Holes in medical safety net

SINGAPORE - Some 115 patients received a faulty hip implant in Singapore between 2006 and 2010.

Made by DePuy, a subsidiary of pharmaceutical giant Johnson & Johnson, it was called the articular surface replacement (ASR) implant system.

The ASR was once in widespread use. But many reports have surfaced of the ASR wearing off much faster than the minimum 15-year lifespan expected of hip implants.

Made of cobalt and chromium, it was also causing cobalt or chromium poisoning in implant recipients. Patients suffered pain and swelling in the groin and hip, making walking a torture. The ASR had to be removed and replaced with tried-and-tested hip implants.

At least seven patients here have undergone revision surgery. Over 8,000 lawsuits have been filed against DePuy in the United States for its ASR.

In Singapore, new rules mandating the approval and registration of all medical devices to be used here kicked in only in January this year, whereas the ASR was globally marketed from 2003. The Health Sciences Authority (HSA) requires only an abridged evaluation of devices already approved by the US regulator, the Food and Drug Administration (FDA), or its European counterpart.

In practice, local doctors still look to FDA certification of medical devices as being safe and effective. So how did the ASR slip through the FDA safety net?

Unfortunately, it was approved under what is called the 510(k) Process for devices the FDA deems to be only of medium risk, such as infusion pumps and so on. This process requires no clinical trials. The device is approved by FDA's internal reviewers, a workforce that has shrunk in size because of budget constraints.

In 510(k), the device maker just needs to show that its new device is "substantially equivalent" to another that has been legally on the market for about the same use. The latter is called the "predicate". If FDA reviewers decide that the new device is "substantially equivalent" to a "predicate" cited by the maker, they approve it without having to call for an advisory committee to scrutinise it.

And once the maker makes a 510(k) submission, FDA must ascertain within 90 days if the device is "substantially equivalent". If it is, the device may be immediately marketed.

If it is not, the device is reclassified as a high-risk one - examples include heart valves or stents - for which an advisory committee is formed. This comprises experts from academe and industry as the FDA does not have the expertise to assess every possible device.

The approval process for high-risk devices is thorough but expensive. Still, few high-risk devices present themselves. In 2009, for example, only 20 high-risk devices were submitted to the FDA for approval. In that year, by contrast, 3,600 medium-risk devices were submitted for 510(k).

The ASR saga shows why 510(k) approval for medium-risk devices by an undermanned FDA is cause for serious concern.

Last year, the FDA's internal processes were scrutinised by the Institute of Medicine (IOM), medical advisers to the US government. The review found that the device makers could cite predicates even if they were no longer in use or had been recalled as they did not show up in FDA databases as being obsolete or recalled. Then there were predicates cited that had themselves been approved based on earlier predicates, a chain that could go back many decades.

So, through 510(k), some manufacturers never had to provide independent proof of safety or effectiveness of their devices at all. The IOM found that 510(k) did not establish device safety and effectiveness, so it should be thrown out and replaced completely.

Yet a recent study by the industry association casts 510(k) in a good light. Between 2005 and 2010, only 77 devices or 0.16 per cent of all 510(k) approved devices had to be recalled for being very seriously defective.

But this surprising finding may just reflect FDA tardiness in rescinding its 510(k) approvals. The few withdrawals of 510(k) approval came only when manufacturer fraud was revealed, such as through consumer lawsuits.

This institutional tardiness may spring from FDA's weakness in data collection and analysis of device safety in actual use on the market. When problems arise with approved devices in widespread use, FDA post-market surveillance frequently fails to detect them.

The ASR failed within months of implantation in some patients. Such news appeared widely on social media. But it was only in August 2009 that the FDA asked DePuy for additional safety data. Instead of supplying it, DePuy simply stopped making the ASR the following month. But it continued selling off devices already made, to clear its inventory worldwide. In August 2010, DePuy recalled the ASR voluntarily.

Singapore's market is too small to justify thorough pre-market approval of all medium- and high-risk devices here. A more practical approach is for HSA to encourage doctors, patients and families to report adverse effects of devices they are using. This would help to catch another ASR case much earlier, which could boost patient safety.


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