Cytel’s 7th East User Group Meeting (EUGM) will take place on November 14 & 15, 2018 at Merck in Darmstadt, Germany, bringing together industry experts, thought leaders and applied statisticians to discuss the future of clinical trials.

The agenda has been developed collaboratively by the EUGM Scientific Committee, and keynote speakers will include Stephen Senn, Meinhard Kieser, Thomas Burnett, Robert Greene and Simon Kirby.

In this blog, we took the opportunity to talk to one of the speakers, Thomas Burnett, Senior Research Associate in Medical and Pharmaceutical Statistics at Lancaster University, about his presentation topic “Bayesian Optimization of Enrichment Designs” and his perspectives on what EUGM delegates will be able to take away from his talk.

Cytel: What sparked your interest in the topic of Bayesian Optimization of Enrichment designs? 

Thomas Burnett (TB): My PhD Thesis “Bayesian Decision Making in Adaptive Clinical Trials” was focused on the optimization of Adaptive Enrichment trials and evaluating their overall performance in comparison to fixed sampling methods, I found it such an interesting topic that it has continued to be part of my work.

 Cytel: Why is this an important topic?

TB: The drive for efficiency in clinical trial design is clear from both a patient and sponsor perspective and enrichment designs can offer that under the right circumstances, however it is also important to understand when and how they may offer a benefit. The Bayesian decision framework not only allows us to optimize the adaptive trials, but also make performance comparisons between competing designs to understand which is most suitable under a given scenario.

Cytel: What can those who hear the talk expect to take away?
TB: I hope the delegates will gain an understanding of how to construct Bayes optimal Adaptive Enrichment trials and insight into when these designs may be helpful to them (or at least knowledge on how to efficiently assess this for a particular trial).

Register today and take advantage of the early bird discount (closes September 30th 2018)

Register for both days and save over 30% - click the button below to review the full agenda and to register.

EUGM Insights

The EUGM offers a unique perspective on clinical trials by combining methodological and practical scientific talks with the ability to gain hands-on training with East software.

Day 1 is the Innovations in Clinical Trials Symposium and this year’s overarching theme is Multiplicity.
This day’s sessions will open with a keynote talk from Stephen Senn “70 Years Old and Still Here”, followed by a range of presentations covering hot topics like: “The Randomized Clinical Trial and its Critics: Selection Bias from Picking Treatments Only with Phase 2 Trials” and “Multiplicity Issues in Decision Making”.

Day 2 is a hands on East training day – participants will benefit from practical training in Cytel's East software, with the unveiling of three new features: Population Enrichment, Program Simulation and MCPMod (Design and Analysis).

References 

1) John Wiley & Sons, Ltd. Statist. Med. 2017, 36 4423–4426

We have written on the blog in the past about the value that a statistical consultant can bring to your team, and to the overall clinical development process. Statistical consultants can be instrumental to the success of your development program, providing a variety of input from creating innovative trial designs that improve information quality and efficiency, to supporting regulatory interactions.

By Gordhan Bagri and Munshi Imran Hossain with  H A S Shri Kishore

Shiny (from RStudio) is one of the most popular R packages. The package allows programmers to create applications with interactive user interfaces. These applications can then be deployed for non-programmers to perform analysis. Non-programmers can, therefore, make use of the statistical capabilities of R by means of point and click. This is one of the reasons why its use has been on the rise in the last few years.

In this blog, we share a new infographic based on this popular blog post illustrating some of the critical interactions that need to take place between data management and statistics groups to help ensure efficiency and data quality. 

At Cytel our strategic consulting team works on a wide range of projects including: Identifying the best clinical trial design, implementing adaptive designs, developing a regulatory strategy and interacting with regulators.

In this blog we talk to Sam who lives in the Boston area, to find out more about his career path, current role at Cytel, industry experience and his interests outside of work.

A recent article published by Cytel authors Samadhan Ghubade, Sharayu Paranjpe, Kushagra Gupta, Anil Gore and colleague Krishna Asvalayan in the journal Current Science, tackles the topic of adverse drug reactions (ADRs) – a matter of great concern in drug research. The authors focused their research on drugs which had been either banned or withdrawn due to a serious problem of ADRs and applied quantitative modeling techniques to see if a systematic pattern of safety signals could be detected within the ADR count data. In this blog, the publication’s authors share their thoughts on the goals, takeaways and next steps for the research and we also link to the full article.

In this blog we share a case study of how we established and ramped up a functional service outsourcing partnership for biostatistics, programming and data management.

 It’s shaping up to be a busy year for Cytel’s software development team with a number of upgrades and planned launches across our range of tools. (Watch this space for announcements soon on new quantitative decision-making software OK GO and an upgrade to EnForeSys). East, our industry leading platform for clinical trial design, simulation, and monitoring will be unveiling version 6.5 in the Fall, and delegates at the PSI conference in early June had the chance to grab a sneak peek of the new functionality in one to one demos.

We’ll also be opening the hood on the new design capabilities you can expect in East 6.5 at a complimentary webinar on Wednesday July 18, 11:00AM - 12:00 US EDT (16:00 UK, 17:00 EU).

Our presenters Pantelis Vlachos and Charles Liu, will introduce the 3 new available modules and share their insights on the supporting methodologies and their practical applications. New developments in the East software are typically derived from two sources: our team’s interaction with our customers, particularly during East training; and from our consulting practice when we help clients design their trials.

The new modules in East 6.5 include:
MCPMod (design with Multiple Comparisons Procedures)

MCPMod allows you to measure the likelihood that particular dose-response curves are the right mathematical model for a given set of data. East MCPMod will allow designing a trial using optimal allocation and then analyze the trial data using various dose/model selection criteria resulting
into a solid base (target dose) for the next phase confirmatory trial.

Population Enrichment (Adaptive designs)

An adaptive enrichment design allows the full population is segmented during interim analyses. Recently, we worked with TRACON Pharmaceuticals to design their TAPPAS trial that incorporated a population enrichment component to help overcome the potential heterogeneity of treatment effect between subpopulations for an angiosarcoma design.

Program-Level Design
It is important to take a strategic approach to clinical development to minimize the potential for Phase 3 attrition. This new module will help users apply simulations to optimize their clinical trial programs.
Click the button below to secure your place at the webinar. 

A number of the Cytel team were in Amsterdam, 3rd- 6th June 2018 for the PSI Conference. This year’s conference was held at the magnificent Beurs Van Berlage, a venue full of history and interesting architectural features. We took the opportunity to give delegates a first look at OK GO, our new clinical trial Go/No-Go decision-making software in this magnificent setting.

In this blog, we'll summarize some of the particular highlights from the sessions that our team members attended.

By Esha Senchaudhuri

With thanks also to Jitendarreddy Seelam and Ramanatha Saralaya for their input.

The fact of the matter is that I now want to recall everything, every trifle, every little detail. I still want to collect my thoughts and - I can't, and now there are these little details, these little details...”
― Fyodor Dostoyevsky, The Meek One

Old Fyodor was hardly talking about clinical trials, but early phase trial sponsors can probably relate to a regulatory environment which requires systematic attention to details, the little details and all these little details. When conducting early phase studies, global regulators require submission of Non -Compartmental Analyses (NCAs) that measure factors such as extent and rate of exposure to a drug, without the complexity of strenuous assumptions or complex models. Through the use of rudimentary methods such as linear trapezoidal rules, NCAs make it relatively easy to measure the concentration of a drug in a body over time. They can capture length of exposure, and time of peak exposure, without the challenges of models that require independent validation [1]. While those other models are also becoming more common in quantitative pharmacometrics, ideally NCAs can complement these other methods.

It may be tempting to assume that due to the ease of measurement, it is unnecessary to invest in statistical expertise and reliable software for NCAs. While the calculations may not be as complex as other forms of pharmacometric modeling, taking shortcuts at this stage can prove problematic later on. 
Widely recognized for being ‘assumption-free’ [1] NCAs are a common subject of regulatory inquiries. Exposure and absorption data is obviously important for early phase trials, so NCAs are required for submission throughout the process. A strong data management system with reliable software can ensure that findings collected at this stage are streamlined across several early phase trials, making such information easy to access and ensuring a rapid response for regulators. Further, NCAs are often required to be submitted with early protocols making it useful to have statistical designers familiar with the NCA findings. As NCAs are an integral part of establishing an early phase audit trail, it is important to use NCA software that streamlines a detailed and complex workflow such as Phoenix WinNonlin. 

Accurate NCAs can combine with other forms of quantitative pharmacometric models like PK/PD analysis to build strong dose-response models for Phase 2. It is common knowledge that unreliable dose-response models in Phase 2 can create headaches for Phase 3 tests. Only 13.2% of Phase 3 trials that are accepted after initial rejection, are rejected on grounds of efficacy. More common reasons are dose selection, choice of endpoints, and other challenges that better Phase 2 modeling can prevent [2]. Working with statistical experts as early as Phase 1 can ensure that knowledge gleaned from NCAs can be employed to build stronger Phase 2 models, thus avoiding Phase 3 pitfalls.

Cytel has a dedicated team that has developed efficiencies and experience in early phase trials, including Non-Compartmental analyses. To learn more about our capabilities in this area, please click on the button below.

[1] Gabrielsson, J. and Weiner, D., 2012. Non-compartmental analysis. In Computational toxicology (pp. 377-389). Humana Press, Totowa, NJ.
[2] Sacks, L.V., Shamsuddin, H.H., Yasinskaya, Y.I., Bouri, K., Lanthier, M.L. and Sherman, R.E., 2014. Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000-2012. Jama, 311(4), pp.378-384.

At the recent PCMG conference in Malta, Adrian Otte ( Independent Consultant, formerly VP Global Development Operations at Amgen) presented to delegates the strategic choices open to sponsors when  choosing an outsourcing model and the three fundamental issues in play: standardization, flexibility and cost. In Dr. Otte's view, standardization of systems and processes is key, but is often overlooked as a factor by companies of all sizes when deciding how to outsource clinical trial activities. In this blog, Dr Otte joins us to share his insights on this topic, as well as this views on how outsourcing has evolved in recent years, and the future trends that will have most impact. 

In this blog, Paul Fardy, Executive Director of Data Management at Cytel shares his thoughts on how the data manager role has evolved. 

Cytel data scientists apply advanced statistical techniques including predictive modelling of biological processes and drug interactions to unlock the potential of big data.

In this blog from our Career Perspectives series, we talk to Andrea Hita, at Data Scientist at Cytel, to find out more about her career path, her current role at Cytel and her interests outside of work.

By Esha Senchaudhuri

An important trend in clinical development involves integrating strategic pharmacometric analysis with program level decision-making, to make the most use of available data. This can occur in various forms, from leveraging preclinical data for go-no-go decision making [1], to the need for improved comparative effectiveness frameworks [2].

Here we have five reasons why you should consider utilizing model-based meta-analyses ( MBMAs)  for your program or portfolio development.

Our Industry Voices series showcases our clients’ innovative work and breakthrough therapeutics in oncologic indications and other critical areas of medical unmet need.

In this article, we sit down with Charles Theuer, M.D., CEO of TRACON Pharmaceuticals to discuss
his work, his views on the key advancements in oncology development, the unmet needs yet to be overcome, and the importance of efficient trial design in rare cancers. Click here to download a .pdf of the article, or read on. 

 At the recent CDISC EU Interchange in Berlin,  Angelo Tinazzi, Director of Clinical Data Standards and Submissions at Cytel, showcased a popular poster presentation analyzing the differences between the Pinnacle 21 enterprise (P21e) and community versions. Those working in the field of data standards, will know that Pinnacle 21 is led by the team that created OpenCDISC, and is now the leader in software and services for managing CDISC compliance and clinical data quality.  The organization continues to offer a community based software tool, in line with the OpenCDISC model, but now offers an enterprise version to sponsors and CROs, that is also used by the FDA itself. 

Our Industry Voices series showcases our clients’ innovative work and breakthrough therapeutics in oncologic indications and other critical areas of medical unmet need.

In this article, we are delighted to share an interview with Kurt Gunter, M.D., Chief Medical Officer of Cell Medica in which he discusses his work, his views on the key advancements in oncology development, the unmet needs yet to be overcome, and the importance of strategic biostatistics input to his organization. Read on, or click here to download a copy of the article to read offline.

As we prepare to head to ASCO in under a month's time, we are pleased to share a new ebook that showcases some key applications of innovative trial designs in the oncology development space.

PSI is a global member organization dedicated to leading and promoting best practice and industry initiatives for statisticians in the biopharmaceutical industry. The PSI annual conference is going from strength to strength, attracting increasing numbers of delegates from Europe and beyond. With the 2018 conference taking place in Amsterdam in only a month’s time, we took the opportunity to sit down with Lucy Rowell, Senior Principal Statistical Scientist at Roche and the Conference Chair, to learn more about this year’s venue, themes, and new hot topics, along with insights on Lucy’s vision for the future of the PSI organization. We look forward to seeing you in The Netherlands! 

Cytel has industry-leading experts in Statistical Programming, our programmers have years of SAS® Programming expertise, combined with in-depth knowledge of the specific clinical subject matter, which allows for competent and on-time completion of tasks.

In this blog, we talk to Omar, who is based in Geneva to find out more about his career path, current role at Cytel and his interests outside of work.