Michael Kurman, MD

 

Patrick Melvin

How CROs Help Oncology Sponsors Produce Results

Two industry insiders offer scientific and operational insight into oncology clinical trials.

The National Cancer Institute recently reported concerns that the United States will experience a shortage of medical oncologists, which will put pressure on oncology clinical research and trials. In addition, physicians cite a lack of time as the reason they fail to recruit into these trials. However, only two-thirds of those physicians are involved in clinical trials.

How are CROs positioned to address this shortage as well as get physicians more engaged into enrollment?

Kurman: I'm not sure there's a shortage of oncologists, but I do think there is a shortage of oncologists that are able to do clinical trials. And some of the numbers you cite by the NCI are certainly consistent with our experience.

I think oncologists today, whether you are in an academic center that's directly supported by the NCI or you're in community practice, you're very busy. There's incredible pressure today to generate fees and to see patients. And that just doesn't leave a lot of time to conduct clinical studies.

I think [CROs] can help because through our breadth of experience with all the clinical trials that we do, we can help sponsors design studies that are more user friendly, that are easier to do, perhaps require a few less procedures, maybe that answers a more important question, that an investigator will want to take the time to be part of. And so I think we can provide some guidance to sponsors. And whether that sponsor is the NCI or a pharma company, to help design trials that are a little bit more pragmatic and have a better chance of gaining participation by investigators.

Recent reports have stated that oncology has the lowest overall success rates at Phase III. Then drilling down into specific cancer types, the overall success rates range from 2% to 19%, depending on the type of cancer that's involved.

Specifically, in regard to the low success rates at Phase III, what is this a function of? Is it a fact that the drug is just going into more subjects or is there a factor of trial design or something else that we're not understanding yet?

Kurman: I think it's a function of both expanding the size of the trials and the design of the trials. We characteristically do Phase II studies in oncology that are rather small, and part of this is because it's very hard to find patients for the trials. You know, for many people, this is their treatment of a very serious disease. It may be their last treatment in many cases. And so finding subjects is difficult. So Phase II trials have tended to be small.

And, when you have a small study, the result may not be reliable because you have a very large confidence interval because you have a small sample size. And so we'll see success in Phase II, take the drug into Phase III, and now we have a larger sample size and more variability; and all of a sudden that great result we found in Phase II, we don't see in Phase III.

So it's partly a problem of the size of the studies and how we do studies. We are changing that paradigm more and more; both pharmaceutical sponsors as well as cooperative groups are now doing randomized Phase II studies. They are larger. They do take more time, and they're more expensive. But the value of the data that you get afterward is much greater, and it really gives you a much better picture as to whether or not the drug is worth taking forward into Phase III.

Melvin: I would echo Dr. Kurman's comments noting the criticality of the trial design.

There are a lot of things that go into clinical trial design, not just from a scientific standpoint but also at the clinic standpoint. So the hematologists/oncologists out in the community, they need to want to enroll these trials. They have to be easy enough for the hematologist/oncologist to enroll. They have to be easy enough for their site support staff, for their study nurses, and their data collection staff to collect and interpret those data and appropriately interpret those data.

We're out there monitoring those trials on a regular basis, but if it's too difficult for those investigators and their sites to have to enroll these trials, they're just not going to enroll them. And so from that standpoint, the trial can be a failure.

It also has to have minimal impact on these patients. As Dr. Kurman mentioned, these patients are critically ill. A lot of them are in the end stages of their life and know that they have a terminal disease, and they don't want to spend the last months of their life enrolling or participating in a trial that has them going to a clinic seven days a week or multiple, multiple hours on end.

So there are a multitude of things; but it really boils down to appropriate clinical trial design and opening them in the right locations.

How does contract research and trial research outsourcing make cancer trials more successful?

Kurman: Part of it is just helping sponsors design trials that are going to be successful, knowing where the investigators are who have the time or the staff or the interest or whatever it might be to enroll the patients and make the trial successful.

Mostly it comes down to our breadth of experience. A lot of sponsors who may have three or four cancer drugs in development, and over the course of each of those drug's life cycle, each drug may be involved in maybe four or five or six trials. So each company may do 25 trials over many years. But at any one time, we may be doing between 50 and 100 trials. And so, again, I think the breadth of experience that we bring and all of what we see I think can help sponsors design those studies that will answer important questions but that still can be completed in a reasonable period of time for a reasonable cost.

Melvin: Sponsors, in particular in the oncology community, look to CROs for their expertise and efficiencies in running these trials and enrolling these trials and then collecting the data on the trials and interpreting those data. It's what we do every day, and pharmaceutical sponsors look to the CROs for those processes and that consistency.

That's what we do every day, and that's why the clinical trials' sponsors come to us. Our processes are predictable. Our outcomes are reproducible. And so that predictability is what the oncology clinical trial sponsors look for, that's what they need, and that's why they come to us because of those efficiencies and success rates that we bring to the community.

As far as that reproducibility and efficiencies, do you find that it is more difficult in oncology to achieve that, only by virtue of its disease, or can you take similar efficiencies and processes from other therapeutic areas that work fine and just apply it to this complex area?

Melvin: In the area of hematology and oncology clinical research, we're dealing frequently with very rare diseases. Remember that in a lot of patient populations, if we're doing sinusitis studies or flu studies, these diseases or indications are very widespread and not hard to find those patients. And in a lot of cases there's not a high degree of competition for finding those patients.

There is a higher degree of complexity that comes into play in the oncology trials, and what we've talked about, we're dealing with real patients with real diseases at the end of their life in a lot of cases. And so all of those things factor into whether or not patients even want to participate in clinical trials. And so it's absolutely critical that we have these structures and these processes and that we invest this time and these resources and that we have these technologies to determine exactly where we need to go to find these patients so that we can bring these trials into the community settings, penetrate the community of patients to find those trials, and make those trials available to those patients so that we can successfully enroll them and provide those key services to our clients and to the oncology community.

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