Seamless Adaptive Clinical Trials: A Brief Overview
06 Nov 2018
The Seamless Adaptive Clinical Trials are combined phase studies which reduce the time required for the complete drug development process. A seamless trial combines two or more phases of trial into a one single trial. A Seamless trial is termed as Seamless Adaptive Clinical Trial if the final analysis will use data from patients enrolled before and after the adaptation.
In Seamless Adaptive trials, few extra treatment arms are added in the initial phases of the trials for dose ranging and different disease states. At later stages, successful arms are studied further with additional patients while the less successful arm(s) can be terminated. These trials provide data for long term safety and efficacy of the drug due to the continuity of the patients.
These trials are more suitable for the products approved via 505(b) (2) regulatory pathway as it reduces the cost and time for the trial as compared to the separate conduction of Phase 3 and 4 traditional trials.
Origin of Seamless trials:
Seamless trials were initially started for cancer therapy. The desire of early access of anti-cancerous drugs resulted into first in human trials. The very first-in-human seamless Adaptive Clinical Trials was conducted by Merck in 2011 for pembrolizumab. Pembrolizumab is a humanized monoclonal antibody specific for programmed cell death. This trial was conducted for determining safety and efficacy of monoclonal antibody pembrolizumab in the patients with advanced solid tumors.
Earlier results of this trial demonstrated impressive efficacy in the patients of metastatic melanoma or non-small-cell lung cancer. Hence, the sample size of the cohort was increased to more than 1200 people for the final evaluations. Within three years, the drug received a fast track approval reducing the overall time for development and approval.
Types of Seamless trials:
- Inferentially seamless trials: These are the trials in which some of the data used prior to the interim look also play an inferential role after the interim look.
- Operationally seamless trials: In these trials, data evaluated after the interim look is kept separate from the data obtained prior to interim look.
Advantages of Seamless trials
- Beneficial for reducing time of trial
- Reduces sample size
- Reduces cost of trial
- Early access of the drug
Seamless development programs are reserved for the breakthrough therapy designated drugs in which preliminary clinical evidences indicate substantial improvement over available therapy. Seamless trials provide a way to these drugs to get into the market quickly. Seamless trails are less flexible as compared to that of traditional clinical trials as it reduces the number of arms for the study. Seamless trails are significantly smaller trials as compared to the traditional trials which make it worth for the sponsors even though they are less flexible.