A Department of Health review into the Poly Implant Prothèse (PiP) breast implant scandal has found that although the UK regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), acted appropriately and followed scientific and clinical advice, there are “areas where improvement can and should be made for the future.”

Back in March 2010 the French regulator found that the manufacturer of the PIP silicone breast implants had been using a grade of silicone filler that was not of the standard previously approved for implant use.

The marketing, distribution and export of PIP silicone breast implants was suspended across Europe, and the MHRA, issued a medical device alert on 31 March to all UK clinicians and cosmetic surgery providers, asking them to cease use of the implants, and to quarantine and return all of the affected devices to the distributor.

But the follow up differed. The French Ministry of Health told women to have their implants removed as a precautionary measure. The MHRA said that, on the basis of the available evidence, women in the UK should not be advised to seek removal of PIP implants in the absence of clinical symptoms.

And therein lies one of the major problems with medical implant regulation—available evidence. As the BMJ has reported over the past few years, a paucity of data plagues decision making when it comes to medical implants, even though these are used influence health outcomes in a similar way as a drug treatment.

Premarket clinical trials will not have picked up the problems with PIP implants (although it’s worth noting that these implants did not make it past the FDA’s more robust system for premarket approval). However, what is now clear is that much more effective post-marketing surveillance is needed.

Health minister Earl Howe has made the following suggestions, but the question will remain do these go far enough. He says there is a “system wide responsibility for maximising reporting of adverse device incidents and for ensuring that reports are of high quality.”

The MHRA, he said, should continue to work with various health organisations and ensure that professionals have a duty to report.

The current system of reporting adverse events through the “yellow card” reporting system, but even this system is widely acknowledged to be unreliable. Studies have suggested that there is a large underreporting rate of adverse events.

A recent health technology appraisal publication on adverse drug reactions and the “yellow card scheme” concludes that improvements to reporting systems are justified and there is a need to educate patients that they can and should submit their own reports.

Doctors do not always realise that a presenting complaint is actually an adverse reaction to a drug or device—particularly if it has not been associated with the treatment in the past or it is an emerging condition, such as those being observed with elevated metal ions released from some types of hip prostheses.

Even when the side effects are known, doctors do not always notify the regulator. In one study at John Radcliffe Hospital in Oxford, only 6.3% (30 out of 447) of drug reactions were reported to the UK regulator—and the majority of these were well-known reactions to established drug (Br J Clin Pharmacol 1996; 42: 423–429 ). The system for devices is much less opaque: systems do exist for online reporting of adverse incidents involving medical devices but there is no comparable ‘yellow card system.’

This presents substantial problems in understanding how many and how often adverse events are reported to the MHRA. The inadequacy of device reporting is highlighted by the fact that the regulator has to actively request reports on adverse effects in patients who have a medical device.

The MHRA also needs to be far more supportive of clinicians–and other health professionals, as well as patients—when they raise a concern. Doctors risk ire from other doctors if they raise alarm. Indeed, they may be blamed for the problems rather than the companies themselves.

Throughout the course of the investigations, the BMJ has spoken to doctors and patients who have felt they have received short shrift from the MHRA. This has to change if doctors are to keep their faith in the ability of the MHRA to protect patients. Much focus is given to registries as a source of post-marketing surveillance—and it’s not the first time the use of registries has been mooted.

The report Disease Registers in England, commissioned by the Department of Health, highlighted in 2002 that there is “heterogeneity in every aspect of registries,” which reflects the “fragmentation of policy and lack of strategy in this area.” Therefore it is not surprising the Breast Implant Registry was closed in 2005 because most women registered declined to participate in follow-up research. The report says “while registries are to be encouraged they are not a panacea on their own.”

Nor are industry sponsored registries the answer. Professor Stephen Graves, director of the Australian National Joint Replacement Registry, has described the importance of being at arms length from industry in an interview with the BMJ.  If industry are part of the decision making panel there is a risk that data may be used for the wrong reasons.

The report suggests that “nothing about this case provides evidence to suggest the system for regulating medical devices is fundamentally unsound and that there needs to be a shift to a system like that used to regulate pharmaceuticals in the EU, or the system used to regulate higher risk devices in the United States.”

Perhaps not in this case, but the issues surrounding the regulation of hip implants suggests otherwise.
The breast implant scandal captured the imagination of the press because it was a straightforward story—silicon in a breast implant being replaced with industrial grade product, which leaks into women’s bodies with unknown long term consequences. The problems with some types of metal on metal hips and other implants are much more complicated. It perhaps would take an inquiry into these that would really flush out the true impact of under-regulating implants.

While the report concedes that the MHRA and government should endeavour to ensure that future reform of devices regulation at European level is based on a “rigorous and transparent assessment of the evidence,” it suggests that these should be costed. As BMJ investigations have shown, the current system is far from transparent and there is a lack of evidence about safety and effectiveness for current devices on the market. See also these articles:

http://www.bmj.com/content/344/bmj.e1410

http://www.bmj.com/content/342/bmj.d2748

If medical device companies don’t need to conduct any clinical studies to be sold throughout the EU, where is the incentive to do this? Currently, one of the key reasons to conduct such studies is to get approval from the FDA and thus access to the US market. Those against more premarket hurdles have argued that there is no evidence that the US system for approval, has stopped more faulty devices from entering the market there than in the EU. They say there is also a cost attached to generating more data.

But what is the cost of a failing implant? Until we know the real cost of failing devices—to patients, to the NHS and to other parts of the social care and security systems—this is a question that is difficult to answer.

Earl Howe said: “Serious lessons must be learned from this scandal. The MHRA needs to look at how it gathers evidence so it is able to identify problems early. It needs to better analyse reports about higher-risk medical devices. And it needs to improve the way it communicates with the public.”

One thing for certain is that the MHRA needs to be independent, transparent and supported to make difficult decisions that may disagree with policy, but ultimately protect the public.

Deborah Cohen is investigations editor, BMJ
Carl Heneghan is Reader in Evidence-Based Medicine, Director of the Centre of Evidence-Based Medicine at the University of Oxford’s Department of Primary Health Care Science, and a GP.