On May 20, 2008, Chris Wilcox underwent a decompressive hemilaminectomy and posterior lumbar fusion at levels L5-S1 in which Infuse was used. Off-label. The surgery was performed by Ralph Katz, M.D. The use of Infuse was off-label in this surgery because it was implanted by means of a posterior approach and the requisite LT-Cage was not used.
There were serious complications so the patient (Wilcox) sued Infuse manufacturer Medtronic, Inc., on June 2013 in the U.S. District Court, Eastern District of Louisiana. Wilcox is accusing the company of promoting Infuse to his and other surgeons for off-label uses when they knew it was dangerous and therefore is to blame for his complications.
Post-operative imaging studies, according to his attorneys, revealed that Wilcox had developed uncontrolled bone growth and resulting pseudoarthrosis and radiculopathy related to bone overgrowth at or near where the Infuse was implanted.
The Lawsuits Start
This isn’t the first lawsuit that has been filed against Medtronic over complications arising from the off-label use of Infuse. Medtronic continues to defend itself by invoking its hard won Riegel Supreme Court decision which held that companies that have received FDA approval for their products are preempted from being sued in state courts for tort claims.
But a recent decision by a Minnesota state judge pierced the preemption defense and allowed a defendant to proceed with his lawsuit against Medtronic.
Wilcox’s “Complaint for Damages” charges Medtronic with: Inadequate Warning; Design Defect; Breach of Express Warranty and Breach of Implied Warranty.
Wilcox Allegations
Within the lawsuit are allegations that Medtronic improperly promoted off-label uses of Infuse. Wilcox’s lawyers try to prove those allegations by presenting testimony of former Medtronic employees regarding off-label promotion in a shareholder derivative action, undisclosed payments to opinion leaders, letters from U.S. Senators regarding promotion and marketing of Infuse, the June 1, 2011 issue of The Spine Journal and the October 25, 2012 U.S. Senate Committee on Finance “Report on Medtronic’s Manipulation of the Infuse Studies and Close Financial Ties with Researchers.”
The case also brings in the settlement of two whistleblower lawsuits with the Department of Justice and the imposition of a Corporate Integrity Agreement (CIA).
While Wilcox’s lawyers have thrown the kitchen sink into their 94-page Complaint, we focus only on specific allegations made by unnamed former Medtronic employees identified as “Confidential Witnesses” who claim first-hand knowledge of company actions. We will not recount the well-known political and controversial charges leveled by The Spine Journal and U.S. Senators.
The Off-Label Conundrum
The case boils down to one simple question: Did Medtronic promote Infuse for off-label uses? The case also raises important questions about who has a right to speak about off-label uses in light of a recent U.S. Appeals Court decision holding that a device sales rep has a First Amendment right to speak truthfully about a product to physicians and patients.
Wilcox’s complaint says Medtronic employees and company consultants “thought leaders” acting in the name of the company conducted meetings, held seminars and published papers promoting the use of Infuse.
Medtronic directly and indirectly promoted, trained, and encouraged surgeons to perform spinal fusion procedures utilizing Infuse in a dangerous off-label manner, claims Wilcox. The company “recklessly and/or fraudulently promoted and marketed Infuse.”
Limited FDA Approval
Wilcox recounts that the initial FDA approved labeling for the product in 2002 indicates in bold underlined formatting: “These components must be used as a system. The Infuse Bone Graft component must not be used without the LT-Cage Lumbar Tapered Fusion Device component.”
Medtronic, Wilcox points out, sells Infuse separately from the LT-Cage to surgeons who use the product off-label.
Soon after FDA approval, Medtronic issued a “Safety Alert” letter to surgeons on September 14, 2004, informing them that the company had received reports of complications associated with off-label use of Infuse in anterior cervical fusion procedures.
On July 1, 2008, the FDA issued a Public Health Notification to healthcare practitioners entitled “Life-threatening Complications Associated with Recombinant Human Bone Morphogenetic Protein in Cervical Spine Fusion”.
In other words, says Wilcox, Medtronic had plenty of notice that the off-label use of Infuse was dangerous.
But, he continues, the company tried to find a way around the complications because sales of the product eventually exceeded $3.6 billion since the launch of the product and off-label uses accounted for 85% to 90% of all spine surgeries involving Infuse.
Confidential Witnesses
He cites a “Confidential Witness” (CW) who claims former COO Michael DeMane, former president of Medtronic Spinal and Biologics Pete Wehrly, and former worldwide vice president and General Manager, Biologics, Jon Serbousek, were all aware of the adverse events related to Infuse.
Confidential Witness # 13 (CW13) claims he was rebuffed for raising concerns about off-label promotion, and was told “we’re paying you a lot of money to launch this. Shut your mouth and take the money. Let us worry about what is off-label or isn’t.”
Indeed, to set sales projections for Infuse, another confidential witness (CW2) stated that Medtronic’s marketing department accounted for the scope and number of procedures performed, including the numbers of off label procedures, such as PLIFs and TLIFs, to predict sales projections.
Final sales quotas were dictated by senior management, and were far in excess of what the Spinal Division had projected, or could be achievable absent promotion of the product for off label uses, according to CW2.
“Aggressive” Sales Goals
Numerous confidential witnesses, including CWs 1, 9, 12 and 14 (a senior manager for Medtronic’s Spinal and Biologics division from 2005 to 2008), allegedly confirm the intense pressure management placed on its sales representatives to meet the sales quotas. Like CW2, CW14 claims that sales goals were set by a handful of Medtronic executives, and that they were “very, very, very aggressive.”
Wilcox goes on to allege that the company directed its own sales representatives to promote off-label uses of the product, “many of whom… guide[d] surgeons through off-label uses of the product during surgery.”
“Although undisclosed by Medtronic, the first-hand accounts of its former employees demonstrate that this extraordinarily high off-label use was driven by Medtronic’s sales force. Specifically, Medtronic’s marketing and sales employees directed spine surgeons to Medtronic-compensated consultants or ‘Opinion Leaders’ or ‘Thought Leaders’—other spine surgeons paid enormous sums of money by Medtronic—the sole purpose of which was to promote off-label uses of Infuse.”
According to Wilcox, several spine surgeons have already testified under oath at depositions that Medtronic sales personnel overtly and directly promoted to them the off-label uses of Infuse in the spine.
Infuse Marketing
CW13 said he was brought into the company to develop a marketing plan; which included:
- Development of a “referral marketing” campaign designed to promote the product for off-label uses via a physician referral network;
- Identifying which surgeons should be targeted as part of Medtronic’s off-label campaign and what claims Medtronic would make about the product;
- Development of a “cookie-cutter” CD series that outlined Medtronic’s off-label campaign and included information on off-label procedures that was distributed to Medtronic sales representatives.
According to CW13, the referral marketing program involved having surgeons meet with other surgeons as a means of prompting discussion of off-label uses of Infuse among practitioners. CW13 also stated that Medtronic used a physician training program involving cadaver labs as a means to instruct surgeons regarding off-label applications.
Sales Rep Activity
Another confidential witness alleges the following actions by the company:
- Company sponsored physician meetings during which paid consultants made off-label presentations to local physicians.
- Instructions to sales representatives regarding various off-label uses of Infuse, including how much to use with cervical fusions when instructing physicians.
- Directions to sales representatives that they be present during off-label surgeries “to assist and direct and give advice when asked.”
- Creation of sales quotas that were described by the CWs as impossible to reach without pushing off-label use.
- Sales representatives’ references to data from published literature (presumably funded by Medtronic) when questioned by surgeons, the purpose of which was to provide surgeons with information regarding proffered techniques for off-label procedures and to educate them regarding off-label uses.
- Development of smaller-sized bone graft kits under the guise of selling them for FDA-approved uses, when, in actuality, the company had designed each kit to be used in an off–label cervical fusion surgery.
When questioned by a physician about how to use Infuse off-label, the witnesses claim sales representatives directed physicians to other surgeons who used the product off-label and also would demonstrate or explain how to do so.
The unnamed CW claims that during quarterly meetings in at least one sales region, a national biologics specialist would attend to explain how to conduct off-label applications of Infuse.
Sales representatives were also allegedly told to instruct physicians to use half the dose of rhBMP-2 during cervical fusion, and, aware of adverse events, instructed the representatives to tell physicians to use steroids to combat potential inflammation. They also directed physicians using the product in cervical spine fusion to throw away up to half of the rhBMP-2 dosage. Physicians were allegedly given a small book containing no reference to Medtronic, which contained information regarding the volume or dosage of rhBMP-2 that should be used for off-label applications of Infuse.
Finally, the CW claims the company instructed sales representatives and others during sales presentations regarding how to “get around” restrictions on off-label promotion.
Off-Label Information
Medtronic has demonstrated its willingness to push these cases to the highest court, so we don’t see these Complaints going to a jury anytime soon. However, if the lawsuits are allowed to proceed, Wilcox and Medtronic may set new legal standards for how off-label information can get into the hands of patients and physicians. More information never hurt a patient.
