• Dose Finding in Drug Development using MCP-Mod

    Dates: 01 – 02 Mar, 2017

    presented by

    Frank Bretz & Björn Bornkamp
    Statistical Methodology and Consulting, Novartis Pharma

    including regulatory perspectives from
    Rob Hemmings 
    Statistics and Pharmacokinetics Unit Manager, MHRA, UK 

    This course will introduce and discuss methods for Phase II dose finding studies, including a review of basic multiple comparisons and modelling methods, as traditionally used in these studies. A unified strategy for designing and analysing dose finding trials denoted MCP-Mod, combining multiple comparisons and modelling, will be the focus of the course.
    Click here to see the full event flyer

    CLICK HERE TO REGISTER!


    Day 1

    The first day will provide an overview of dose finding in drug development. The application of multiple comparison procedures (MCP) and modelling approaches (Mod) will then be covered, including a review of contrast tests as well as nonlinear regression methods for dose response and target dose estimation. Then a step-by-step description of MCP-Mod will be provided, including a detailed discussion of its five main steps across the design and analysis stages:

    1. Identification of candidate parametric models, which are likely to represent the underlying dose response shape.
    2. Derivation of optimum contrast coefficients, such that the marginal power to detect a specific dose response shape associated with the respective candidate model is maximized.
    3. Evaluation of the significance of the individual models in terms of a multiple contrast test based on the previously derived optimal contrast coefficients.
    4. Model selection or model averaging, provided statistical significance has been shown in the previous step.
    5. Use the selected model(s) to produce inferences on adequate doses, employing a model-based approach.

    MCP-Mod will first be introduced in its originally published version for a single, normally distributed efficacy endpoint. The extension of this framework will be described for count data and time-to-event endpoints as well as situations involving generalized non-linear models, linear and non-linear mixed effects models, and Cox proportional hazards models. 

    Day 2

    On day two, considerations will be given to practical aspects around the design and analysis of dose finding trials using MCP-Mod. This includes importantly a discussion of its design aspects, in particular sample size derivations. As MCP-Mod is a hybrid procedure, focusing on hypothesis testing and estimation, sample size calculation procedures for both objectives will be presented and their application on the design illustrated with a real dose finding study. A variety of further practical considerations will be discussed that summarizes the collective experience over the past 10 years in using MCP-Mod in Phase II dose finding trials. The application of the DoseFinding R package will be demonstrated in detail, including a description of functions for the design and analysis of dose finding trials using MCP, Mod or MCP-Mod. Hands-on exercises allow the course attendees to the experience the capabilities of the DoseFinding R package and how to use its functions to implement the MCP-Mod methodology. The course ends with a review of regulatory considerations. 

     Speaker About the Speaker 
    Frank Bretz
     

    Frank Bretz joined Novartis in 2004, where he is currently Global Head of the Statistical Methodology and Consulting group. He has supported the methodological development in various areas of drug development, including dose-finding, multiple comparisons, and adaptive designs. He is a co-founding editor of the Springer Series in Pharmaceutical Statistics and the incoming editor of Statistics in Biopharmaceutical Research. He has authored or co-authored more than 120 articles in peer-reviewed journals and four books.

    Björn Bornkamp
    Björn Bornkamp works as a Senior Expert Statistical Methodologist in the Statistical Methodology group at Novartis Pharmaceuticals. He has research and practical experience in the design and analysis of dose-finding studies and the interface of pharmacometrics and statistics. He joined Novartis in 2010 after obtaining a PhD in Statistics from the Dortmund University of Technology in Germany.
    Rob Hemmings Rob Hemmings has been with the Medicines and Healthcare products Regulatory Agency for 16 years and heads the group of medical statisticians and pharmacokineticists.  Much of Rob’s time is spent educating medical colleagues in the importance and artistry of clinical trial statistics; their use in proof and in obfuscation.  Rob is a member of the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) and the chair of the CHMP’s Scientific Advice Working Party.  These positions, and involvement at the Biostatistics Working Party of CHMP and the EMA’s extrapolation and modelling and simulation groups, have presented the opportunity for pursue a particular interest in understanding ‘dose’ and he has been actively involved in recent EMA initiatives in this area.

     

    Agenda
     9.30 - 10.00 Registration
     10.00 - 17.00  Day 1
     9.00 - 16.30  Day 2

     

    Registration
     PSI Members £495 + VAT 
     Non - Members  £570 + VAT (includes PSI membership for 1 year)

    Registration costs includes lunch and refreshments
    PSI are holding a limited number of hotel rooms until the 31st January which will be allocated on a first come first served basis.

    Rob Hemmings
    Rob Hemmings
    CLICK HERE TO REGISTER!

    Please contact the PSI Secretariat on +44 (0) 1730 715 235 or at PSI@mci-group.com for further information.
  • Schools Event 2017: Maths Meets Medicine, Guildford

    Dates: 13 – 13 Mar, 2017

    Time: 10.00 - 14.00

    The Careers and Academic Liaison Committee (CALC) are planning a Schools Event, to be held at two locations during Science, Technology, Engineering and Mathematics (STEM) week next March. Students aged 14-15 will be selected from schools in the regions close to the events to take part in a number of interactive and fun statistics-related workshops, which aim to complement and extend the statistics concepts being taught at KS4 and KS5 levels.  The workshops aim to show the students how statistics is used in industry and other fields, provide some insights into some of the interesting careers that are available using mathematics and statistics, and help them to discover new career options beyond the traditional applications, e.g. finance, research and teaching.

    If you’re local to either location and would like to hear more about this event, please contact us at pharmastatisticsfair@gmail.com, or please click here to view the flyer for the Guildford event.

  • Toxicology SIG Workshop 2017

    Dates: 14 – 15 Mar, 2017

    Click here to register!

    Click here to view the flyer!

    The Toxicology SIG provides a forum for statisticians working in regulatory and investigative toxicology to discuss issues and interact with one another.

    This 1.5-day workshop will involve hopefully approximately 20 statisticians, focusing on discussions around “best practice” in the statistical analysis of various data types.

    Topics to be discussed include:-

    • Repeated measures – in general for all data types (Body weight, activity data, etc)
    • Historical Control Data/outliers/control charts
    • Outlier determination
    • Carcinogenicity studies
      • How to deal with treated groups sacrificed earlier than control
      • Impact on label of running transgenic instead of 2 x 2 year studies
    • How do we empower our scientists to do some routine analyses, whilst also ensuring quality of results?
    Registration Costs
     £236 incl VAT Inclusive of food and one night’s accommodation 

    Click here to register!

  • Schools Event 2017: Maths Meets Medicine, Bath

    Dates: 16 – 16 Mar, 2017

    Time: 10.00 - 14.00

    The Careers and Academic Liaison Committee (CALC) are planning a Schools Event, to be held at two locations during Science, Technology, Engineering and Mathematics (STEM) week next March. Students aged 14-15 will be selected from schools in the regions close to the events to take part in a number of interactive and fun statistics-related workshops, which aim to complement and extend the statistics concepts being taught at KS4 and KS5 levels.  The workshops aim to show the students how statistics is used in industry and other fields, provide some insights into some of the interesting careers that are available using mathematics and statistics, and help them to discover new career options beyond the traditional applications, e.g. finance, research and teaching.

    If you’re local to either location and would like to hear more about this event, please contact us at pharmastatisticsfair@gmail.com.

  • Free PSI Scientific Meeting. Translational Statistics: Ideas-Evidence-Innovation-Communication

    Dates: 30 – 30 Mar, 2017

    Traditionally, Translational medicine aimed to improve the flow from laboratory research through clinical testing and evaluation to standard therapeutic practice. Translational Statistics facilitates the integration of biostatistics within clinical research and enhances communication of research findings in an accurate and accessible manner to diverse audiences.  Statistical analyses has often focused on methodological approaches for the scientific aspects of the studies; translational statistics aims to make the scientific results useful in practice.

    This Scientific Meeting will focus on blurring the hard line between non-clinical and clinical and move to a more iterative discussion and investigates innovative designs in early phases of drug development to increase efficiency of the development process whist also considering reproducibility, relevance, and communication.

    Please click here to register!

    Time Session 
    9.30  Registration & Refreshments
    9.45

    Translational Statistics: Relevance, Reproducibility, and Communication – John Hinde (University of Galway)

    10.30 Translation, a two way street - A Case Study of Event Related Potentials (ERPs) as a Neuroscience Biomarker – Claire Brittain (Lilly)
    11.15 Refreshments 
    11.30

    TBC - Richardus Vonk (Bayer)

    12.15

    Improving Design, Evaluation and Analysis of Early Drug Development Studies (IDEAS) – Thomas Jaki & Haiyan Zheng (University of Lancaster)

    13.00 Lunch
    13.45

    The use of biomarkers in translating from pre-clinical to first in human trials in Immunology – Alun Bedding (Roche)

    14.30 Integrative modelling of experimental medicine clinical data shows that target engagement predicts clinically relevant biological effects – Fabio Rigat (GSK)
    15.15 Design of Drug Development Programs with Biomarkers:  A stratified medicine approach – Paul Frewer (AZ)
    16.00  Wrap-Up (John Hinde)
    16.15  Refreshments and Networking

    Speaker   Abstract
    Translational Statistics: Relevance, Reproducibility, and Communication

    John Hinde

    (University of Galway)

    Translational medicine, often described as “bench to bedside", promotes the convergence of basic and clinical research disciplines. It aims to improve the flow from laboratory research through clinical testing and evaluation to standard therapeutic practice. This transfer of knowledge informs both clinicians and patients of the benefits and risks of therapies.

    In an analogous fashion, we propose the concept of Translational Statistics to facilitate the integration of biostatistics within clinical research and enhance communication of research findings in an accurate and accessible manner to diverse audiences (e.g. policy makers, patients and the media). Much reporting of statistical analyses often focuses on methodological approaches for the scientific aspects of the studies; translational statistics aims to make the scientific results useful in practice.

    In this talk we will consider some general principles for translational statistics that include reproducibility, relevance, and communication. We will also consider how modern web-based computing allows the simple development of interactive dynamic tools for communicating and exploring research findings. Various examples will be used to illustrate these ideas.

    Translation, a two way street - A Case Study of Event Related Potentials (ERPs) as a Neuroscience Biomarker 

    Claire Brittain (Lilly)
    In early clinical drug development, biomarkers capable of providing proof of mechanism are considered critical tools and can help reduce attrition during phase II clinical trials.  However, with neuroscience drugs it’s common to use different measures in rats and humans e.g. Water mazes in rats and ADAS-Cog questionnaires for Alzheimer’s in humans. They are both excellent measures in their own right but translation can be greatly improved if you start by comparing apples with apples.

    This gives us 3 options:

    1.         Ask volunteers to swim in circular tanks looking for a hidden platform

    2.         Teach rats to answer complex questions on their cognitive impairment

    3.         Find a new measure that can used in both species and thus allows us to compare directly

    This presentation will take you through the journey of how we selected our biomarker (Auditory Evoked Related Potentials) and the considerations in designing and analysing the experiments between species. I hope to show what can be achieved if we blur the hard line between non-clinical and clinical and think of it more of an iterative discussion.

    Title TBC - Richardus Vonk (Bayer)

    TBC

    Improving Design, Evaluation and Analysis of Early Drug Development Studies (IDEAS) 

    Thomas Jaki (University of Lancaster)

    Abstract: Drug development is a long and costly process which suffers from the major shortcoming that frequently failure is often only determined during the final stage. Advanced statistical methods for study design, evaluation and analysis, employed already at the early phases of drug development, have a great potential to increase the efficiency of the development process.

    IDEAS is a European training network for 14 early stage researchers working on statistical methods for early drug development. The network is funded by the European Union’s Horizon 2020 research and innovation programme and comprises of 8 full partners and three associated partners at major European universities, the pharmaceutical industry, and consulting companies.

    In this talk we will outline the structure of IDEAS and highlight two specific projects that are focusing on translation between pre-clinical and clinical studies.


    The use of biomarkers in translating from pre-clinical to first in human trials in Immunology – Alun Bedding (Roche)

    Abstract:  In the study of immunology the use of specific biomarkers of the immune system is critical to early develop of compounds to treat auto-immune disorders such as type I diabetes and ulcerative colitis.  Whilst one biomarker may be elevated for a positive response another may also be elevated, which might lead to a safety concern.  It is important to use these understand the dose response of the drug, with respect to these biomarkers, with the hypothesis that they will translate into a clinical effect.

    This talk will discuss how a drug program can be developed in the area to ensure proper understanding of the dose response curve.  This is first done from the translation of pre-clinical discovery into the first time in human study.  The importance of this cannot be underestimated given drugs of this nature have the potential to cause a cytotoxic storm if doses too high.  Thoughts around addressing this will be presented.

    Integrative modelling of experimental medicine clinical data shows that target engagement predicts clinically relevant biological effects – Fabio Rigat (GSK)
    Abstract: Experimental Medicine studies measure multiple dependent parameters in a relatively small number of subjects. This situation, commonly known in Statistics as the “large p, small N” paradigm, calls for the use of multivariate inference to extract robust low-dimensional inferences for data interpretation and to support clinical decision making. This talk demonstrates that quadratic discriminant analysis, a simple and well established multivariate method, can be used in this context to identify a relation between target engagement (TE) of a therapeutic monoclonal antibody and the downstream changes in multiple biomarkers at the site of action. The multivariate distribution of all biomarker changes within each TE class (high or low) is used to estimate the Bayes-optimal allocation of each subject within each TE class. The accuracy of the resulting classification is found to be higher than that resulting from a random allocation, thereby establishing the statistical significance of a relation between TE and the biomarker changes. Leveraging this result, the probability distribution of the most clinically meaningful biomarker is used for planning of a proof of concept (PoC) trial endpoint focussing in on patient transitions across different disease statuses. The marginal transition probabilities showing patients’ improvement during the trial are estimated using a conjugate Bayesian Multinomial classification model.

    Design of Drug Development Programs with Biomarkers:  A stratified medicine approach – Paul Frewer (AZ)

    Abstract: In oncology is it becoming increasing common to have targeted treatments based on a patient’s biomarker status.  The talk will focus on types of designs which could be used in investigating a treatment with this intention.  For example designs allowing assessment of both biomarker positive and negative populations and designs incorporating a number of different investigational medicines targeted at specific patients.  There are advantages and challenges to the designs and we will focus on the statistical considerations to be aware of when developing the clinical plan.

    Numbers are limited to 70 for this free event and therefore registration is a commitment to attend.  Registration includes all refreshments and lunch.

    Click here to register!


    For information regarding the scientific content, contact:
    Rachael Lawrance (rachael.lawrance@rlbiostats.co.uk), Jennifer Gilbride (jennifer.gilbride@sumofsquares.co.uk) or Nick Manamley (Nick.manamley@amgen.com).

  • Introduction To Industry Training Course 2017

    Dates: 01 Oct, 2017 – 31 Jul, 2018

    Are you a PSI member with approx. 1-3 years experience as a Statistician or a Statistical Programmer within the industry?


    THE INTRODUCTION TO INDUSTRY TRAINING COURSE NEEDS YOU!

     PLEASE CLICK HERE TO VIEW THE FLYER

    NEXT COURSE STARTS OCTOBER 2017: £1050+VAT
    AIM: To describe the drug development process from research right through to research, toxicology, data management & role of the CRO, clinical trials, product development & manufacture and marketing.

    Limited places available!

    Application forms must be received by 30th July 2017!

    Please discuss your application with your manager
    Final dates to be confirmed.

    CLICK HERE TO DOWNLOAD THE APPLICATION FORM 

    For further information contact:

    Helen McCafferty

    PPD, Fleming House, Strathclyde Business Park

    Bellshill ML4 3NJ

    Tel: 01698 575334

    Email: helen.mccafferty@ppdi.com