NEWSLETTER 5: VIOXX IRB DISASTER

There are some real problems emerging as the Vioxx controversy unfolds. What began with Mr. Gilmartin stating that his wife was on Vioxx and that his company stands behind its research ethics is obviously only one side of the story.

One entity to blame for this mess is the IRB (Institutional Review Board) that approved the research and continued to let it go on with yearly reviews, obviously not enough oversight in retrospect. Traditionally, the IRB only oversees the research process itself, but maybe they should be responsible for the long-term safety of FDA approved drugs also. The revelation that Merck's popular painkiller rofecoxib (Vioxx), as well as other drugs in the COX-2 inhibitor class (Bextra, Celebrex), might pose an increased risk of heart attack and stroke in patients who take them has led the research community to question whether the IRBs at the sites where the drug was tested failed in their mission. Disclosure by investigators and the FDA regulators that they knew of clinical data indicating a statistically significant number of adverse cardiovascular events among study subjects has only added to the controversy. If IRBs are charged with protecting the interests of human research subject volunteers enrolled in clinical research, many wonder how could a drug like Vioxx with such glaring risks be approved without having the appropriate safety studies being conducted?

The IRB could and arguably should have demanded a new study be performed to address the CV (Cardiovascular) risk along with a non-blinded DSMB (Data Safety Monitoring Board) to monitor the risk proactively in an on going fashion. The study should have been designed to enroll subjects that were at high risk for CAD (Coronary Artery Disease) and Stroke. This way, the proper number of events (Heart Attacks and Strokes) would accumulate in a reasonable amount of time to analyze the data quickly. One group could have received Vioxx and the other Placebo. This would have discovered the casual relationship between these events and Vioxx, thus preventing it from appearing on the market, along with Celebrex and Bextra.

Such revelations lead many in the public and clinical research arenas to look at failure of proper IRB oversight as one of the contributing factors that lead to the Vioxx disaster. The public expects the IRB to be able to prevent abuse, misconduct, or an adverse event form occurring. They would rather not have a potentially life saving drug or deal with rather extreme discomfort from their disease than risk even the most minor side effect from a drug, even if it occurs very infrequently. Failing that, they expect IRB’s to know when these shortcomings occur and they expect prompt action. Until the sponsoring pharmaceutical companies, IRB’s and medical researchers understand this concept; research disasters like Vioxx will continue to occur.

Part of the problem is Vioxx did work well as a pain reliever. And, it was really safer in some aspects. For example, be sparing COX-1, it is at least theoretically a safer drug. So, it seemed like a "no-brainer" to physicians that cost aside, Vioxx was a safer alternative to the traditional non-COX-2 selective NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) like: Advil, Ibuprofen, Aleve, etc… And, Aleve is now implicated as being bad also. These drugs do help arthritis pain, but the majority of people would rather suffer with their pain than subject themselves to even the slightest risk no matter how rare it is. And, the concern over drug side effects itself can be a very significant injury to many people.

Currently, IRBs are simply unable to perform the added oversight functions that the public increasingly seems to be asking them to assume. At the same time, sites and sponsors feel that IRBs are asking questions and demanding assurances that were at least viewed by some in medical research as excessive. In this less than perfect setting of an experimental drug study, how is a potential research subject volunteer going to make informed decisions on whether to participate? And, when does the IRB approve research and should they be demanding future safety studies or otherwise be involved in the decision of how to prove a drug is safe for the market. And, should IRBs be involved with continuing approval of already marketed drugs?

Improvements in oversight are the responsibility of the IRB. They are the component of the social structure set up to protect the public and are entitled to a voice at the table on drug policy. It will be difficult to begin to enforce a paradigm shift like described without large putative settlements serving as precedents for future IRB oversight. I feel implementing this will help safe guard the public against harmful drugs like Vioxx in the future.

Sincerely:

Joseph Saponaro, MD, DABIM, FACP, CPI, CCI, CCTI, CCRC, CCRP
Expert Medical Witness, ExpertMD
PI (Principal Investigator), DSI (Drug Study Institute)
Board Certified Internist, JPMC (Jupiter Preventive Medicine Center)
DABIM (Diplomat American Board of Internal Medicine)
FACP (Fellow American College of Physicians)
CPI (Certified Physician Investigator) by the AAPP (American Academy of Pharmaceutical Physicians)
CCTI (Certified Clinical Trial Investigator) by the ACRP (Association of Clinical Research Professionals)
CCI (Certified Clinical Investigator) by the DIA (Drug Information Association)
CCRC (Certified Clinical Research Coordinator) by the ACRP (Association of Clinical Research Professionals)
CCRP (Certified Clinical Research Professional) by SoCRA (Society of Clinical Research Associates)
Member, SIMPD (Society for Innovative Medical Practice Design)
Member, ACPM (American College Preventive Medicine)
Ethics Committee Member, Jupiter Medical Center
IRB Member, Jupiter Medical Center
Founder, CertifiedResearchers.com