What led you to this project?
My interest in this topic grew directly from my own frustrations and those of my patients. The number of times a patient would specifically come to see me for a clinical trial, and I could not enroll that person because they didn't meet eligibility, was astounding. So often those exclusion criteria didn't seem rational or justified.
I'll give you an example of the first ones I encountered. Most of the patients I see with lung cancer have stage four or metastaticdisease, which is a very serious disease. I would have patients come to me in excellent health otherwise, but they would have had an earlier cancer. One of them was a retired surgeon who for years before had stage one prostate cancer. And the clinical trials that we looked at for him all excluded people who had earlier cancer before lung cancer.
I put together a research team and we got some federal grants, and we found out that 85% of lung cancer clinical trials excluded people who had earlier cancer.
Believe it or not, among people with stage four lung cancer, it didn't matter what the type of the earlier cancer was. The timing, in terms of when it occurred or the stage of prior cancer, never had an adverse effect on how long people lived once they had stage four lung cancer.
We published that information and took it to the National Institutes of Health and the FDA. They changed their policies. Most pharmaceutical companies have followed. So because of that work, most clinical trials for lung cancer are far less likely to exclude people because of an earlier cancer.
Why does the FDA feel the need to loosen restrictions of this type?
Over decades, clinical trials, especially in cancer, have become more complex:
- The number of eligibility criteria have increased.
- Restrictions on enrollment have become more stringent
- Requirements of patients once they are accepted in and start a clinical trial have also increased.
For this reason, a very small proportion of patients with cancer participate in clinical trials. That leads to a few problems:
- It takes longer to complete trials.
- Some trials never finish.
- When we do complete trials, it's possible that the results may not be generalizable to a broad population if those patients who did qualify to participate were so selected.
There is a concern, though, about disparities, in enrolling people of color?
I'll give you an example: Laboratory tests that are required for patients to qualify for clinical trials. This is really a moving target because the laboratory test results from blood tests are used again to determine the safety of the treatment that's under study.
For example, if we're studying a chemotherapy drug, chemotherapy routinely lowers blood counts by affecting the bone marrow. So, it's probably important for chemotherapy studies to have certain minimum blood count requirements for patients to go on a trial. That way, when they do lower after starting, it doesn't become dangerously low. But there are lots of treatments that don't usually lower blood counts.
Immune therapy drugs can be very effective, but they almost never lower blood counts. And yet, when you look at most immune therapy clinical trials, they still use the same blood count requirements that are carried over from chemotherapy trials.
I think this is especially an issue because it may unintentionally affect the diversity of participants in clinical trials. We know from large population studies that African American individuals in general have lower white blood cell counts than white adults. For that reason alone, it sometimes may be more difficult for an African American individual to qualify for a clinical trial.
Why are there tighter restrictions in this process for clinical trials?
First of all, you want to make sure that what you're doing is likely to be as safe as possible. Some of the restrictions on enrollment don't have so much to do with safety as just defining the nature of the disease under study to make sure that we can render conclusions about what's been observed.
What specifically does the FDA want to do?
The forthcoming document from the FDA is considered a guidance document — suggestions, not mandates. The FDA has proposed a specific approach to eligibility criteria for clinical trials for stage four or metastatic lung cancer.
And we believe that this is going to serve as a paradigm and that this type of approach can then be taken to other cancer types and other stages of lung cancer.
And not only does the document describe suggestions for specific criteria, but the FDA is also giving sponsors a framework to think about the types of eligibility criteria we should be thinking about and what's the order in which we should present them. And I think it may make it easier for patients, their caregivers, and physicians to find potential clinical trials.
So you're talking about how can you make it convenient for people to participate in trials?
Absolutely. We want it to be as feasible as possible for not only the patient but also for the health care system. If clinical trials are super complex and have many, many procedures beyond what we would do as part of standard treatment, it may not be possible for many important clinical sites that are safety net health care systems. You know, in Dallas County, that's Parkland (Hospital). Those are sites that may just not have the resources to do a lot of extra steps beyond standard treatment because there's such demand to meet the regular oncology clinical needs of their patient population.
Why should the average person listening to this be concerned with this problem?
Inefficient clinical trials mean fewer opportunities for people who have cancer to benefit from participating in trials, and there are multiple benefits that go beyond getting access to promising therapies.
And then beyond that, inefficient clinical trial processes make it take longer to get new therapies. And for all we know, there may be trials that were stopped and never finished that could have otherwise shown something promising.
It could mean missing out on potential treatment that could benefit you?
Yeah. The biggest hurdle in bringing new therapies to patients really is clinical trials. The discovery that happens in laboratories is critical and an extremely important step, but the steps that take the longest and cost the most money are the clinical trials.
RESOURCES:
Cancer researchers push to relax rules for clinical trials
