What if the optimal design for your early-stage study is an innovative or novel design? Would it be worth the additional time and effort upfront to explore such designs given that the overall benefits to the development program could be significant?  Although the decision to use an innovative design depends on several factors, below are 3 considerations.

First, regulatory authorities have an increased understanding of such designs, have embraced their use and are focusing on providing more guidance regarding their implementation. This is evidenced by FDA’s Complex Innovative Trial Design (CID) Paired Meeting Program, originally established under PDUFA VI, to support the goal of facilitating and advancing the use of complex adaptive, Bayesian, and other novel clinical trial designs. FDA’s previous guidance on Adaptive Designs for Clinical Trials of Drugs and Biologics also was a major step in providing support for their use. The commitment to encourage their use is also reflected in the goals outlined by EMA’s Regulatory Science to 2025. Clinical trialists traditionally have been concerned about being first to advocate for a particular design in meetings with the regulatory agencies. However, an increasing number of innovative designs have been used and can serve as a guide.

Second, in areas such as oncology, rare disease and pediatrics, innovative designs have advanced quickly over time to keep pace with the challenges and importance of these indications. Oncology is an area where many such designs have emerged over the past few years to address the unique challenges in early phase studies especially in dose finding. Adaptive and Bayesian methods such as mTPI, BLRM, BOIN, seamless 1a/1b, 1/2 or 2/3 designs and other novel clinical trial designs have become more common. Rare disease studies where one must deal with the challenges associated with small sample sizes demand innovation to address the questions of interest. Other methods such as master protocols (like basket and umbrella trials), use of real-world data, and external controls have also emerged. In general, more flexibility is often afforded for indications that are rare and life-threatening, have large unmet needs, or are more difficult to study.

Third, in the past, the complexity of such designs and the need for computer simulation to determine operating characteristics has limited their widespread use. Although this may continue to be a challenge, the availability of online resources and software has expanded making the ability to generate and compare several potential designs less time consuming and costly.

Innovation in early-stage studies presents the best opportunity to streamline the drug development process. Such designs may not only reduce costs and accelerate timelines but give us better flexibility to address the questions of interest in an increasingly evolving clinical development landscape.

If you have questions about the design of your study contact one of our design experts.

Patricia Stephenson, Sc.D., Associate Director, Biostatistics is a Harvard graduate with over 10 years of experience working in oncology, including working with researchers at the Dana-Farber Cancer Institute. Dr. Stephenson has served as the lead statistician for multiple oncology studies, including a Phase 1 study pivotal for an NDA submission for accelerated approval. As a result, she was involved in several submission activities including supporting the statistical preparation and review for the Summary of Clinical Efficacy (SCE) and Summary of Clinical Safety (SCS) as well as preparation for a FDA Advisory Committee Meeting.  Previously, Dr. Stephenson also served as the lead statistician for multiple Phase 1 and 2 studies in ovarian cancer, renal cell carcinoma, gastrointestinal stromal tumors, and non-small cell lung cancer.