Cytel Blog

Bjoern Bornkamp, Statistical Methodologist at Novartis and Jose Pinheiro, Senior Director, Johnson & Johnson provided their insights on adaptive designs for dose finding in Cytel’s latest webinar. Finding the right dose in Phase 2 gives a potential new therapy its best chance to demonstrate efficacy during Phase 3. A well-executed dose-ranging trial therefore has the potential to alter the course of the entire clinical development program. This webinar demonstrates how adaptive and Bayesian techniques can be implemented for optimal dose-finding.

This two-part blog series will provide a summary of the webinar. In this first part, get key highlights from the presentation by Jose Pinheiro on the need to conduct dose finding Phase 2 studies, dose selection comparisons and the use of MCP-Mod for dose finding. Click the button to access the webinar recording and download the presentation slides

Cytel’s Biostatistics and Statistical Programming team provides integrated solutions, by blending the expertise of programming and experience of statistics. Being a notable Functional Services Provider (FSP) in the industry, we take pride in supporting our clients as they navigate the intricacies of 21st century drug development. As our FSP division continues to grow, we are looking to hire programmers and biostatisticians. Cytel's recruitment and FSP teams are hosting a one hour long Virtual Careers Open Day on Thursday, September 10th at 11:00AM EDT. Join us to learn more about our expanding FSP team, open career opportunities and what it means to be part of Cytel. Click on the button to register for the virtual event.

While there is increasing optimism about the discovery of a COVID-19 vaccine, one of the less talked about aspects of such vaccines development are the lessons that can be used in other therapeutic areas. After all, COVID-19 vaccines development has uncovered numerous ways to design and execute trials within shorter time-frames and with less data.

One theme that has emerged consistently is the need to optimize the use of clinical information available, an endeavor well-supported by Bayesian methods.

Recently a biotech approached Cytel for support with a Phase 2 Study in oncology. Regulators had requested a natural history of disease study, which tracks disease progression in the absence of any form intervention. These studies are used to build disease-models that can then inform a range of development opportunities within a drug development program.

A March 2019 FDA Guidance highlighted the importance of such studies for rare diseases, with former FDA Director Scott Gottlieb acknowledging that a lack of knowledge about the natural history of certain diseases is a significant obstacle in rare disease drug development.

Cytel is conducting two pilot projects on head-to-head comparisons using real world data. These projects in oncology and cardiovascular will occur in real time and will take place across our latest webinar series on the topic. The aim of this series is to introduce our audience to head to head to comparison using Real World Data (RWD) while focusing on practical application and results from the pilot projects.

The second webinar from this series was held on July 28, 2020 and outlines the design of the cardiovascular pilot investigation. None of the existing randomized trials of recently developed second-line antihyperglycemic agents can provide adequate information on their comparative effectiveness and safety regarding cardiovascular outcomes. Conducting Target Trials to get information of interest would be costly, difficult to perform, and would take many years to complete. As a result, we need to use observational databases to emulate it. This blog provides a brief on the design of the cardiovascular pilot project. Our team of experts also discussed the data requirements and the data source to be used in the pilot investigation, with the primary challenge focusing on how to assess if data are sufficient for the purposes of trial emulation. Continue reading the blog for a summary of the webinar.

Get access to the webinar recording and download the slides by clicking the button.

Last year, Paul Terrill, Associate Principal of Strategic Consulting at Cytel, presented an engaging webinar on the topic of Estimands. The webinar covered a range of issues from what is an estimand to how to structure early discussions on estimands. On popular demand, Paul will re-run this webinar on August 13, 2020, and add recent developments on this topic. He will share the bottom-line on estimands and discuss their implications for a trial's objectives, design, data collection, statistical analyses and conclusions. Paul will also share his guidance on managing the communication about estimands between multiple internal stakeholders, gaining internal buy-in, and ensuring that a trial’s objectives, design, conduct, analysis and interpretation are in line with the addendum. Register today by clicking on the button.

Continue reading this blog to understand the concept of Estimands, their role in clinical trials and the purpose of the final ICH E9(R1) addendum.

A new peer-reviewed article co-authored by several Cytel scientists re-examines the way in which adaptive trials are designed and implemented within the oncology space. The wide ranging paper spans numerous topics including data considerations, statistical considerations, the commercial and scientific value of flexibility in adaptive designs, and also a “Holistic Approach” to program development, wherein development plans are not created study by study, but across phases.

CDISC standards have been around for a while with the first SDTM Standard version released in 2004. However, it was only in the last decade that it became “The Standard”, particularly when Health Authorities (HA), such as the US FDA and Japanese PMDA, made it a requirement for data submissions to support most of the regulatory requests for market approval. Additionally, most of the Pharma companies made the CDISC standards a part of their operational data model and consequently, the number of studies using the CDISC standards increased across phases of development.

The benefit of receiving data in standard formats was soon recognized by HA reviewers as they now require lesser time to understand the structure of the data they receive. Integration of data provided by different sponsors, for example on the same indication, for better understanding of safety signals, has become possible with data submitted in standard CDISC format.

However, the HAs such as the US FDA, soon realized that this was not enough, for two main reasons:

1. sponsors sometimes make bad or different interpretations of the standard
2. lack of standards or use cases in specific disease areas or indication

The first issue has been addressed by a number of specific HA conformance technical guidance ^[1,2] and regular public webinars where the HAs presented to the Industry real examples of bad standards implementations ^[3]. For the second issue, it was soon clear that the gap to be fixed was bigger and required more investment and resources. The CDISC Therapeutic Area User Guidance (TAUGs) are an “attempt” to fill this gap and reduce interpretation, and misinterpretation, of the standards ^[4].

Cytel is conducting a webinar series on complex innovative trial designs. Dr. Thomas Burnett, Senior Research Associate in Medical and Pharmaceutical Statistics at Lancaster University, joined us as the presenter in the latest webinar from this series. In this webinar, “Adaptive Enrichment Designs in Clinical Development”, Dr. Burnett provides us a brief introduction to population enrichment and explains where it fits in clinical trials. He offers his insights on the topics of hypothesis testing and decision making, which is a key component of adaptive designs. You can also learn about a real-world case study (TAPPAS Trial) where this approach was used. Continue reading this blog for highlights from the webinar.

Watch the webinar recording and download the slides by clicking the button.

Read an interview with Dr. Thomas Burnett on adaptive enrichment.