In letter to Franken, FDA defends handling of Medtronic's Infuse study

The U.S. Food and Drug Administration is defending a decision to accept more than 1,000 patient injury reports from Medtronic in summary form, years after they were supposed to be submitted.

The FDA responded earlier this month to questions from U.S. Sen. Al Franken of Minnesota by saying it took no action against Medtronic for the late reporting of a study of its Infuse bone graft because the information was consistent with data the agency already had.

Franken had inquired after the Star Tribune recently reported about the study, which Medtronic shut down in 2008 without reporting injuries it had found. The FDA didn't get the study data until 2013, though federal law requires companies to report injuries within 30 days of discovering them.

The revelation of the lost study followed years of questions about how forthcoming Medtronic has been about Infuse, a product that has brought in billions of dollars in sales while attracting multiple government investigations and thousands of patient injury claims.

After receiving the FDA's response to his questions, Franken says the handling of Medtronic's Infuse study signals a broader need to change how the agency safeguards the public's health. He called for "a more robust, proactive medical device surveillance system to avoid potentially dangerous reporting errors."

"While the agency's response provided some valuable information about the process that FDA and Medtronic undertook once the company came forward with the new adverse event information, I remain concerned that the FDA did not disclose patient injury data in either a timely or a transparent fashion," Franken told the Star Tribune.

In the FDA's response to Franken, Acting Associate Commissioner for Legislation Dayle Cristinzio said the agency determined that "no enforcement actions were warranted" because the Medtronic study did not reveal new information.

"The types of events in these reports were similar to events seen in other reports from 2006-2013," Cristinzio wrote.

Starting in 2007, Medtronic enlisted doctors at two dozen locations to examine medical records of 3,647 Infuse patients and report any injuries or complications.

The product is an unusual medical device, a bioactive solution to promote bone growth that is often used in combination with a cage or other hardware.

According to the FDA, Medtronic documented "1,041 serious injury reports, four death reports, and 55 device malfunction reports." A Medtronic spokesman said the company made clear to the FDA "that its reporting of these events did not constitute a conclusion that they were either caused by, or related to, the use of Infuse" and that the 55 malfunction reports related to hardware and not the Infuse bioactive solution.

In 2008, Medtronic shut down the project, which the company had hoped would support more approved uses of Infuse. The company has said employees collected details of all the adverse events as they were received but did not know they were supposed to report them to the FDA.

When Medtronic told the FDA about the study in 2013, the government accepted the company's explanation that it had not previously evaluated the adverse events for "reportability." In 2014, the agency allowed the device maker to summarize 1,039 serious injuries in a single report, then redacted the total number of injuries and a supporting spreadsheet detailing the nature of those injuries from public view.

Franken asked the agency if it considered penalizing Medtronic, considering that the company had received warning letters for failing to report serious injuries related to different devices in 2007 and 2009.

In her June 6 letter, Cristinzio wrote that the agency decided against any sanctions after considering the findings of inspections that included reviews of Medtronic's reporting practices.

The agency also reviewed Medtronic's summary of serious injury reports in the Infuse study and found it didn't add to what the FDA already knew about the bone graft's safety by 2013.

A 2006 consent form for one of the study's participants promised that sharing information about Infuse "may lead to a better understanding of the safety and effectiveness of this product for future patients with medical conditions similar to yours."

Company officials now say they stopped collecting data and never produced a final study report. The company also says it misfiled the study results until early 2013, despite multiple requests for Infuse information from government investigators.

In its letter to Franken, the FDA acknowledged that it "inadvertently" redacted the total number of patient injuries from the summary report. The FDA revealed the number in September 2015 after the Star Tribune challenged the decision to redact it as a corporate trade secret.

Sarah Sorscher, an expert in health research for the consumer group Public Citizen, said the FDA had been too lax in allowing a summary report.

"It remains troubling that they [Medtronic] still have not published this as a study," she added. "It definitely has valuable information that patients need, and still don't have."

Infuse has been used in more than a million surgeries since its approval, and doctors widely support keeping it on the market. But in published papers and interviews, doctors have also criticized the company for not being more forthcoming with information about the product.

Dr. John G. Stark, a Minneapolis orthopedic surgeon who submitted patient chart data in the 2007 Infuse study, said he sensed very early on that some of the doses of the bioactive solution recommended by Medtronic were causing problems because they were too large.

"But we had to figure that out on our own," Stark said in an interview. "This was an incredibly valuable and powerful tool, incredibly powerful. It's like a sharp, sharp knife. You can do incredibly powerful work with it, or you could fumble around with it and hurt yourself."

Jim Spencer • 612-270-1266

Joe Carlson • 612-673-4779