Niseritide, the “Lost Decade”, and the Pinto

Patricia Salber

First posted 7/14/11 on The Doctor Weighs In

Eric Topol, MD wrote an interesting commentary in the July 7, 2011 issue of the New England Journal of Medicine, titled “The Lost Decade of Nesiritide.” Nesiritide is a drug for heart failure symptoms (e.g., shortness of breath) that was approved by the FDA in 2001. Since that time, according to Dr. Topol, “well more than $1 Billion was wasted on purchasing the drug.”

It turns out that the FDA approved the drug was based on a relatively small, not particularly well done clinical trial that showed improvement in self-reported symptoms of shortness of breath 3 hours after the drug was administered. Once the drug was approved, the drug was marketed like crazy. For profit outpatient heart failure “tune up” clinics opened so that heart failure patients could get weekly intravenous infusions of the drug.

Over the ensuing decade, small studies were published that suggested Nesiritide was associated with a worsening of kidney function and perhaps an increased rate of death. These studies led to a recommendation that a large clinical trial be conducted so issues of safety and efficacy could be more definitively determined.

As a result a large international clinical trial of the drug was conducted from May 2007 to August 2010. It involved 7141 patients in 398 centers around the world. The results of the study, published in the same issue of the NEJM as Dr. Topol’s commentary, failed to find any statistically significant benefit of the drug on heart failure symptoms. It also failed to find any worsening of kidney function, but it did identify increase in rates of hypotension (low blood pressure). The authors conclude “one the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure.”

Thus, over a ten year time span, Neseritide was infused into the veins of many, many patients with heart failure, costing payers (insurers and, in the case of public programs like Medicare, tax-payers) over a $1 billion, without bringing any significant benefit to the end-user (AKA, the patient). Of course, not everyone lost as a result of this wasteful spending – that $1 billion benefitted the manufacturer(s), shareholders, owners of the “tune up” clinics and everyone else along the supply chain.

Dr. Topal calls this the “Lost Decade of Nesiritide” likening it to the “lost decade” of the Japanese economy in the 90s and perhaps the “lost decade” the US economy may be in the midst of experiencing. He is probably right. We spent the money. We did not get the expected health benefits. Nothing to be done? Right?

I suspect somewhere in the bowels of the manufacturers’ files are calculations on how much money could be made on the drug regardless of its marginal – if any – benefit. This tale reminds me a bit of the story of the Ford Motor Company executives who calculated the cost-benefit ratio of keeping quiet about the known flaw in the gas tank design of the then popular Pinto.

Ford ultimately paid much more than the $137 million it would have cost to prevent the gas tank ruptures to settle lawsuits, recall the cars, and fix the problem – the insertion of a plastic barrier between the gas tank and the exterior.

If the Nesiritide story was more like the Pinto story, we would see efforts to recoup that lost $1 Billion. But fortunately patients weren’t seriously harmed by the administration of the drug, so there won’t be any lawsuits for damages and there won’t be any public outrage. After all, we are used to waste in health care – we have been talking about it – and documenting it – for years.

So the manufacturers and “tune up” clinics will keep their profits from a drug they most likely knew was not worth the price they were charging. The large scale study that refutes the drugs benefit will eventually lead to a slow decline in the use of the drug as insurers change their policies regarding reimbursement for the drug and…the business of medicine will keep on going, mostly unchanged by yet another expose of poor oversight practices that let waste flourish in our non-system.

An FDA with teeth – one that would have the strength to not approve a drug on the basis of only one, not particularly well-done study – or at the very least was able to tie an interim approval to the rapid design and implementation of a more definitive study – is probably too much to wish for in this era of hatred of all things regulatory. What’s to be done….?

Pat Salber MD MBA is a medical management consultant and the former Chief Medical Officer of several large health plans.