Cytel Blog

A 2018 publication in the  Biometrical Journal by Cytel’s Cyrus Mehta, Lingyun Liu and Sam Hsiao, ‘Optimal Promising Zone Designs’ (1) marks a new milestone for adaptive sample size re-estimation. Inspired by insights from the team's work with a number of Cytel's strategic consulting clients, it presents an easy to implement and new iteration of the popular promising zone design. The basic principle? That any investment of sample size at an interim analysis should be contingent on a minimal acceptable return on the investment. This return is expressed in terms of guaranteed conditional power, By identifying a minimum rate of return upfront, the new design offers greater efficiency to clinical trial planners. Importantly, the design concept is both easy to communicate, and easily understood among statistical and clinical stakeholders alike.
In this blog, Cytel Co-Founder and Fellow of the American Statistical Association, Cyrus Mehta shares his insights with us on the goals and key takeaways of the publication, and how it adds to the growing toolkit of intuitive adaptive designs available to drug developers today. We also share full access to the publication itself.

Happy New Year! As we look ahead to future successes and the new advancements in drug development that 2019 will bring, we are taking a moment to reflect on the topics that resonated most with our community on the Cytel blog in 2018. While these 6 most popular blogs encompass a variety of topics from across the data science, statistics, and statistical programming space, they all have in common a focus on innovative practices and application of statistical, data management, and data science excellence to achieve better outcomes in drug development.

Cytel biostatisticians Cyrus Mehta and Lingyun Liu, together with Charles Theuer, CEO of TRACON Pharmaceuticals have recently co-authored a publication in the journal Annals of Oncology: “ An Adaptive Population Enrichment Phase 3 Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients with Advanced Angiosarcoma (TAPPAS Trial)”. The paper explores the features of this innovative population enrichment, adaptive sample size re-estimation trial and how it overcomes some fundamental challenges of clinical development in ultra-orphan oncology indications. The publication is timely, in the context of the August 2018 news that the FDA has launched a complex and innovative designs pilot program to facilitate and advance the use of complex adaptive, Bayesian, and other novel clinical trial designs in late-stage drug development. The initiative seeks to further innovation by allowing the FDA to publicly discuss those trial designs that are being considered through the pilot program. Indeed, the TAPPAS trial incorporated regulatory input from both the FDA and EMA and received a Special Protocol Assessment from the FDA. As of the date of publication, the authors were not aware of any other pivotal population enrichment trial that has been implemented in oncology, and therefore the paper’s deconstruction of the design’s key elements will be invaluable to researchers considering similar innovative approaches.

On August 29th 2018, the FDA announced (1) that it would be establishing a Complex Innovative Trial Design (CID) Pilot Meeting Program. This follows the release earlier in August of a draft guidance (2) to help advance effective and innovative clinical trial designs early in drug development that can expedite new cancer therapies.

At Cytel we believe that expert statistical input has the power to shape the future of clinical development: de-risking portfolios, accelerating timelines, and increasing the probability of success.

In this blog we talk to Benjamin who lives in France, to find out more about his career path, achievements, current role at Cytel and his interests outside of work. 

We extend our congratulations to Lipopharma and the CLINGLIO project consortium on their recent 6,15M€ grant award by the European Union’s Horizon 2020 program. Led by Lipopharma, the multinational consortium brings together 12 academic and industry organizations from Europe, Israel, and the USA.

A recent publication in Biometrics ‘A Gatekeeping Procedure to Test a Primary and a Secondary Endpoint in a Group Sequential Design with Multiple Interim Looks’ greatly extends the results of Glimm et al. ( 2010) and Tamhane et al ( 2010) which studied the problem of testing a primary and secondary endpoint, subject to a gatekeeping constraint, using a group sequential design (GSD) with K = 2 looks. This extends the methodology to provide for multiple (K>2) looks. The methodology is applied to the data from the RALES study (Pitt et al., 1999; Wittes et al., 2001).

In 2011, Cytel organized its first East User Group Meeting (EUGM) in Paris. Since then, we have held an EUGM almost every year, alternating between locations in Europe and North America.  These meetings have been a great success, giving opportunities for customers and industry colleagues to meet each other as well as with key opinion leaders, whilst learning more about our East software and providing critical feedback. 

This year, the EUGM was held in Cambridge MA on the 25th and 26th of October. In this blog we are delighted to share the slides from some of the speakers' presentations. 

We continue our case study series with this example of a Phase 3 design that uses Bayesian decision making combined with frequentist final analysis.

Clinical Development Background

Our biopharmaceutical client’s lead drug candidate is a late clinical-stage cancer immunotherapy for treatment of a rare oncology indication.  Clinical development of therapies in this indication faces inherent challenges of patient recruitment and scarcity of data.

Sponsor Challenge

The sponsor had previously conducted a randomized, double-blind, placebo-controlled Phase 2 study. Moving into a confirmatory clinical trial setting, they came to Cytel for support with a trial design to address their key questions: