Study on Minimizing Exclusion for AML Patients in Clinical Trials | Andrew Hantel, MD | ASH 2023

Hi, I'm Andrew Hantel. I'm a medical oncologist and leukemia researcher at Dana-Farber Cancer Institute. And some of our research that we're presenting here at ASH 2023 was looking at the impact of eligibility criteria for clinical trials based on patient safety data versus on the criteria that were actually used. And what that means is that we know enrollment criteria for clinical trials can be very restrictive in that it can exclude a lot of patients. And ostensibly, this is done because of safety reasons in that we want to make sure that we're not putting patients in harm's way by exposing them to different drugs that, because of whatever other medical conditions they have or because of their organ function, they might be at increased risk for having complications. At the same time, we know that making the enrollment criteria as broad as possible within those kind of constraints of safety means that we will know then in the end whether or not a drug is safe for the general population that the drug would then be used in after it's approved by the FDA. But to this day, we hadn't really known whether or not all of the criteria that were used were really based in drug safety or whether or not there was just kind of additional restrictions that were being placed in kind of excluding patients without a good reason. And so we took a look at about 250 different Phase II and Phase III clinical trials, the kind of the last two steps before FDA approval, to see if between the Phase II and the Phase III trials, did the criteria match the drug safety data that was really known at the time and make it so that as broad of a population that could be included in the study was so that the eventual drug could have then been tested in kind of the population where it's being used or whether or not there was some kind of restriction that means that certain populations couldn't be as involved. What we ended up seeing kind of the opposite of what we had hypothesized was that actually Phase III studies were at least as restrictive, if not more restrictive, than Phase II studies and that there wasn't really a better concordance of the study's enrollment criteria with the actual safety data from the drugs. We had expected that as trials are going on, we're getting more knowledge about these drugs, how they work in different populations, and are able to really better match the criteria that we're using to the drug safety data that we know when we're starting a trial. This was in fact not the case and in some cases these Phase III trials were actually more restrictive and doing so without good justification based on drug safety. So in the end this shows that we need to really look at each point in our drug development pathway at Phase II, at Phase III, and even beyond to say are we able to include everybody who's actually going to be exposed to this drug once it's approved and also do so in a way that's safe. So these data kind of point to the individual criteria that are either too restrictive, not restrictive enough, and really show us which ways we need to change things as we're moving drugs along the pathway towards FDA approval. And ideally with using these we're also going to look to see if those kind of differences that we saw, if those ended up making it so that particular populations like African Americans or Hispanics who we know have been under enrolled in clinical trials, if these criteria and kind of the ones that were too restrictive were actually the ones that were responsible for that kind of lack of inclusion. So that's the next step for this project and we hope in the end we can work with the FDA and with investigators to really make sure that their criteria are both as broad and as safe as possible.