FDA’s Failure to Act in 1998 Foreshadowed Its Later Mishandling of Vioxx and Bextra

A June 2005 article in The New York Times ("NYT") by Gardiner Harris and Eric Koli provided insight about how the FDA made mistakes with regard to the recalled heartburn medicine Propulsid, and how those mistakes have parallels with how the FDA mishandled the more recent drug-safety issues surrounding the painkillers Vioxx, Bextra, and Celebrex.

To put things into context, let’s start where the authors started in their NYT article:

Dozens had died and more than 100 patients had suffered serious heart problems by March 1998 after taking Propulsid, a popular medicine for heartburn. Infants, given the drug to treat acid reflux, seemed particularly at risk. Federal officials told Propulsid’s manufacturer, Johnson & Johnson, that the drug might have to be banned for children, or even withdrawn altogether. Instead, the government and the company negotiated new warnings for the drug’s label – though not nearly as tough as regulators had wanted.

Despite the drug-safety issues, sales of Propulsid surpassed $1 billion in 1998, fueled in part by Johnson & Johnson’s promotional efforts directed towards getting doctors to prescribe Propulsid use in children. Evidence of their marketing success was reflected in a survey taken in 1998 showing that about 20 percent of babies in neonatal intensive care units were being given Propulsid.

But two years later, just before a government hearing was convened to investigate the growing number of reports concerning heart injuries and deaths — a hearing which Johnson & Johnson ("J&J") probably regarded as threatening to "draw attention to the drug’s long, largely hidden, record of trouble" — Propulsid was pulled from the market by J&J. 

Mr. Harris and Mr. Koli state that they constructed their article using "newly obtained corporate and government documents", about which they remark: "Many of the documents relating to Propulsid obtained by The New York Times were filed under seal in the lawsuits."  These documents, as pieced together by the authors in their June 2005 NYT article, provide us with what they describe as "an in-depth view of a pharmaceutical company trying to save a lucrative drug in the face of growing evidence of harmful side effects."

The Propulsid story, unfortunately, is not the first example of the FDA’s inability to monitor and regulate prescription drugs effectively once they are on the market, nor would it be the last.  The FDA’s handling of the drug-safety issues surrounding the painkillers Vioxx, Bextra, and Celebrex provides a more recent example of the problem.

The June 2005 NYT article by Harris and Koli reveals several new facts, from which one can seemingly draw some parallels with the more recent FDA action — or inaction, perhaps — as regards Vioxx, Bextra, and Celebrex:

• J&J "did not conduct safety studies urged by federal regulators and their own consultants that could have revealed Propulsid’s danger early on."
• The FDA "did not disclose company research that cast doubt on Propulsid’s effectiveness against digestive disorders it was being used to treat, since the studies are considered trade secrets."
• "Dozens of studies sponsored by Johnson & Johnson that might have warned doctors away were never published…."
• "And even though Propulsid was never proved effective in children, the company helped finance programs that encouraged the drug’s pediatric use, according to internal company documents."

In fact the parallels between Propulsid and the painkillers is so striking that the FDA advisory panel which heard evidence in February 2005 about whether Vioxx, Bextra, and Celebrex increased the risk of heart attacks and strokes made reference to Propulsid.  As reported by Mr. Harris and Mr. Kol:

Members of a federal advisory committee on those painkillers cited Propulsid as an example of how even the strongest warnings – known as black box warnings – do not stop physicians from prescribing a drug inappropriately.

Dr. Alastair Wood, the chairman of the panel, said in an interview that label warnings of a drug’s potentially lethal effects do not protect all patients. Eventually, Johnson & Johnson made five significant changes to Propulsid’s warning label and sent five letters to doctors across the country.

But Dr. Wood, an associate dean at Vanderbilt University Medical Center, said, "The case of Propulsid proves this: When people are falling off a cliff, you don’t put up more signs; you put up a fence."

In a relatively low-profile announcement made in Februaruy 2004, Propulsid’s manufacturer, Johnson & Johnson, agreed to pay up to $90 million to settle numerous lawsuits filed around the nation alleging that 300 people died and as many as 16,000 were injured from taking Propulsid.

(Posted by: Tom Lamb)