Just before my treatment for breast cancer began and during a consultation about what chemotherapy drugs I was about to receive, my oncologist stepped away from my exam room to check on something. When she returned to the room, she told me that she was determining whether or not I qualified for a clinical trial. I had no idea what this meant at the time. All I knew was what she told me -- that my prognosis was too good at that moment to qualify for anything currently under study. I did not fit a profile for anything. I was not a candidate for a clinical trial. I now know that clinical trials are a critical component of research -- they validate a drug's success or weakness and they provide hope for many who may be at the end of their treatment rope and need something new to consider. A clinical trial is a comparison of standard treatments to newer treatments in an effort to discover better methods for the diagnosis and treatment of cancer. Doctors, scientists, and other health professionals conduct these tests according to strict guidelines set by the Food and Drug Administration -- which establishes mandatory guidelines to ensure the maximum safety of the patient.
Clinical trials rely on volunteers -- and sadly, there is a current shortage of patients willing to participate in trials. Experts say that, for the past few decades, just five to 10 percent of all cancer patients in the United States have joined a clinical trial. There is an urgent need -- because the demand for willing, eligible participants far exceeds the supply. Some experts are even recommending that the small pool of candidates that does exist be rationed to only the most important cancer studies -- leaving other studies with no hope for completion. There is no good solution in sight. But the reasons for the shortage are becoming apparent. It's not that patients are unwilling to join. It's that they are unaware, uninformed, not even sure this opportunity is possible -- because doctors are not suggesting trials to their patients. Treatment on a protocol is more demanding for doctors than routine medical care. And it costs doctors to submit to a trial. And trials burden doctors with regulations and paperwork. And some doctors worry about litigation if something experimental goes wrong. So they often don't approach the topic -- and the result is that a wonder drug may sit in a dark freezer because there are not enough people to test it. This potential wonder drug may never show promise, may never save a life, may never see the light of day.
So I guess my oncologist was ahead of the game in this matter -- she compared my diagnosis and prognosis with the needs of all available clinical trials and found that there was not match. Had she not done this, I would have never thought to ask about the possibility -- which is exactly what patients should do instead of waiting for a doctor to make the suggestion. Because it may never happen.
For more information on clinical trials, please visit the Coalition of Cancer Cooperative Groups.
1. All the rigorous clinical trials identified are the best treatments for the average patient. But cancer is not an average disease. The tumors of different patients have different responses to chemotherapy. And tumor response (shrinkage) should not be the criteria for approving cancer drugs. A patient responds to therapy when their tumor shrinks, but apparently this has nothing to do with survival. A tumor responds, that is, shrinks a little, then quickly grows and spreads. The cancer comes back with a vengeance and the cancer patient is given a death sentence.
The FDA is signaling that it's open to developing better approaches to the design of clinical trials, approaches that can shift midcourse. It is something called "adaptive trials" that allow them to route larger groups of patients to more promising treatments in the middle of trials, and drop treatments that seem ineffective in early testing. The FDA has begun to show some openness to accepting these new types of trials in its assessment and approval process.
Dr. Scott Gottlieb, Deputy Commissioner for Medical and Scientific Affairs, spoke about this at a recent speech before the Conference on Adaptive Trial Design. He said "clinical trials are highly empirical, testing drugs on general populations and then look for clinical response and a treatment effect that is not likely to be a chance result." He added, "new scientific tools and approaches could help to learn more about the safety and efficacy of new medicines perhaps more quickly and earlier in the development process."
Getting better drug development tools from advances in proteomics, genomics, and cellular profiling, holds the key to solving some of the problems confronting a healthcare system that is seeking ways to best allocate available resources while accomplishing the critical task of matching individual patients with the treatments most likely to benefit them.
Genomic testing with cell culture analysis is a good way to start in developing a program to discover gene expression microarrays, which predict for responsiveness to drug therapy. The way to identify informative gene expression patterns is to have a gold standard and cell culture assays are by far the most powerful, efficient, useful gold standard to have.
The assay is the only assay that involves direct visualization of the cancer cells at endpoint. This allows for accurate assessment of drug activity, discriminates tumor from non-tumor cells, and provides a permanent archival record, which improves quality, serves as control, and assesses dose response in vitro, and includes newly-emergent drug combinations.
Posted at 6:14PM on Jul 13th 2006 by Gregory D. Pawelski