Master protocols and platform clinical trials have become an innovative and efficient approach to testing multiple compounds in a single and consistent framework. But how can they be applied to animal studies? At the BAYES2022: Bayesian Biostatistics conference (October 12–14, 2022, in Bethesda, Maryland), Cytel’s VP of Scientific Strategy and Innovation Kyle Wathen and Senior Research Principal Krishna Padmanabhan will be presenting. Dr. Wathen’s abstract on such platform trials is below along with his commentary on this important and timely upcoming talk (See our previous post for more information on Dr. Padmanabhan’s talk.)
Navigating Comparative Effectiveness in the Inflation Reduction Act: Methodological Approaches for Healthcare Challenges
The Inflation Reduction Act (IRA), passed in August 2022, marks a significant shift in the US healthcare landscape, particularly for Medicare. The IRA introduces reforms to Medicare’s prescription drug program (Part D), inflationary caps in Medicare (Part B), and Medicare price negotiation. To effectively navigate these changes, pharmaceutical companies must develop robust evidence-generation programs that support evolving value requirements throughout a drug’s life cycle. Read more »
Navigating the Clinical Development Landscape: Insights for Success in 2024
After explosive and frenetic activity in the clinical trial industry during the COVID era, the past two years have seen challenging market dynamics and a drop-off in activity. Every one of us working in clinical development has felt this slowdown, but as we begin 2024, there is reason for optimism. The future looks promising. Here are some things to consider as you go forward.
Read more »
On Frequentist and Bayesian Sequential Clinical Trial Designs
In clinical trials, patient enrollment is often staggered, with data collected sequentially. When designing a clinical trial, it is usually advantageous then to plan for interim analyses, which take a look at the accumulating data and present the potential for modifying the trial. Appropriately placed interim analyses are crucial because once a clinical trial has achieved enough data to determine its success or futility, decision-makers can plan for an early stop, saving resources and avoiding unnecessary enrollment. In a recent co-authored publication, University of Chicago Professor Yuan Ji, serving as Cytel’s executive advisor, describes the fundamental and philosophical differences between two approaches to determining this critical stopping point in such adaptive clinical trials: frequentist and Bayesian sequential clinical trial designs.
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.
Leveraging Advanced Statistical Software to Optimize Clinical Development
Traditionally, clinical trials are expensive, long in duration, and have low success rate. But with the advent of rich and abundant data, development teams can now optimize decision-making by integrating quantitative modeling approaches in their study strategy and planning. These approaches have become necessary to strengthen regulatory submissions, demonstrate competitive effectiveness, and reveal the full value of your product. Additionally, innovative trial designs can play a key role to improve the speed, savings, and probability of success of your clinical trials.
In a recent webinar, Cytel’s Chief Scientific Officer Yannis Jemiai illustrates how quantitative sciences play a critical role in a product team’s ability to make optimal decisions, earning the statistician a place at the strategic development table.
Managing Uncertainty: Simulation-Based Assurance in Clinical Trial Design
The past two decades have seen the adoption of great innovation in clinical trial design. Statisticians have risen to the challenge by proposing a myriad of solutions to the ever more complex questions being posed by the trial team. Bayesian statistical techniques have been key among the various methodologies proposed in solving difficult problems, but only recently have they come into their own as computation and simulation power have matured.
One of the chief concepts at the heart of Bayesian inference is Read more »
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.)
How to Determine if Your Clinical Trial Has Sufficient Data?
It can be difficult to estimate just how much time and data you need to address the multitude of considerations that underpin the success of your clinical programs. However, beyond a certain point there are scientific, rational and ethical reasons not to continue enrolling patients onto a clinical trial. Defining this conceptual point, Cytel experts have developed the Sufficient Information Threshold to aid decision-makers in determining whether their trial has accumulated sufficient data for their various goals. 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 »