ParagonRx Blog

- Guest blog by Wendy Kaplan Nickel -

Perhaps one of the greatest downfalls in drug history was the steep tumble of VIOXX after it was voluntarily pulled from the market in 2004.  VIOXX was approved by the FDA in 1999 and quickly became “the” drug for arthritis.  It gained widespread acceptance among physicians and over 20 million people were prescribed VIOXX at some point in its 5-year tenure.  In fact, in the year prior to VIOXX’s withdrawal from the market, its manufacturer, Merck, experienced sales revenue of $2.5 billion from VIOXX alone.  It is assumed Merck certainly had no intention of harming patients with its product, and in fact, celebrated in the fact that so many patients benefitted from the medication.  However, it is worth exploring what might have happened if VIOXX’s safety issues had been discovered during the post-FDAAA era.

Problems with the drug came to light early in its history – how early has been a hotly contested debate in the industry.  It is known that VIOXX led to an increased chance of heart attack and as early as 2000 the FDA pressed Merck to add warnings on its VIOXX dispensers.  A Merck-sponsored study, “VIGOR,” found the risk of cardiovascular problems, including heart attack, chest pain, stroke, blood clots and sudden death, was more than two times higher in the VIOXX group than in the control group.  Other independent clinical studies also revealed cardiovascular risk, including heart attacks.  In 2002, the FDA mandated labeling changes for VIOXX.  After a new long-term study confirmed participants had twice the risk of heart attack than other participants taking a placebo, Merck voluntarily withdrew VIOXX from the market on September 30, 2004.  According to a study which analyzed medical records of 1.4 million members of Kaiser Permanente, VIOXX may have contributed to an additional 27,785 heart attacks or sudden cardiac deaths between 1999 and 2003.

Could VIOXX’s withdrawal have been prevented had an effective REMS been in place prior to its release to market?  One thing is for certain, if a well-executed REMS was in place, actions to mitigate risks would have been much swifter.  One could speculate that in light of the FDAAA, a REMS probably would have been required due to the size of the population likely to use the drug and the expected duration of the treatment.  A theoretical VIOXX REMS might have looked something like this:

First, early on in the process, internal stakeholders would have met to discuss potential risks associated with VIOXX.   This risk management team would characterize risks – those associated with drug toxicity and those associated with care delivery.  The team would then develop a risk management plan.  The plan would have probably incorporated at least some of the following elements:

• A medication guide and patient labeling would have been designed to clearly outline the risks associated with VIOXX.  These would be required to be dispensed with the drug
• A strategic and comprehensive communication plan would have been developed, including targeted communications to healthcare providers and professional societies
• Patients prescribed VIOXX would have been enrolled in a registry and would have been required to sign a consent indicating their understanding of the risks associated with taking VIOXX
• Prescribers would have been required to review educational materials and undergo certification in order to demonstrate their understanding of the risks and benefits of VIOXX
• A toll-free hotline and web portal would have been established for prescribers to report any adverse events

The risk management team would have then developed an assessment plan to better understand the effectiveness of their interventions and make improvements if necessary.  A database of all prescribers and users would have been developed, as well as surveys to assess both the practitioners’ and patients’ understanding of the communications and educational materials.  The team would have then conducted an assessment at 18 months, reviewing any adverse event data and survey results measuring both practitioner and patient comprehension of risks associated with VIOXX.   Perhaps at this juncture, risks would have been identified and the risk management team would have conducted a root cause analysis to better understand the risks.  The REMS would have then been re-designed to mitigate these risks and the improved program would have prevented additional adverse events.

An alternate ending is that VIOXX would have been pulled from the market after the initial 18-month assessment, when it was discovered that the risks associated with the drug greatly outweighed the benefits and re-vamping the REMS would not have assuaged these risks.  Regardless, had a REMS been in place in reality, actions to minimize the risks associated with VIOXX would have occurred much earlier – perhaps even before the 18-month assessment mark.  One could argue that in the age of REMS, a VIOXX-type debacle could have conceivably been prevented and thousands of lives saved.

– Wendy

This entry was posted on Monday, February 15th, 2010 at 3:56 pm and is filed under REMS. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.