Acute: A term used to describe conditions that are short-lived and usually sudden or unexpected. This term is used in contrast to chronic, which refers to conditions that worsen over time.

Anaphylaxis: A severe allergic reaction that can cause hives and swelling of the throat, neck, and other exposed areas. In severe cases, anaphylaxis can cause the body to go into anaphylactic shock, which involves a sudden drop in blood pressure and a swelling of the airways. It can be fatal if not treated within minutes; emergency measures may include CPR and adrenaline injections.

Autoimmune Disease: Any disease of the immune system in which the immune system attacks tissues and/or materials that are not normally harmful to or are a part of the body. The immune system normally protects the body from infection and helps to promote healing, but in patients with autoimmune disease, the immune system becomes overactive and attacks non-infected materials, or even entire areas of the body. For example, in the case of Rheumatoid Arthritis, the immune system attacks the lining of the joints, causing pain and inflammation.

Ankylosing Spondylitis (AS): A degenerative form of arthritis primarily affecting the spine. AS is an autoimmune disease (see above definition) and is believed to be caused by a genetic predisposition.

Arthritis: A class of diseases involving pain and inflammation of the joints, caused by one of several factors affecting the cartilage that cushions the joints.

Black Box Warning: A printed warning included on the packaging of a drug, which is enclosed in a black box to distinguish it from other packaging information and to draw the user’s attention. In the case of Vioxx, in 2002, a black box warning was added describing the risk of cardiovascular complications associated with the drug. Celebrex, which is still on the market, carries essentially the same black box warning concerning cardiovascular complications.

Chronic: Term describing any condition that recurs continually or repeatedly, or that worsens over time. This term is used in contrast to acute, which refers to short-lived or single-instance conditions.

Codeine: The most commonly used opiate drug. Codeine is found in analgesics (pain killers), cough medicines, and anti-diarrheal medications. Opiates are derivatives of the poppy plant.

DMARD: Disease-Modifying Anti-Rheumatic Drug. DMARDs are used to slow the progression of diseases like Rheumatoid Arthritis, which are directly caused by a malfunction of the immune system. These drugs attempt to prevent the immune system response from worsening the disease, and are often used in conjunction with pain killers, which merely treat the disease symptoms.

Inactive Ingredients: All of the ingredients of a medication besides the “active” ingredient. In the case of Vioxx, “rofecoxib” is the active ingredient. Inactive ingredients may include things like coloring, flavoring, and texture stabilizers. These ingredients may vary between different manufacturers of the same drug; however, the active ingredient must be the same.

Juvenile Rheumatoid Arthritis (JRA): Now called Juvenile Idiopathic Arthritis (JIA), JRA formerly referred to any form of inflammation of joint tissue that appears in childhood, and may be chronic or acute.

Lipid: Any fat-soluble molecule found in the body. Lipids come in various forms and have multiple physical functions, including energy storage, assisting in neural (nerve-related) communication within the body, and even making up part of the structure of cell membranes.

Method of Administration: This term refers to the format of a drug. Methods of administration can be capsules, tablets, liquid, injection, etc.

Naproxen: A non-selective NSAID that has been used in various clinical trials as a base of comparison to test both the safety and efficacy of selective COX-2 inhibitors, including Vioxx.

NSAID: Non-Steroidal Anti-Inflammatory Drug. NSAIDs treat pain by reducing swelling, or inflammation, without the use of steroids.

Osteoarthritis: A type of arthritis in which overuse or normal wear-and-tear of the joints causes the cartilage, which normally cushions the movement of the joints, to become damaged and worn. The body responds with inflammation, which in turn causes pain. Osteoarthritis is considered a degenerative condition because it usually worsens with the passage of time.

Prostanoids: A subclass of fatty acid molecules, found in every body system, which interact with the enzyme cyclooxygenase (COX) to cause inflammation of tissues. Prostanoids come in three forms: prostaglandins, which are associated with pain and inflammation; thromboxanes, which assist in forming necessary blood clots; and prostacyclins, which are involved with platelet production and also assist the blood in clotting.

Rheumatoid Arthritis (RA): A type of arthritis in which the immune system attacks the cartilage that cushions the joints from the friction of movement. In some cases, the immune system also attacks other organs. The symptoms of RA can be treated with NSAIDs, but the disease itself is an autoimmune disorder and must be treated with a class of drugs called DMARDs.

When Vioxx was withdrawn from the worldwide market in 2004, patients had no choice but to stop taking the medication. The only other COX-2 inhibitors on the market were Celebrex and Bextra, both manufactured by Pfizer. Patients who did not wish to continue taking COX-2 inhibitors were given the option of trying a non-selective NSAID.Below, you will find information about the medication alternatives of former Vioxx patients, including other COX-2 inhibitors and non-selective NSAIDs.

Cox-2 Inhibitors

Celebrex

Celebrex (generic name celecoxib), manufactured by Pfizer, was the first COX-2 inhibitor approved by the FDA. Celebrex was released in 1999, mere months ahead of Merck’s competing drug, Vioxx. The two drug giants used their strongest marketing efforts to snatch up the new customer base of arthritis sufferers, who numbered in the millions and had been offered no notably effective medications up to that point. Celebrex is also approved by the FDA for the treatment of Ankylosing Spondylitis (spinal arthritis), dysmenorrhea (severe menstrual pain), Familial Adenomatous Polyposis (precancerous colorectal polyps), and acute pain.

Bextra

Bextra (generic name valdecoxib), also manufactured by Pfizer, was withdrawn from the US market in 2005. Shortly after the withdrawal of Vioxx, the safety of the entire class of COX-2 inhibitors was called into question. The FDA determined that the benefits of Celebrex outweighed its risks, and it was allowed to remain on the market. In the case of Bextra, however, the elevated cardiovascular risks, and a rare incidence of a potentially fatal skin reaction, caused the FDA to recommend its withdrawal.

Arcoxia

Arcoxia (generic name etoricoxib) was intended to be the new COX-2 inhibitor by Merck, but in April of 2007, Merck’s request for FDA approval of Arcoxia was denied. The FDA has requested further safety and efficacy data in support of Arcoxia be provided before it will approve the drug. Arcoxia is currently approved in more than 40 countries, but not in the US.

Prexige

Prexige (generic name lumiracoxib), manufactured by Novartis, was first approved for use in the European Union in November of 2006, and it was quickly approved in several other countries around the globe. By August of 2007, Prexige was withdrawn in Australia. In September of 2007, the FDA denied approval of Prexige in the US pending further safety data. In October of 2007, Prexige was withdrawn in Canada, and in November, it was withdrawn from several countries in the European Union.

Although Prexige is a selective COX-2 inhibitor, it works slightly differently from other COX-2 inhibitors like Celebrex or Vioxx. The chemical makeup of Prexige causes it to bond to a different area on the COX-2 enzyme. The basic effect of suppressing the COX-2 enzyme is the same, but Prexige was withdrawn because of a high incidence of severe liver damage, rather than cardiovascular complications as in the cases of Vioxx and Celebrex.

Licofelone

Licofelone (also called ML3000) is a new kind of NSAID called a COX/LOX inhibitor. While COX inhibitors react with the enzyme cyclooxygenase, LOX inhibitors react with the enzyme lipoxygenase. Both enzymes are involved in the production of prostaglandins, which are the pain- and inflammation-causing agents targeted by this entire drug class. Licofelone was developed by a German pharmaceutical company called Merckle GmbH for the treatment of osteoarthritis. Licofelone is still in testing stages and has not yet been submitted for approval. It is designed to have even fewer gastrointestinal (GI) side effects than other selective COX-2 inhibitors. In clinical trials, Licofelone has shown fewer GI complications compared to naproxen in osteoarthritis patients.

Non-selective NSAIDs

Non-selective NSAIDs are another option for former Vioxx patients. NSAIDs have been around much longer than COX-2 inhibitors, and have never been shown to cause the same severity of complications. Unlike selective COX-2 inhibitors, like Vioxx, non-selective NSAIDs inhibit both the COX-1 and COX-2 enzymes. The COX-2 enzyme is responsible for pain and inflammation, while the COX-1 enzyme helps to protect our stomach and intestinal lining from corrosion. By inhibiting both enzymes almost equally, NSAIDs offer pain relief accompanied by a higher risk of gastrointestinal side effects, including ulcers. Ulcerations of the stomach and intestines can lead to internal bleeding, and in extreme cases, death. The risk of these serious side effects is relatively small, but many people experience some gastrointestinal complications with prolonged or high-dosage NSAID use.

Several NSAIDs are available over-the-counter, including aspirin and ibuprofen, which are sold under various brand names. Prescription NSAIDs currently approved in the US include:

• Diclofenac
• Diflunisal
• Etodolac
• Indomethacin
• Ketoprofen
• Ketorolac
• Nabumetone
• Naproxen
• Oxaprozin
• Piroxicam
• Salsalate
• Sulindac
• Tolmetin

These medications may be prescribed for various pain or inflammation-related conditions, as determined by your doctor. Because individuals react differently to drugs, it is not unusual for your doctor to try different NSAIDs until you find the one most effective for your condition and body chemistry.

While Merck & Co., Inc. has paid out billions in settlements to former Vioxx users, not all Vioxx lawsuits against the drug manufacturer have been successful. The caps on lawsuits vary by state, and the scientific evidence is considered specifically for each case. This means that some cases are stronger in court than others.

One of the most well-publicized Vioxx suits took place in Texas. The court awarded the widow of a Vioxx patient $253 million in damages after the death of her husband. The award was later reduced to the maximum amount allowed in the state of Texas, which was $26 million. In April of 2008, the verdict was overturned when the appellate court found that the prosecution had not established enough supportive evidence that the deceased man’s heart attack was a result of his Vioxx use.

In New Jersey, an appellate court overturned a $9 million award in punitive damages to a Vioxx patient who survived a heart attack. However, the court upheld the $4.5 million award for compensatory damages. The portion of the lawsuit that was overturned concerned accusations of consumer fraud by Merck. It was decided that, because the FDA had affirmed the safety of Vioxx, Merck essentially could not be considered guilty of selling an unsafe product.

Critics of the New Jersey decision say it brings to light a problem with the practice of “federal preemption,” which in effect kept the jury from considering evidence heard at trial because the FDA’s approval of Vioxx was considered to take precedence.

These two verdict reversals eliminated the two largest payouts by Merck for individual Vioxx lawsuits. A press release on the web site for Merck & Co., Inc. states that Merck’s record in court has given the company a positive outlook. The Merck site adds that of the eighteen cases that went to trial, only three resulted in settlements that were not overturned on appeal.

However, in May of 2008, on the heels of the reversals of the Texas and New Jersey verdicts, Merck agreed to pay a $58 million settlement in a class-action suit brought by 29 different states. The suit accused Merck of misleading advertising, both to consumers and doctors, that concealed the known cardiovascular risks of Vioxx. This decision also established more rigid legal guidelines concerning drug advertising practices.

In June of 2008, the New Jersey Supreme Court ruled that Vioxx patients who did not experience a cardiovascular event may not seek damages to cover the costs of tests to measure cardiac function. This decision, while possibly eliminating similar lawsuits, was not considered a major blow to Vioxx plaintiffs nor a major victory for Merck.

While it is impossible to predict the outcome of Merck’s legal battles over Vioxx, the billions in profits Merck enjoyed from the sales of the drug continue to hang in the balance. The Wall Street Journal dubbed Merck’s recent aggressive promotion of the drug Gardasil a “help pay for Vioxx” campaign, in recognition of the company’s need to boost income while facing massive litigation. Despite the major verdict reversals in New Jersey and Texas, Merck has paid more than $5 billion in settlements, and that amount continues to grow. In the end, these ongoing legal battles will mean a big chunk of Merck’s Vioxx profits are gone forever.

If you are considering bringing a Vioxx lawsuit, you may be running out of time. Each state has specific deadlines for filing this type of personal injury lawsuit. It is strongly recommended that you inquire with a legal professional, as soon as possible, if you are concerned about these lawsuit-filing deadlines.

Find the Right Vioxx Lawyer

Choosing the right lawyer is the first step toward a successful lawsuit. You should use the same care in selecting a lawyer as you expect your lawyer to use in handling your case. This means you should be prepared to do some legwork. You may need to contact several different lawyers before you find one you want to work with.

Vioxx lawsuits are considered personal injury cases, but that doesn’t mean just any personal injury lawyer will be right for you, even one with drug company experience.

Things to consider before you make a final decision about a lawyer:

• Don’t settle for the first lawyer you meet, or assume that your family lawyer can handle your case. Contact different law firms and see what kind of responses you get. Ask yourself these questions after the initial phone call:
  • How easy was it to talk to a live person?
  • Did the call leave you with a good impression?
  • Did you get to speak to an attorney right away?
  • Did the lawyer do more talking than listening?
• Beware of attorneys that make snap judgments about your case without gathering the details. Also, beware of any attorney who offers you a cash advance or guarantees you a large settlement. Even the best attorneys sometimes lose.
• Find an attorney with experience working against drug companies, preferably one with specific Vioxx litigation experience. This will cut down on the amount of preparation time your lawyer will need to spend on your case.
• Don’t pick a law firm based on its hourly fees alone. Expensive lawyers are not necessarily better. Likewise, don’t pick a lawyer just because he/she is the most affordable.

Get Your Own Information and Ask Questions

Don’t depend on your lawyer to tell you everything you need to know about Vioxx. Your lawyer’s responsibility is to know the law, but as a consumer, it is your responsibility to become educated about your medications.

This web site is designed to provide you with a solid basis of information, which can help you figure out what questions to ask your lawyer. Remember, your lawyer is there to be of service to you.

Information Your Vioxx Lawyer will Need

Your lawyer will need to know how long you took Vioxx, at what dosages, and for what condition it was prescribed by your doctor. If you were covered by health insurance at the time, your insurance company may be able to provide you with records of how many Vioxx prescriptions were filled.

You will need medical records showing that you suffered an adverse cardiovascular event in close proximity to your Vioxx use. You may need to provide a list of all expenses related to your heart problem, such as hospitalization, surgery, and/or rehabilitation costs, if you are trying to recover these expenses in your lawsuit. If you are a family member bringing a suit on behalf of a deceased patient, you will need records of all of the death-related costs, such as burial, cremation, etc.

Your lawyer will ask you for specific documentation related to your case, and will be able to tell you where to get the information if you don’t have it.

Next Step: Start Contacting Lawyers

Each page of The Vioxx Advisor contains contact forms, through which we encourage you to submit questions and other requests for information. We can assist you in finding the right law firm to handle your case. Please feel free to use these forms, as their purpose is to provide a convenient and helpful resource for our readers.

Note: Bringing a lawsuit against Merck does not guarantee that you will receive a cash settlement, nor does it assure a verdict in your favor if your case goes to trial. Additionally, even in successful lawsuits, verdicts and awards can be reversed on appeal.

As explained below, generic drugs are identical to their name-brand counterparts in everything but appearance and inactive ingredients. The information on this web site applies to name-brand Vioxx as well as its generic version, rofecoxib. If you took rofecoxib, or generic Vioxx, your rights and responsibilities, as well as your entitlement to safe, high-quality medication, are the same as those of someone who took the name-brand drug.

Drug Patent Process

When a new drug is first created, the manufacturer holds the patent so that no other drug company may produce the drug. This patent begins with the very first preclinical trials and lasts for 20 years. By the time a drug is available to the public, the patent usually has 7-12 years remaining, during which time a generic version is not available. The justification for this extended patent period is that the original manufacturer of a drug invests the lion’s share of the research money. The exclusive rights to the drug’s profits pay the company back for that initial investment.

Once the original patent on a drug has expired, other manufacturers are free to produce a generic form of the drug. Often, the original manufacturer of a drug will produce a generic version of its own drug, while also continuing to produce the name-brand version.

FDA Guidelines for Generic Drugs

According to FDA guidelines, a generic drug must be equivalent to its brand name version in active ingredients (inactive ingredients may vary), dosage, method of administration, side effects, and safety. While generic drugs vary in appearance from their name-brand cousins, in every other way, they should be considered the same. In other words, any information provided on a name-brand drug also applies to its generic counterpart, and vice versa.

The FDA inspects American drug manufacturers on a rotating basis to ensure that their production meets safety and quality standards. The FDA does not, however, inspect prescription drug manufacturers located outside of the US.

After the withdrawal of Vioxx in 2004, consumers panicked. The news of heart attacks in thousands of Vioxx patients hit the headlines, and the ensuing media frenzy attempted to uncover the explanation, and more to the point, decide who was to blame.

In the beginning, Merck stood by its safety data regarding Vioxx, insisting that there had been no apparent risks until patients had taken the medication for 18 months. Merck said it regarded the deaths among Vioxx users as notable, but statistically insignificant. However, the families of Vioxx patients who suffered heart attacks and strokes believed the risk had been too high.

Vioxx lawsuits, however, are not only coming from patients and families of patients who have suffered cardiovascular events they believe to be linked to Vioxx. Class-action Vioxx suits against Merck also include patients who did not experience complications, but nonetheless feel that they would not have taken Vioxx if they had known about the possible risks. Additionally, Merck has faced multi-state class-action lawsuits accusing the company of false advertising and manipulation of study results. Even labor unions whose employees received Vioxx through union-sponsored health insurance programs are filing suits against Merck.

Lawsuits against Merck accused the drug giant of false advertising; essentially omitting their own findings concerning cardiovascular events in their massive marketing campaign to sell Vioxx to consumers and doctors. Merck’s advertising of Vioxx touted the drug as a stomach-safe aspirin alternative. Vioxx advertising did not include any mention of the drug’s cardiovascular risks. Even in its marketing to doctors, Merck downplayed the heart attacks that occurred in Vioxx clinical trials.

Vioxx Lawyers

The internet is flooded with ads for Vioxx lawyers, but if you believe you were injured by Vioxx and you need legal representation, make your choice carefully. Don’t pick a lawyer solely based on low fees or the promise of a huge settlement. Find a personal injury lawyer with experience in the area of medications or drug companies. Your lawyer should be willing and able to answer all of your questions, and it is your responsibility to become educated about what questions to ask.

Beware of any Vioxx lawyer who offers you a cash advance on a projected settlement, because even a great lawyer can’t be 100 percent sure that your case will be successful. The contact forms provided on the Vioxx Advisor can provide you with access to professional legal advice and representation. These forms are located on the right side of each page on this site.

Damages Claimed by Vioxx Patients

Most Vioxx litigants are seeking reimbursement for all expenses related to cardiovascular events they experienced while taking the drug. This could include lost time at work, medical expenses, travel expenses, as well as any measurable, emotionally-related expenses like psychotherapy. In the cases brought by the families of now-deceased Vioxx users, the damages also typically include burial or similar death-related expenses paid by the family.

Non-material damages in lawsuits, which are much more difficult to measure, can cause settlements to reach the millions or billions. These damages include such things as pain and suffering, loss of life enjoyment, loss of career opportunities, loss of physical abilities, etc. Because these types of damages are not measurable in dollar amounts, the amount awarded depends on the judge’s decision, which might be based on damages awarded in similar cases or on an agreement between the attorneys in the case.

Merck Attempts to Ward off Future Lawsuits with a Huge Settlement

In November of 2007, Merck announced that it would place $4.85 billion into a special fund; Vioxx litigants could then petition to receive settlements out of that fund. This act was not considered a settlement by Merck, but rather an attempt to prevent having to pursue each and every case separately. One firm in Alabama, whose lawyers planned to pursue this settlement fund, had more than 5,500 Vioxx plaintiffs in 2007.

At the time of Merck’s announcement, it was estimated that this massive payout by Merck would settle up to 47,000 Vioxx lawsuits out of court. In order to be eligible to receive part of the settlement money, patients had to have evidence of a cardiovascular event within 14 days of taking Vioxx, and they had to have taken at least 30 doses of Vioxx in total.

The deadline for filing a petition to receive a portion of this settlement money was June 30, 2008. Thousands of plaintiffs came forward just before this deadline.

Although Merck originally set aside just under $1 billion for its projection of Vioxx lawsuits, it has now paid out more than $5 billion, and many more lawsuits are still pending.

All drugs come with some package warnings, which include contraindications (outlining who should not take the drug). Contraindications take into account pre-existing conditions as well as other medications a patient is currently taking.

Vioxx was Not Recommended for Patients Who:

• Had a history of gastrointestinal bleeding or ulcers. These patients were shown to have a 10-fold increased risk of developing an ulceration of the stomach or intestines while using Vioxx.
• Were pregnant, nursing, smoked, or drank heavily.
• Suffered from renal insufficiency, and additionally the drug was not well absorbed by these patients. (See Vioxx Dosage Information for more about Vioxx absorption rates.)
• Had a known allergy to rofecoxib, aspirin, sulfur, or any NSAID drugs. In rare cases, severe allergic reactions occurred, including hives, swelling, and even symptoms of anaphylaxis.

Vioxx was Contraindicated for Patients Taking the Following:

• Hepatitis A or B medications
• HIV drugs or certain antivirals and antiretrovirals used in HIV patients
• Immunosuppressive medications, often used in transplant patients
• Other NSAIDs or low-dose aspirin therapy
• Certain muscle relaxers, including those used for Multiple Sclerosis or severe muscle spasms

There were literally hundreds of medications that were listed as having potential interactions with Vioxx, most of which fell into the above groups.

On September 30, 2004, Merck announced its decision to withdraw Vioxx. In its report, Merck cited the then-new results of the APPROVe study as the reasoning behind its decision. Merck’s analysis of the APPROVe study showed an increased risk of cardiovascular events in patients who had been taking the drug for 18 months or longer. Merck explained that the results of APPROVe were not complete until this time, and that early results of the study had not demonstrated the same cardiovascular risk that was evidenced by the study results as a whole.

In this statement, Merck also said it would conduct further investigations into its other COX-2 inhibitor, Arcoxia, to determine whether that drug’s prescription information should be amended to include further warnings.

Merck also announced that the value of its stock was expected to fall as a result of the news about Vioxx. In the year preceding the Vioxx withdrawal, Vioxx sales had accounted for just over 10% of Merck’s net earnings.

The Martin Report

In 2005, Merck hired the firm of Debevoise & Plimpton to conduct an investigation of all Vioxx study results and communications by Merck, including internal communications related to Vioxx. The firm was paid $21 million for the report, which was called the Martin Report after Judge John S. Martin, Jr., who headed up the investigation. The report concluded that Merck’s senior management had acted in good faith, and that the source of all the misunderstandings about the clinical safety of Vioxx was the sales team’s overzealousness.

The nearly 200-page Martin Report gave a detailed timeline of events surrounding Vioxx and explained Merck’s honest intentions at every turn. The report specifically addressed 27 different allegations against Merck, including its mishandling of APPROVe and other clinical trial results, its aggressive marketing tactics, and the idea that Merck purposefully withheld information about the risks of Vioxx. In each case, the report found that Merck scientists and officials had handled the data in good faith, and that any errors were the result of oversight, not intentional omission of data. The Martin Report did conclude, however, that Merck’s marketing team had exaggerated the safety of Vioxx and had intentionally used sales tactics in place of thorough information.

Read the entire Martin Report on Merck.com. (The report is a pdf so Adobe Reader is necessary to read.)

Diffusion of Responsibility

In response to the Martin Report, which was published in February of 2006, Merck stated that it was reassured that the findings of the report revealed no negligence on the part of Merck scientists or executives. Merck promised to consider the recommendations contained in the Martin Report, presumably by reconsidering and better supervising its advertising strategies. Whether or not Merck ultimately changed its marketing techniques is unclear, but the total spending for the advertising of drugs in general has not decreased.

Merck had hoped the Martin Report would serve as a definitive explanation of Merck’s position on Vioxx, both in the press and in the courtroom. However, in 2006, Merck announced a correction to its original statistical findings in the APPROVe trial.

Merck scientists reportedly made an error in calculating the cardiovascular risk in relation to the passage of time. In light of the corrected calculations, Merck retracted its claim that the risks of Vioxx were negligible during the first 18 months of treatment. This statement blew a gaping hole in Merck’s legal defense, which supported the 18-month benchmark theory, while also hurting the theory that marketing was entirely to blame for the Vioxx problem.

Throughout the investigations of Merck’s role in the handling of Vioxx, lawsuits have swept through courts across the US, costing Merck billions in settlements. The 2006 announcement only served to invite more lawsuits by destroying the 18-month theory and opening up claims of complications from short-term Vioxx users.

Vioxx was released just months behind Pfizer’s competing drug, Celebrex, and both drugs were aggressively marketed to doctors and to consumers. Direct-to-consumer drug advertising is any form of advertising that targets potential users of the drug, such as television, radio, and magazine ads. Merck is reported to have spent more than $500 million on advertising of Vioxx, including maintaining and training a massive sales force.

A WebMD investigation concluded that direct-to-consumer advertising, aimed at inducing consumers to visit their doctors and potentially inquire about advertised drugs, has been shown to cause up to a 2% increase in doctor visits. Additionally, direct-to-consumer advertising attempts to create a positive impression of a new drug in patients to whom it has not yet been prescribed, which increases the likelihood that they will continue taking the drug after the initial trial period.

Examples of Vioxx Direct-to-Consumer Advertising

Vioxx was touted in every form of media as a safe and effective pain killer. Television ads featured figure skater Dorothy Hamill skating to the Young Rascals’ tune “It’s a Beautiful Morning.” Dorothy Hamill appeared in print advertisements as well, endorsing the benefits of Vioxx for osteoarthritis relief. Presumably, if this drug provided relief for someone who pushed the limits of her joints to the degree of a professional figure skater, Vioxx could easily handle the average case of sore joints. Celebrity endorsements are an age-old advertising method, creating unparalleled product recognition. Merck not only used Dorothy Hamill as a celebrity endorser, but the company pursued every other avenue of marketing for Vioxx, from television to radio to online sources.

Free samples are another type of advertising that is common to all drug companies. Free samples allow doctors to introduce patients to new drugs at no cost to the patient, which increases the chance that the patient will continue taking the drug once the free samples run out.

Selling Doctors on Vioxx

While direct-to-consumer advertising is the only kind we see as consumers, doctors are exposed to the most effective marketing techniques of all. Not only do doctors receive free samples, as mentioned above, but they often receive massive amounts of promotional material — pens, tissue boxes, notepads, coffee mugs — which increase name recognition and keep the medications on doctors’ minds. In addition, doctors are visited by pharmaceutical representatives, otherwise known as salespeople. These representatives make up the drug producer’s sales force; often, they are only moderately informed of a drug’s clinical history. Their job is to sell pharmaceuticals, and that starts with getting doctors to write the prescriptions.

According to a critical report in the New England Journal of Medicine (NJEM), Merck’s sales team was trained in subliminal techniques for gaining the trust of doctors and creating the image of a relationship between the doctor and the pharmaceutical company, which in turn made doctors more likely to prescribe their drugs to patients. An example of a subliminal technique is the mirroring of a person’s physical movements, which supposedly increases trust. The NEJM article reminds us that providing thorough and objective information about new drugs should take precedence over making sales.

Such techniques were publicly criticized after the Vioxx withdrawal brought Merck into the limelight. Even the Merck-sponsored Martin Report revealed that Merck’s marketing of Vioxx was overzealous, and ultimately contributed to the drug’s being over-prescribed.

As recently as May of 2008, Merck agreed to pay $58 million to settle a multi-state lawsuit accusing the company of deceptive advertising of Vioxx. If Merck hadn’t yet reconsidered its advertising strategies, this latest settlement surely made the drug giant think again.

In April 2005, the Center for Drug Evaluation and Research (CDER), a branch of the FDA, sent out letters to the manufacturers of all NSAIDs, even over-the-counter (OTC) NSAIDs, urging them to include with their products more detailed information about the cardiovascular and gastrointestinal risks of the entire class of NSAIDs. The statement was directly aimed at the manufacturers of Celebrex, Bextra, and OTC NSAIDs.

This statement was not intended as a call for consumers to stop taking COX-2 inhibitors, but rather for drug manufacturers to assure consumers that their products were well labeled and that patients were provided with accurate information about their risks. It also recognized the need for further research on the safety of selective COX-2 inhibitors.

Statements regarding Bextra and Celebrex

At the same time as it announced these new packaging requirements, the FDA recommended the withdrawal of Vioxx’s sister drug Bextra, produced by Pfizer. As reasons for its decision, the FDA cited safety concerns about Bextra, including unpredictable and potentially fatal skin reactions, and known cardiovascular complications in bypass patients. In addition to bearing these serious risk factors, the FDA noted, Bextra had not demonstrated any advantages over other COX-2 inhibitors. At that time, Pfizer agreed to suspend advertising of Bextra in the US pending a follow-up with the FDA. The drug was withdrawn soon after.

Pfizer’s Celebrex was allowed to retain its FDA approval, leaving it the only available COX-2 inhibitor. Pfizer was instructed to include additional labeling warnings in the Celebrex packaging regarding cardiovascular risks. It was also recommended that Celebrex be used in the lowest effective dosages, and that a clinical trial measuring its long-term risks be conducted immediately.

Searching for the Culprit in the Vioxx Snafu

When Vioxx was withdrawn, Merck was the immediate target of public outrage. All Merck-sponsored clinical studies of Vioxx were examined and re-examined; in several cases, it was discovered that Merck had improperly reported or calculated the cardiovascular events in clinical studies.

Merck was questioned not only for its handling of Vioxx clinical trials, but also for its mass marketing of Vioxx as a safe alternative to aspirin. Merck spent more than $146 million to advertise Vioxx in 2000 alone. The company was criticized for neglecting to mention the cardiovascular risks of Vioxx in its marketing. Many critics claimed that, as a result of massive advertising directed both at consumers and at doctors, Vioxx was grossly over-prescribed. This led some of the blame to be placed on doctors, as well. According to the New England Journal of Medicine, 100 million patients were prescribed Vioxx between its release in 1999 and its withdrawal in 2004.

Whether the fault lay with Merck’s scientists, Merck’s marketing, the FDA, or the prescribing doctors, is hard to determine. It was really a combination of all of these factors that helped Vioxx reach so many uninformed or ill-informed patients.

New England Journal of Medicine Report on Vioxx

In June, 2005, the New England Journal of Medicine (NEJM) published an editorial examining Merck’s marketing of Vioxx. The article criticized Merck for having published incomplete results of the VIGOR study in the publication.

The editorial recounts a meeting between the Arthritis Drugs Advisory Committee of the FDA and Merck in 2001 to discuss the results of the VIGOR study, which had shown an increased risk of myocardial Infarction (heart attack) in patients taking Vioxx compared to those taking naproxen. At this meeting, the FDA argued that this imbalance in the VIGOR results was evidence of the protective anti-platelet effects of naproxen. The FDA concluded that this explanation was insufficient and ordered Merck to notify physicians about the results of the study. In reaction to this meeting, the NEJM article reports, Merck instructed its sales force not to discuss the results of the VIGOR study except to say that VIGOR showed a reduction in gastrointestinal complications.

To comply with the FDA’s orders, Merck created the “Cardiovascular Card,” a short pamphlet that included a non-specific summary of some Vioxx pre-approval trials. The Cardiovascular Card did not mention the VIGOR study and did not include data about cardiovascular events during the trials. The NEJM article claims that the information on the Cardiovascular Card, which was written by Merck’s marketing team, was misleading and only sought to further minimize the apparent cardiovascular risks of Vioxx that had been evidenced by multiple clinical trials.

Further, the article reports that Merck offered special training to its sales team, including using subliminal techniques and other misleading sales tactics, to influence doctors’ overall impressions of Merck. All of this was designed to sell more drugs and to downplay their possible risks. Merck, which had had a solid reputation with the FDA prior to the Vioxx dispute, was now accused of transparent salesmanship at the expense of objective drug information.

The article closes by observing that the questionable marketing practices employed by Merck were most likely representative of drug companies as a whole, and advising that the FDA take a larger role in overseeing the approval process for new drugs.

Off-Drug Follow-ups of Vioxx Trials

In 2006, Merck released results of its off-drug follow-up of the APPROVe study. The research showed that, in the year following treatment, Vioxx patients were 74% more likely to experience a cardiovascular event. Merck claimed that these results were statistically insignificant, but many experts in the medical field disagreed. Merck lawyers still insisted that the risks of Vioxx had only been conclusively demonstrated after the drug had been taken for 18 months.

Cardiologist Steve Nissen of the Cleveland Clinic was among medical professionals who believed these off-drug results were significant, in that they may have indicated that Vioxx caused some kind of arterial damage that might be permanent.

In April of 2008, the Journal of the American Medical Association, or JAMA, reported on the off-drug follow-up results of a Merck-sponsored study called Protocol 078. This study, published in 2004, measured the effectiveness of Vioxx in preventing the symptoms of Alzheimer’s Disease. During Protocol 078, 39 deaths occurred, 24 of which were in the Vioxx group. In the off-drug period, 22 additional deaths occurred, 17 of which were in the Vioxx group. In another study, called Protocol 091, 11 deaths were recorded as non-drug-related, 9 of which were in the Vioxx group. In the opinion of the AMA, these results showed a disproportionate number of deaths among Vioxx users, both during the trials and after they stopped taking the medication.

Merck’s official conclusion on these trials upon publication was that Vioxx was “well tolerated” by patients. Nissen and others in the medical community, as well as representatives of the AMA, disagreed.

Read more about how Merck reacted to the Vioxx withdrawal.