Re: NEWS - Vioxx MI risk seen in 2000: drug should have been withdrawn then, says meta-analysis

[Guest guest]

check them out online.........there are plenty...type in remicade litigation

Ruf-Caimi <ruf-caimi@...> wrote: ,

Do you know how you find out if there is a class action against a drug?

Due to what happen to me with the remicade my son wants me to just look into

it. Or how do I find a lawyer who handles this kind of thing?

Lynn

wrote:

> Rofecoxib MI risk seen in 2000: drug should have been withdrawn then,

> says meta-analysis

>

> Rheumawire

> Nov 4, 2004

> Zosia Chustecka

>

> London, UK - An independent meta-analysis of clinical trial data with

> rofecoxib (Vioxx, Merck & Co) published by the Lancet online November 5,

> 2004 [1] shows that a doubling of the risk of myocardial infarction (MI)

> with the drug could be seen by 2000, and the researchers suggest that

> the drug could and should have been withdrawn then4 years before it was

> taken off the market.

>

> When Merck withdrew rofecoxib on September 30, 2004, the company said in

> a press release: " Given the availability of alternative therapies, and

> the questions raised by the data, we concluded that a voluntary

> withdrawal is the responsible action to take. " The authors of the new

> meta-analysis, Dr Juni (University of Berne, Switzerland) and

> colleagues say that this " same statement could and should have been made

> several years earlier, when the data summarized here first became

> available. Instead, Merck continued to market the safety of rofecoxib. "

>

> This discovery points to astonishing failures in Merck's

> internal systems of postmarketing surveillance, as well as to lethal

> weaknesses in the US FDA's regulatory oversight.

>

> " This discovery points to astonishing failures in Merck's internal

> systems of postmarketing surveillance, as well as to lethal weaknesses

> in the US FDA's regulatory oversight, " blazes an accompanying editorial

> by Lancet editor Dr Horton [2]. This report will " add

> significant weight to ongoing litigation against Merck by patients who

> believed they were harmed by this drug, " he adds.

>

> The meta-analysis was funded by the Swiss National Science Foundation

> and reviewed all randomized controlled clinical trails in adult patients

> with chronic musculoskeletal disorders that compared rofecoxib with

> placebo or with other nonsteroidal anti-inflammatory drugs (NSAIDs). In

> total, 63 reports were reviewed, covering 18 clinical trials (involving

> 25 273 patients) with 5 extension studies and 11 observational studies.

> All of the trials were sponsored by Merck & Co.

>

> Fatal or nonfatal myocardial infarction was the primary end point, and

> 64 events were found: 52 in the rofecoxib groups vs 12 in the control

> groups (combined relative risk 2.24, 95% CI 1.24-4.02), with little

> evidence of between-trial heterogeneity.

>

> Cumulative meta-analysis showed that an increased risk of MI became

> evident in 2000; at that point, 14 247 patients had been randomized and

> 44 events had occurred. At the end of 2000, with 52 MIs in 20 742

> patients, the relative risk was 2.30 (95% CI 1.22-4.33, p=0.01). " The

> effect was both substantial and unlikely to be a chance finding, " the

> authors write.

>

> Juni, the lead author of the meta-analysis, tells rheumawire that the

> study shows that " by the end of 2000, there was enough evidence

> accumulated to show that the risk of myocardial infarction with

> rofecoxib was more than doubled. "

>

> After that, until the end of 2001 when more data on cardiovascular end

> points were coming in, this point estimate remained stable, only the

> statistical precision increased, he says. After 2001, no additional

> cardiovascular safety data were reported from musculoskeletal trials

> with rofecoxib.

>

> By the end of 2000, there was enough evidence accumulated to

> show that the risk of myocardial infarction with rofecoxib was more than

> doubled.

>

> In an interview, asked whether there was enough evidence at the end of

> 2000 to remove the drug from the market, Juni answered carefully, saying

> the statement that Merck released recently when withdrawing the drug

> could have " arguably " been made several years earlier.

>

> Juni tells rheumawire that the meta-analysis also shows that this

> increased risk of MI with rofecoxib did not vary with controls (similar

> for placebo, naproxen, or a nonnaproxen NSAID), did not vary with the

> daily dose of rofecoxib used (12.5 mg, 25 mg, and 50 mg), and did not

> depend on length of treatment (it was similar for trials of duration

> less than 6 months and those of more than 6 months). " So, the reassuring

> statement from Merck that these risks occur only after 18 months of

> treatment cannot be confirmed with our data, " he comments. " Our findings

> indicate that patients are at risk even if rofecoxib is taken for a few

> months only. "

>

> This published meta-analysis of rofecoxib data is part of a larger

> network meta-analysis of analgesics in osteoarthritis, Juni explains.

> All of the data used for the rofecoxib meta-analysis were contained

> within the FDA databases, and he estimates that it took about 1600

> working hours and cost about CHF40 000 to perform.

>

> " This is ridiculously little compared with the potential impact that

> this study may have, " Juni comments. " So, one of the questions raised is

> shouldn't these types of analyses be routinely performed by

> drug-approval bodies, which have appropriate access to the original

> data? " He adds that, as the data were all there, the FDA could have done

> an analysis much earlier than they themselves did (they began in

> April/May 2004).

>

> As part of their review, Juni et al also combed through the trial data

> to check for evidence of a cardioprotective effect of naproxen. This has

> been proposed as the explanation for the difference in the MI findings

> seen in the VIGOR trialie, that the fewer MIs seen in the naproxen group

> were a result of its cardioprotective effect, rather than the increased

> number of MIs in the rofecoxib group being an adverse effect of the

> drug.

>

> Juni et al report that the risk of MI was indeed greater in trials

> comparing rofecoxib with naproxen than with other controls but say this

> finding was " probably attributable to chance. " Taken together, data from

> their analysis and from other observational pharmacoepidemiological

> studies indicate that " if a protective effect of naproxen exists, it is

> probably small, and, as pointed out earlier [by others], not large

> enough to explain the findings of VIGOR. "

>

> That rofecoxib could increase the risk was not discussed,

> despite the fact that, since the mid-1990s, the drug has been known to

> reduce prostacyclin, a vasodilator and inhibitor of platelet

> aggregation.

>

> One lesson for the future from this is that " we can never be sure we

> know all there is to know about mechanisms, " say the researchers. " The

> VIGOR study group presented the myocardial infarction data exclusively

> as a 'reduction in the risk of myocardial infarction in the naproxen

> group' on the basis of documented inhibition of platelet aggregation by

> naproxen, but not rofecoxib. That rofecoxib could increase the risk was

> not discussed, despite the fact that, since the mid-1990s, the drug has

> been known to reduce prostacyclin, a vasodilator and inhibitor of

> platelet aggregation. "

>

> Another lesson to be learned is directed at the FDA and other

> drug-licensing authorities, which have a duty to carefully and

> continuously monitor the evidence on the adverse effects of drugs, say

> the researchers. " Clearly this has not happened in the case of

> rofecoxib: the most recent labeling information in the USA, for example,

> mentioned only 3 clinical trials. Had accruing data been analyzed

> cumulatively as soon as they became available, appropriate and timely

> decisions could have been taken. "

>

> In the accompanying editorial, the Lancet withdraws its earlier praise

> of Merck for acting promptly in the face of new findings about the

> safety of Vioxx and cites the revelations made earlier this week in the

> Wall Street Journal that the company knew about the cardiovascular risk

> of rofecoxib for years. This " disturbing contradiction, " where Merck

> understood Vioxx's true risk profile but attempted to gloss over these

> risks in its public statements at the time may spell the end for the

> company, it suggests. " It has been financially disabled and its

> reputation lies in ruins. It is not at all clear that Merck will survive

> this growing scandal. "

>

> 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 organizational reform.

>

> The FDA also comes in for stinging criticism. " The agency was urged to

> mandate further clinical safety testing after a 2001 analysis suggested

> a 'clear-cut excess number of myocardial infarctions.' 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 organizational reform, " Horton writes.

>

> Researchers involved with rofecoxib are also blamed " allegedly credulous

> specialists who should have asked tougher questions about the drug they

> were prescribing. " The editorial comments that why clinical

> investigators studying rofecoxib did not do more to raise concerns is a

> " fair question that needs to be answered. But in doing so, we must not

> diminish the importance of the covenant of trust that society has

> established with powerful commercial and governmental institutions. "

>

> " For with Vioxx, Merck and the FDA acted out of ruthless, shortsighted,

> and irresponsible self-interest, " the editorial thunders. " The licensing

> of Vioxx and its continued use in the face of unambiguous evidence of

> harm have been public-health catastrophes. This controversy will not end

> with the drug's withdrawal. "

>

> Merck & Co has published a detailed scientific critique of

> this Lancet meta-analysis on its web site [3], in which it explains why

> it disagrees with the conclusions. In a press release, the company

> reiterates that it was vigilant in monitoring and disclosing the

> cardiovascular safety of rofecoxib and " absolutely disagrees with any

> implication to the contrary. Until the APPROVE study, data from Merck's

> clinical trials showed no significant difference in cardiovascular risk

> between Vioxx and either placebo or nonnaproxen NSAIDs. "

>

> Merck's main criticism of the meta-analysis is that it

> violates the basic principle of combining " like with like, " as the

> authors combined data from studies with 3 kinds of comparators (placebo,

> naproxen, and nonnaproxen NSAIDs). " The authors justify combining the

> data across the comparators because confidence intervals against

> individual comparators were wide and the statistical test for

> interaction was not significant. This use of an underpowered statistical

> test as the sole justification for combining the data is scientifically

> inappropriate. . . . There are known different biological effects of the

> comparators on platelet function and the data demonstrate large

> differences in relative risk between the comparator groups. " This

> inappropriate combining of heterogeneous data " invalidates the results

> and the conclusions of their meta-analysis, " the company says.

>

> Sources

>

> Juni P, Nartey L Reichenbach S, et al. Risk of

> cardiovascular events and rofecoxib: cumulative meta-analysis Lancet;

> published online November 5, 2004; available at http://www.lancet.com.

>

> Horton R. Vioxx, the implosion of Merck, and

> aftershocks at the FDA. Lancet; published online November 5, 2004;

> available at http://www.lancet.com

>

> Merck & Co. Response to article by Juni et al

> published in the Lancet on Nov 5, 2004. November 5, 2004. Available at:

> http://www.merck.com/statement_2004_1105/lancet.pdf

>

>

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

>

>

>