Belgian researchers, commissioned to perform a health technology assessment into the use of transcatheter aortic valve implantation (TAVI) have concluded the technique is only justified in a small proportion of the thousands of candidates in whom it is currently being implanted. In an article published on Medpage today, which can be found here, the researchers reportedly concluded in an analysis article written by the Belgians on British Medical Journal online, here, that European regulatory laxity means the device is being used on thousands of heart valve candidates when the evidence suggests it can only be justified in patients rendered inoperable by conventional surgical techniques.
The two principle TAVI products, Medtronics’ Corevalve and Edwards’ Sapien, were both CE marked back in 2007, according to the team “long before any substantial clinical trial evidence was available.”
In June, as reported on our pages, Edwards’ Sapien got its FDA approval extended to include patients considered at high risk for conventional surgery (Its previous approval was only for patients considered inoperable by other means). This approval came on the back of the FDA panel’s expert panel who considered the high stroke risk found in studies to be not enough reason to withhold their recommendation. Again the Belgians disagree, stating that “it is difficult to see how healthcare payers can justify reimbursing TAVI for patients suitable for surgery, given that the risk of stroke is twice as high after TAVI.”
So where do we end up with all this? While the study ostensibly looked into cost and cost effectiveness, it appears to have ended up looking rather more closely at the regulatory situation and particularly the issue of transparency, fuelled in its quest for evidence by a distinct sense that all the facts are not on the table and that the extensive use of these devices might not be justified if they were.
In the meantime Edwards grew its Q2 2012 figures nicely, fuelled exclusively by Sapien, including 15% revenue growth in Europe alone, all suggesting anything but a restriction in patient selection by clinicians enthusiastically adopting the procedure.
If the “facts” are that TAVI carries a level of stroke risk that make it less successful than currently available data suggest, that it can only be economically justified on a very limited patient cohort, and that 1 year outcome figures show mortality in one third of “inoperable” patients rather than a fifth of patients treated conventionally, then maybe the Belgians are right to raise the question.
And then they conclude with the hammer blow of hammer blows if they really want to stir up the cauldron of “conflict of interest”. It turns out the original developer and principal investigator, one Martin B. Leon, MD, from Columbia University stood to benefit from gaining regulatory approval.
The article states “According to the Belgian researchers, part of the deal involving the sale of Leon’s valve company to Edwards included future payments from Edwards “on the achievement of three milestones: successful treatment of 50 patients, regulatory approval in Europe, and limited approval in the U.S.”
These three milestones were not disclosed in the original paper (on the valve study) published in the New England Journal of Medicine, they said.
This all goes back quite along way, for example in this Bloomberg article from 2006. But looking past the implied potential conflict of interest cited by the Belgians, surely the main issue remains the availability of evidence. If FDA restricts use, then the reasons should be understood in Europe and somehow acted on. If there’s a whiff of lack of transparency in the data used to support even FDA’s limited indication then the only way to clear that up is to get the whole lot on the table. Clinicians and healthcare providers really ought to be asking these questions.
Meanwhile the Belgian research team is clearly asking its own question; “how can it be right that the lead investigator in pivotal clinical work has a financial interest, disclosed or otherwise, in a favourable result?”
It’s a case study of so many issues, probably the most unnerving being European regulators’ willingness to CE mark the product five years ago. It sounds like the evidential data was wafer thin(not that we know this because there remains no obligation to disclose it) and that maybe the promise of saving the lives of inoperable patients, while being a laudable goal, might just have ended up somewhere rather less well justified by evidence provided either then or more recently.
Source: Medpage today, British Medical Journal, Bloomberg Businessweek