• 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.

    Registration for this meeting has now closed.

    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

    Statistics for Decision Processes: Transitions between Research and Development Phases - 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.

    Statistics for Decision Processes: Transitions between Research and Development Phases - Richardus Vonk (Bayer)

    The high costs and long duration of clinical development, paired with high levels of attrition, require the quantification of the (un-)certainty when moving from preclinical animal research
    to clinical development. One other, less often observed area of translation is the translation between the different development phases, where through the course of development the focus moves towards the target population. In the management of the transition risks, biomarkers may play an important role.

    Further to the regulatory requirements, statistics and statistical thinking are integral parts of the internal decision making processes, particularly in early clinical development. This presentation offers an overview of the current challenges, and then concentrates on innovative statistical methods that facilitate the transitional efforts. We review the role of Bayesian methodology in this endeavour. We provide examples from the area of biomarker development, early clinical trials and proof of concept situations.

    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.

    Registration for this meeting has now closed.

    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).

  • Personalised Medicine: Statistics for Companion Diagnostics

    Dates: 04 – 04 May, 2017

    PSI Webinar
    Personalised Medicine: Statistics for Companion Diagnostics
    Date for Webinar: Thursday 4th May. 2-3.30pm UK time

    Personalised medicines - which are designed to treat particular groups of patients -  are becoming increasingly prominent. In order to identify patients suitable for treatment a companion diagnostic assay is often needed. The Personalized Medicines Coalition (PMC) recently published an article stating that 25% of NME approved by FDA in 2016 included a companion diagnostic.

    This webinar will introduce and examine some of the considerations required for statisticians working in the field of companion diagnostics and will include information from an FDA (CDRH) speaker and perspectives/ case-studies from representatives from both a pharmaceutical company and a diagnostic company.

    CLICK HERE TO VIEW THE FLYER

    Speakers:

    Meijuan Li, CDRH
    Peter Cooper, Qiagen
    Rachel Hodge, AstraZeneca

    Abstracts:

    Meijuan Li (CDRH)

    Applications of personalized medicine are becoming increasingly prominent. A companion diagnostic assay (CDx) is often desired for patient enrollment in device-drug pivotal clinical trial(s) so that FDA can ensure that appropriate clinical and analytical validation studies are planned and carried out for CDx. However, such a requirement may be difficult or impractical to accomplish. A clinical trial assay (CTA) instead of CDx may be used for patient enrollment in drug-device pivotal clinical trial(s). A supplemental agreement study of CDx and CTA will be required to bridge the clinical results from CTA to CDx. In this webinar, we will discuss statistical challenges in study design and data analysis for bridging study. Particularly, we aimed to provide statistical methods on how to estimate the drug efficacy in CDx intended use population using results from bridging study and CTA-drug pivotal clinical trial.

    Peter Cooper (Qiagen)
    Perspective from Diagnostic Company

     
    Rachel Hodge (Astrazeneca)
    Perspective/Case-study from Pharmaceutical Company

    CLICK HERE TO REGISTER! (Attendance is free)

    iCalendar PLACEHOLDER - PLEASE REGISTER WITH PSI to attend. You will be sent dial-in details for the webinar during the week of the webinar as long as you have registered with PSI first.

    ***Please note that this registration provides PSI with your details in order to register interest for the Webinar (please note there is a limited number of participants so please only register if you plan to attend).

    In the week before the webinar you will be sent another email and you will need to REGISTER AGAIN with the WEBINAR (GoToWebinar) to get your personal dial-in details to attend the webinar.***

  • Expert Working Group on Confidentiality of Interim Results

    Dates: 11 May, 2017

    The confidentiality of interim results of on-going trials is a topic on the agenda of the EMA Biostatistics Working Party (BSWP).  ICH E9 states that all staff at the investigational sites and at sponsor (except those directly involved with the execution of an interim analysis) should remain blinded to any interim analysis results. The BSWP recognised that this advice may need to be re-evaluated, especially for some complex situations (eg the use of interim analyses in Cardiovascular Outcomes Trials to rule out harm or for gene therapy where the full results may not be available for 15 years).

    The BSWP therefore asked the PSI/EFSPI Regulatory Committee to set up a PSI/EFSPI expert working group on this topic and to provide thoughts and recommendations.  The expert working group has been formed under the leadership of Jürgen Hummel (PPD), Erika Daly (ICON) and Robin Mukherjee (Astra Zeneca), and are planning to meet face to face on 11 May with the aim to get back to the BSWP by September 2017.

  • Estimating Sample Sizes in Clinical Trials

    Dates: 28 – 29 Jun, 2017

    How to find us: Novotel, London Excel, UK

    Presented by Steven A. Julious
    Steven is a Professor of Medical Statistics at The University of Sheffield but through his career has worked in both the academic and pharmaceutical sector and is a former editor of the journal Pharmaceutical Statistics.  He has an interest in applied methods for clinical trials and has a particular interest in clinical study design and sample size estimation.  He has written two books one on early phase trials and one on sample size estimation and has also developed an App called SampSize for the estimation of sample sizes.

    About the course:
    The three most important aspects of a clinical trial are: design, design and design.  A sample size estimate is just one aspect of a clinical study design. 

    The course describes calculations for sample size estimation in the design of clinical trials. It will be highlighted how the objectives of a clinical trial will impact on sample size calculations. The course is a practical course and all methods will be illustrated with examples and case studies.


    The following topics will be covered:

    Introduction to Key Concepts
    - Type I error
    - Type II error
    - Power

    Sample Sizes for Different Clinical Trial Objectives
    - Superiority
    - Equivalence
    - Non-inferiority
    - Precision based
    - Bioequivalence
    - Pilot studies

    Sample Sizes for Different Types of Data
    - Normal
    - Binary
    - Ordinal
    - Survival

    Clinical Trial Designs
    - Cross-over
    - Parallel Group

    How Design Considerations Impact on the Sample Size
    - Baselines/covariates
    - Multiple endpoints

    Other Considerations when Designing a Trial
    - Sensitivity analysis
    - Optimising variance estimates

    Considerations which Impact on the Sample Size
    - Adaptive designs for efficacy
    - Assessing futility
    - Sample size-re-estimation

    Course runs from:
    10:00 – 17:30 (registration from 9:30) on Day 1
    09:00 – 16:30 on Day 2.

    Registration costs (includes lunch and refreshments)

    Before 30th May 2017

    PSI Members

    £495 + VAT

    Non-Members

    £570 + VAT (includes PSI membership for 1 year)

     

    After 30th May 2017

    PSI Members

    £595 + VAT

    Non-Members

    £670 + VAT (includes PSI membership for 1 year)

     

    PSI are holding a limited number of hotel rooms at an extra cost until the 30th May 2017 which will be allocated on a first come first served basis.  Please contact the PSI Secretariat for more information.

    CLICK HERE TO REGISTER.

  • 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