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Sci Tech
Vioxx safety data manipulated
R. PRASAD
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A Merck’s internal communication talks of the drug being associated with an increased risk of causing deaths
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The likes of Merck have found a match. The pharmaceutical industry may have mastered the act of clinical trial data manipulation. But the Food and Drug Administration Amendment Act (FDAAA) passed last year has made it compulsory for the industry to submit trial results in a publicly accessible registry.
The amended Act which came into effect from October 1, 2007 will make things difficult for companies like Merck.
The Act requires the companies to submit the results to the National Institutes of Health (NIH) within one year.
It requires results of trials that form the basis of an efficacy claim. This includes registered trials for approved drugs too.
The registry where the results are available are required to be linked to results information that includes: FDA summary documents, FDA assessments of clinical trial results, FDA public health advisories regarding the drug among other things.
Compliance is likely as FDA is authorised to impose penalties and also empowers the NIH to post a notice describing the infractions on the registry data bank. This initiative comes after the medical journal editors made trial registration mandatory. — R.P.
The ghost of Vioxx is coming to haunt the pharmaceutical company Merck four years after it withdrew the drug from the market. Prescribed as a pain killer for arthritis in 1999, the drug was linked to heart attacks before it was pulled out of the market.
Blockbuster drug
Vioxx went on to become a blockbuster drug in the five years that it was in the market.
New evidence published in the reputed Journal of the American Medical Association (JAMA) confirms that the company was well aware of its dangers even before it withdrew the drug in 2004. The paper looked at human clinical trials done for Alzheimer’s starting 1999.
It may well turn out to be one of the greatest drug scandals in the recent past. And it once again confirms that many pharmaceutical companies will stoop to any level and act in an unscrupulous manner to get a blockbuster into the market. Never mind that volunteers and patients are put to great risks.
“Where patients come first,” ironically, is the drug maker’s slogan!
Merck, like many other drug companies, has been found to have suppressed and manipulated certain critical data that misled the regulatory body — the U.S. Food and Drug Administration (FDA).
The confidential information provided by Merck to the FDA and internal analyses conducted by the company reveal how systematically it went about the process.
The clinical trials for Alzheimer’s were quite different from other trials. Apart from looking at the safety issue during the course of the trial (on-treatment safety), the trials looked for safety even after the completion of the trial duration (intention-to-treat). At least, that is how the company projected it.
Results published in journals had stated that the drug was “well-tolerated” and safety was not an issue. But any data on deaths that may have occurred 14 days after the completion of the trials were not included.
The authors found that even the Safety Update Report (SUR) filed in 2001 by Merck to the FDA did not explain how it arrived at the number of deaths seen during the trials. It did not include deaths, if any, that had occurred after the 14-day period.
Suppressing data
“In other words, it appears that the sponsor presented only an on-treatment and not an intention-to-treat analysis for total mortality,” the authors noted. This was a clear case of Merck withholding crucial safety data from the FDA.
The proof of misleading and withholding critical safety data from the FDA came in the form of an internal memorandum sent by Merck’s statistician few months before it submitted the Safety Update Report to the regulator in 2001.
The internal memorandum revealed that in the intention-to-treat analysis (looking for safety after the completion of the trials), Vioxx was found to be “associated with an increased risk of mortality in each of the studies.” And based on the internal memorandum data, the authors conclude that “in a combined analysis, refecoxib [Vioxx] was associated with a 3-fold increase in total mortality.” Why, even the number of deaths reported to the FDA raised a flag. “Small numeric differences…most consistent with chance fluctuations” was how the company dismissed the FDA query.
Though it was in possession of the high mortality risk data as early as 2001, the actual submission to the FDA was made only two years later. It used a variety of counting methods, including on-treatment rather than intention-to-treat analysis, an approach that minimized the appearance of the mortality risk,” the authors concluded.
FDA makes it compulsory to submit clinical trial results
The likes of Merck have
found a match. The
pharmaceutical industry
may have mastered the act
of clinical trial data
manipulation. But the Food
and Drug Administration
Amendment Act (FDAAA)
passed last year has made it
compulsory for the industry
to submit trial results in a
publicly accessible registry.
The amended Act which
came into effect from
October 1, 2007 will make
things difficult for
companies like Merck.
The Act requires the
companies to submit the
results to the National
Institutes of Health (NIH)
within one year.
It requires results of trials
that form the basis of an
efficacy claim. This includes
registered trials for
approved drugs too.
The registry where the
results are available are
required to be linked to
results information that
includes: FDA summary
documents, FDA
assessments of clinical trial
results, FDA public health
advisories regarding the
drug among other things.
Compliance is likely as
FDA is authorised to impose
penalties and also
empowers the NIH to post a
notice describing the
infractions on the registry
data bank. This initiative
comes after the medical
journal editors made trial
registration mandatory. - R.P.
FDA makes it compulsory to submit clinical trial results
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