Case Analysis #1
Tuesday, January 22, 2013
Matt Janes

Merck & Company, Inc: The Recall of Vioxx
Introduction
Geroge W. Merck stated once stated, “We try never to forget that medicine is for the people. It is not for the profits. The profits follow. Initially, Vioxx was the blockbuster drug that Merck needed due to the upcoming Zocor patent cliff in 2006. With an estimated 27,785 heart attacks and sudden cardiac deaths that could have been avoided if Celebrex had been used instead of Vioxx, Merck faces the possibility of not only having to pay enormous civil and criminal penalties, but also losing the trust of patients. Many parties are partially culpable, but Merck faces the severe uphill battle of regaining a reputation that once served as a market differentiator; in the 1980’s, Merck was voted the “Most Admired Company in American Business” for seven consecutive years. A critical issue in this case is to analyze the events listed in the case and propose an alternate course of action that may help prevent future deaths from other pharmaceutical drugs while not prohibitively restricting innovative research that could potentially save lives if tested properly.
Critical Points and Issues Merck was relying on the success of Vioxx due to Zocor’s expiring patent and the direct competition Vioxx was engaged in with Celebrex, which had a first mover advantage. While Celebrex was also a Cox-2 inhibitor, Vioxx was the only Cox-2 inhibitor proven to be beneficial for ulcers and gastrointestinal bleeding. Once studies came out suggesting that Vioxx contributed to a greater number of cardiovascular problems than naproxen, Merck seemed to opportunistically interpret these results. Furthermore, Merck did not institute any studies that might have found negative cardiovascular results, and management failed to perform a study that focused specifically on the cardiovascular risks of Vioxx. Instead, Merck spent a record amount on advertising the gastrointestinal benefit of the drug in a period of uncertainty. The advertising in the time of uncertainty is really unparalleled, and opens the door to questioning (Appendix).
Stakeholder Impacts

Merck Merck wanted to discover a drug in the Cox-2 inhibitor class that would compete with another class of drugs known as nonsteroidal anti-inflammatory drugs (NSAIDS). Cox-2 inhibitors were developed to eliminate the most common side effects of other NSAIDs, ulcers and gastrointestinal bleeding, as an estimated 15,000 people die from GI bleeding annually; Vioxx was designed to treat those high-risk candidates. Vioxx was the only Cox-2 inhibitor proven to have a benefit for ulcers and GI bleeding. Thus, the blockbuster status was created: a stronger drug with a proven benefit for ulcers and gastrointestinal bleeding. As the events unfold in the case, the crucial errors occur prior to the decision to recall the drug on September 30, 2004. After Merck learned that patients had double the risk of heart attack or stroke than if they took placebo and two new competing Cox-2 inhibitors were introduced, Merck decided to pull the drug, but it was already far too late. Dr. Eric Topol, a highly regarded cardiologist conducting research at the Cleveland Clinic, was the first researcher to raise questions about Vioxx. While he concluded that Vioxx produces a risk of heart attack five times greater than naproxen sodium, some believed that Merck’s scientists interpreted the data opportunistically; by saying the difference was due to the protective effect of naproxen, this downplayed the important possibility that Vioxx was contributing to cardiovascular problems. Some scientists say that the protective effect of naproxen argument is implausible, and noted that naproxen would have to be three times as effective as aspirin to account for the difference. While the FDA didn’t buy this argument and issued a warning on all Vioxx labels, many began to wonder if this was the first sign of an unethical deception, cover-up, and manipulation by Merck.
Additionally, as the label was added, Merck would later ironically cite the VIGOR study in defense of Vioxx: it increased the risk only in those patients believe to be a high risk. However, Dr. Gregory D. Curfman, editor of the prominent New England Journal of Medicine noted that it had “solid evidence that important data on cardiac events was deleted or withheld.” Dr. Curfman argued that the three deleted heart attacks occurred in people who were otherwise at low risk for heart problems, which would ultimately discredit Merck’s claim that is only increased the risk for high-risk patients.
The FDA’s mild warning hardly curbed the widespread use of the drug, yet Merck continued to advertise its big benefit to consumers more than any other company in 2000 (Appendx): it causes fewer cases of stomach bleeding. However, this is only a problem for a very small percentage of patients. Thus, there was evidence that hundreds of thousands of people were using the drug that didn’t really benefit from its one advantage. Merck seemed to engage in deceptive marketing practices highlighting this benefit and not the immense risks to compensate for its declining financial situation, nor the fact that the drug was designed specifically for consumers that were in the high-risk gastrointestinal category.
In March 2000, management first learned the results from a study of 8,100 rheumatoid arthritis patients that began to take the medication in January. The results from the Vigor study should have alerted management to the potential dangers and risks of using Vioxx. However, since the FDA repeatedly approved the drug, this psychologically this seemed to create the illusion that the drug was safe. While evidence was mounting against the potential risks, in 2000 alone, Merck spent $160 million in direct-to-consumer advertising, the highest that year for all drugs.
FDA
The FDA has commonly been criticized for requiring superfluous testing. However, others argue that drugs are rushed through testing due to enormous pressure from the drug companies. Even after a drug has been approved, many of the risks are still unknown. The mild warning given by the FDA seemed entirely inappropriate, an action that ultimately prolonged the use of Vioxx for consumers that were not high-risk candidates. In Merck’s defense, it was promoting a product that did in fact reduce pain and gastrointestinal problems; however, it omitted the crucial detail that it increased the risk of cardiovascular problems. The FDA responded by giving Merck a warning, but ultimately, the FDA failed in its ultimate duty to protect the American consumer.
Doctors
The doctors prescribing the medications failed to sufficiently research the medication and seemed to rely too heavily on the influence of Merck salespeople and/or the general public. If physicians were cognizant that only a small percentage of the population would actually benefit from the fewer gastrointestinal problems, but would expose themselves to a potentially higher risk of developing heart problems, the doctors should have at least informed the patients that NSAIDS might be a safer alternative. The risk-benefit for many patients simply was not justified. The mild warning given by the FDA did not prompt most doctors to research the warning, as essentially all drugs have notable risks.
Doctors and patients are also usually affected by the psychological affect of new drugs-these drugs are perceived to be better than existing drugs on the market. Knowing this psychological affect on consumers, the doctors may have felt pressured to prescribe the drug if consumers were asking for it after seeing the advertisements. However, Vioxx was first approved for people with a high risk of GI problems. It is estimated that only about 10% of the prescriptions for Vioxx were most likely for patients that had a high risk of GI problems; the drug was widely overprescribed and was not the optimal treatment for many patients.
Patients and Advertising As Merck spent over $500 million advertising Vioxx, many critics try to blame Merck for promoting a product that many believed had a risk that severely outweighed the benefit, especially for patients without a prior history of gastrointestinal problems.
An underlying problem in the case is that medicines in America are overused. Many health problems can be avoided by a lifestyle change. Patients need to know that all medications are potentially dangerous and should be used sparingly. However, in the Vioxx case, many consumers were ultimately oblivious about the risk-benefit tradeoff, as it was not mentioned in the advertisements or consultations with physicians.
Options and Solution Implementation Considering that Merck adheres to the philosophy of its founder, George Merck, “medicine is for the people. It is not for the profits,” the course of action taken by modern-day Merck executives followed a path seemingly motivated by financial pressures. The executives seemed to believe that the success of the company was heavily reliant upon Vioxx, and wanted to mitigate any negative associations the drug had with cardiovascular problems. When evidence began to come in showing a potential link between Vioxx and cardiovascular problems, Merck did not run any studies that attempting to reveal the cause of the negative cardiovascular results. Management should have listened to Dr. Deepak Bhatt, a cardiologist at the Cleveland Clinic, who proposed a study of Vioxx in patients with severe chest pain to Merck management. Dr. Bhatt commented at the time “they {Merck} should have done a trial like this. If they {Merck} internally thought this drug was safe in patients with heart disease, there was no reason not to do it.” Management never ordered a test that would directly explain the results of the clinical trial in 2000. The FDA sent Merck a warning letter for minimizing the serious cardiovascular findings. However, a better option would have been for the FDA to put a black-box warning on Vioxx’s label, or stop the direct-to-consumer advertising until the issue was sorted out. Considering Merck operates under the aforementioned motto, Vioxx was not the optimal treatment for the majority of the patients that took the medication. The patients were not aware of this, and Merck’s aggressive marketing campaign reinforced the belief that this was the proper medication for all patients. Many patients were unnecessarily exposed to a risk due to aggressive marketing tactics when other NSIDS would have been the optimal medication for many patients, not to mention at a lower cost. The government should pay for tests that compare new drugs to older drugs. Many older drugs are simply ignored in favor of newer, heavily advertised drugs. Ultimately, it may take several years following approval for side effects to be exposed-a phenomena that could be avoided altogether if this analysis is done.
In addition, the patent life of drugs should be extended. Obviously after this tragedy, drug makers should be required to conduct more studies, but the patent life should be extended to mitigate the pressure to rush drugs to market. Another year of testing means another lost year in terms of patent coverage, and many companies feel pressured to rush drugs to market due to the declining exclusivity period. Bringing a drug to market takes roughly 14 years at a cost of $1.3 billion. If companies are forced to go through additional testing, patent lives should be extended to ensure the incentive for future innovation. Additionally, this could help alleviate the pressure placed upon the FDA to rush drugs to market if companies have longer exclusivity periods, allowing the FDA to conduct additional testing that could potentially prevent future problems.
Communication Analysis Vioxx was a medication that was designed to alleviate the gastrointestinal problems for high-risk patients. Vioxx was effective for these high-risk patients that did not have weak hearts. The drug should have never been prescribed to 90% of the patients that received the medication. In the end, some people who shouldn’t have been taking the medication died, and the people who could actually benefit from the medication couldn’t use it because it was pulled from the market. Once preliminary evidence began to mount that there was evidence of this potential link, the aggressive advertising should have stopped immediately.
Management should have communicated more clearly to the physicians that this medication was primarily for high-risk patients and articulated the cost/benefit more clearly. In addition, ignoring negative evidence seemed to prove management’s confirmation bias. Management’s deceptive promotion of the drug to increase sales has marred the reputation of a company that may never sufficiently recover. The rigidity of management, unethical, and criminal behavior has tarnished a once respected name.
Appendix
Advertising Direct-To-Consumer 2000 Analysis Rank | Name | Drug | DTC Spending (millions) | 1 | Vioxx | Antiarthritic | 160.80 | 2 | Prilosec | Antiulcerant | 107.50 | 3 | Claritin | Oral Antihistamine | 97.00 | 4 | Paxil | Antidepressant | 91.8 | 5 | Zocor | Cholesterol Reducer | 91.2 | 6 | Viagra | Sex Function | 89.5 | 7 | Celebrex | Antiarthritic | 78.3 | 8 | Flonase | Respiratory Steroids | 73.5 | 9 | Allegra | Oral Antihistamine | 67 | 10 | Meridia | Antiobesity | 65 | | | | |

Works Cited