replacement?”
4:49 p.m.: “One of the weaknesses of registries is the completeness of the database,” Cheng said. “How do we account for differences in the completeness of the different databases?”
“There are some differences,” Graves said. “What happens is we get notified about 96% of the procedures, so it doesn't matter if patients move from hospital to hospital ... our coverage is about 99.6%. The ones we have lost are those who have gone to another country for their revision surgeries.”
4:45 p.m.: The presentations on the topic of registries have ended. The panel is now asking questions of the presenters.
Lyman has praised the efforts of ICOR, saying it may be the only way to truly answer some of the questions being asked about MoM hip systems today.
4:44 p.m.: “For those who argue against innovation and progress, would you like a 67% failure rate at 16 years, or would you like to make progress?” McMinn said.
4:13 p.m.: Sedrakyan is discussing further details regarding the ICOR pilot project: It spans from 2001 to 2010 and is focused on total hip arthroplasty and not resurfacing. It focuses on patients with osteoarthritis and also looks at varying head sizes. Sedrakyan noted much worse survival in MoM implants as they increase in head size.
4:12 p.m.: Graves has finished his presentation. The next speaker is Art Sedrakyan, MD, PhD, Associate Professor, Director of Comparative Effectiveness Program at NYP at Weill Cornell Medical College of Cornell University, speaking about ICOR, its methodologies and pilot study results.
“We have over 3,000,000 patients worldwide in a distributed system of registries,” Sedrakyan said. “As you can see, this is a very powerful tool.”
Sedrakyan described ICOR as a system that helps remotely access clinical and other data resources which are secured and controlled by data owners. This can, he said, reduce security, proprietary, legal and privacy concerns. It also eliminates the need to create, maintain and secure access to a central data repository.
4:03 p.m.: “Patient factors don’t appear to be as important [with large-head MoM stemmed THR] as with resurfacing,” Graves said. “There is no subset of patients that has been identified as doing better.”
Graves noted evidence suggests there is no benefit or indication for the use of large-head MoM implants.
3:57 p.m.: “When talking about resurfacing THR, some patient factors are important,” Graves said. “Gender, femoral head size and to a lesser extent age impact outcome in a major way. A subset of patients may have an outcome that is equivalent to the average outcome of conventional THR. Experienced surgeons do have better outcomes, but the impact is not strong.”
Graves added that he found significant variation in revision rates depending on the prosthesis used, with only a small number having better outcomes. He added there is a different revision profile for resurfacing when compared to conventional total hip replacements.
3:52 p.m.: Graves noted that while there is much talk of there being differences between outcomes among different registries, the comparisons he has made between UK and Australian registries find that results are “virtually the same.”
3:34 p.m.: The panel is taking a 15-minute break and will reconvene at 3:45 p.m.
3:32 p.m.: Durgin has also expressed frustration with the discussion’s lack of specificity, especially in light of how varied the reported outcomes have been.
“I think we have to fit into this algorithm of follow-up the performance of particular devices,” he said. “What is also non-specific is the discussion of the soft tissue reactions themselves ... lastly, I think we have to step back as good scientists and ask ourselves what the appropriate control is.”
3:28 p.m.: “When you are the patient with a failed implant, the statistics do not matter,” Berney said. “So I guess my question is: What is an acceptable rate of failure?”
“I think it’s important people understand what they are getting into before they get a new joint,” Whittington said. “I think our patients need clear, easily understandable information before they go into it ... it needs to set the tone for what the patient can expect in terms of outcomes.”
“From the surgeon's side, they need to be getting information to the patient that is very clear,” she added. “Hopefully that will improve their feedback to us health care providers so we know what does work and improve the outcomes for these patients.”
“Registry data is useful for an early warning system,” he added, “but they may not give you the cause of the problem.”
3:11 p.m.: “What I'd like some more clarity on in the next day or so is if some of the problems we are seeing with [MoM] are problems with metal or problems with the procedure,” Rao said.
“Metal-on-metal, ceramic-on-ceramic and metal-on-ceramic are unforgiving couples,” panel member Michael B. Mayor, MD, of Dartmouth Medical School. Thayer School of Engineering, said. “They all show evidence of impact loads delivered by the edge of the acetabular component onto the surface of the head in the form of edge stops and gouges. Those are fairly severe alterations of articular surface.”
“We don't know much about patient factors at all,” panel member Stuart B. Goodman, MD, PhD, said. “There also seem to be differences between different nations. I look forward to hearing a robust discussion as to why there might be differences ... in the outcomes and complications from different nations.”
3:03 p.m.: “The identification of a cost-effective screening test to refer these patients to MRI would be critically important," Lyman said.
2:23 p.m.: Gilbert noted that you cannot have wear of metal alloy hip implants without corrosion because as soon as wear occurs and the film over the metal is breached, the extremely reactive metal underneath is exposed and reaction begins.
“Corrosion is about metal ions, but for every charge of metal ion you create, you have these negative charges you have to reduce, and those are essential to what is going on here,” he said. “It’s not just about the metal ions and the debris, although those are clearly important.”
2:20 p.m.: Kurtz has finished his presentation. The next speaker is Jeremy L. Gilbert, PhD, FBSE, Professor of Biomedical and Chemical Engineering at Syracuse University, whose presentation focuses on implant corrosion mechanisms and effects.
“I know we have heard from our colleagues and others that wear creates ions, but that is not true,” Gilbert said. “Wear creates corrosion, which creates ions ... it is not just the consequence of the ions, but the process by which they are generated.”
2:16 p.m.: Kurtz noted that the reason for taper corrosion being an issue with MoM is not well explained right now, citing several studies that all point to various reasons.
"All of these theories are on the table, but we really have not figured it out," he said.
According to Schemtisch, the Canadian experience demonstrated a small number of patients revised where elevated ion levels were a significant factor in the indication for revision. No cases of clinical toxicity were reported, he said, and all patients had increased abduction angles when analyzing socket implantation.
MoM resurfacing, he added, was best performed in male patients under 60 years of age with good bone quality and without significant acetabular deformity. MoM resurfacing, he reported, had essentially halved between 2006 and 2011.
11:49 a.m.: Ludgate said that it is important that one is not taking action based on one result – consider symptoms, ion levels and X-rays and build up your recommendations on that report.
11:42 a.m.: According to Ludgate, an Expert Advisory Group was set up when issues with MoM hips began to become more apparent. A result of their analysis was a medical device alert, which featured recommendations such as 5-year annual follow-ups and metal ion level analysis in the event of symptoms.
9:11 a.m.: Ann Morrison, BS, PT, is presenting her bilateral MoM hip implant failure.
Rajkumar D. Rao, MD, of the Department of Orthopaedic Surgery at the Medical College of Wisconsin,
asked Kwon about the tribofilm and if he sees similar cell death in total hips that use metal-on-polyethylene bearings.