Physician lack of awareness. A common reason physicians fail to refer patients to
clinical trials is a lack of awareness about existing trials. Primary care physicians
often leave the discussion of clinical research to the patient’s oncologist. Yet
Figure 5. Traditional
“3+3” Study Designs
vs. Adaptive Trial Designs
many oncologists outside of the academic setting may not be aware of available
trials close to home or choose not to refer their patients to settings where they
could participate in studies. Referring patients to another care center could mean
oncologists lose income should patients choose not to return. Even within an
academic institution, physicians are oftentimes unaware of all of the oncology
trials that are recruiting patients. Such trials can number more than a hundred
at large institutions.
vs.
Strategies for Breaking Down Enrollment Barriers »
Adaptive trial design. In traditional, “3+3,” study designs, three patients are
enrolled at an initial dose, and once that dose is deemed safe, three more
patients are enrolled into the next highest dose level. This approach is valuable
for determining what is a safe and possibly effective dose and is most often
utilized in phase 1 oncology trials.
Adaptive clinical trial designs are based on using accumulating data to decide
how to modify aspects of the study as it continues, without undermining the
Changes
planned in
advance
rather than
on an ad hoc
basis
Flexibility: Fewer patients,
earlier enrollment
Fewer patients treated at
ineffective doses
validity and integrity of the trial. Changes are planned in advance rather than
on an ad hoc basis. The flexibility of adaptive trial designs can lead to having
trials with fewer patients, which makes enrollment easier to achieve. In oncology
trials, adaptive trial designs can also mean fewer participants are treated at
ineffective doses. Properly conducting a trial through adaptive design can be
challenging and works best when preclinical data are comprehensive.
Potential drawbacks of adaptive trial design in early phase trials include increased complexity and cost. In our recent webinar, only 19% of
participants responding to a polling question reported using adaptive trial designs in their clinical trials. Reviewing data in real-time has been
shown to be an effective evaluation tool when conducting early phase trials. Monitoring the safety data is always a part of the trial, but evaluating
the trial endpoints on an ongoing basis may also provide enough data to change the trial design, especially if the targets are being met.
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