Adaptive trial designs emerged as a means to improve clinical trials based on all available information. High failure rates and increasing costs have driven the industry toward adaptive trial designs. In The Adaptive Designs for Clinical Trials of Drugs and Biologics Guidance for Industry, the FDA defines adaptive clinical trial designs as, “a clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects in the trial.”
Adaptive designs present numerous benefits for clinical trials. The approach can reduce potential costs, by creating greater upfront flexibility and allowing for the ability to compare more treatments, providing insights for earlier decisions. Researchers can determine to stop the trial earlier, drop treatments or dosage early and test more treatments simultaneously. The trial design also creates a higher likelihood of success, with better statistical efficiency and the potential to improve the study in response to live, real-time data. Finally, adaptive designs enable the research team to answer more questions, evaluate unviable treatments and increase stakeholder buy-in with lower potential costs coupled with a greater success rate. At the same time, patients are more likely to participate and stay engaged when they believe there is a greater probability of getting the best treatment.
Challenges to Adopting Adaptive Designs
This increasingly popular strategy comes with its own challenges. Adaptive designs are commonly more complex. They also require significantly more upfront planning around the designated adaptations. The types of adaptations, the rationale for each adaptation, the timing and frequency of interim analyses, and any special analytical methods being used, must be all be planned and documented in advance.
In March 2020, The European Federation of Pharmaceutical Industries and Associations (EFPIA) published Innovation in Clinical Trial Design: A Review of the Clinical Trial Landscape. The report focuses on the top four innovations currently being employed in clinical trial designs, including adaptive designs. It defines adaptive trials and describes ongoing industry initiatives, practical experiences, and perceptions of adaptive trials.
The report references a DIA survey where, “Respondents to the survey highlighted some of the persistent barriers to implementing adaptive designs as very practical issues including education of teams on methodology; lack of validated software available; team preference; lack of time to conduct clinical trial simulations; negative experience; and perceived regulatory risk.”1
The benefits of adaptive design trials impact multiple stakeholders. Adaptive trials can be more efficient than traditional designs by answering research questions more quickly. They can support a broader range of doses across wider populations where any inferior options are removed from the study more quickly. This means more participants get access to proper doses more quickly, as the trial progresses. In this manner, adaptive design trials can shorten development processes. They provide sponsors with greater flexibility and increase the likelihood of achieving the study objective.
As mentioned in previous blogs, health authorities also recognize the value and the complex nature of adaptive designs. The FDA has issued guidance and continues to encourage sponsors to discuss their complex innovative trial designs with agency teams.
The complicated nature of adaptive trials requires rigorous planning and expertise. To realize the benefits of adaptive designs, sponsors need access to biostatistical expertise throughout the planning, design, and trial conduct. Flexible technology is also key to implementing adaptations throughout the trial. iMednet offers proven capabilities combined with the unprecedented flexibility to support adaptations and the complex underlying rules required to execute them throughout the trial.
Adaptive designs are changing the way medical devices and treatments are being researched and developed. As the industry becomes more familiar with adaptive design practices, we expect the need for greater flexibility along with the need for more powerful capabilities to continue to expand. The iMednet team is monitoring trends, supporting current trials, asking important questions, and most importantly, delivering flexible technology solutions. We understand clinical trial designs are going to get more complicated. We are building our solutions so that we can support today’s requirements while positioning our customers for tomorrow’s requirements.