Northwestern U. Gets Renewed Grilling Over Unauthorized Tests on Patients

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Northwestern University has been accused by a U.S. senator of withholding key documents from a long-running inquiry into allegations that its chief of cardiac surgery experimented on unsuspecting patients.

The researcher in the case, Patrick M. McCarthy, a professor of cardiothoracic surgery, also appears to have “made contradictory statements” in explaining his own actions, Sen. Charles E. Grassley said in a letter on Tuesday to Morton O. Schapiro, Northwestern’s president, and Richard J. Gannotta, the new president of Northwestern Memorial Hospital.

The letter from Mr. Grassley, a Republican of Iowa, revives the case more than two years after the university made clear its support for Dr. McCarthy by removing from its faculty his onetime research partner and now accuser, Nalini M. Rajamannan, a former associate professor of medicine.

Mr. Schapiro said he would not comment on Mr. Grassley’s letter or anything else about the case.

From 2004 to 2006, Dr. McCarthy led a study of 128 patients needing implanted heart rings—silicone-and-metal devices used to pinch together leaky heart valves. Of those patients, he gave 36 his own altered version of a standard heart ring, which he later acknowledged was part of an effort to develop a variant more effective against myxomatous degeneration, the leading cause of heart-valve failure.

The patients were not told at the time that the implants, called Myxo rings, had been altered or that the change lacked the approval of the U.S. Food and Drug Administration. Dr. McCarthy and the university have maintained that they were following federal rules that treat altered medical devices as legally authorized if they are substantially similar to a device that has already won the FDA’s regulatory approval.

Despite asserting that application of FDA rules, Dr. McCarthy gave conference presentations in 2007 and wrote two medical-journal articles in 2008 that emphasized the novelty of his invention and the need to design different rings for different patients’ conditions.

A Change in the Ring

Mr. Grassley’s letter listed five documents he considers relevant to the case that Northwestern did not produce in response to his initial requests, in 2008 and 2009. They include the report of a June 2006 decision by Northwestern’s institutional review board, which gave Dr. McCarthy permission to review the postsurgical health records of his Myxo-study patients without telling them what he was doing or why.

Outside experts, asked about the situation, said they could not be sure whether the review board had acted improperly in granting such approval because it remained unclear whether Dr. McCarthy had fully explained to the board what he was doing.

As a general rule, patients should be informed of anything that a reasonable person would want to know, said one IRB expert, Robert L. Klitzman, a professor of psychiatry at Columbia University who serves as director of its master’s program in bioethics.

“If the device had any significant changes at all from what was FDA-approved,” Dr. Klitzman said, “it seems to me that he should also have informed subjects.”

The documents cited by Mr. Grassley are publicly available in court records, turned over by defendants in court cases brought by at least two patients who received the altered rings. The defendants include Northwestern Memorial Hospital and Edwards Lifesciences, the company that manufactured the Myxo and other rings designed by Dr. McCarthy.

The case has already highlighted concerns about the process through which the FDA allows companies to sell a new device by declaring it substantially similar to an existing device.

Once the FDA demanded that the Myxo ring win its own legal clearance, Edwards changed its name to the dETlogix ring and omitted any reference to myxomatous degeneration. By changing the ring’s name, Edwards may have saved years of time and expense in winning FDA approval, experts said. That’s because the FDA gives much quicker clearance in cases where the medical reasons for using a device match the reasons for a device that the FDA has already approved.

A spokeswoman for Edwards, Sarah Huoh, confirmed that, other than the name change, the dETlogix ring cleared by the FDA for sale in 2009 “is the exact same device as the Myxo ring.” She did not respond to a request to explain the reason for the name change, and FDA officials said they had no immediate explanation of the agency’s decision to approve the device under the new name.

Losses in Court

The FDA does try to guard against maneuvers in which an inventor takes a shortcut in the review process by asserting a patient condition that does not match the product design, said Nathan Cortez, an associate professor of law and associate dean for research at Southern Methodist University. But that’s not easy for the FDA to monitor, he said, even in cases such as the Myxo ring, in which the record shows Dr. McCarthy repeatedly emphasized his design as applying to myxomatous degeneration.

First, Mr. Cortez said, the FDA has lost a series of major court cases in which manufacturers have asserted First Amendment rights to publicly discuss off-label uses of their products. “And with the current Supreme Court being extremely friendly in commercial-speech cases, FDA has not pressed its position in court,” he said.

Second, even though Dr. McCarthy and Edwards made their assertions about myxomatous degeneration before the FDA considered their renamed ring, the FDA might not have the standing to insist that they stick to its original medical purpose, Mr. Cortez said.

Statements at medical conferences are clearly considered free speech beyond the FDA’s power to regulate, he said. And the company is not bound by any press statement, “though it might make FDA suspicious, if agency reviewers were really paying attention,” he said.

Mr. Grassley also questioned whether Northwestern, to this day, had properly informed the patients of what had happened to them. In a September 2008 letter responding to an inquiry from a patient who had been given the Myxo ring in April 2006, two Northwestern officials said Edwards had “confirmed that the device was commercially available at that time and was not investigational in nature.”

As such, said the officials—Don E. Workman, then executive director of the Office for the Protection of Research Subjects, and Ann K. Adams, associate vice president for research integrity—the surgery “did not require IRB approval.”

But Edwards, according to its regulatory filings and press statements, officially put the Myxo ring on sale in January 2007.

“It is not clear,” Mr. Grassley told Mr. Schapiro and Mr. Gannotta, “whether patients received sufficient notice of the safety questions that arose regarding the Myxo ring implanted at Northwestern Memorial Hospital.”

Correction (3/6/2014, 12:15 p.m.): This article originally misstated the professorial rank of Dr. McCarthy’s onetime research partner. Nalini M. Rajamannan is a former associate professor of medicine, not assistant professor. The article has been updated to reflect this correction.