Warning Label Spin: Further Reflections on What the FDA is Up Against

This article is part of the series:

When modern businesspersons are faced with an obstacle, they do not ask themselves, “How will I overcome this challenge?” Instead they say, “How can I turn this challenge into an opportunity?” This is at heart a marketing philosophy, since it implies not the protection of existing territory, but expansion of it. Marketing is the strategic growth arm of every corporation.

There are large examples and small. In the 1990s, Eli Lilly & Co. faced the challenge of finding a replacement blockbuster for Prozac, which was going off patent. A third of the company’s revenues came from the single drug. The opportunity came from the fact that many people on Prozac weren’t getting better anyway. This spelled “opportunity” for Lilly (and the other atypical antipsychotic marketers) to promote the idea that the reason people weren’t improving on SSRIs was that they had been misdiagnosed with unipolar depression, when in reality they were bipolar!

In Lilly’s detailed Zyprexa marketing plan of 1997 (made available to us at great risk by Dr. David Egilman), the drug reps were instructed: “7 in 10 people with bipolar disorder are initially misdiagnosed… [the] most common misdiagnosis is unipolar depression.” The solution was for Lilly to broaden the definition of bipolar disorder through “condition branding,” then redefine their antipsychotic drug Zyprexa as a “mood stabilizer” (itself a marketing and not a scientific designation) and prophylactic for bipolar disorder. Presto! Prozac’s challenges became Zyprexa’s opportunities. (Required reading: David Healy’s ‘Mania: A Short History of Bipolar Disorder’)

That’s an elaborate example of how a successful expansion strategy was built on the same foundation and using salvaged components of an earlier marketing edifice. A less noticeable form of the application of marketing’s challenge/opportunity orientation is when companies must respond to a direct threat to a brand’s reputation. This is the work of spin. Karl Rove and George Bush (our first MBA president) showed us how to spin weaknesses into strengths. They learned their trade from marketing.

In this post, I illustrate this principle at work in how Merck & Co. answered the threat of the FDA’s demand for a revised warning label on Vioxx in 2001. This was the moment in the brand’s history when Merck could no longer suppress the clinical trial data showing that patients on Vioxx were having four times as many heart attacks and twice the rate of other thrombotic events as people taking over-the-counter naproxen. One can only imagine the Merck marketers facing the label changes recommended by the FDA, and asking themselves: How can we turn this threat into an opportunity?

The subject should be of interest to us because of the ongoing debate about pre-emption. Pre-emption refers to when a drug company claims that it cannot be sued for damages caused by its product because the FDA had approved it. Merck successfully used this defense for Vioxx. An important precedent was set last week in the decision against Wyeth in the case of the musician from Vermont who lost her arm as a result of insufficient warning on the drug label (http://www.nytimes.com/2009/03/05/opinion/05thu2.html?ref=todayspaper).

The Vioxx story is familiar to most of us. Vioxx was the reigning heavyweight champion of ethical violations in the drug industry through the early to mid-2000s. It is also one of the most telling examples of FDA failure to convert available safety data to policy. Although the FDA has been given a couple of more teeth since 2001—largely as a result of the Vioxx debacle—it nevertheless remains important to understand how warning labels are put together. What follows is a sampling of how the warning label for Vioxx was reworded in October 2001, after the news about the dangers of the drug finally broke.

As early as 1997, the company was gerrymandering trial subject populations and suppressing data to conceal the drug’s tendency to cause heart attacks. Ironically, the damaging truth escaped into the public during an aftermarket study designed to expand use of Vioxx by demonstrating that the drug caused fewer gastrointestinal problems than naproxen. This study was called Vioxx Gastrointestinal Outcomes Research, or VIGOR.

The full story of how serious the findings were and how defiantly Merck went on marketing the drug in the face of these findings is told in many places. The short of it is that even while the inevitable end to Vioxx was in sight, Merck’s marketing war machine was in full tilt. Merck continued to report to the public and to doctors that the results of VIGOR were all positive. On 22 May 2001, Merck issued a press release entitled “Merck Confirms Favorable Cardiovascular Safety Profile of Vioxx.” On 16 June 2001 they issued a European press release entitled “Vioxx Similar to Placebo and Three Widely Prescribed NSAID’s Regarding Cardiovascular Events.” The company maintained its annual half billion dollar budget for promotions to doctors, and another $160 million for direct to consumer advertising. Meanwhile, behind the scenes, Merck prepared to lock horns with the FDA regarding the results of the VIGOR study.

On 15 October 2001, the FDA insisted upon amendments to the Vioxx label. The negotiation over wording in the 39-page document was released during trials filed against Merck (http://dida.library.ucsf.edu/pdf/yjb00a10). Throughout the revision, what is clear is not only Merck’s attempt to muffle the alarm bell the FDA was trying to ring, but to further the campaign to protect and sanitize the word environment around the brand name, and to market trust in the company’s scientific reputation as expressed through the clinical trial process.

Beyond the apparent damage control exercised through the removal of harsh-sounding consequences of taking Vioxx, or even of symptoms that might frighten a patient into quitting the drug (chest pain and shortness of breath), the Merck version reveals subtle alterations in emphasis. Merck’s version protects the brand’s identity as an autonomous, efficacious medicine. “Treatment with VIOXX is not recommended in patients with advanced renal disease,” accentuates Vioxx’s identity as a treatment, and not a threat to treatment. Moreover, Vioxx come out feeling like an entity unto itself, a sphere into which outsiders such as doctors, patients and regulators enter on Vioxx’s terms. The FDA, by contrast, places control in the hands of an outside expert, who is there to decide whether treatment with Vioxx is appropriate and safe. There is no floating brand autonomy in the declarative litany of the FDA’s version: “VIOXX 50 mg should not be given more than once a day. Chronic use of VIOXX 50 mg daily is not recommended. Use of VIOXX in advanced renal disease is not recommended.”

Merck saves its declarative sentences for when it wants to shut down thoughts that might lead to doubt: “No substantial difference in safety and effectiveness were observed between these subjects and younger subjects.” A reader is discouraged from reading to the end of that sentence, much less to the end of the paragraph. All the information you need is found in the words “no substantial difference.”

Elsewhere in the document Merck says, “Cardiovascular Safety in VIGOR: In the VIGOR study there was a significant difference in the incidence of serious cardiovascular thrombotic events between patients treated with VIOXX 50mg once daily (twice the highest dose recommended for chronic use in OA) and patients treated with naproxen 500mg twice daily (common therapeutic dose)…(See Table 3)” [p. 12].

A hurried reader (especially one who has just been shown the infamous cardiovascular card: http://content.nejm.org/cgi/content/full/352/25/2576) might take this to mean that if you take 40 times the amount of Vioxx than is normally prescribed, bad things might happen. Since that’s what naproxen takers are doing, Vioxx must be much safer than naproxen.

Brand-mindedness is evident also in the acronyms give to the clinical studies: The VIGOR, APPROVe (Adenomatous Polyp Prevention On Vioxx), and ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness) studies were, like their names, marketing and not scientific endeavors. In the Vioxx label of 2001, Merck rewrote the FDA’s “Study 102/903 (ADVANTAGE study)” to “The ADVANTAGE Study,” to remove the harsh undifferentiated numerical rubric, which would be unflattering for a branded identity.

The foregoing is no substitute for a proper discourse analysis of the labels over time. The organization and length of the labels, the strategic use of Greek versus Germanic rooted words and vice versa, intentional obfuscation through long or passively worded sentences, and other syntactical tactics can form the basis of a proper reading of the role of label language in the marketing of drugs. One can be certain that professional wordsmiths are employed by the company to get the language right. When billions of dollars are at stake, nothing is left to chance. By contrast, the poor FDA has to rely on the layman skills of busy, hapless, unsuspecting bureaucrats.

We ordinarily think of advertising strictly in relation to products—Buy Lux because it smells good! But the work of marketing is to protect the entire biography of a company’s products, from the laboratory to the doctor’s office to the courts. Its work includes management of image risks associated with brand and company. Merck’s eventual decision to take Vioxx off the market can be traced to the marketing motivation of doing so before the drug’s bad publicity climbed up the feed tube and poisoned the brand of the mother ship.

Further reading:

Healy, David. Mania: A Short History of Bipolar Disorder. Johns Hopkins University Press (2008).

Hill KP, Ross JS, Egilman DS, Krumholz HM. The ADVANTAGE seeding trial: a review of internal documents. Ann Intern Med (2008) 149:251-258. Available at: http://www.annals.org/cgi/content/full/149/4/251

Henry A. Waxman. The Lessons of Vioxx — Drug Safety and Sales. NEJM. (2005) 352:2576-2578. Available at: http://content.nejm.org/cgi/content/full/352/25/2576

3 Responses to Warning Label Spin: Further Reflections on What the FDA is Up Against

  1. Fascinating and appalling. It’s also important to note the severe side effects of Zyprexa/Olanzapine – a history in some ways similar to Vioxx.

    -Sara Bergstresser

  2. Pingback: The political economy and everyday life of pharmaceuticals | EDS Info (Ehlers-Danlos Syndrome)

  3. Pingback: Deceiving Warning Labels | What can you do with anthropology?

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