Mark Warren, MD: Randomized controlled trials don’t always reflect real-world experience because people are calling patients: the study coordinators are making sure they come in for their appointments, to make sure they’re getting the medications. In the real world, there are issues with accessibility to the medication, affording the medications, affording the co-pays—issues with the Medicare gap. So, there are always issues with the real world that we don’t see in the clinical trials. A randomized controlled trial may show us a more robust effect than we would see in real world.
However, sometimes we see just the reverse. Sometimes, the real world allows us to adjust medications based on our experience and what we think the patient will do versus a standard protocol where we can only do what the protocol allows. Sometimes, a real-world effect is actually better than randomized controlled trials. Randomized controlled trials do allow us to compare the effect of one drug versus another versus placebo. It gives us a glimpse of what we might expect in real-world experience. It really depends on how the protocol is made in the randomized controlled trial. Is the protocol so stiff that they can’t adjust their insulin except by the protocol or is there some investigator discretion in there as well? So, really, it depends on the protocol. We have to look at all that when we decide, is that randomized controlled trial going to reflect what we expect in our patients?
One of the weaknesses of a randomized controlled trial is that there are inclusion/exclusion criteria, such that you can’t include someone, for example, with an A1C under 7%, because they were already considered to be at the target. Or you don’t include patients with a very high A1C of over 10%, depending on the clinical trial. Randomized controlled trials may not apply to all of our patients because of the limitations in the patients they include or exclude. When we look at the results of the randomized controlled trials, we have to look at what patients were included or excluded to see if it does apply to our patient population.
When I look at the results of a trial, I look at what population and what countries were involved. And if it’s not the population I serve, I do look at it with some reservations, although it generally will apply. I always have some reservation in looking at and accepting those results. But it does give us some glimpse of what it could do, and now that the trials are done internationally, that’s not usually the case. There may be some differences in genetic responses and medications that we’re not aware of when you’re just using one country versus another. For example, in the United States, we have a very heterogeneous population, whereas in northern Europe, it may be very homogenous and that response rate may not be the same.