Greetings from 1st EFSPI regulatory workshop T. Huttunen SSL spring meeting 20.4.2017

Contents -EFSPI regulatory statistics workshop in Basel September 12-13, 2016 ” Our first Statistical Workshop will be dedicated to opportunities and challenges of statistical topics between regulators, academics and industry with dedicated time for interaction and discussion” - Short summary of the topics - 2nd workshop and other forthcoming events 6.12.2018

Background Regulatory statistics, what it means? Requirements for a submission of new drug Can the drug be approved? Who should use and how? What is the right price? The entire program need to be designed so that these hurdles can be surpassed At least, the statistician should be aware of these steps Interaction between multiple stakeholders

Workshop 5 different sessions 1) Estimands I 2) Estimands II 3) Extrapolation 4) Risk-benefit assessment 5) Statistics in quality and quality attributes

Estimands I Tom Permutt (FDA topic leader E9 R(1)) Frank Petavy (EMA) ”The per protocol principle” ITT = comparison of treatment policy PP = something else, what? Frank Petavy (EMA) ”Estimands one way forward” Mouna Akacha (Novartis) “Are we estimating what we intend to estimate?” Is the effect of the treatment-policy really always of clinical interest? Some solutions, e.g. separation of testing and estimation

Estimands II Ann-Kristin Leuch (BfArM) ”Estimands in pain studies” Kaspar Rufibach, Hans-Ulrich Burger (Roche) ”Estimands and time-to-event endpoints” Good examples on survival analyses Chrissie Fletcher (Amgen) ”Incorporating estimands in a trial protocol” ICH E9(R1) will have implications on how we design clinical trials, write protocols, conduct trials and perform statistical analyses Christoph Gerlinger (Bayer) ” Some Thoughts on Estimands in a Chronic Pain Indication”

Extrapolation Kristina Weber (Hannover medical school) ”On the road to clinical extrapolation” Example on Kidney transplant study Steffen Ballerstedt (Novartis) ”Supporting a Pediatric Investigational Plan in liver transplantation – An example using a pharmacostatistical approach” See also EMA Reflection paper on extrapolation of efficacy and safety in paediatric medicine development

Extrapolation (reflection paper) All existing data should be systematically reviewed to describe the mechanisms and characterize differences between source and target population on the following aspects: Medicine disposition and effects Disease manifestation and progression Clinical response to treatment Key words: source/target, prediction/validation

Benefit-Risk assessment David Wright (AZ, former statistical assessor at MHRA) “Practical Benefit Risk Assessment” Reflections on 16 years and 11 months of assessing licensing applications. How to decide whether or not to recommend a drug is licensed. Benefit risk assessment for decision making. Opportunities for statisticians to improve regulatory decision making. Alexander Schacht (Lilly, EFSPI/PSI benefit-risk SIG) ” What’s going on in benefit-risk and what is our role as a statistician?” The understanding of data – its strengths and limitations –is a core compentency of statisticians. Thus, they need to play a key role in helping others to understand and interpret the efficacy and safety data correctly http://www.benefit-risk-assessment.com/ George Quartey (Genentech) case study

Statistics in Quality Jens Lamertz (Roche) Bruno Boulanger (Arlenda) “The role of statistics in ensuring quality in pharmaceutical manufacturing” Bruno Boulanger (Arlenda) ”Assessment of analytical biosimilarity: the objective, the challenge and the opportunities”

Recap: 1st and 2nd workshop 1st workshop, see the presentations http://www.efspi.org/EFSPI/Events/Annual_Regulatory_Meetings/Past_Meetings Teppo’s cherry picks: Petavy, Fletcher, Wright 2nd workshop October 5-6, 2017 Basel (CH) Registration open SC: Norbert Benda, Egbert Biesheuvel, Hans Ulrich Burger, Christoph Gerlinger, Rantell Khadija, Armin Koch, Franz König, Frank Petavy, Kaspar Rufibach, Ferran Torres, Thomas Yaki and Emmanuel Zuber. Go to see flyer at www.efspi.org

Other forthcoming events See a separate document, list generated by Egbert Biesheuvel (EFSPI council, Chair of Scientific affairs working group)