"Off-label" Prescribing Is At Center Of Ongoing Natrecor Controversy

A recent article of interest is "The Rise And Fall Of Natrecor For Congestive Heart Failure: Implications For Drug Policy", by Aaron S. Kesselheim, Michael A. Fischer, and Jerry Avorn, in the July/August 2006 edition of the journal Health Affairs.  This recently published article uses Scios’s drug Natrecor as a vehicle for exploring three important aspects of our nation’s prescription drug policy: drug approval by the FDA; drug promotion by the drug companies; and, drug prescribing by the doctors.  In the authors’ words:

We use [Natrecor] as a case study to assess how FDA standards for drug approval, marketing practices by drug manufacturers, and physicians’ prescribing choices can shape the risk-benefit relationship of new drugs. Based on the [Natrecor] experience, we suggest several ways to improve policies for drug approval, postmarketing surveillance, and drug utilization.

Coincidence or not, a June 28, 2006 article in The New York Times (NYT) included a discussion of Natrecor which gave us some insight into how some conduct engaged in by Scios (and other drug companies) might serve to influence the opinion of certain doctors.  In relevant part, this NYT article by Reed Abelson, entitled "Charities Tied to Doctors Get Industry Gifts", focuses on the more than $300,000 Scios reportedly gave to the Midwest Heart Foundation — which, in the article, is described as a nonprofit entity that is closely related to a for-profit Illinois medical group that includes a cardiologist by the name of Dr. Mitchell T. Salzberg.

As background, while doctors are free to prescribe FDA-approved drugs for any purpose they deem appropriate, a practice commonly known as "off-label" prescribing, a drug company is prohibited by federal law from actively promoting in any manner such off-label prescribing by doctors.  In this instance, Natrecor was approved by the FDA in 2001 to be administered only to hospitalized patients who were in an extreme, or decompensated, stage of heart failure. 

In mid-2005 two medical journals published articles which raised safety concerns about Natrecor, specifically whether Natrecor was causing kidney problems in some patients.  In turn, there was renewed debate about whether or not this heart failure drug is properly used when administered not in a hospital setting but, instead, in outpatient clinics on a periodic or "tune-up" basis, i.e., "off-label" use.

According to the June 28 NYT article, some Midwest Heart doctors were in the practice of administering Natrecor to patients in outpatient clinics when these safety issues concerning Natrecor surfaced.  For the purpose of accuracy, we refer to Mr. Abelson’s description of the situation:

In mid-2005, after researchers elsewhere published an article in a scholarly medical journal raising concerns that Natrecor could seriously impair kidney function, one of Midwest Heart’s cardiologists, Dr. Mitchell T. Saltzberg, continued to staunchly defend the drug.  Dr. Saltzberg, who has also been a paid Scios consultant, wrote to Medicare officials in July 2005 to argue that the drug was being "unfairly targeted."

Dr. Saltzberg’s letter cited a study of Natrecor’s outpatient use — a study for which the foundation had provided some work — saying that this research and "the body of anecdotal experience" indicated the drug posed no kidney risks.

His comments to Medicare, though, came a few days after Scios itself sent a safety alert to doctors warning against the outpatient use of Natrecor. The Scios alert, issued in consultation with the F.D.A., relied on the findings of an expert panel that the company had asked to look into issues involving the drug’s safety.

The Scios alert referred to the very study Dr. Saltzberg had cited and found it lacking. That study "was not powered to adequately assess the effectiveness or safety of serial infusions of Natrecor," the alert said. "The size of the study, its design and its findings provide an inadequate basis to recommend the use of intermittent, serial or scheduled repetitive infusions of Natrecor." Through the foundation, Dr. Saltzberg declined to comment. Foundation officials, though, said they agreed with the Scios panel’s findings.

The Department of Justice (DOJ) has been investigating whether Scios improperly marketed Natrecor so as to encourage its "off-label" use in outpatient clinics, and the DOJ has reportedly issued a subpoena to the Midwest Heart Foundation among others as part of this investigation.

(Posted by: Tom Lamb)