Some 212 people who believed they have been harmed by the arthritis drug are part of a global bid for compensation, writes David Labanyi
The approval process for new pharmaceutical drugs by regulatory agencies should be reviewed following the Vioxx controversy, a leading clinical academic has claimed.
Dr Gurkirpal Singh, clinical professor of medicine at Stanford University and one of the Vioxx whistleblowers, said clinical trials are designed to study efficacy, not safety.
Arthritis drug Vioxx was withdrawn by its producer Merck in 2004 after a trial found it increased the risk of heart attacks and strokes in patients using it for more than 18 months.
Specialist health legal firm Malcolmson Law represents 212 Irish people who believe they have been harmed by Vioxx and plan to sue Merck. Approximately 10 cases involve a fatality.
Merck faces up to 4,000 lawsuits from among the 20 million people worldwide taking the drug. The number of patients who used Vioxx in Ireland is unclear. In 2003 it was prescribed to more than 117,400 medical card holders. Some were repeat prescriptions.
Merck has decided to fight the claims, setting aside a $650 million war chest for its legal team in the US.
However, regardless of the outcome of the legal cases, the issue has focused debate on the pharmaceutical approval mechanism.
In testimony to the US House of Congress Singh, who worked as a consultant to Merck, criticised the system operated by the US Food and Drug Administration. Dr Singh said when Merck filed for approval for Vioxx, the trial results led an FDA reviewer to write: "With the available data, it is impossible to answer with complete certainty whether the risk of cardiovascular and thromboembolic events is increased with patients on rofecoxib [ Vioxx]".
Singh says it was at this point the problem occurred. Rather than request a larger and more detailed study, Vioxx was approved by the FDA. Singh added there was no urgent need to approve the drug because there were nearly 20 pain-killing drugs available then which were as effective.
To counter such a situation recurring, Singh has proposed a system of time-limited or conditional approvals. "This way, if there are any emerging safety problems with a drug after its approval, the FDA can require companies to do large safety studies within a certain time frame," he says.
Prof Oliver Fitzgerald, consultant rheumatologist at St Vincent's Hospital, Dublin, prescribed Vioxx to many of his patients and said it had positive elements. "The problem with traditional anti-inflammatories is they cause ulcers. These can bleed or burst and become a major problem. That's why Vioxx, which had a reduced incidence of these problems, took off."
The first note of concern came through "rumours on the research grapevine" rather than evidence of adverse reactions among his patients, Fitzgerald says.
"It was only when Vioxx was compared in a trial with a placebo, which is a difficult study to do because it means leaving arthritis patients in pain, that a significant rate of myocardial infractions was noticed."
Fitzgerald says: "Part of the problem in identifying whether there had been an increase in cardiac events was that a patient population with a form of arthritis in their fifties, sixties and seventies might, in the normal course of events, be expected to suffer heart attacks and strokes," says Fitzgerald.
"Once Vioxx was withdrawn I was asked by patients who were on Vioxx " Should I be worried, should I get a cardio-angiogram, or can I just ignore the issue"?"
Fitzgerald says the long-term side effects are not known. "I think we all need to learn from this. Clinical trials need to be designed to address issues of long term safety just as much as drug efficacy.
"We need to look at the regulatory authorities and the mechanisms by which new drugs are evaluated. I am not suggesting that they didn't do their jobs properly, just that maybe they didn't study the drug for long enough."
The Vioxx controversy also raised questions about the reporting of trial data on new drugs. Last month the respected New England Journal of Medicine accused Vioxx researchers of withholding damaging data on a clinical trial of the drug in an article submitted six years ago.
This data showed that 20, rather than 17 as the article reported, of the 2,000 patients taking part in the Vioxx study had suffered a heart attack. As a result, the level of heart attack risk appeared slightly lower than it should have.
The company said in response that the three deaths had occurred after the cut-off date of the trial and were disclosed to the FDA.
Dr Gregory Curfman, the journal's executive editor, said the publication had been too accepting of the assertions by researchers working on the study.
Curfman said he believed the article should have presented two hypothesis, that of the Vioxx researchers and an independent one, examining the possibility that Vioxx was causing a problem.
Raymond Bradley, managing partner of Malcolmson Law, said the issues faced by the Journal showed the difficulty faced by prescribing doctors.
"If you are a medic working in Ireland you are relying on certain basic journals. If the information is inadequate then inevitably your prescribing is going to be compromised.
"Likewise, European regulatory authorities must to some extent rely on the FDA for their approval of drugs and if either are given inadequate data, inevitably approval can be granted or continued in circumstances where it shouldn't. If both those safeguards are compromised then that is a huge public issue."
Bradley expects most cases from Irish claimants to be heard in the next two to three years, mostly likely in the Federal court in New Jersey, where Merck is headquartered.
So far, three individuals have brought cases against Merck. A Texas jury awarded $253 million (€211 million) to the relatives of Robert Ernst (59) who died suddenly after taking Vioxx. Merck is appealing this award.
"A large proportion of the Texas decision was punitive damages and the jury appears to have been appalled by the level of concealment revealed in court. [ however], the award goes beyond what are the accepted values," said Bradley.
He said most of the firm's Irish Vioxx clients had suffered heart attacks, strokes or cardiac conditions. Bradley said up to 500 people contacted the firm looking to pursue a claim but most had been rejected.
"In some people the link between their illness and Vioxx was tenuous and in those circumstances it would be wrong to put them in a situation where they are litigating with little prospect of success."
He said the class action structure was the only way individuals could take on a multinational pharmaceutical company.
"Malcomson and its US co-counsel Lieff Cabraser Heimann & Bernstein, are proceeding with actions before the US courts where procedures allow determination of the liability issue with minimal legal cost exposure to the individual," said Bradley.