Take only as directed

A case unfolding in the Federal Court throws a spotlight on the practices used by drug manufacturers to market their products.

IMAGINE you are sitting in your doctor's office. You have arthritis in your hip or maybe your knee. Like most patients, you just want something to make the pain go away. You do not know the advantages or disadvantages of one anti-inflammatory over another; how the drugs have been tested, which companies are behind them.

You trust your doctor to know these things and tell you. The thought that one of these drugs could cause your heart to stop does not even cross your mind.

Look around the office. You notice that your general practitioner, as he takes notes, is scrawling away with a Vioxx-branded pen. The calendar beside him is marked with the same brand. You see an expensive-looking model of a knee joint sitting on the desk with the words Merck & Co at the bottom. They are clues but do not tell you the full story: the extent to which pharmaceutical companies will go to ensure doctors prescribe their drug.

The case being argued in the Federal Court during the past month against Merck & Co, maker of Vioxx, is that from the time the blockbuster anti-arthritis drug was launched on the market in 1999 to the day it was withdrawn amid concerns it caused heart attacks in 2004, the company waged a sophisticated battle for market share dominance aimed primarily at doctors.

At the centre of the class action against Merck and its Australian subsidiary Merck Sharp & Dohme is Graeme Peterson. The former navy medic is the lead plaintiff in the compensation bid that represents thousands of Australians who took Vioxx.

He claims he used the drug for pain relief of his arthritis and it caused his heart attack in December 2003. Peterson alleges that not only did Merck know Vioxx caused cardiovascular problems long before it voluntarily recalled the drug but it went to extreme lengths to cover up these concerns and protect its multi-billion-dollar product. He argues that neither he nor his trusted family doctor were made aware of these cardiovascular risks during the time he was on the drug and that if they had been informed by Merck their decision-making about taking Vioxx would have been different.

Merck's lawyers are adamant the company acted responsibly on the clinical research it had at the time and did nothing wrong. Limited to cross-examination and objections for the past month while the plaintiff's case was presented, Merck will begin its legal defence today.

But the most confronting evidence to emerge from this case so far is what happens just beyond the view of the patient: what goes on behind the scenes to cause a doctor to write a prescription for one particular drug over its competitor.

That decision-making process and the factors that contribute to it - from the role of regulatory agencies and product advisory information to academic journals and advice from medical specialists - is the target of aggressive marketing techniques from drug companies. Such tactics allegedly employed by Merck to infiltrate these processes ranged from creating fake medical journals promoting the virtues of Vioxx to conducting in-house research and getting outside scientists to put their names on it.

The company even formed an arthritis advisory board to help doctors with latest treatment developments of the disease but with the secret aim of promoting the product.

If this did not succeed in getting doctors over the line, the court heard, Merck would wine and dine GPs and specialists and shower them with branded merchandise such as pens and bone-model sets. It even trained its sales staff in how to overcome objections that doctors had about the drug's links to increased cardiovascular problems. Doctors who were publicly critical of the drug in the US were even compiled into a "to be neutralised" list.

As the counsel acting for Peterson, Julian Burnside QC, told judge Christopher Jessup in his opening address, Vioxx was incredibly important to Merck. Sales hit $US2.5 billion just before its withdrawal in September 2004 because the drug did not cause the same stomach problems as traditional anti-inflammatories. "So the last thing they wanted was suddenly for the world to say, 'It might not give you indigestion but it will give you a heart attack', because that's not a very convenient way of marketing something," Burnside said.

He argued that Merck management used every trick in the book to get doctors to prescribe Vioxx and the company targeted each individual source of information that busy GPs relied on to make decisions about prescribing one drug rather than another.

This began with the doctors themselves. Merck's Vioxx sales training manual divided doctors into three categories - younger male, older male and younger female - and suggested tailored sales techniques for each group. "This is where the representative can tap into feelings that drive the GPs' decisions," it states.

According to tendered sales and marketing documents, younger male GPs (under 50) were more accepting of the business of running a practice and "hence are quite receptive" to earning more money. "They get their knowledge from two sources," it reads. "1) reps 2) dinners and seminars. Hence they are very much influenced by reps ... Not as cynical as their older counterparts."

The court heard that Merck described younger female doctors as a group that preferred a holistic approach to healing, where "work-life balance is extremely important" and most worked shorter days and saw fewer patients.

But the most important thing to recognise about younger female doctors was their emphasis on safety. One slide presentation to sales representatives had "Safety is a high priority!! Vioxx is limited by a 'safety' cloud" stamped across it.

The final group identified by Merck's marketing department was the over-50 older male GP. This doctor "enjoys a high standard of living" and the social status of a GP, and the document recommends sales staff appeal to the doctors' desire to help patients when trying to convince them to prescribe Vioxx.

Once Merck had the doctors down pat, according to the plaintiff, the next step was journal articles.

Marketing expert Robert Donovan, from Curtin University of Technology in Perth, testified that these were a key resource in the prescribing habits of doctors and therefore crucial in Merck's promotion of Vioxx.

So what did the international pharmaceutical company do? Burnside alleged that Merck conducted in-house research, paid outside scientists to put their names on it so it could be submitted to medical publications and even manufactured an entire journal of its own.

"The Australasian Journal of Joint and Bone Medicine ... was presented as an independent peer group journal which turned out to be a production of Merck wholly," Burnside said. "The whole thing was a Merck magazine but didn't declare itself to be so."

The court also heard the company put its spin on its research in 2000 that found Vioxx did increase the risk of heart attacks and strokes compared with another anti-inflammatory drug.

Burnside argued Merck management came up with the hypothesis that, rather than Vioxx causing cardiovascular problems, the other drug had protective properties.

The next box to tick for Merck sales staff was getting to the specialists. As Donovan testified, GPs often relied on their advice for treatment of specific conditions.

Emails tendered to the court revealed a "cunning plan" by Australian Merck staff to bring out a leading rheumatologist from the US to speak at a so-called independent medical seminar on the latest class of inflammatory drugs. But this "Vioxx friendly" expert would promote the company's product as well as drop "a few concerns" about its competitors.

"Yes, it is a cocky idea, but I want to know if it will be a foolish idea," an Australian Vioxx product manager asked in one email.

The final key to getting GPs to prescribe Vioxx was the work of the sales staff. They were equipped by management with a range of "objection handling cards" to reassure doctors about any cardiovascular concerns and even a Vioxx motivation CD to play inthe car on their way to their meetings, which included a Ricky Martin-style "Go Vioxx" song.

Internal Merck documents tendered by the plaintiff showed sales representatives visited Peterson's doctor 124 times in just under four years and gave him dozens upon dozens of samples of the drug. Merck's budget for samples of Vioxx in Australia alone was $4.3million in 2000.

Burnside has argued during the month-long presentment of his case that there are essentially two questions the judge has to consider: first, whether the drug caused Peterson's heart attack and, second, how much the company knew about the cardiovascular risks and whether it used these marketing tactics to cover up that knowledge.

"Did Merck know about the risk of this in advance or did it all suddenly burst into their consciousness on September (17), 2004? Our case is they had so many warning signs all the way along that plainly they knew there was a difficulty and they kept quiet about it. And not only kept quiet about it, (they) misrepresented the facts that they knew and massaged the figures in order to put the best face on it," Burnside said.

The trial continues today.