When a hip prosthesis must be rejected : Three things you might not know about the regulation of medical devices
While the ability to innovate is something we wish to foster in health care, our ability to avoid putting on the market a medical device that causes harm may prove equally important. This is what Deborah Cohen (2011), an investigations editor for the British Medical Journal, shows in her story of a regulatory failure, one in which DePuy —a subsidiary of Johnson and Johnson—finally recalled its ASR hip prostheses in August 2010. Her detailed analysis draws our attention on three issues we might take for granted.
1. Incremental improvements may cause unforeseen problems
The ARS is a “metal on metal” hip prosthesis, e.g., the head and the lining of the cup it fits into are made of cobalt chrome metal rather than ceramic or polyethylene. This incremental change to the design of hip prostheses was brought thinking that it would increase their longevity, a strategic matter considering that increasingly younger and more active patients have their hips replaced or resurfaced (e.g., the femoral head is not replaced, but trimmed and capped with a metal covering). It is estimated that around a million total hip replacements are performed on an annual basis worldwide (Skinner and Kay, 2011). Not surprisingly, several manufacturers have sought to seize this market opportunity. Although patients might not choose or even know which implant they will end up with, surgeons could in theory choose from 1539 head and cup combinations that already exist (according to 2010 data from the Australian National Joint Replacement Registry).
DePuy sold around 93 000 ASR implants after it obtained approval from the European regulatory authorities in 2003. However, both pre- and post-market studies showed that, over a relatively short period of time, revision rates observed with ASR were troublesome and that metal debris led to the destruction of soft issues surrounding the joint causing pain and disability in patients. Furthermore, research indicated that variable concentrations of ions of cobalt and chromium were found in the blood and cerebral spinal fluid of patients with metal on metal prostheses (Langton et al., 2009). How come ARS obtained market approval then?
2. Market approval does not imply that a device is safe
ARS was first approved in the European Union market as a class IIb device, which does not require the manufacturer to submit results of clinical studies. In scientific circles, several observers agree that the American Food and Drug Administration (FDA) has a more rigorous premarket approval process than European countries where various private organizations, called notified bodies, operate on behalf of EU governments. Yet, the FDA has a clearance process —the 510(k)— that offers a “similar equivalence” route by which manufacturers do not have to submit results of clinical studies if their device is similar to one already approved. Up to 90% of devices gain US approval through the 510(k) process. It is through this less stringent route that DePuy obtained FDA approval for ARS XL for hip replacement, but not for resurfacing because it was considered a new technique requiring clinical testing. US surgeons could nevertheless use the device for another purpose than the one for which it was cleared by the FDA (see the position statement on “off-label” use of the American Academy of Orthopaedic Surgeons here: www.aaos.org/about/papers/position/1177.asp)
Hence, the regulatory processes by which public authorities decide whether or not a medical device can be introduced on the market are complex, vary from one country to another, differ in several ways from those applied to regulate drugs (e.g., requiring proofs of safety and effectiveness for the intended use) and are not a guarantee of safety.
3. Post-marketing surveillance is necessary, but not sufficient
Once devices are approved, most countries rely on a policy of voluntary disclosure of adverse events wherein the burden is on the shoulders of clinicians and patients who are asked to report those events (see adverse reaction database of Health Canada here: http://hc-sc.gc.ca/dhp-mps/medeff/databasdon/index-eng.php). Such policy posits that medical device manufacturers will act upon such information in due course. The ARS story shows nonetheless that because the clinical outcomes of surgical devices are thought to be closely associated to the experience and skills of the surgeon, a manufacturer may not straightforwardly recognize that poor outcomes are due to the device itself.
This is why Stephen Graves, an orthopedic surgeon and the director of the Australian National Joint Replacement Registry, argues that post-marketing surveillance systems should include the systematic gathering of clinical information. The Australian joint registry enables monitoring over time the revision rates associated to the use of different prostheses. Interestingly, Stephen Graves explains how some devices may be more “usable” than others since they perform well in the hands of different surgeons and for different patients (listen to his interview to the BMJ: http://www.bmj.com/content/342/bmj.d2905.full). In other words, the design of some devices may prove superior in that their outcomes would be less variable.
There have been other hip implants recalled since the late 1990s, including the 3M Capital Hip, which led to a parliamentary investigation in the United Kingdom (Cohen, 2011). While some may argue that there is necessarily a trade-off between innovation and safety, the ARS story shows that regulatory frameworks may also be in need of redesign.
Because the long-term effects of the observed metal concentrations are unknown, the FDA recommends close monitoring of patients with metal on metal hip prostheses, paying attention to cardiovascular, neurological, renal and thyroid signs and symptoms.
|Author :||Pascale Lehoux, Ph.D.
Cohen, D. (2011). Out of joint: The story of the ASR. British Medical Journal, 342:d2905.
Langton, D.J., Sprowson, A.P., Joyce, T.J., Reed, M., Carluke, I., Partington, P., et al. (2009). Blood metal ion concentrations after hip resurfacing arthroplasty: a comparative study of articular surface replacement and Birmingham Hip Resurfacing arthroplasties. Journal of Bone and Joint Surgery -British volume. 91:1287-95.
Skinner, J., and Kay, P. (2011). Commentary: Metal on metal hips, British Medical Journal. 342:doi:10.1136/bmj.d3009.