It was a pleasure to team with my industry colleague, Chris Mackay, Project Director, Early Phase Pharma, University of Kansas Cancer Center, for a recent webcast on “Best Practices for Boosting Enrollment in Oncology Trials”. We received a lot of great feedback during and after the presentation, so we’re working on a series of blog posts to address many of the questions received.
One of the hot topics of discussion was around the shift from traditional trial design such as 3+3, to adaptive design clinical trials. We posed the following live polling question to our attendees, and received interesting feedback:
Has anyone used an adaptive design other than 3+3 in a phase I trial?
- No (81 percent)
- Yes (19 percent)
While the vast majority of attendees are still using the traditional 3+3 trial design, 19% of our attendees have used other design methodologies in their early-phase oncology trials. Examples of other designs used by the attendees included:
- Modified Titration
- ‘Rolling Six’ Design/ Continuous Reassessment Method
- Randomized Discontinuation Design
- Modified Continuous Reassessment Method
- One patient accelerated dose escalation until Grade 2 adverse event, then 3+3
While the 3+3 modified Fibonacci design (see Figure 1 below) is still most often utilized in early phase oncology trials, as you can see from our polling results, other adaptive designs are beginning to be leveraged more often.
Figure 1. Traditional 3+3 Trial Design
In an adaptive trial design (see Figure 2), changes are planned in advance rather than on an ad hoc basis. The adaptive design uses accumulating data to determine modification aspects of study without undermining the validity or integrity of trial. The flexibility of an adaptive trial design can lead to trials with fewer patients, making enrollment easier to achieve and fewer patients treated at ineffective doses.
Figure 2. Adaptive Trial Design
Properly conducting a trial through adaptive design can be challenging and works best when preclinical data are comprehensive. The drawbacks, however, may be increased complexity and cost, especially in early phase or first-in human trials, so you have to weigh the benefits of this approach.
To learn more on this topic, you can watch the recorded webcast “Best Practices for Boosting Enrollment in Oncology Trials” on-demand at http://ow.ly/kbFNz.