Cytel Blog

Cytel has recently revealed its Advanced Design Framework, a method developed by Cytel’s thought-leaders after a decade of fine-tuning clinical development processes. The framework consists of three parts: Thoroughly Explore, Decide Together, and Communicate Trade-Offs.

The Framework demonstrates how to unify statistics and strategy in the era of cloud-computing, by making strategic use of well-resourced statisticians. This week, we take a deeper look into the first part of this Framework, revealing how to explore hundreds of thousands of designs available to sponsors, rapidly and in real-time, to improve the chances of identifying the design that optimizes for speed, success, and savings.

For over a decade, advanced trial design techniques have promised efficient trials with accelerated timelines, reflecting the ability to quantify uncertainty and de-risk trials using adaptive tools. Despite the emergence of these complex innovative designs, the success of Phase 3 trials has continued to hover at 33% while the average time to market remains about 6 years.

Even before the era of COVID-19, significant attention was channeled to the overwhelming potential of adaptive MAMS designs. Short for multi-arm multi-stage designs, these trials enable numerous therapies to be tested on a single platform with a single comparator arm. When patients are too few or there are several therapies in competition with each other to enroll, adaptive MAMS designs expedite the discovery of new drugs.

Methods involving Group Sequential Designs is one of the earliest deviations from a traditional two-arm clinical trial with no interim looks at the data. They add incredible value to trials through their abilities to safeguard patients, reach positive conclusions early and keep trial designs simple and streamlined.

Sequential trials also help reduce costs and the number of patients involved, but finding a positive conclusion earlier is quite important too. In the drug development process, where patent lifetime is limited, reaching a decision six months or a year earlier is a big advantage. Sample Size Re-estimation is another key tool in the modern trial designer’s toolkit that proves to be useful. Continue reading this blog to learn how to use these methods and understand how they can improve trial design.

Cytel has recently designed and implemented the TOGETHER Trials, funded by the Bill & Melinda Gates Foundation to generate knowledge to help fight COVID-19, particularly in low and middle-income countries. The trials, with sites in Brazil and South Africa, test three existing interventions as possible treatments for COVID-19 in high-risk adults who do not require hospitalization, compared to a placebo.

The TOGETHER trials use an adaptive platform design. This type of design is particularly useful for contexts such as COVID-19 response, where there are many unknowns and a need for accelerated and resource-efficient answers, for 5 reasons.

Cytel has designed and implemented a novel adaptive platform trial for early stage COVID-19. The severity of the coronavirus emerges in five stages, with the majority of clinical trials focusing on therapies for the final stage of the disease. According to the Cytel Clinical Trial Tracker, only 6 of 2000 trials are focused on early stages; staggering given that only 5% of coronavirus cases are considered severe.

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.

A recent Cytel panel led by Vice President of Strategic Consulting Natalia Muhlemann evaluated the role that Bayesian methods played in development of a COVID-19 vaccine. The wide-ranging discussion covered the structure and utility of platform trials and the role of master protocols in infectious disease vaccines development, but also addressed the importance of adaptive Bayesian methods in the search for COVID-19 therapies.

Cytel is conducting a webinar series that introduces biostatisticians to some of the more commonly used complex innovative trial designs. Our second webinar from this series was held on June 3, 2020, with Professor Christopher Jennison. Professor Jennison spoke about the modern uses of Group Sequential Designs and Sample Size Re-estimation. Group Sequential Designs were one of the earliest deviations from a traditional two-arm clinical trial with no interim looks at the data. They still add amazing value to trials through their abilities to safeguard patients, reach positive conclusions early and keep trial designs simple and streamlined. Sample Size Re-estimation is another key tool in the modern trial designer’s toolkit.

Cytel also did an interview with Professor Jennison where he spoke to us about these methods, their origin and how they add value to the industry. Continue reading this blog for a summary of the webinar. Click on the button below to access the webinar replay and download the presentation slides.