[Debbie L.]

I agree that trial eligibility both for vaccines and in general can be confusing. There are many reasons for this. For example, usually the early trials (stage I and sometimes II) are designed more to look at best dose, and safety (rather than efficacy). They are designed to get results quickly, so that if things are looking good, they can move fast to the stage III trials (which enroll more patients and can lead to the agent's approval). In order to get those quick results, they need to monitor measurable disease. Trials in an NED setting (whether after primary tx or for stage IV) have to follow patients much longer, which means more expense and more delay in getting the drug approved.

Trials also can be restrictive because we know that by limiting enrollment to cancers with a specific target (or, in the case of vaccines, certain details of the person's immune system like HLA type), they can get a higher percentage of responses. From a business standpoint (which, whether we like it or not, is the bottom line for Pharma), there is a push-pull here. Finding an agent that is highly active for a tiny segment of cancers means that the company will have only a small market for that agent. The book "The Philadelphia Chromosome" by Jessica Wapner is an interesting read about the challenges of developing a drug for a small market (and touches on many other interesting aspects and frustrations of drug development). The wider the net, the larger the market will be (if the agent is successful). But if the trial design spreads the net too wide, they risk having a negative trial, even though within the large group there may be subgroups with positive results (that they couldn't see because they didn't look).

Like most of us, I'm excited by the progress that has been made with immune therapy for cancer, but that is somewhat dampened by the fact that at least so far, we just don't know enough. Immune function is incredibly complex, and each step forward in knowledge gained also results in more questions and more awareness of the complexity. There have been so many trials that were "positive" in terms of measured immune responses but that did not result in clinical responses. In addition, it's early days as far as discovering the downsides (side effects) of tinkering with immune functions.

It's so hard to be patient with the slow process of drug or vaccine discovery. Some of the slowness could be remedied with better trial design and attention to the incredible barriers of the red tape (both within the FDA and the drug corporations). But much of the slowness, though frustrating, comes out of concern for safety. We can cite examples of agents that turned out to be wildly successful (Herceptin would be one), and say that they should have been approved sooner, and could have saved more lives. But for every success, there are also stories of failures -- of treatments that looked good initially but turned out to have major flaws (toxicities, lack of efficacy). The "gold standard" cautionary tale in that regard is bone marrow transplants for breast cancer. The book "False Hope" by Richard Rettig tells that story well, and gives an idea of the challenges, in general, of getting a treatment to market.

I know this doesn't really answer your questions, nor help with our frustration at the slowness. Especially in the short term, there is not much we can do. But advocates at the tables (trial design, drug development, research grants) can help bring that needed sense of urgency. In the last 10-20 years, the value of advocacy has been increasingly recognized, and the opportunities for both education and participation have grown. There are many programs to educate advocates in both the science and the research process. I encourage everyone to take advantage of the educational programs and become active advocates. I think I'll start a new thread where we can list ways that we are aware of, for patients to educate themselves, join with other advocates, and make a difference.

Debbie Laxague