Regulatory Trends: 2018 FDA Adaptive Design Draft Guidance and the Increasing Use of Adaptive Designs in Industry

In September 2018 the FDA released a new draft guidance for adaptive trials and opened it for comments. In essence, the new release brings more clarity on expectations from the FDA for the planning and reporting from adaptive trials, and is part of the effort from the FDA to foster the use of “complex innovative trial designs”. In this presentation we will highlight the main take-outs  from this guidance for adaptive trials in all clinical phases. We will relate it to what is known about who is using adaptive designs and the perceived or actual hurdles in implementing them, and how this guidance may help to increase the appropriate use of adaptive designs wherever they are contributing to a faster and better drug development.

About the speaker

Ursula Garczarek, Ph.D. is Associate Principal, Strategic Consulting at Cytel. She has extensive experience in providing statistical support for clinical and non-clinical aspects of product development within both pharmaceutical and consumer companies.

As a member of Cytel’s Strategic Consulting team, Ursula guides trial sponsors on optimizing their development strategy, and successfully implementing trial design innovations. She applies new and pragmatic methodologies to address the needs and requirements of the sponsor within the regulatory environment.

Before joining Cytel, Ursula was the Program Leader Data Science at Unilever R&D (NL), and Biostatistician at Roche Diagnostics GmBH (DE) developing multi-marker diagnostics based on proteomics and metabonomics approaches. She received her Ph.D. from the University of Dortmund (DE), in the context of a project on Machine Learning and Statistics within a collaborative research center on complexity reduction in high-dimensional data spaces.

Bayesian Borrowing from Historical Data: Case Studies

 In rare diseases where adequate recruitment is problematic, being able to borrow from historical data in a meaningful way can have a huge impact on feasibility. While in the frequentist framework this can be achieved by using matched patient level data from historical studies, in the Bayesian framework, this is achieved using informative priors. This open the door for historical meta data as well. One concern regarding borrowing is Prior-Data conflicts when the distribution of the treatment effect size or of the endpoint of interest do not agree between historical studies and the current studies. We discuss Bayesian adaptive borrowing strategies which control the influence of informative priors on the posterior inference via case studies using Cytel’s centralized tools. These methods can also be useful for medical devices with predicate versions in the market as well as for pediatric studies borrowing from adult studies.

About the Speaker

Rajat Mukherjee is Principal, Strategic Consulting at Cytel. He has more than 20 years of professional experience as an industry and academic statistician, and brings a range of expert knowledge to Cytel’s customers. This includes work in Pattern Recognition problems for devices and biomarker discovery, Bayesian clinical trials, adaptive designs, and design and analysis of complex epidemiological studies.

Predictive Analytics in Healthcare

If we had imagined a brain that could access all medical treatments and their outcomes for known disease in the world plus the capacity to analyze that information and integrate it with a patient's own medical profile - then it is becoming a reality today: artificial learning algorithms working on real world data empower a new kind of predictive analytics with applications from anticipating patients' drug response to hospital readmission rates.

About the Speaker

Sabine Rossbach is a skilled biostatisician and data scientist with a broad range of interests across preclinical and clinical development, including pharmacology, modeling and simulation, missing data handling, Bayesian trial design, real world evidence, advanced big data analytics, and machine learning. Sabine is also an experienced project manager and team leader. 

Sabine joined Cytel after a position at Teva Pharmaceuticals as a developer of disruptive trial designs & Artificial Intelligence applications for pharmacology, first-in-human & bio equivalence studies. Sabine also supported Real World Evidence projects. 

East Hands-on Training

Pantelis will be speaking about existing and new developments in East. The training will cover an overview of Cytel software and East modules, phase 1 dose escalation, phase 2 statistical methodology and dose-response, multiplicity in clinical studies, phase 3 group sequential designs, phase 2/3 multi-arm multi-stage designs, and phase 3 adaptive designs. 

About the Speaker

Pantelis is Director/Strategic Consultant for Cytel, Inc. based in Geneva. He joined the company in January 2013. Before that, he was a Principal Biostatistician at Merck Serono as well as a Professor of Statistics at Carnegie Mellon University  for 12 years. His research interests lie in the area of adaptive designs, mainly from a Bayesian perspective, as well as hierarchical model testing and checking although his secret passion is Text Mining. He has served as Managing Editor of the journal “Bayesian Analysis” as well as  editorial boards of several other journals and online statistical data and software archives.