The recent voluntary recall of rofecoxib (Vioxx) by Merck & Co., Inc., illustrates all too well the importance of well-designed clinical trials and vigilant surveillance for any new drug or medical product. Some 3 years after FDA approval and widespread use, rofecoxib was found to be associated with a two-fold increased risk of cardiovascular toxicities in people who took the drug for 18 months or longer in a clinical trial to prevent colon adenomas. The recall has resulted in the careful review of any cardiovascular effects of other drugs in the class of drugs known as COX-2 inhibitors.

COX-2 inhibitors have shown tremendous promise in the prevention and treatment of several different cancers. NCI is sponsoring more than 40 clinical trials with the COX-2 inhibitor celecoxib (Celebrex), most of which are phase I and include studies on cancer prevention and treatment. Based on the safety concerns reported in the rofecoxib trials and the possibility that these concerns may extend to other COX-2 inhibitors, such as celecoxib, NCI is rapidly reviewing data from our studies of COX-2 inhibitors with our Data Safety Monitoring Boards (DSMBs), starting with the largest studies with the longest follow-up. And, as appropriate, we have added additional cardiovascular expertise to our prevention and treatment trial DSMBs.

Clinical trials are our most powerful weapons in the war against cancer. And the rofecoxib recall is further affirmation that our patients must be clearly informed about the safety and side effects of any new or experimental treatments or drugs they are taking. It also highlights the need for evolution of our national clinical trials program.

In the future, clinical studies will routinely use advanced imaging techniques to get information in minutes about whether an intervention is achieving its intended aim. We will also know whether an intervention may be having unintended consequences or, in the case of COX-2 inhibitors, how they might best be used in individual patients. Taking advantage of the efficiencies offered by new imaging technologies and more powerful databases and monitoring systems, we will shorten the time it takes to complete large clinical studies by years, not just months, offering safe and effective treatments to patients far sooner than is currently possible. NCI will also provide leadership in the study of off-label uses of approved drugs and advocate for increased emphasis on post-market, phase IV trials, especially for chemoprevention drugs, where healthy patients will be taking these agents for long periods of time. Underlying these changes is the immediate need for electronic medical records and a national, integrated, health care monitoring system. NCI is in a position to advance the transformation of clinical research.

Our goal in all of this is to ensure we are providing the right intervention to the right patient for the right reasons, at the right location, at the right time, with outcomes that can be monitored in real time. We are going to be ambitious, aggressive, and smart, as we design a clinical trials program that establishes the principles of 21st century medicine, with patient safety always as the top priority.

Dr. Andrew C. von Eschenbach
Director, National Cancer Institute