Professional Engineering

Wilkinson says substantial equivalence “is a matter of balance”. “Repeating expensive and extensive trials on products, where it’s pretty demonstrable that there is substantial equivalence in terms of materials and design, seems to me to be an unnecessary step. But equally, I think there’s a degree of scrutiny that needs to be placed on what constitutes substantial equivalence – that needs to be addressed. Perhaps a few things have slipped under the bar in the past, and we need to make sure that doesn’t happen in the future.”

Joyce would like to see a much greater use of clinical trials of new products. “When a product works, brilliant. When products don’t turn out to be as good as they should be, as with large metal-on-metal hip replacements, there is an argument for clinical trials. Under controlled conditions, you can prove a device is successful. Proving it’s successful helps to convince scientists, medical professionals and patients. 

“There is an argument that by doing clinical trials, you don’t reduce innovation; you go through a process that proves your product is good. It’s possible to go through the clinical trial route and come out with a product that’s better than anything else on the market.”

Wilkinson acknowledges that some aspects of the current system have drawbacks. “There’s no doubt in my mind that products that should have been subjected to more in the way of clinical investigation in the past will probably not get through the system in the future.”

He suggests, as in the case of the changes to the MHRA guidelines on monitoring of large metal-on-metal hips, that a key role for the agency lies in “post-market surveillance”. “The sooner you can pick up signals that suggest things aren’t performing as they were expected to, the more effectively you can limit the damage.”

An early warning? Alarm bells are now ringing in some quarters over yet another medical device, the transcatheter aortic valve. The transcatheter implant is a minimally invasive method for replacing the aortic valve in patients who are unwilling or unable to undergo open heart surgery.

But some doctors are now worried that implanting the device dramatically increases the patient’s risk of subsequently suffering a stroke. One such is Belgian cardiologist Hans Van Brabandt, who directs the Belgian Centre for Evidence-Based Medicine. 

The procedure, known as transcatheter aortic valve implantation (TAVI), involves passing a replacement valve through a hole in the groin by a puncture of the femoral artery and pushing it up to the ascending aorta. The technique was first demonstrated in Europe in 2002 but approved by the US’s FDA only last year. Already many thousands of such operations have been carried out.

Brabandt argues that the primary concern is that TAVI increases the risk of a subsequent stroke. Some patients have undergone the procedure because it is difficult or impossible to access their aortic valves through traditional surgery. In these, the implant has been found to double the risk of stroke after one year compared to patients treated by “pure medical treatment”, or medication and other remedies aside from surgery. Brabandt says: “The medically treated patients have sustained a stroke in 5% of cases. If they have been treated by TAVI, the figure is 10%. For patients that are operable through traditional means, the risk of a stroke is lower, at 4%. But patients who are operable who are treated with TAVI also double the risk of suffering a stroke, at 8%.”

The worry, in this case, is that patients who could be treated via surgery are opting for TAVI because it is more palatable than invasive methods. “If you ask a patient with aortic stenosis [a disease in which the opening of the aortic valve is narrowed] whether they would prefer to have their chest cut open with a saw or, alternatively, a small catheter introduced via the groin, many patients will prefer the less 
invasive methods.

“But the patient is often unaware of the fact that their risk of having a stroke doubles.”

Brabandt believes it is too easy for medical implants to be approved for the European market. High-risk devices are gaining CE marks without a proper assessment of their safety, he suggests. To receive the CE stamp, manufacturers may have to demonstrate that a device meets quality standards and that the production process is repeatable but, much like Joyce, Brabandt believes that more rigorous trials 
are necessary.

“What is needed is a randomised control trial that shows the benefits of the device before a CE label is granted. Randomised control trials are the only devices that allow us to demonstrate that a given medical device is beneficial to patients.”

The money involved in TAVI is significant. A device may cost €20,000 and the procedure as a whole close to €50,000. “In Europe, it has the potential to be a billion-euros-a-year market,” says Brabandt. 

“But our recommendation is not to use this technique in patients other than those who cannot be operated on because of anatomical or mechanical restrictions. It is our estimate that only about 10% of those who are treated with this technique should be.”