Yesterday we (among others) reported on claims made in a BMJ article by Belgian researchers that transcatheter aortic valve implantation (TAVI) was being adopted at a rate beyond that justified by the evidence. They had furthermore alleged a number of other misdemeanours including a lack of transparency , and a suggestion that the pivotal clinical work might have had the whiff of self-interest and non disclosure. Edwards Lifesciences, manufacturer of the Sapien valve at the heart of the debate, has responded quickly and forthrightly.
Companies with a revenue stream and growth so heavily dependent on a new technology have two options when it comes to handling bad publicity: Ignore it and hope it goes away or come out fighting with a robust defence. Which one they choose usually revolves around how significant the work is and where it’s published. When something pops up in BMJ they have little choice but to respond, especially when there’s an immediate negative impact on the share price as was the case briefly yesterday.
In a nutshell, Edwards’ response took the following form:
On the claims that Dr Leon, developer and principal investigator was compromised by non-disclosure of a financial interest, Edwards emailed US medtech news site MassDevice to say:
“We believe Dr. Marty Leon has conducted himself throughout the Partner trial in accordance with the highest ethical standards. In his role as co-principal investigator of the trial, he has only been reimbursed for travel-related expenses,”
“Dr. Leon also has – throughout the Partner trial – remained in compliance with the strict conflict-of-interest standards of both the FDA and Columbia University. As previously reported, the sale of PVT to Edwards took place in 2004 and the single milestone payment (that Dr. Leon donated to charity) was made in 2006, well before the beginning of the pivotal trial.”
On the claims that treatment and control groups were imbalanced Edwards said the differences were “known, analyzed and discussed at the FDA panel that resulted in an overwhelmingly positive panel recommendation for FDA approval and was subsequently approved by the FDA in November 2011.”
On the higher risk of mortality highlighted by the 90 “inoperable” patient study, Edwards points out that this was a small subset with no statistical power or significance.
On the argument that TAVI is not cost-effective, Edwards retort that multiple studies have found the opposite to be the case, citing the NEJM study albeit accepting the claim that the transapical group data was not as favourable, due to it being a small cohort operated early in the experience curve.
So there you have it. Two sides of what is probably not a two-sided story. The only thing that is clear is the regulatory approval both sides of the pond, but the plain fact remains that we know nothing of the data used to gain European approval, such as it was, and the data we have in USA limits use to a smaller patient group than seems to be getting the product in Europe. Setting aside the conflict of interest stuff, which might be a red-herring, what we’re left with is a situation where evidence-based medicine, while being something all would sign up to, is not that straightforward.
Source: BMJ, NEJM, MassDevice