The Australian court case on Vioxx, pitched as a landmark judgement against its makers Merck, flashed past in a blur. Certainly the impression left behind in the media coverage was that a plucky pensioner Graeme Peterson, a former naval officer who suffered a heart attack in 2003 after being prescribed the drug for nearly three years, had “won” the case. The compensation payout of $287,000 seems to back that up. But the reality is far different when you start going through Justice Christopher Jessop’s judgement — all 500 pages of it. In fact, there may  be reasons for thinking that the Merck legal team was pretty successful.

The case has been important to critics of big pharma. It was meant to show that Merck had known (or should have known) about the risks of Vioxx well before 2004 when it decided to voluntarily pull it from the market. The key allegation: it ignored the weight of clinical evidence, which began to emerge as early as 2000, in a bid to protect its billion dollar pill, a decision that was meant to have resulted in about 138,000 heart attacks or strokes worldwide and thousands of preventable deaths.

In short, Justice Jessop found that this allegation was untrue. Not that you would know this reading the newspapers.

VIOXX (rofecoxib) was developed as a first-generation COX-2 inhibitor in the 1990s by Merck, and first approved for use by the US Food and Drug Administration in 1999.

Its main use was the control of pain associated with arthritis. Vioxx’s success was virtually instant in a market that was soon worth billions.

The first clinical trial to raise questions about its safety was known as VIGOR, a study of patients with rheumatoid arthritis, and was designed to compare the risk of gastrointestinal perforation or obstruction, symptomatic ulcers and upper GI bleeds for patients on Vioxx with those on traditional anti inflammatory drugs known as NSAIDS — in this particular case a drug called naproxen.

Preliminary results came through to the company on March 15, 2000, with disturbing news. Vioxx patients were shown to experience significantly more serious thromboembolic cardiovascular adverse events than those on naproxen — a five-fold increase of heart attack or stroke.

According to the court judgement, Merck’s scientists scrambled to understand what was going on, especially because two other studies then running showed no such links. The results didn’t make sense.

Dr Alise Reicin, a vice-president of Research and Early Development at Merck, concluded the difference between the two drugs was in fact due to a protective effect of naproxen, rather than any inherent danger from Vioxx.

The company issued a press release on March 27, 2000, on the VIGOR results, which sold the idea that the trial had in fact uncovered a benefit that had not been “observed previously in any clinical studies for naproxen”. It is this interpretation that has been subject to much analysis since the drug’s withdrawal, with allegations that Merck was peddling weak scientific theories to smother the reality of the drug’s potential risks — a claim it has always denied.

It was made during US Senate hearings into the saga. But perhaps the most prominent proponents were the authors of a meta-analysis of the safety of Vioxx published in The Lancet in the weeks after the drug was pulled.

The Lancet editor at the time wrote: “[T]he real picture of cardiovascular risk has been apparent for some time and Merck’s vigorous defence of this drug in the past was clearly an error. If the dangers associated with rofecoxib [Vioxx] were not proven, they were certainly possible, even probable, given the available data.”

In the Melbourne case, Justice Jessup went into minute detail about what was known from the mass of clinical data following the preliminary VIGOR results right up until 2004. He took evidence from an array of medical specialists, some critical of Merck, some not. He explicitly rejected the claim that Merck “knew or ought to have known” in 2000 that Vioxx had significant cardiovascular toxicity.

He also rejected claims the company’s naproxen theory was an unreasonable response to the VIGOR results. VIGOR was, according to one cardiologist who testified, “hypothesis generating”. The judge agreed, concluding that it was only in 2004 that enough clinical evidence emerged to suggest that legally Merck should have taken a different view.

This was not to say VIGOR was unimportant. In a phrase used widely in the media coverage of the case, the judge said “those results represented a worrisome and important signal” of cardiovascular risk.

The issue for the judge then became what a responsible course of action was for Merck in the US and its Australian subsidiary, Merck Sharpe & Dohme Australia. The companies, the judge ruled, did have a duty of care to inform doctors about the implications of the VIGOR study.

One step in this process was to change the official product information, which is used to inform doctors in Australia about any known risks of the drugs they prescribe. Surprisingly this did not happen for well over a year after the VIGOR trial, not until November 16, 2001, when agreement was reached with the Therapeutic Goods Administration, Australia’s drug regulator, about the wording.

What becomes clear from Justice Jessup’s written judgement is that the TGA was unhappy with many of the proposals made by Merck Sharpe & Dohme Australia about what the product information should say.

The TGA’s clinical evaluator wrote at the time: “The adverse reactions section that is proposed makes no mention of the cardiovascular event data, which in my opinion, is completely unacceptable, particularly given the comments of Merck’s own expert report!”

In the end, the precautions section of the final version of the product information for Vioxx included this wording: “The rate of serious cardiovascular thromboembolic adverse events was significantly lower in patients receiving naproxen than in the rofecoxib group … In other controlled clinical trials, spontaneous reports of these cardiovascular events were similar between VIOXX and non-selective NSAID comparators …”

Justice Jessup thought this wording (essentially the naproxen theory] was an adequate reflection of what the science at the time was suggesting. But he accused Merck Sharpe & Dohme Australia of making “every effort to render inconspicuous the message that Vioxx might well be pro-thrombotic” during the months it took to draw up the TGA product information.

One of the men at the centre of the court case was Dr John Dickman, the GP who first prescribed Vioxx to Graeme Peterson in 2001.

Like many doctors, Dr Dickman’s prescribing practice was influenced by information he gathered from a range of sources, such as specialists, educational events, the medical press and journals. He also saw drug representatives. He told the court that he was well aware they were there to push their products, but he assumed what he was told was truthful.

Dr Dickman saw Merck Sharpe & Dohme Australia reps 16 times during 2001 and nine times in 2002.

According to the court, the company’s reps had a responsibility to ensure their information was in line with the VIGOR results, and once it came out, in line with the product information changes Merck Sharpe & Dohme Australia had signed up to.

But it found the company failed in this duty in the case of Dr Dickman.

Dr Dickman, despite his briefings with drug reps, said he became aware of the possible cardiovascular risks of Vioxx only at an educational meeting a couple of months before it was withdrawn in 2004. By that time, Peterson had already suffered his heart attack.

However, Justice Jessup restricted the scope of his judgement. Peterson’s lawyers argued that the misrepresentation by Merck Sharpe & Dohme Australia sales reps would have applied to the doctors of others who were prescribed Vioxx. The judge described this reasoning as an “impressionistic conclusion”, one that could not be used to infer “every relevant practitioner in Australia” had been given the same sales pitch as Dr Dickman.

In short, each individual case of the other patients lined up in the class action would have to be determined on its merits.

The other key questions for the court included whether Dr Dickman would have stopped prescribing Vioxx, even if the company had discharged its duty of care, and whether Peterson would have stopped taking it. Dr Dickman and Peterson testified that they would have ditched the drug. But Justice Jessup disagreed.

“[M]y impression is that [Dr Dickman] would have placed rather more emphasis upon the benefits of Vioxx and rather less upon the cardiovascular risk.” The judge concluded the sales pitch to Dr Dickman was not responsible for Peterson’s subsequent heart attack.

What eventually did Vioxx in was the APPROVe study. In 2004 it showed an increased risk of heart attack and stroke, beginning 18 months after treatment started. It suggested that long-term use of Vioxx resulted in almost twice the risk of heart attacks and stroke compared with placebo.

The public announcement by Merck to withdraw the drug was made on September 30, 2004.

The fallout has been immense. There have been hearings in the US Senate into the company, as well as the role the Food and Drug Administration in the US played to regulate the drug industry and protect the public. It has also sparked a close examination of big pharma and the way it markets its products. Those debates still rage.

But Vioxx fell foul of Australian law because the judge ruled that it breached Australia’s Trade Practices Act. It was a product that was not of merchantable quality, one that was not fit for its stated purpose — to relieve arthritic pain. The Trade Practices Act provided the legal basis for the $278,000 compensation awarded to Peterson.

Yes, the court ruled that the drug did double the risk of a heart attack and it ruled that Peterson’s heart attack was a result of taking the drug. And yes, Merck Sharpe and Dohme Australia failed in it duty of care to properly inform Dr Dickman of the possible risks.

Peterson’s legal team say the court case will be a trigger for other claims that could total up to $300 million. Merck has indicated it will appeal.

But the grander claim against Merck were not proven. Far from being a cloak behind which the potential risks of the drug could be hidden, the naproxen theory expounded by Merck’s scientists — according to the court — was justified in a situation where no hard conclusions could be made.