Medtronic Saga: Corrupt Science, Belated Warning

As the result of an unusual effort designed to bolster transparency in clinical trials, two independent analyses have found that a Medtronic (MDT) product used as a bone graft substitute in spinal fusion surgeries offers little benefit over conventional procedures and may be linked to an increased risk of cancer as well as the possibility of sterility in men.

Beyond the findings, the significance of these analyses is that they were funded by Medtronic, which was widely criticized after reports disclosed that doctors with financial ties to the device maker were aware of serious problems with the Infuse spinal fusion product, but never disclosed potential health complications in articles in medical journals. Their articles greatly boosted usage, including off-label use (see earlier Pharma news and this).

And what does Wall Street think? The findings are mixed, and one editorial published in the Annals of Internal Medicine “suggest InFuse will continue to have a role in certain fusion procedures,” writes Wells Fargo Securities analyst Larry Biegelsen. He expects Infuse sales this year to hit $422 million, which would represent a 22 percent decline and he notes that the product is now likely to account for just 2.5 percent of overall Medtronic sales in the current fiscal year.

MDT Revenue TTM Chart

MDT Revenue TTM data by YCharts

The conflicts not only prompted an investigation by the US Senate Finance Committee, but an entire issue of The Spine Journal was devoted to reviewing 13 studies previously published elsewhere and discovered that side effects were downplayed or omitted. As a result, Medtronic agreed to provide the Yale University Open Data Access Project with patient-level data for independent review.

The publication “heralds a historic moment in the emerging era of open science,” according to an editorial in The Annals of Internal Medicine, which published the two reviews. “The YODA project seeks to address the problem of unpublished and selectively published clinical evidence. Nearly half of clinical trials are never published and many that are have long delays in publication.”

“…Amid the current dialogue about open science in medicine, few imagined that such a prominent company would voluntarily make available all of its internal patient-level clinical research data on one of its major products. At a time when many companies express verbal support of open science, Medtronic joined the YODA project and demonstrated what is possible.”

Such proclamations are a decided contrast from a widely held view just two years ago that Medtronic, which paid YODA $2.5 million to fund the reviews, was a poster child for corrupt science. The Infuse product, which was approved by the FDA in 2002 and contains a genetically engineered version of a naturally occurring protein, was implanted in nearly 1 million patients and racked up hundreds of millions of dollars in annual sales before the scandal broke.

As for the findings, YODA tapped two different institutions to sift through the data. Researchers at Oregon Health and Science University in Portland, Oregon, found Infuse did not appear to offer any advantages over a bone grant and may pose a small risk of cancer, as well as a complication that may cause sterility in men and the formation of excess bone.

Meanwhile, researchers at the University of York in England found that Infuse was more effective than a bone graft in improving pain and quality between six and 24 months after surgery, but nonetheless, the “improvement fell below clinically meaningful thresholds.” In other words, the reviews offered a mixed bag, at best – limited efficacy benefit and safety concerns.

Moreover, both reviews found high levels of reporting bias in the papers that were published by Medtronic, which resulted in underreporting of adverse events. “In conclusion, we found substantial evidence of reporting bias and no evidence that (Infuse) is more effective than (the most-favored procedure) in spinal fusion, with some evidence of an association with important harms.”

The findings are likely to accelerate the push for greater disclosure of patient-level trial data, an issue that is controversial among drug and device makers. In the pharmaceutical industry, for instance, the PhRMA trade group earlier this year lambasted the idea in response to the creation of the AllTrials campaign that has the support of BMJ, one of the most widely read medical journals.

Separately, AbbVie (ABBV) recently filed injunction to prevent the European Medicines Agency from releasing data for its Humira rheumatoid arthritis treatment. And Roche has been squabbling with Cochrane Collaboration researchers over data for its Tamiflu treatment, although the drugmaker is preparing to release some data.

Last week, the American Diabetes Association called for several drugmakers – Merck (MRK), Eli Lilly (LLY), Novo Nordisk (NVO), AstraZeneca (AZN), Bristol-Myers Squibb (BMY) and Boehringer Ingelheim – to release patient-level data about their GLP-1 diabetes medicines over concerns about causal links to pancreatitis and pancreatic cancer. The drugmakers have agreed to discussions, but nothing else so far (read earlier Pharma news).

To read the remainder of this article, go to Pharmalot.

Ed Silverman, a contributing editor of YCharts, is the founder and editor of Pharmalot. He previously reported on the pharmaceutical industry and other business topics for the Star-Ledger of New Jersey, New York Newsday and Investor’s Business Daily. He can be reached at editor@ycharts.com. You can also request a demonstration of YCharts Platinum.

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