NuvaRing: another ethical crisis at Merck
The glare of the ethical spotlight is once again pointed at Merck & Co., Inc. In December, a sensational article in Vanity Fair put a human face (“24-year-old Erika Langhart—talented, beautiful, bound for law school”) on the controversy swirling around the company's NuvaRing contraception product. Ms. Langhart died on Thanksgiving 2001 from a pulmonary embolism resulting from a blood clot allegedly triggered by NuvaRing. The author of the Vanity Fair article, Marie Brenner, questions “why, despite evidence of serious risk, a potentially lethal contraceptive remains on the market.”
Reached by email, Laine Keller, Director, Global Communications, for Merck, stated that “we disagree with many of the statements in the Vanity Fair article,” and she pointed to Merck's previous statement that the patient and physician labeling contain a “boxed warning” about the “well-established” clinical finding that combined hormonal contraceptives, whether NuvaRing or oral pills, are associated with the risk of blood clots.
So is this a case of a greedy drug company marketing a drug without disclosing known, potentially lethal dangers? Or is this a situation where many young women have been tragically struck down and society needs a villain to blame and hold financially responsible? There are not only legal questions here but also important ethical and public policy questions that affect the ability of women to make informed choices about their bodies and reproductive rights.
Merck acquired the NuvaRing franchise, and the legal liabilities that went along with it, when it merged in 2009 with Schering-Plough, which had itself only two years earlier purchased the Dutch-based developer of NuvaRing—Organon. NuvaRing has been prescribed over 44 million times in the United States since winning FDA approval in 2002. It is marketed in over 50 countries throughout the world. With patent protection through 2018 and near-blockbuster annual sales exceeding $600 million, NuvaRing is a steady bright spot for a company desperately searching to replace lost sales from expiring patents on its Singulair asthma, Procepia baldness, and Clarinex allergy medications.
Over 1,000 NuvaRing-related lawsuits have been filed against Merck. What the suits boil down to is the claim that the “third generation” etonogestrel hormone used in the vaginally inserted NuvaRing causes it to be more likely to cause blood clots than “second generation” oral contraceptives, that Merck knew about this increased risk, and that it failed to inform doctors and patients about the risk.
Exactly how much riskier NuvaRing is for healthy, non-smoking young women is a matter of some controversy. The FDA's 2011 historical study of over 800,000 women found that NuvaRing users had a 56% increased chance (relative to users of “second generation” hormonal combinations found in oral contraceptives) of developing dangerous blood clots. However, while the FDA noted the finding “raises concerns” it also stated “it needs to be replicated in other studies.”
The NuvaRing controversy bears eerie resemblance to the Vioxx scandal that severely tarnished Merck's once stellar corporate reputation. Merck voluntarily took Vioxx off the market in 2004 after a study linked the drug to increased cardiovascular risk. In 2007, the company entered into a $4.5 billion settlement agreement with the families of 3,100 people who died of heart attacks or strokes allegedly brought on by Vioxx.
The company never formally acknowledged wrongdoing in the plaintiff settlements. However, in a 2010 settlement of a related shareholder derivative suit, Merck agreed to a wide-ranging set of governance reforms establishing greater board oversight for medical and scientific ethics and established, in theory at least, a strong role for the newly created role of Chief Medical Officer. (As a paid consultant to the plaintiff's attorneys, I was one of the principal architects of these reforms.)
In the case of Vioxx, paying out $4.5 billion and changing the way your corporation is governed at the highest levels certainly amounts to a tacit admission of massive wrongdoing, even if Merck continues to cling to a legal loincloth of innocence. In fact, paying out so much money to plaintiffs where no wrongdoing was acknowledged may have a perverse effect in the NuvaRing case. Merck is now on record as being willing to pay out large settlements even when, in its own estimation, it has done nothing wrong. This should provide significant encouragement for NuvaRing plaintiffs and their lawyers.
What seems to be missing in the NuvaRing case, however, are any smoking guns similar to the record in the Vioxx case which suggested that the company may have underplayed negative clinical data prior to the 2004 study which led to taking Vioxx off the market. The lawyers in the NuvaRing case think they have such a smoking gun in Organon's omission of information in the summary portion of its FDA application about spikes of estrogen in four of the women who participated in the original drug trial. “This is a standard subterfuge used by Pharma,” plaintiff's attorney Hunter Shkolnik told Vanity Fair. “You bury your bad news in one of 500 studies you have done on ease of use or lipid disorder. Then when the FDA comes back to the drug company, the drug company can say, ‘You had it in your documents.' If it isn't in the 30-page summary, the FDA is so understaffed it will never be noticed.” It remains to be seen how compelling an argument this will be for juries.
Another important difference between NuvaRing and Vioxx is the benefit provided by the drug. Vioxx was massively overprescribed because it provided an incremental pain relief benefit over other drugs in its class only for those at danger of developing peptic ulcers. Given its riskier profile, Vioxx might possibly have been targeted, with an appropriate warning, to the subset of patients at risk of peptic ulcers from using other NSAIDS—a risky drug for patients seeking pain relief who might face greater risks from competing drugs. Instead it was prescribed to 80 million people worldwide.
By contrast, NuvaRing provides an important benefit for women. It can be utilized once a month instead of once a day like the pill. As such, NuvaRing provides an important alternative for millions of women who want to avoid pregnancy and exercise their reproductive rights.
Of course, women also have the right to informed choice. Thus the question of whether Merck withheld information about any known risks of NuvaRing at any juncture is of critical importance. The litigation process will help establish the truth about what Merck knew and when they knew it.
Whatever the legal outcome in the NuvaRing cases, Merck would do well to revise the information provided on the NuvaRing website. Women deserve straight talk about risk, but the information on the website reads like it was written by a trial lawyer, not a medical counselor. Here's what it says: “The risk of getting blood clots may be greater with the type of progestin in NuvaRing than with some other progestins in certain low-dose birth control pills. It is unknown if the risk of blood clots is different with NuvaRing use than with the use of certain birth control pills.” Can't someone at a world-class company figure out a way to protect its legal position and still speak plainly and clearly to women who want to make an informed choice?
And what about Erika Langhart and the other women who used NuvaRing and suffered catastrophic consequences? If Merck is able to prove it gave adequate warning from a strictly legal standard, might juries, swayed by a natural empathy, nonetheless return a verdict for the plaintiff? It will be interesting to see how these cases develop. Many criticize our legal system because it engenders expensive and random jury awards that increase costs for everyone. However imperfect this system is, however, it does work as a method of compensation for the families of unfortunate victims such as Erika Langhart. Is it unfair to Merck that it should bear the responsibility for such verdicts? In some sense, yes, but in another sense such responsibility comes with the territory. Pharmaceutical companies have a very special role in our society. They make profits by serving patients. This role comes with many special ethical responsibilities. One is to continually innovate safety as well as efficacy. Another is to share, not hide, scientific and medical truth with doctors and patients. Neither of these ethical responsibilities ought to be delineated by craftily drawn legal lines.
Michael Santoro is a professor of management and global business at Rutgers Business School. For over a decade he has co-taught a course on the ethical, legal, and regulatory aspects of the pharmaceutical industry. He is the co-editor of Ethics in the Pharmaceutical Industry (Cambridge University Press, 2005). As a paid expert in the Vioxx shareholder derivative lawsuit, he was the principal architect of the corporate governance reforms adopted by Merck as part of the Fagin settlement. His website is www.michaelAsantoro.com.