We refer to the recent withdrawal of one of the new drugs on the market, namely VioxxR or rofecoxib, due to the fear of increased risk of heart attacks and strokes.

The president of the Pharmaceutical Association of Malaysia as well as the managing director of Merck Sharpe and Dohme, Malaysia, have both given assurances in the press that patient safety is the highest priority. However, the Consumers Association of Penang (CAP) remains concerned.

Based on information from the US Food and Drug Administration (FDA) homepage, in June 2000, Merck apprently did submit to the FDA data from a safety study called Vigor (Vioxx Gastrointestinal Outcomes Research).

This study found that there was an increased risk of serious cardiovascular events, including heart attacks and strokes, in patients taking Vioxx compared to patients taking naproxen.

After reviewing the results of the Vigor study and other available data from controlled clinical trials, FDA consulted with its Arthritis Advisory Committee in February 2001 regarding the clinical interpretation of this new safety information.
In April 2002, FDA then implemented labelling changes to reflect the findings from the Vigor study. The labelling changes included information about the increase in risk of cardiovascular events, including heart attack and stroke.

Apparently, based also on the FDA homepage, recent other studies in patients taking Vioxx have suggested an increased risk of cardiovascular events. FDA was in the process of carefully reviewing these results when Merck informed the agency of the results of the new trial and its decision to withdraw Vioxx from the market.

According to an Oct 8 Associated Press story, the FDA made things rather difficult for one of their top experts, Dr. David J Graham, who raised concerns about Vioxx's safety. This was weeks before Merck withdraw the drug from the market.

Testifying before a panel of US Senate investigators, the doctor told of intense pressure, exclusion and intimidation, and thinly-veiled threats by his colleagues at the FDA for raising a red flag about the drug's safety.

Graham was a lead author on a research project that studied the records of 1.39 million Kaiser Permanente patients, including 40,405 treated with Pfizer's Celebrex and 26,748 treated with Vioxx. The study found that high doses of Vioxx tripled risks of heart attacks and sudden cardiac death.

CAP's question is this - why was there a delay in pulling the drug off the market in view of the fact that data on the risk of serious cardiovascular events had already been surfacing for some time?

How many patients have been affected and worse, how many deaths, have occurred due to the delay in pulling the drug off the shelves, or at least, in calling a halt to the usage of the drug pending further review?

It is disturbing to note that Vioxx apparently received a six-month priority review, as opposed to a normally longer review period, simply because this drug potentially provided a significant therapeutic advantage over existing approved drugs due to fewer gastrointestinal side effects. Why did the drug not go through normal review channels?

At present, there is also concern over some of the antidepressant drugs belonging to a newer drug class known as an SSRI, or Selective Serotonin Re-uptake Inhibitors.

Evidence from controlled clinical trials and post-marketing case reports show that children and adolescents who were prescribed some of these drugs were twice as likely to become suicidal compared to those given a placebo.

Now, following recommendations by the FDA, these drugs must carry a 'black box' warning, the US government's strongest safety alert, linking the drugs to increased suicidal thoughts and behavior among children and teens taking them.

What happens next? Will the use of these drugs be prohibited after increased incidence of suicides warrants stronger action?

CAP reiterates its fear that overseas authorities are approving patent drugs too early - before they have been tested rigorously and long enough to ensure safety. The FDA has been known to approve drugs with relatively short-term clinical data.

Post-launch studies may not always be carried out, or else, not carried out properly. There may also be less of a sense of urgency, seeing the drug has already been approved for the market.

There are also concerns that clinical trials may be biased in favour of drug manufacturers, especially if researchers are on the company payroll, or receive some form of reward or kickback, which may not always be apparent to authorities and the public.

CAP calls on Malaysian authorities to be more stringent when approving overseas drugs for registration in Malaysia. Clinical trial data needs to be scrutinised in detail, and if studies do not support, for instance, safety on prolonged use, the drug should not be registered until sufficient long-term data is in, and has been found to be satisfactory. The independence of clinical trial studies also needs to be ascertained.

Furthermore, if serious risks associated with a drug surface thereafter, the drug concerned should be withdrawn from the market, or at the very least, its usage put on hold pending proper review.

We acknowledge that there are probably drug companies and professional associations that do have patients' interests very much at heart.

Shame, though, if drug companies are putting their own interests before the safety of patients, and shame on professional bodies too, if they protect drug companies rather than giving the highest priority to guarding the safety and lives of patients.

The writer is the resident of the Consumers Association of Penang (CAP).