In the ever-changing field of clinical trial design, there is often a need to evaluate design options quickly and efficiently. But when it comes to evaluating options, which is better: commercial or open-source software? And does it need to be a question of either-or? Read more »
Introduction to Evidence Synthesis and Bayesian dynamic borrowing
In the last few years, there has been a growing interest in historical borrowing or augmented trials. There is an increasing level of comfort in using these methodologies even in confirmatory trials setting. The key challenge in borrowing external information is the selection of appropriate historical studies or external data sources. There are benefits to historical borrowing but also potential risks (for example, Type I error and power can be impacted by the drift).
However, despite the risks, several projects submitted to the FDA’s Complex Innovative Designs (CID) initiative aim at using historical controls in Phase III studies. Many data-sharing initiatives such as, TransCelerate, Project Datasphere and others, are all working towards making clinical trial data available for repurposing and reuse across the industry. There are also several working groups such as, the European EFSPI/PSI Historical Data Special Interest Group and DIA Bayesian Working Group who are interested in this area. This blog aims to introduce the concepts of evidence synthesis and Bayesian dynamic borrowing.
MCMC vs. INLA in Bayesian Adaptive Clinical Trial Designs
Integrated Nested Laplacian Approximations (or INLA) are now starting to be used by statisticians as a key tool for Bayesian inference. Geared toward approximate calculations of Bayesian regression model posterior estimates, it can bring significant computational advantages over MCMC methods often used by practitioners. At the BAYES2022: Bayesian Biostatistics conference (October 12–14, 2022, in Bethesda, Maryland), Cytel’s Senior Research Principal Krishna Padmanabhan and VP of Scientific Strategy and Innovation Kyle Wathen will be presenting invited talks. Dr. Padmanabhan’s abstract on INLA is below along with his commentary on this important and timely upcoming talk. (For more information on Dr. Wathen’s talk, click here.)
Measuring Estimates and Confidence Intervals in Adaptive settings?
As the use of advanced and innovative clinical trial designs continue to rise, sponsors often wonder which estimation methods are best used for measuring treatment effects with novel trial designs. A variety of estimation methods exist, and it is essential to understand their strengths and limitations. However, the FDA’s most recent guidance on adaptive designs only mentions controlling Type I error, not estimation. More research is needed to evaluate methods for point estimates and confidence intervals within adaptive settings.
Cytel statisticians and colleagues at Harvard University and Vertex Pharmaceuticals, recently employed extensive simulations to examine the strengths and weaknesses of various estimation methods for adaptive settings. Their findings place sponsors on the path to preparing even stronger evidence packages for regulatory submissions involving complex designs.
How and Why to Implement Optimal Adaptive Promising Zone Designs
When determining the best possible statistical design for a particular trial, large pharmaceuticals and small biotechs benefit from different quantitative strategies. A new line of study from Cytel statisticians, with colleagues at Harvard University, Bristol Meyers Squibb, and Vertex Pharmaceuticals, reveals the tactical advantages of different approaches to sample size re-estimation. Using the familiar promising zone design, Cyrus Mehta, Pralay Senchaudhuri, Apurva Bhingare and Lingyun Liu demonstrate how to optimize for power, bearing in mind considerations like resource constraints and commercial goals.
How to Ensure Your Adaptive Trial Is Appropriate for Regulatory Submission
Adaptive clinical trial designs have become increasingly popular among developers and investors due to the many advantages they offer over traditional designs, but how can you ensure your adaptive trial is appropriate for regulatory submission? Read more »
Design Considerations for Early Phase Trials of Immuno-oncology Drugs
Ever since the first immune checkpoint inhibitor was approved for market nearly twelve years ago, the industry has witnessed a steady rise in the search for new immunotherapies. This has aligned with the broader curation of a number of new dose-escalation and efficacy designs for clinical development in oncology.
Hastening the search for novel treatment options therefore benefits from exploration of how these complex early and late-phase designs interact with each other, and what special design considerations can be implemented in early phases of clinical research for strategic late-phase clinical development. A nuanced understanding of these considerations enables sponsors to ask more complex questions like: Read more »
Dynamic Bayesian Borrowing to Bolster Limited Sample Sizes in Rare Indications
Evaluating the efficacy and safety of novel therapies in rare indications can be challenging due to the difficulty of recruiting enough patients to conduct a well-powered clinical trial. To address these challenges there has been growing interest in the use of Read more »
Embracing Innovation: Exploring the Design of Umbrella and Basket Trials
Medical research has come a long way in recent years, fueled by innovative trial designs that challenge traditional approaches. Umbrella and basket trials are two such groundbreaking methodologies that hold tremendous promise in revolutionizing the field of clinical trials. By allowing researchers to explore multiple treatments or target multiple patient populations simultaneously, these designs have the potential to accelerate the discovery of effective therapies and bring us closer to personalized medicine. Here, we will delve into the design of umbrella and basket trials, shedding light on their significance and the benefits they offer to patients and the scientific community.
Celebrating 35 Years of Innovation and Impact: An Interview Series
For 35 years, Cytel’s scientific rigor and operational excellence have enabled biotech and pharmaceutical companies to navigate uncertainty, prove value, and make evidence-based decisions with confidence.
To celebrate this milestone, we invited Cytel’s Co-Founders, Nitin Patel and Cyrus Mehta, and CEO, Joshua Schultz, to offer their reflections on Cytel’s beginnings, its innovations in technology and statistical strategy over nearly four decades, and predictions for the future of the industry.