MERCK, the global drug company which developed and marketed the prescription pain-killer Vioxx, widely believed to have been the cause of an increase in the incidence of heart attacks and strokes world-wide, would not provide information on the amount of the drug distributed in Bermuda.

But a source told the that the island's doctors had been prescribing 20,000 tablets each month prior to the drug's recall on September 30.

Chief Medical Officer Dr.John Cann was contacted by Tracy Marra, president of the Bermuda Pharmaceutical Association, who volunteered to contact Merck to plan the recall. According to Ms Marra, that effort has not reached the stage of a final plan.

"Merck's idea was that they would collect Vioxx from customers by the 'reverse distribution' method," said Ms Marra, "which is unlike what they are doing in Canada or the US, but is what they claim they are doing in every other country, which is clearly untrue.

"That means that the customer brings the Vioxx back to the pharmacy, which refunds their money, then collects from Merck and refunds to the insurance companies. This is not going to work. Our pharmacists are really unwilling to do that, because they would have to do all of the work in a very busy season, and they feel that Merck should take a more active r?le.

"Merck has agreed in principle, but it's been like pulling teeth. They were hoping to wrap this up by December 1, which is not going to happen."

However, in spite of the voluntary and unpaid efforts of Ms Marra, there is no formal reporting system which would allow Government medical personnel to know the number of residents who were prescribed Vioxx, or any other prescription drug.

"All of the importers of drugs have to let us know the volume of drugs imported, if we ask for that information," advised Dr. Cann. "Also, the pharmacies have an obligation to report the amount dispensed, if we ask for that.

"It is true that we do not have a passive system for the reporting of prescription drugs dispensed, and I am not sure what purpose that would serve. But where there are any problems or concerns, the pharmacies readily co-operate with us, in situations where they feel that a drug is being misused or abused, but we don't have a ready system in place to deal with recalls."

Ms Marra believes that pharmacists have enough information to be able to track prescription drugs, and does not believe that centralised reporting to Government would be productive.

It has been alleged that Merck was aware of the fatal side-effects of its multi-billion-doIlar drug, but chose to ignore that information for four years.

In a further blow to Merck, the US Food and Drug Administration (FDA), excoriated by the international medical establishment for having reacted too slowly to complaints about the dangers of Vioxx, has decided to delay the approval of Merck's successor drug Arcoxia until more safety data are available, although Arcoxia has been prescribed in Bermuda for more than a year.

It is understood that, since 1999, Vioxx and, more recently, Arcoxia have been imported and distributed in Bermuda by Merck, Sharp and Dohme International, a Bermuda-based subsidiary or affiliate of Merck.

No one at the local entity was authorised to comment in response to any inquiry about Vioxx or any other Merck product, but a knowledgeable source confirmed that Merck distributed its own products in Bermuda.

The same source confirmed that there was no system for reporting to Government either the amount of this or any drug distributed and prescribed, or the number of patients who took this drug to relieve arthritis or other severe pain.

However, given one-a-day dosage, 20,000 tablets per month would suggest some 700 patients. Bermuda's pharmaceutical health is controlled by the skills and knowledge of its medical practitioners and pharmacists, and by the Pharmacy Act 1979.

"The Ministry of Health is ultimately responsible," advised the source, a pharmaceutical professional, "but the Bermuda law pertaining to the importation of pharmaceuticals is the Pharmacy Act which states that the product has to have been licensed in one of a number of countries, including the US, the UK and Canada."

A local doctor who preferred anonymity confirmed that Vioxx had been widely prescribed in Bermuda prior to its recent recall.

"It was probably one of the most popular of the anti-inflammatory medications," the doctor advised. "It was never promoted as being stronger than any of the older anti-inflammatories. The advantages of the 'cox-2 inhibitors' was that they were easier on the stomach, and longer-lasting, so that the dose would be once a day, rather than the four-times-a-day regimen of ibuprofen.

"Although they were supposed to be easier on the stomach, there were expected to be some side- effects similar to all of the older anti-inflammatories: some stomach troubles like heartburn, or even as serious as a bleeding ulcer, and other things like kidney and liver troubles ? quite rare but still to be taken into account when you prescribed them."

The doctor pointed out that, in the case of Arcoxia, it was not unusual for a drug to be used here before it was approved by the FDA if it was already approved in Europe, or for a US drug to be used here before it was approved in Europe.

He confirmed that, to his knowledge, local doctors had not become aware of any increased incidence of heart attacks or strokes among their local patients taking Vioxx.

"You need these huge trials to see any difference," the doctor advised, "although there is no particular forum here for having such discussions. There are continuing-education things at the hospital that we attend where that sort of thing could be discussed, often with a person from overseas as a facilitator.

"Hopefully, doctors don't receive their only education about a drug from drug company representatives. Although the 'reps' will often distribute copies of their 'landmark' studies, we always have a healthy scepticism of drug company marketing, but this (Vioxx) situation should bring home the point that we have a healthy scepticism."

E went on:"We have to go with the opinions of the agencies and colleagues overseas, unless there are some obvious 'red flags'. Now that everybody in the news media has jumped on it, you can go back and see that a study showed, in retrospect, an increase in cardiovascular deaths, and that we didn't get suitable explanations for that.

"It's probably 'pie-in-the-sky' to think that governments are going to undertake completely independent drug studies, so that no drug company ever finances any part of them.

"Most of the studies are done by university centres and hospitals with high ethical standards and appropriate ethics committees, and the drug companies put up the money, but the studies are usually devised by specialists in the relevant field and are done with integrity.

"The raw data from these studies have integrity, but the drug companies may 'spin' the findings, as Merck may have done here, and some drug companies will ignore or not publish a study that does not put their drug in a good light.

"I must say, though, that I find the amount of money they spend on marketing distasteful, and particularly the amount they spend on direct marketing to the consumer. It puts a lot of pressure on doctors, in the sense that they may prefer to prescribe a cheaper generic, or the cheaper of two widely-advertised drugs that are essentially identical, but the patient comes in convinced by TV advertising that they want a particular drug. Mostly, patients will take my advice, but sometimes they just want the one they saw on TV."

One of the most damaging and widely-reported accusations of foot-dragging by Merck and dereliction of duty by the FDA came from the British medical magazine In the November 13 edition, editor Dr. Richard Horton, also a visiting professor at the London School of Hygiene and Tropical Medicine, was unequivocal in his condemnation of both Merck and its putative regulatory overseer.

"Today we publish results from a cumulative meta-analysis which show that the unacceptable cardiovascular risks of Vioxx (rofecoxib) were evident as early as 2000 ? a full four years before the drug was finally withdrawn from the market by its manufacturer, Merck.

"This discovery points to astonishing failures in Merck's internal systems of post-marketing surveillance, as well as to lethal weaknesses in the (FDA's) regulatory oversight. The evidence showing that Vioxx caused significant adverse effects was apparent well before data from (Merck's) APPROVe trial triggered Merck's overdue intervention."

Dr. Horton alleged that the findings of researcher Peter J?ni and five colleagues, reported in the same issue of , came in the wake of new disclosures that suggest Merck was fully aware of Vioxx's potential risks by 2000.

Investigations by the have revealed e-mails that confirm that senior executives had been warned that the risk from their drug's "adverse cardiovascular profile" was "clearly there", according to one senior researcher.

The study by Peter J?ni and his team reported in described the background to the study, and their summary findings.

"The cyclo-oxygenase 2 ('cox 2') inhibitor rofecoxib (Vioxx) was recently withdrawn because of cardiovascular adverse effects. An increased risk of myocardial infarction (heart attack) had been observed in 2000 in the Vioxx Gastrointestinal Outcomes Research study (VIGOR)."

The increased risk of heart attack, in comparison with the "control" drug naproxen, had been attributed to the heart protection afforded by naproxen rather than the "cardiotoxic" effect of Vioxx. The study concluded that "our findings indicate that rofecoxib (Vioxx) should have been withdrawn several years earlier. The reasons why manufacturer and drug-licensing authorities did not continuously monitor and summarise the accumulating evidence need to be clarified."

Dr. Horton pointed to a marketing strategy, also highlighted in a segment of last week's CBS television news-magazine , which appeared to instruct Merck representatives on how to respond to or finesse certain questions about the drug, and which strategy Merck had, perhaps unwisely, labelled "Dodge Ball Vioxx".

"Given this disturbing contradiction," wrote Dr. Horton, "(between) Merck's own understanding of Vioxx's true risk profile and its attempt to gloss over these risks in their public statements at the time, it is hard to see how (Merck's CEO) Raymond Gilmartin can retain the confidence of the public, his company's most important constituency.

"The FDA's position is no less comfortable. The public expects national drug regulators to complete research, such as that published by J?ni and colleagues, in their ongoing efforts to protect patients from undue harm.

"But, too often, the FDA saw and continues to see the pharmaceutical industry as its customer ? a vital source of funding for its activities ? and not as a sector of society in need of strong regulation."

The web site News Target Network reported that Dr. Horton said that "in the case of Vioxx, the FDA was urged to mandate further clinical safety testing after a 2001 analysis suggested 'a clear-cut excess number of myocardial infarctions (heart attacks)'. It did not do so.

"This refusal to engage with an issue of grave clinical concern illustrates the agency's built-in paralysis, a predicament that has to be addressed through fundamental organisational reform. With Vioxx, Merck and the FDA acted out of ruthless, short-sighted, and irresponsible self-interest."

was launched in 1999, and has been sold in more than 80 countries. Commenting on the APPROVe study which led to the recent recall, Dr. Peter Kim, president of Merck Research Laboratories, said: "While the cause of these results is uncertain at this time, they suggest an increased risk of confirmed cardiovascular events beginning after 18 months of continuous therapy."

Yesterday morning at 10 a.m. in Washington, in the Dirksen Senate Office Building, Merck CEO Dr. Raymond Gilmartin, FDA Acting Commissioner Lester Crawford, FDA Associate Director, Office of Drug Safety, David Graham, and two medical professors from Stanford University and the University of Washington were scheduled to testify before Senator Charles Grassley's Senate Finance Committee in a hearing titled "FDA, Merck, and Vioxx: Putting Patient Safety First?"

According to a local source, although Merck, Sharp & Dohme has an office and personnel here, and a warehouse which distributes Merck drugs locally and overseas, the Merck personnel responsible for the distribution of Vioxx to Bermuda and the Caribbean, and for its recall, are based in Puerto Rico. Merck did not respond to requests for information about the amount of the drug distributed on the island.

Merck sold $2.5 billion of Vioxx in 2003, and since launch, spent $500 million to market it. The company's market capitalisation has fallen about $30 billion since the allegations that Merck withheld negative information on Vioxx.

A drug stock analyst with Sanford C. Bernstein has estimated that Merck will face product liability claims of some $12 billion.