Diana Zuckerman, PhD, National Center for Health Research, November 13, 2019
Thank you for the opportunity to speak at this Advisory Committee meeting today regarding immunological responses to metal in implants.
The National Center for Health Research is a nonprofit research center that focuses on the quality of medical products and procedures and does not accept funding from medical device companies or pharmaceutical companies. I’m here today to share my perspective as a scientist as well as a patient. I am trained in epidemiology and served on the faculty at Vassar and Yale and as a researcher at Harvard. I’ve also worked in the U.S. Congress on FDA issues and as president of the National Center for Health Research I have a great deal of experience with FDA regulatory issues.
In addition, I got a hip implant 10 years ago, and I’m glad to say my experience has been a very good one. But at the time I was deciding on the surgery, neither the surgeons I interviewed nor the research literature provided the kind of information I needed to make an informed choice. In fact, one surgeon recommended a metal-on-metal hip for me because I was relatively young and active. Fortunately, I was already aware of metal debris issues so I did not make that choice. But the lack of information then and now was very clear to me as a patient. I was not able to obtain scientific data from the surgeons or online, including PubMed.
I want to say that this has been one of the most interesting and informative FDA meetings I’ve attended, and the speakers have provided a great deal of important information.
What Research is Needed?
I’m here to talk about the big picture. We’ve heard this morning about a great deal of research findings and the need for more and better research. I want to emphasize that we need much better pre-market studies, not just post-market studies. Pre-market clinical trials are often lacking because of the 510(k) process, but even when premarket clinical trials are conducted, they are often inadequate to provide the information patients deserve.
We need clinical trials and other well-designed studies of large number of patients, and as one of the speakers said this morning, we need to compare information about patients who have good experiences with their implants with those who do poorly with their implants. These studies need to include a patient population with sufficient diversity in terms of age, sex, race, BMI, activity levels, allergies, and metal sensitivity, to determine how safe and effective the products are for these subgroups.
We need clinical trials and big data analyses that follow patients for years in order to evaluate the effects of wear and changes in immune responses over time.
We heard this morning that patch testing is inadequate to identify which patients will have a negative reaction to an implant, and that other diagnostic testing also has limitations.
I also want to express our concern with the tendency to extrapolate results from an implant used in one part of the body to implants made of the same materials that are intended to be used in another part of the body. We know from listening to patients that this can result in terrible problems.
We are also concerned about extrapolating results from an earlier version of an implant to a newer implant, when the newer implant differs in ways that could affect safety and effectiveness. Those differences might be different metals, changes in size or shape, differences in manufacturing, or numerous other changes typically made in an effort to improve implanted devices.
We encourage the FDA to require that studies specifically look for adverse events that are related to immune reaction or wear. These adverse events might be local or might be systemic, and some of these events would not necessarily be included in studies asking about all adverse events.
Perhaps most important, we need comparative effectiveness studies that compare clinical effectiveness and patient-centered outcomes. I know that the FDA rarely requires comparative effectiveness studies, but those are the types of studies that are most likely to provide useful information for patients and their physicians.
If certain implants seem to be causing certain reactions with certain kinds of patients, wouldn’t it be very important to know how that compares to other alternatives of the same kind of implants? We can’t treat all hip implants that are polyethylene and metal as if they’re all the same. We can’t treat all metal-on-metal implants as if they’re the same. We need to compare different models, different implants made in different ways with different materials by different companies and get the kind of real data that patients and physicians can use to make informed decisions. Until then, it won’t be possible to figure out to what extent negative responses and implant failures are due to patient vulnerabilities or sensitivities and how much is due to the difference between various devices.