Why Are Only 3% of US Cancer Patients in Clinical Trials?

John L. Marshall, MD


January 17, 2013

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Hello again. I'm John Marshall for Medscape. I want to tackle the beginning of what will be a very important issue for 2013 and beyond, the issue of clinical research and participation in clinical trials.

Go back to 2012. If I said, "99%," you would know what I am talking about. If I told you the number "47%," you would know what I am talking about, particularly here in Washington, DC. These are prominent numbers. But if I told you the number "97%," would you know what I am talking about?

That is the number of patients in the United States with cancer who receive the so-called standard of care, meaning that 3% of patients go on clinical trials and 97% receive standard of care -- lemmings that are following the one before them, doing what we did years ago. There is no advancement, no progress. We know the shortcomings of these treatments, but for whatever reason, there is an element of safety and security or a complicated environment where patients are not demanding clinical trials and they are not being offered clinical trials.

So, this year, as part of our Ruesch Center for the Cure of Gastrointestinal Cancers Annual Symposium: Fighting a Smarter War Against Cancer, we tried to tackle this. We tried to bring everybody together in a meeting about a month ago, to get all the key stakeholders -- from the US Food and Drug Administration (FDA), the Cancer Therapy Evaluation Program (CTEP), and industry to patient representatives, patients, and academic folks -- together and ask why we aren't doing a better job with clinical trials. We had a fascinating day in discovery on this and I think some answers may have emerged.

Let's first look at what the priorities are for the different stakeholders. Let's start with the FDA. Their priority is safety and efficacy. That is what they are charged to do. The priority of the payers, the ones funding all the clinical treatment as well as paying for clinical research, is to control costs. Their job is to control cost in an ever more expensive world. Sponsors, pharmaceutical companies, and CTEP want access to high volumes of patients and high-quality data. They want a crisp, pure world in which they can test their drugs to get things moving forward. In community oncology, where most cancer care is delivered, I think you would argue that their stake -- their priority -- is going to be high-quality, highly efficient care. That is success in the community. In academic oncology, we are judged by how many patients go on clinical trials. What percentage of patients can we put on a clinical trial? We do a little bit better in a comprehensive cancer center (10%-20%), but it's nowhere where it needs to be.

As for patients, nobody ever asks them what their motivation is and why they would want to do this. So, at this meeting, we asked them, and it was pretty clear that they don't see what's in it for them to go on one of these clinical trials. They are very put off by the whole placebo thing, even though they don't have a good understanding of what is out there. They have these visions of what this means. They don't see how they are a part of it, how they are helping to drive the answer. We have done a terrible job of educating our public. I think we have done a terrible job of designing clinical trials that have significant value to them. We do these great big clinical trials that result in very small improvements in outcome, which, honestly, are a big waste of time.

We had Deborah Schrag give a wonderful talk on her study in rectal cancer, which challenges the need for radiation in rectal cancer.[1,2] Here is a big study that no one is going to fund -- maybe the federal government, depending on how steeply we go off the cliff -- that is trying to remove a therapy that may be unnecessary in the treatment of colorectal cancers, namely radiation. She spoke about how difficult that study was to put into play. This is a very interesting study that would make things easier for patients, but it took more than a year for the study to get up and running.

There are so many barriers out there. One of the things that really emerged for me was that we need to start over and think about this in a different way. We have some good leads. Take the I-SPY2 clinical trial in breast cancer.[3] This is a great new model for us, a parent protocol where molecular profiling is done and treatment assignment is based on an individual's molecular profile based on our best understanding of the molecular biology.

I think that every single major disease, maybe every disease, needs exactly this type of parent protocol. In order to do this, we are going to need better and quicker pathology. We need to change a few laws around molecular profiling -- the timing, who pays for it, and all of those things. I think it will require a more centralized pharmacy, because if everybody is going to participate in this, all of us can't keep all of these drugs on the shelf. We would need some sort of centralized management for access to investigational drugs throughout the community, not just at comprehensive cancer centers but throughout our medical community. I think the opportunity here is ripe, because many of our healthcare systems are merging and coming together. One of the things that we can do as not just academic ivory towers but corporations is begin to provide the community with this type of centralized tissue analysis, pharmacy support, and clinical research support. Then, a patient, no matter where he comes into the system, can get that tumor analysis. He can get access to what we think is the best new therapy -- not just improving things a little bit, but trying to make major leaps forward.

I don't think we are too far away from where we need to be. We have the conceptual protocols in breast cancer and some new ones in lung cancer. I think we need to develop them in colon cancer, pancreas cancer, gastric cancer, and hepatocellular cancer in the gastrointestinal world, and then split the cancers into their individual types and treat patients according to our best guess at the moment, tagging it with drug development and moving forward. It will be biomarker co-development. We will increase our accrual rate from the puny 3% up to 25%, ask good questions, answer them quickly, and then move on.

I think the future is bright for us in clinical research and cancer medicine. It will take some cooperation, but I think that together with our patient partners, we can drive this forward. Looking forward to a bright 2013, I'm John Marshall for Medscape.