Merck, the FDA, and the Vioxx Recall

Merck was one of the world’s leading pharmaceutical firms. The company ranked 4th I sales after Pfizer and Johnson & Johnson and it ranked 5th in assets and market value. Merck ranked 1st in profits, earning $7.33 billion on $30.78 billion in sales. In 2006, Merck faced major challenges with their once best selling prescription painkillers, Vioxx which was pulled off the market in September of 2004 after Merck learned it increased the risk of heart attacks and strokes. In 2004, the Justice Department opened a criminal investigation into whether or not the company had “caused federal health programs to pay for the prescription drug when its use was not warranted.” Merck was renowned for its research labs which had decades of achievements, turning out one innovation after another, including drugs for tuberculosis, cholesterol, hypertension, and AIDS.

In the early 2000s Merck spent around 3 billion in research; some felt that the company culture was shaped by its research agenda. The company was described as “intense, driven, loyal, scientifically brilliant, collegial, and arrogant” Trying to estimate the company’s financial liability from the Vioxx lawsuits would be difficult. From 1999-2004 over 84 million people had taken the drug worldwide. The FDA estimated that 139,000 people in the United States had had heart attacks or strokes as a result of taking Vioxx and 55,000 of those had died. Merrill Lynch estimated the company’s liability for compensatory damages along anywhere from 4-8 billion. In the US, prescription medicine such as Vioxx were regulated by the Food and Drug Administration (FDA).

Before a new drug could be sold in public, the manufacturer had to carry out clinical trials to demonstrate both safety and effectiveness. Advisory panels outside of the medical experts had to review the results of these trials to recommend whether or not the drug should be approved or not. When FDA shortened their approval time, the percentage of drugs recalled following approval increased from 1.56 percent for 1993-1996 to 5.35 percent for 1997-2001. Vioxx was the ninth drug taken off the market in seven years. The pharmaceutical industry’s success in increasing the approval of new drugs reflected its strong presence in Washington. Merck spent 40.7 million in lobbying from1998-2004.

The most effective technique was to hire former elected officials or members for their staff. In the 1990’s, 80 percent of pharmaceutical firms growth came from “blockbuster” drugs; medicines that serve vast swaths of the population and garner billions of dollars in annual revenue; drugs such as Vioxx. In 2003, Merck spent 422 million to market Vioxx to doctors and hospitals. Marketing to doctors and hospitals were important but in the late 1990’s the focus shifted when the FDA allowed drug companies to advertise directly to consumers. Merck spent another 78 million on DTC (direct to consumer) marketing. The DTC was often criticized the advertising saying that it would put pressure on doctors to prescribe drugs that might not be the best for the patient. Vioxx was known as a selective COX-2 inhibitor, cyclo-oxygenase or COX was associated with pain and inflammation.

There were essentially 2 COX enzymes, COX-1 was found to protect stomach lining while COX-2 contributed to pain and inflammation. Other drugs such as Advil suppressed both enzymes which is why some users had stomach irritation. Many drug companies including Merck were interested by the possibility of developing medicine that could just block COX-2 leaving the stomach-protective COX-1 intact. After several years of research and testing by Merck scientists, in May of 1999, the FDA approved Vioxx for the treatment of osteoarthritis, acute pain in adults, and menstrual symptoms. Vioxx quickly became a blockbuster drug for Merck and in its peak in 2001, it generated 2.1 billion in sales in the United Sates alone. Even before Vioxx was approved, there was evidence that casted doubt on the safety of the drug.

Merck Research suggested that some scientists had been worried about cardiovascular risks and VIGOR found that Vioxx was easier on the stomach but caused five times as many heart attacks in the study group, this concerned the FDA and it required Merck to add an additional warning language to its label. Kaiser/Permanente study showed that patients with big doses of Vioxx had three times the rate of heart attacks than patients on Celebrex (c a competing COX-2 drug), and the APPROVe study by Merck was used to monitor patients enrolled in a trial to see if those taking Vioxx had more heart attacks and strokes than those who were taking a placebo. The study was designed to determine if Vioxx reduced the risk of recurrent colon polyps, Merck hoped the study would lead FDA to approve the drug for this condition .APPROVe was planned before the VIGOR results were known.

On Thursday, September 23rd, 2004, president of Merck Research Lab received a call from scientists monitoring the APPROVe study that after an 18 month trial, individuals using Vioxx were more than two times likely to have a heart attack or stroke than those taking a placebo. The scientist recommended that the study be stopped because of “unacceptable risk” The president of Merck Research Lab recommended that Vioxx be withdrawn from the market and the CEO agreed. The FDA was contacted and the drug was removed. Section II

The major issue or problem in this case is if Merck should be held responsible for the potential deadly side effects of patients using Vioxx and whether or not Merck “caused federal health programs to pay for the prescription drug when its use was not warranted”. Vioxx is a selective COX-2 inhibitor that was created for pain and inflammation but unlike other drugs it had a COX-2 enzyme as well that protects the stomach lining from damage such ulcers. The evidence that there is a problem is the fact that the company had to pull the drug from the market and that the Justice Department opened a criminal investigation against Merck. Vioxx was presented to the market in May of 1999 when the FDA approved the drug for the treatment of osteoarthritis, acute pain in adults, and menstrual symptoms.

During the time that the FDA approved this drug, the approval time was shortened and the drug was approved by the FDA before all studies were completed. There was evidence that there would be problems with Vioxx even before the drug was approved by the FDA. Merck Research showed that during the development stage, scientists were worried with cardiovascular risks, VIGOR was a study completed in 2000 after the drug was on the market that found that the Vioxx group had nearly five times as many heart attacks. “Dr. Edward Scolnick, said that cardiovascular events were clearly there and called them a shame”. The Kaiser/Permanente study found that patients with a high dose of Vioxx had three times the rate of heart attacks as patients on Celebrex (competitor drug) The APPROVe trial was designed to determine of Vioxx reduced the risk of colon polyps but once Merck learned of possibly cardiovascular risk, they decided to monitor the trial.

The risks of using Vioxx were too great not to ignore so in September of 2004, Dr. Peter Kim, president of Merck Research Lab received a call from the scientists on the APPROVe trial that told him after 18 months of monitoring, the individuals were more than twice as likely to have heart attacks or strokes than those using a placebo. The scientists recommended that the study be halted because if the unacceptable risk to the patients. During the next few days of this recommendation, Peter Kim meet with several doctors and recommended that Vioxx be removed from the market. The CEO of Merck agreed and contacted the FDA and Vioxx was removed from the market. Section III

1. Do you believe that Merck acted in a socially responsible and ethical manner with regard to Vioxx? Why or why not? In your answer, please address the company’s drug development and testing, marketing, and advertising, relationships with government regulators and policymakers, and handling of the recall? I do not believe that Merck made a socially responsible decision when Vioxx was introduced into the pharmaceutical market. There were scientists that were involved in product development and testing that knew that there were serious health risks that could be side effects of the medication such as cardiovascular complications.

Merck should have considered what could have been potentially happened and the medication should have been changed in order to minimize the harmful side effects. There were several developments during the Vioxx testing and there were several issues regarding the safety of the drugs that heart attacks resulted from the medication. Merck used an advertising technique called direct-to-consumer, which was new in the pharmaceutical industry as it was the first time they were allowed to advertise to consumers. Consumers would request this medication, making doctors feel obliged to prescribe from the commercials they saw on television and in magazines. The government and policymakers received large sums of money from the development company during the advertising and marketing phase of the drug.

When studies became public of Vioxx users being twice as susceptible to heart attacks, the president of Merck Research Lab, Dr. Kim recommended recalling the drugs due to the elevated risks for users as well as the lack of knowledge as to what was causing the heart attacks. There were mixed emotions for some stating that stronger warning labels should be used and that prescription was to be left for the doctor and patient’s assessment.

2. What should or could Merck have done differently, if anything? There are several things that Merck could have done differently during the development of Vioxx. When the early stages of research and development showed that Vioxx had an increased potential for cardiovascular events, more extensive research should have been done to determine why there was an increased potential for cardiovascular events. Merck should have continued studies such as APPROVe and VIGOR even if the drug was already approved by the FDA. Addition more extensive testing to determine these potential cardiovascular events, Merck should be asked why these studies weren’t completed during the testing and development stage opposed to when the drug was already approved by the FDA. Merck should have held their product to a higher standard than their competitors and fully research all potential possibilities of why cardiovascular events occurred before the drug was put on the market.

3. What is the best way for society to protect consumers of prescription medicines? Specifically, what are the appropriate roles for pharmaceutical companies, government regulators and policymakers, patients and their physicians, and the court system in assuring the safety and effectiveness of prescription medicine? The appropriate role of government regulators and policymakers should be to endure the welfare of the public health. They should ensure that pharmaceutical companies do not interfere with the healthcare system such as limited DTC so that doctors can prescribe the correct medications for their patients not what medication their patients saw on a commercial.

They should also minimize the influence of politics when making healthcare decisions. Pharmaceutical companies should not appoint former politicians to their staff. The pharmaceutical companies’ role in society should be one of the researcher. The companies should clearly state any and all side effects in a way that patients can see them. The pharmaceutical companies should not directly advertise to the patients. The companies should inform the doctors of the potential risks and they should focus on the wellbeing of the patients. The doctors and physicians’ role in this is to regulate the actual prescriptions given to the patients and to make sure they are informing the patients of the potential risks. The patients should take an active role in their healthcare and make sure they are well informed before taking a prescription. The Court Systems role in this is quite simple-ensure that all laws are being followed and those who are not be fined and appropriate action is taken.

4. How should the present system be changed, if at all, to better protect patients? I do not think that the present system should be changed but consumers need to take their health and medical decisions seriously. By having patients more involved in their medical decisions, they won’t have to just rely on the pharmaceutical companies and our doctors to make all our medical decisions. While some doctors are paid by the pharmaceutical companies to introduce new drugs to their patients, it should be about healing the sick and not making money from them. Merck should have remembered their core values of “we try never to forget that medicine is for the people. It is not for profits. The profits follow, and if we have remembered that, they never fail to appear. The better we have remembered that, the larger they have been.” Merck should have remembered to protect the people by doing further research to determine the cause of the cardiovascular events before putting hundreds of thousands of patients in risk of getting heart attacks or strokes.