Merck developed the drug Vioxx to treat arthritis pain. It was approved by the FDA in 1999 but later studies showed it increased risks of heart attacks and strokes. Merck faced thousands of lawsuits and eventually paid $4.85 billion to settle claims after voluntarily withdrawing Vioxx from the market in 2004. The document discusses the history of Merck and development of Vioxx, clinical trials that showed safety issues, lawsuits against Merck, and recommendations for how the FDA could strengthen drug safety processes going forward to prevent similar situations.
![Amro Hussien<br />Randal Williams<br />11/04/10<br />Case Presentation<br />Case: Vioxx Decisions-Were they Ethical?<br />History of Merck and Vioxx:<br />Merck and Co. became an independent company in the United States after World War 1. The roots date back to 1827 with Heinrich Emanuel Merck as the founder who began an industrial-scale production or Alkaloids, plant extracts, and other chemicals. The successful export business in the United States led in 1887 to the establishment of a subsidiary in New York. Under George Merck, a grandson of Heinrich Emmanuel Merck, Merck & Co, was formed in 1891. It became independent from the former Merck in Darmstadt which is the oldest pharmaceutical and chemical company in the world. The two companies are no longer linked today but the one thing that they have in common is the name Merck. Merck & Co. holds the rights to the name in North America and outside this region the U.S Company operates as Merck Sharp and Dohme (MSD) or MSD Sharp & Dohme. Merck KG&A in turn, holds the rights elsewhere in the world and operates in North America under the umbrella brand EMD, formed from the initials of Emanuel Merck, Darmstadt. <br />Information on Vioxx:<br />Vioxx is a nonsteroidal anti- inflammatory drug ( NSAID) that exhibits anti-inflamitory , analgesic, and antipyretic activities. NSAIDs are a large class o0f medications used to treat arthritis pain and inflammation. There are three categories of NSAIDs: Salicylates such as aspirin, the traditional NSAIDs, and the COX-2 selective inhibitors. The FDA approved Vioxx in May 1999 for the reduction of signs and symptoms of osteoarthritis, as well as for acute pain in adults. When they started with this drug, the original safety database for Vioxx showed that 5000 patients did not show an increased risk of a heart of attack or stroke. In the clinical trials conducted, the risk of gastro intestinal side effects was determined through the use of an endoscopy. These studies showed a significant lower risk of gastro intestinal ulcers in comparison to ibuprofen. <br />After Vioxx was approved in 1999, Merck created a VIGOR (VIOXX Gastro Intestinal Outcomes Research) which was designed to look into GI effects which included stomach ulcers and bleeding. The VIGOR study was a large 8000 patient study designed to evaluate the GI safety of Vioxx compared to naproxen, it was done with a rheumatoid arthritis population, who typically required a higher dose of 50 mg of anti-inflammatory medication. The study concluded that there was an increase of serious cardiovascular events including heart attacks and strokes, in patients taking Vioxx compared to patients taking naproxen. VIGOR was a randomized, double-blinded study in 8,076 patients with rheumatoid arthritis requiring chronic NSAID. The patients were not allowed to use concomitant aspirin or other anti-platelet drugs.<br />Vioxx has demonstrated significant reduction in joint pain compared to placebo. Vioxx was evaluated for the treatment of the signs and symptoms on OA of the the knee and hip in placebo and active-controlled clinical trials of 6 to 86 weeks durations that enrolled approximately 3,900 patients. In the placebo- controlled trials, the percentage of patients achieving headache relief for 2 hours after treatment was significantly greater among patients receiving vioxx at all doses compared to those who received placebo. Approximately 3,600 patients with osteoarthritis were treated with VIOXX. Approximately 1400 patients received VIOXX for 6 months or longer and approximately 800 patients for one year or longer. There were several adverse side effects that were found in 2% of the patients who took VIOXX including abdominal distention, chest pains, chills, fever, fluid retention, pelvic pain, trauma, and viral syndrome. Some of the problems experienced in the digestive system include acid reflux, constipation, and an oral infection. Other problems included symptoms of allergy and hypersensitivity in the immune system. Psychiatric problems included anxiety, depression, and mental acuity decreasing. Some of the cardiovascular symptoms included congestive heart failure, hypertensive crisis, appetite change, and weight gain. In the OA and RA clinical trials, it was discovered that the 50 mg of VIOXX , which is the highest dose recommended for chronic use, would be associated with a higher incidence of gastrointestinal symptoms such as abdominal pain, heartburn, nausea, vomiting, and hypertension. All other symptoms would be treated with the recommended doses of 12.5 and 25 mg of VIOXX.<br />Lawsuits regarding VIOXX:<br />The first VIOXX lawsuit, was a wrongful death case heard in a Texas courtroom. The jury decided by 10-2 vote on August 19, 2005, that Merck was liable and awarded $253.4 million to the widow of Robert Ernst, a Wal-Mart employee who died of a heart attack while taking VIOXX. The plaintiff reportedly was seeking $40.4 million in damages. Under Texas law the amount is expected to be reduced to $26.1 million.<br />Merck eventually settled the lawsuits for out of court for $4.85 billion, this agreement settled 27,000 lawsuits and 47,000 plaintiffs. Through the court cases Merck won 11 cases and lost 5. The legal defense for Merck cost them $1.2 billion. The average plaintiff will receive just over $100,000 before fees and expenses, which usually run between 30-50%. The plaintiff’s attorneys will receive almost $2 billion in fees.<br />Merck has also had to settle with unions and insurers for $80 million. Shareholders of Merck filed suit against the officers of Merck on behalf of the company and came to an agreement that the officers would pay $12.5 million in legal fees.<br />The state of Texas filed suit against Merck, the lawsuit alleges that Merck aggressively marketed the drug to the medical community, and in doing so, willfully misrepresented its own studies and the concerns of physicians suggesting the drug may increase the risk of heart problems. The Texas Medicaid program reimbursed pharmacists $56 million for VIOXX prescriptions they filled for patients over a five year period. The attorney general invoked a provision that allowed that amount to triple for acts of fraud. The Medicaid program reimbursed pharmacist for VIOXX prescriptions at the rate of about $1.94 per 25-milligram pill, the most commonly prescribed dosage. Pharmacist filled more than 700,000 prescriptions under the Medicaid program in those years, accounting for over 29 million pills. Merck had the case tossed out in November of 2009.<br />There is a case pending between Merck and its shareholders, on April 27th of this year, the Supreme Court ruled that the lawsuit could proceed. Merck stated that under the Sarbanes-Oxley act of 2002, that the statue of limitations had run out on the lawsuit. Section 804 of the Sarbanes-Oxley act states that in regarding fraud, a lawsuit can be brought within the first two years that the fraud is uncovered. Merck claims that more than two years prior to the filing the plaintiffs had or could have discovered the “facts constituting the violation, and therefore was barred by the applicable statute of limitations.<br />Currently there are lawsuits pending and being decided in Australia against Merck. On March 5th of 2010 the Australian federal court ruled in favor of the Plaintiff (Peterson) and awarded him a settlement of $287,000 Australian dollars. The judge found that Merck failed to warn his Doctor of the cardiovascular risk associated with Vioxx, the judge cited the VIRGO study and said that Merck had violated Australian trade practices.<br />After researching our case and looking up evidence of fraud, we did come across a case involving Dr. Scott S. Reuben. He was a Dr. performing studies for Merck and other pharmaceutical companies. Reuben has now admitted that he never conducted any of the clinical trials on which his conclusions were based “in what may be considered the longest-running and widest-ranging cases of academic fraud. Scientific American has called Reuben the medical equivalent of Bernie Madoff. On June 24, 2010, Reuben was sentenced in Federal Court to six months in jail (after pleading guilty to one count of health care fraud on February 21, 2010) to be followed by three years of supervised release. Further, a five-thousand dollar fine was imposed and he was ordered to provide restitution of more than three hundred sixty thousand dollars.<br />Questions:<br />,[object Object],The decisions that Merck made regarding to Vioxx were not ethical because the company knew before hand that the drug was not safe before it got approved by the FDA in 1999. Through rigorous drug testing before approval by the FDA, Merck had already discovered that Vioxx increased the risk of a heart attack or stroke in 1998. Merck was very well aware of the possible cardiovascular effects such as congestive heart failure that patients would experience if the drug was released in the market. Merck’s decisions were not ethical because they did not display utilitarianism ethics. Utilitarianism is virtue based on utility and that conduct should be directed to the benefit of the greatest number of people. Merck acted immoral in considering how releasing this drug would affect the stakeholders which would include Merck, shareholders, users of the product, the public, and families. Merck acted more on the basis of pure self- interest for the company in gaining profit than understanding the ethics of consequentialism. The consequentialist approach requires for Merck to understand the harms and benefits to multiple stakeholders and to come to a decision that is the greater good for the greatest amount of people. Merck had several problems since the very beginning with Vioxx including the trials in arthritis being extremely challenging and having difficulty in requiring 3 year placebo controlled safety studies prior to the drug’s approval. Merck did not initially act in accordance to virtue ethics either, as virtue ethics requires the character of integrity of the moral actor and looks to moral communities to help identify ethical issues and guide ethical action. Towards the end of the drug in September 27, 2004, Merck requested a meeting to discuss with the FDA to halt the long-term study of Vioxx in patients at increased risk of colon polyps. Merck informed the FDA it would remove the drug from the market voluntarily. The data that they presented showed that there was an increased risk in cardiovascular problems and strokes starting at the eighteen month time point compared to placebo. This was another indication of a difference in comparison to the placebo group and it supported the previous signs observed in the VIGOR trial. Merck decided that this drug was too much of a risk to patients who use it but the major issue at hand is that they already knew about all of the problems from the very beginning. The company understood well the differences that would occur between the actual drug and the placebo during vigorous testing but they allowed the drug to be placed on the market.<br />,[object Object],The FDA is well recognized as having a gold standard drug review. The organization maintains the highest worldwide standards for drug approval and they approve drugs after a sponsor demonstrates that they are safe and effective. Experience has proven that some of the major potential risks of a drug do not necessarily show during the mandatory clinical trials before approval for safety and effectiveness. It is common that severe adverse effects are identified later during post-marketing clinical trials or through constant reporting of these symptoms on patients. In response to this, the FDA has created a strong post-market drug safety program designed to assess these events identified after approval for all of the medical products it regulates as a compliment to the pre-market safety reviews required for prescription drugs in the United States. The FDA will not approve of a drug unless the benefit outweighs its own risk for an intended population. Adverse reactions to drugs include an error in drug prescription, the reactions can be expected because the clinical trials indicate that there are such possibilities or they can be unexpected because the reaction was not evident in drug trials.<br /> In 2004, the FDA announced a five-step plan to strengthen its drug-safety program. First, they will sponsor an Institute of Medicine committee that will study the effectiveness of the U.S drug safety system and figure out what additional steps that could be taken to learn more about drug side effects. Second, they will implement a program that will help address differences in professional opinion between supervisors, managers, and external advisors. Third, they will conduct a national search to find someone who is a drug safety expert with knowledge of drug development to fill up the position of Director of the Office of Drug Safety. Fourth, they will conduct workshops and advisory committee meetings to discuss complex safety and risk management issues. The fifth one is an intention to publish three guidelines to help pharmaceutical firms manage risks involving drugs and biological products. The first of the guidelines is the “Premarketing Guidance” which covers risk assessment of pharmaceuticals prior to their marketing, the second is “RiskMAP Guidance” which is the development and use of risk-minimization of action plans and the third is a “Pharmacovigilance Guidance which discusses post-marketing risk assessment and good pharmacology practices. <br />The FDA could improve its processes as an organization in assessing effectiveness on drug safety by having multiple clinical tests over a sporadic period of time to determine if the drug is completely safe to release into the market. We think that a solution to this problem would be for the FDA to implement a new strategy on the criteria in deciding whether the drug is safe for users. One recommendation is to have several trial runs over a period of 2 to 3 years after the drug has been created. They should test the drug on patients from different demographic regions which would give them a window of time to see if there are any new symptoms that have been discovered. This way the FDA can determine if the product is accepted or rejected for further review and research. This would help prevent future dangerous drug products from entering the market and killing thousands of individuals. <br />Another way we believe the FDA can improve the process of approving drugs for the market would be to have a similar set up as financial statement auditing. We believe all test conducted on the drugs should be performed by an independent firm; we do not think that companies who are introducing the drug should have the final say on the test results of their drugs. By bringing in an independent firm to conduct the testing of the drugs, a more credible non-biased opinion would then result. Just like Enron, WorldCom and Sunbeam, we feel as if greed got in the way of the Merck executives and as result a dangerous drug was introduced to the market.<br />](https://image.slidesharecdn.com/vioxxcasestudy-101206105959-phpapp02/85/Vioxx-case-study-1-320.jpg)
