Speaker

Biography

Abstract

Andrew Thomson (European Medicines Agency)

Andrew Thomson is a statistician at the EMA Taskforce dedicated to Data, Analytics and Methodology, joining the Agency in 2014. He supports the methodological aspects of the assessments of Marketing Authorisation Applications, as well as Scientific Advice, and methodological aspects of Paediatric Investigational Plans. Additionally he is the EC lead for ICH E11A where he leads the statistical workstream. Prior to the EMA, he worked at the UK regulator, the Medicines and Healthcare product Regulatory Agency. Here he worked initially as a statistical assessor in the Licensing Division, assessing Marketing Application Authorisations and providing Scientific Advice to companies. After rising to Senior Statistical Assessor, he moved to the Vigilance and Risk Management of Medicines Division, to be Head of Epidemiology. Here he managed a team of statisticians, epidemiologists and data analysts providing support to the assessment of post-licensing observational studies and meta-analyses. He also managed the team’s design, conduct and analysis of epidemiology studies, using the UK Clinical Practice Research Datalink

Extrapolation – an EU Regulatory Methodological Perspective

In this presentation I will give an overview of the EMA Reflection paper on Extrapolation, focusing on the options available to developers and the role of statistics (and statisticians!) building the extrapolation concept and plan. The opportunities for using Bayesian and frequentist analyses will be discussed, and illustrated with a case study

Ros Walley 
(UCB)

Ros Walley studied at Cambridge University for her degree and post-graduate qualification and has worked in Pharma for 25 years. She has supported a wide range of pre-clinical, early and late-phase clinical and biomarker areas. Since 2017 she has been part of the UCB Centre for Excellence in Statistical Innovation and is now on short-term secondment to lead Training and Development within the department. She has a particular focus on Bayesian statistics but more generally is interested in any statistical methodology that will facilitate clear decision-marking.

The Challenge of Implementing Bayesian Methods in Paediatric Studies: Our Experience at UCB (joint work with Foteini Strimenopoulou)

Bayesian methods are increasing used in the pharmaceutical industry. Using an informative prior for placebo is commonplace in proof of concept studies. Bayesian methodology has been developed for the paediatric setting. And yet to-date there appear to be very few completed regulatory Bayesian paediatric studies. This is intriguing when we consider that for some rare diseases, single arm trials are acceptable, and in the paediatric setting, “full extrapolation” (i.e. not carrying out a paediatric efficacy study) is sometimes acceptable. Both of these scenarios might be viewed as Bayesian positions, with extremely strong priors on placebo and the paediatric treatment effect respectively.

In this talk we present some of the challenges we have faced at UCB when implementing these methods and give epilepsy and immunology examples. We will focus on how Bayesian methodology fits with the concept of extrapolation as described in regulatory guidance, how historical data has been selected to construct informative priors when there are different sources of available information, the difficulty of estimating study-to-study variation and how the impact of using informative priors has been assessed.

Aurélie Gautier 
(Novartis)

Aurélie Gautier has a background in biostatistical methodology, computational modelling and data visualization techniques. For the last 15 years she has been with Novartis pharmaceuticals within the department of Pharmacometrics, and has rapidly gained an understanding and expertise in the use of statistical methodology and quantitative modelling for problem solving during drug development. With a particular interest in the application of quantitative models to frame, evaluate and deliver decision making analysis she has applied these to key areas of drug development process including pre-clinical to clinical translation, dose finding, competitor evaluation and patent extension through sub-group analysis. A key motivation for Aurelie is the use quantitative models together with competitor data as a method for accelerating drug development decisions and in particular the use novel data visualization techniques as a key tool for framing questions for development teams. Aurélie has worked widely across many therapeutic areas, and is currently working in the cardiovascular and respiratory fields.

Successful use of FULL extrapolation approach: Xolair pediatric approval in China for allergic asthma

Omalizumab, a recombinant humanized anti-IgE antibody that inhibits the activity of IgE, demonstrated efficacy and safety in various ethnicities as add-on therapy in patients with moderate-to-severe allergic asthma and has been approved for more than 15 years.As of 2017 Omalizumab was approved in the US/EU and Japan in patients age⩾6years. Omalizumab was also the first biologic approved for asthma patients ⩾12 years in China in 2017. To fulfill an unmet medical need in the asthmatic pediatric Chinese population (ages 6 to <12), a submission containing data from the global and pediatric programs was submission to the NMPA. This submission followed the recommendation of the NMPA “Technical Guidance for the Extrapolation of Drug Data in Adults to Pediatric Populations”,there was no supporting clinical trial data in Chinese pediatric patients.

PKPD extrapolation was used to provide evidence of: 1) a lack of ethnic sensitivity and 2) that the Omalizumab target dosing regimen would achieve an average serum free IgE of 25 ng/mL in the pediatric Chinese asthmatic population. This level has been showed to be associated with clinical improvement in allergic asthma with the particular usage of Omalizumab based on extensive clinical trials. However, there has been no other clinical evidence so far indicating such relationship exists with other anti-IgE antibodies, causes like some difference in epitope binding are explored. Thus, it should be stressed that such extrapolation cannot be generalized beyond Omalizumab. This work, although specific to omalizumab,provided a great example in a context of an emerging use of extrapolation in the development of medicines for pediatrics.

Juan J Abellan (GlaxoSmithKline)

Juan is a statistician by training, by experience and by passion. He studied Maths and Stats and did his PhD at the University of Valencia (Spain), and worked as a research fellow at Imperial College London. He has worked as a statistician in Public Offices, Academia and Industry in Spain, Germany and the UK. He's currently a Statistics Director at the GSK Advance Biostatistics and Data Analytics Centre of Excellence, based in London. One of his current main interests include the use of Bayesian thinking to gain efficiencies in drug development, including methods for evidence synthesis and extrapolation in the development of new medicines for paediatric populations.

Extrapolating information from adult to paediatrics: a case study in systemic lupus erythematosus (joint work with Nicky Best)

The development of medicines for paediatric population presents several ethical and practical concerns. When the paediatric development of a new drug starts, there is already valuable information from the development of the same drug in adults, which can be used to support the limited evidence that can be obtained in children. To this end, several statistical methods have been proposed in the literature to formally include relevant evidence from adults in the analysis and decision-making for paediatric studies. Of those, the Robust Mixture Prior approach (Schmidli et al, 2014) seems to be gaining acceptance. Here we present a case study where such approach was successfully used to partially extrapolate evidence of efficacy from adults to paediatrics to support regulatory approval of a paediatric indication expansion for an approved adult treatment for systemic lupus erythematosus.

Robert “Skip” Nelson (Johnson & Johnson)

Robert “Skip” Nelson, M.D., M.Div. Ph.D. is currently Senior Director, Pediatric Drug Development in the Child Health Innovation Leadership Department (CHILD) at Johnson & Johnson. In addition, he serves as the Pediatric Development Team Leader, Immunology Therapeutic Area, Janssen Pharmaceutical Companies of Johnson & Johnson. In this role, Dr. Nelson leads the pediatric clinical development of medicines for immune mediated diseases.

Before joining Johnson & Johnson in January 2018, Dr. Nelson was Deputy Director and Senior Pediatric Ethicist in the Office of Pediatric Therapeutics at the U.S. Food and Drug Administration, consulting throughout FDA on clinical and ethical issues arising in the development of FDA-regulated products for children and serving as a standing member of the internal FDA Pediatric Review Committee. Dr. Nelson was a member and then Chair of the FDA Pediatric Advisory Committee prior to joining FDA in 2006.