Medical Device Daily Washington Editor
Off-label device use and clinical trials sometimes look one and the same, and a Dec. 17 letter from Sens. Max Baucus (D-Montana) and Chuck Grassley (R-Iowa) implicitly acknowledges the difference even as the letter focuses on a purported clinical trial at the Walter Reed Army Medical Center (Bethesda, Maryland). The letter asks administrators at Reed about the activities of Timothy Kuklo, MD, of Washington University (WU; St. Louis, Missouri), who resigned from his post at WU last year after allegations surfaced that he falsified study data for the Infuse bone morphogenic protein – made by Medtronic (Minneapolis) – while at Reed.
Medtronic is said to have terminated its consulting agreement with Kuklo last year, ending an eight-year relationship during which the orthopedist purportedly earned roughly $800,000. It has also been alleged that Kuklo failed to disclose the consulting arrangement to WU and with the Department of the Army. The falsified data also led to a withdrawal of the article reporting the results of the study, which appeared in the Journal of Bone and Joint Surgery (JBJS). Kuklo is said to have forged the signatures of others whose names appeared in the article.
The Dec. 17 letter from Grassley, the ranking member of the Senate Finance Committee, and Baucus, the committee chairman, is addressed to Major General Carla Hawley-Bowland, who took over at Reed in 2007. The senators acknowledge Hawley-Bowland's September 2009 response to the senators' queries about the article in JBJS, but they inquire into “another study that was conducted“ by Kuklo, David Polly, MD, and Michael Rosner, MD, – all of whom are said to have been employed at Reed – in 2002. This study is said by Baucus and Grassley to have been conducted without approval by the Army, and involved the use of Hydrosorb, a mesh also made by Medtronic, along with Infuse, in spinal surgeries on 35 patients at Reed. Noting that the combination of the two products in this application is “an off-label use of medical devices,“ the letter reminds Hawley-Bowland that the Hydrosorb was “cleared for indications such as support of weak bony tissue,“ but not cleared “for use in a load-bearing capacity.“
Baucus and Grassley note further that senior staff at Reed had informed Finance Committee staffers that the JBJS article dealt with an unauthorized retrospective analysis of surgeries, which would also have required authorization from Reed, and the Senate letter states that Reed indicated that it had no applications on hand for such a study.
The senators note that the patients at Reed “were consented for surgery, but not participation in research,“ and that “physicians are legally permitted to use drugs and medical devices off-label.“ They asked whether the patients were informed that this application of the Hydrosorb was an off-label application of the mesh.
The Senate letter also makes note of a January 2004 letter from Kuklo “to two Medtronic employees“ indicating that the Hydrosorb study “was supported by a restricted educational grant from Medtronic,“ asking for further information about communications between the firm and the physicians. Medtronic e-mailed Medical Device Daily a brief statement in which the firm avers the grant “was given to the TRUE Research Foundation (San Antonio),“ described by Medtronic as “a not-for profit entity established under federal law,“ and that the grant was not awarded by Medtronic “to any individual surgeon or group of surgeons.“
According to a story appearing yesterday in the New York Times, officials at Reed indicated they would respond to the Senate letter with “assurances of improved controls over research and publication“ by mid-January, a response attributed to Col. Norvell Coots, commander of the Walter Reed Healthcare System. Coots said Reed has located 15 of the patients who received the combination treatment, all of whom are said to be doing well. Kuklo's lawyer, Henry Dane, is said to have pointed out to NYT that Army doctors do not need approval for studies of fewer than 10 patients. Apparently a total of 22 patients were treated by the three doctors. Coots is said to have indicated that this notion is “an incorrect reading of the rule.“
Donor service warned over allograft claims
Organ and tissue banks have not appeared in an FDA warning letter for some time, but the Dec. 2 warning letter to LifeNet Health (Virginia Beach, Virginia) makes clear that the agency is intent on resuming oversight of such operations.
The letter states that FDA had sent LifeNet a July 14 letter regarding promotional claims for the MatrACELL pulmonary artery allograft and that the organization had responded 13 days later regarding the promotional claims. FDA states in the warning letter that it became aware that LifeNet was promoting the device with claims of “reduced immune response,“ which the agency states “represents a major change or modification in the intended use of your device that requires a new“ 510(k).
In a statement e-mailed to Medical Device Daily, Michael Plew, LifeNet's VP for quality and regulatory compliance, said the warning letter “was only directed towards one promotional claim, reduced immune response,“ adding that the agency “has indicated animal data are not sufficient to support the claim and human clinical data will be needed.“ However, Plew notes that the warning letter “does not relate to the safety or efficacy of MatrACell for its indicated uses.“ He adds, “since the clearance of MatrACELL in October 2008 there have been no reported adverse events associated with the product.“
Investigator's sponsor warned over problems
The Sept. 22 warning letter to Spineology (Saint Paul, Minnesota) notes that the inspection was of the firm's location and of a clinical investigator, Miguelangelo Perez-Cruet, MD, who also received an FDA warning letter (Medical Device Daily, June 1, 2010). The physician's warning letter states that Perez-Cruet “was being educated on clinical trials“ in an effort to bring his operations into compliance, and the warning to Spineology spells out precisely where the problems fell.
In the warning letter to Spineology, FDA notes that the inspection dealt with trials for the firm's OptiMesh for lumbar interbody fusion study, noting that Perez-Cruet allowed at least one subject to have their follow-up evaluation to be signed by a study coordinator, a problem that extended to a pre-operative evaluation form for two other enrollees.
Perez-Cruet was also said to be in possession of concomitant medication forms that contained discrepancies “between prescribed and recorded medications,“ although redaction makes it difficult to discern whether the listed medications were omitted on prescribed or recorded data. The medications include the use of epidural steroid injections, Vicodin, Valium, and Oxycontin.
FDA makes note of a generic response, describing it as “inadequate in that it does not describe your corrective and preventive actions in detail.“
Karen Roche, VP operations at Spineology, told Medical Device Daily, “we received a response from FDA earlier this month indicating that the proposed action plan appears to be adequate.“ She also said, “we hope from our communications that we're on our way to a close-out letter.“
Mark McCarty, 703-268-5690