• Webinar: MCP-Mod – Theory, Implementation and Extensions

    Dates: 08 – 08 May, 2019

    Cytel sponsored webinar in association with PSI

    Time: 14:00 - 15:30 UK time

    MCP-Mod (Multiple Comparisons & Modelling) is a popular statistical methodology for model-based design and analysis of dose finding studies. This webinar will describe the theory behind MCP-Mod (plus extensions), and how to implement it within available software. Pantelis Vlachos (Cytel) will provide a brief introduction to the methodology and illustrate the MCP-MoD capabilities in EAST 6.5. Saswati Saha (Inserm, Aix-Marseille University) will discuss new variations and alternatives to MCP-Mod and show how to implement them in R. Neal Thomas (Pfizer) will present further technical details of MCP-Mod by evaluating the method using results from least squares linear model theory.

    Abstracts


    Pantelis Vlachos
    Pantelis Vlachos
    (Cytel Inc.) 

     

    MCP-Mod in East®:  Early development dose-finding design and analysis

    Selection of a dose (or doses) to carry into a confirmatory phase III study is among the most difficult decisions in drug development. A prerequisite for informed decision making and dose selection at the end of phase II is a solid characterization of the dose-response relationship(s).The MCP-Mod method combines principles of multiple comparisons with modelling techniques to provide an efficient alternative to traditional dose-finding studies which are either designed and analyzed based on multiple comparisons of active doses vs placebo within an ANOVA framework, of assume a functional relationship between response and dose according to a certain parametric model. We illustrate MCP-Mod design and analysis capabilities with East®.   

     

    Bio: 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.

     
    Neal Thomas
    Neal Thomas 
    (Pfizer Inc.)
     

    Understanding MCP-Mod dose finding as a method based on linear regression

    MCP-MOD  is a testing and model selection approach utilizing contrast-based test statistics and p-values adjusted for multiple comparisons. The MCP-Mod procedure can be alternatively represented as a method based on simple linear regression, where 'simple' refers to the inclusion of an intercept and a single predictor variable, which is a transformation of dose. It is shown that the contrasts are equal to least squares linear regression slope estimates. The test for each contrast is the usual t-statistic for a null slope parameter, except that a variance estimate with fewer degrees of freedom is used in the standard error. Selecting  the model corresponding to the most significant contrast p-value is equivalent to selecting the predictor variable yielding the smallest residual sum of squares. Many of the properties of MCP-Mod procedure can be understood and quantified using results from least squares linear model theory.

    Bio: Neal received a PhD in Statistics from the University of Chicago.  He is the  leader of the Statistical Research and Innovation center at  Pfizer working on clinical and non-clinical applications in several therapeutic areas. Previous work experience includes sample surveys, educational statistics (ETS), and health policy applications.  Statistical research interests include design of observational studies, dose response, missing data methods, matrix sampling, psychometric models, and Bayesian statistics.

     

    Saswati Saha
    Saswati Saha
    (Inserm, Aix-Marseille University)

     

    Model based dose-finding methods in Phase II clinical trials

    The primary objective of this presentation is to discuss dose-finding methods in Phase II clinical trials that can simultaneously establish the dose-response relationship and identify the right dose. MCP‐Mod is one of the pioneer approaches developed within the last 10 years. Though MCP-Mod is identified as an efficient statistical methodology for model-based design and analysis of Phase II dose finding studies under model uncertainty, a major disadvantage of MCP-Mod is that the parameter values of the candidate models need to be pre-specified a priori for the PoC testing step. This may lead to loss in power and unreliable model selection. Off late several new variations and alternatives to MCP-Mod are explored where the parameter values need not be pre-specified in the PoC testing step and can be estimated after the model selection step. We will briefly introduce four such state-of-art dose-finding methods, show how to implement the methods in R software and present a numerical comparison between the different new methods and the MCP-Mod approach.

    Bio: Saswati completed her Ph.D as a part of IDEAS network on December 2018 from the Competence Center for Clinical Trials (KKSB) at University of Bremen under the supervision of Professor Werner Brannath. Her primary areas of research during her PhD were dose response modelling, multiple testing, drug combination studies, dose finding and confidence interval estimation for target doses in drug development.

    Saswati studied at the Indian Statistical Institute, where she completed her Bachelor’s degree (2011) and Master’s degree (2013) in Statistics. After her masters she worked on credit risk modelling in two renowned financial institutions, Ernst & Young and Genpact, for two years and dealt with time series modelling for stress testing and logistic regression modelling for building scorecards.



    Please click here to download the details.

    Registration

    This webinar is free to attend. Please click here to register.

  • PSI Journal Club: PhD Webinar

    Dates: 15 – 15 May, 2019
    Time: 16:00 - 17:00


    Our next journal club is the inaugural PhD webinar, where we will share 4 topics with you from 4 PhD students. Our format will be slightly changed, with each student presenting for 10 minutes, followed by 5 minutes of discussion. 

    Our discussants are formed from the PSI Committee:

  • Alexander Schacht (theeffectivestatistician.com)
  • Priya Gokani (Amgen)
  • Jack Elkes (Imperial University Clinical Trials Unit)
  •  
    SPEAKER: Orlagh Carroll (London School of Hygiene and Tropical Medicine) 
    Topic: How are missing data handled in observational time-to-event studies? A systematic review.

    SPEAKER: Maximilan Pilz (Heidelberg University)
    Topic: Optimal adaptive two-stage designs for normally distributed outcomes

    SPEAKER: Stella Prerussler (Heidelberg University)
    Topic: Optimal sample size allocation and go/no-go decision rules for phase II/III programs where several phase III trials are performed

    SPEAKER: Matthew Smith (London School of Hygiene and Tropical Medicine)
    Topic: Investigating the inequalities in survival of non-Hodgkin lymphoma: results from a non-parametric approach

    To download the flyer please click here.

    To register please click here.

    In preparation and prior to the day of the webinar, please follow the link above to obtain your personal dial in details and register with the webinar software. After registering via this link, you will receive a confirmation email containing information about joining the webinar, including details on how to dial-in via the telephone. Please allow enough time before joining to download the correct software.
  • Estimands and Sensitivity Analysis in Clinical Trials

    Dates: 22 – 23 May, 2019

    Presented by Rob Hemmings, Frank Petavy, Christine Fletcher, Frank Bretz

    • Rob Hemmings is a partner at Consilium Salmonson and Hemmings. He was formally the manager of the statisticians and pharmacokineticists at MHRA; a member of the EMA’s CHMP and chair of the EMA’s SAWP. 
    • Frank Pétavy is Head of Biostatistics and Methodology Support at the European Medicines Agency. He contributes to the provision of scientific advice for drug development and the assessment of marketing authorisation applications across therapeutic areas.
    • Chrissie Fletcher is the Global Therapeutic Head of Biostatistics for Cardiovascular, Metabolic, Neuroscience, Bone, Inflammation and Nephrology, the European Regional Biostatistics Head and leads an HTA Biostatistics group at Amgen.
    • Frank Bretz is Global Head of the Statistical Methodology and Consulting group at Novartis. He has supported the methodological development in various areas of drug development, including dose-finding, multiple comparisons, and adaptive designs.
    All of the speakers are members of the ICH Expert Working Group on this topic.

    About the course: 

    Defining the primary objective of a clinical trial in a precise way to reflect the presence of non-compliance or non-adherence to treatment is crucial for the choice of design, the choice of statistical analysis and the interpretation of the results. This raises the need for a structured framework to specify the primary estimand (i.e. "what is to be estimated"). This is also reflected by the decision of the International Council on Harmonization (ICH) to amend its E9 guidance by discussing estimands and their role in clinical trials. The draft ICH E9 addendum on estimands and sensitivity analysis was released back in July 2017 and is being finalised while considering more than 1000 comments. All stakeholders are gaining the necessary experience and familiarity with estimands along with the associated challenges and methodologies. In this course we provide an in-depth review of the estimand framework as laid out by the draft ICH E9 addendum and present case studies illustrating the implementation of this framework in clinical trials.
     

    The following topics will be covered:

    • Introduction and motivation for the ICH E9 addendum
      - Understanding treatment effects 
      - Scope of the addendum to ICH E9
      - Motivating examples
      - Introduce a generic example to be a thread along the training course
    • A framework to align planning, design, conduct, analysis and interpretation
      - A new framework for clinical trials
      - Alignment between trial objective, design, planning, conduct, analysis and interpretation
      - Implications on design and conduct of clinical trials and in the performance of statistical analyses
      - How this framework can improve discussions between sponsors and regulators on the suitability of designs and the interpretation of results
    • Description, strategies and construction of estimands
      - Attributes that together describe an estimand
      - Strategies for addressing intercurrent events
      - General considerations for the construction of estimands
      - Therapeutic and experimental considerations for the construction of estimands
    • Generic example and case studies (Part 1)
      - Generic example to illustrate the thinking process that aligns estimands and sensitivity analyses with trial objectives 
      - Case studies in specific disease settings: envisage a variety of options at the end of Day 1 and reconvene in the morning of Day 2 to select the preferred option(s)
    • Impact on trial design and conduct
      - Implications on design and conduct of clinical trials and in the performance of statistical analyses
      - Identification of estimand(s) at the design stage requires informed discussion with all stakeholders
      - Certain estimands may require or benefit from non-standard designs and/or endpoints
    • Impact on trial analysis with focus on sensitivity analysis
      - Role and choice of sensitivity analysis and supplementary analysis in light of the estimand framework
      - Main estimation, sensitivity analysis, role and choice of sensitivity analysis, supplementary analysis
    • Documenting estimands and sensitivity analysis
      - Impact of the addendum on protocol writing, study design, data analysis and interpretation
      - Incorporating estimands in the writing of a trial protocol and statistical analysis plan
      - Potential impact of the ICH E9 addendum on study conduct, data analysis and interpretation
    • Generic example and case studies (Part 2)
      - Use examples to review the impact of using the estimand framework on study design and data collection; on the choice of estimation methods and sensitivity analysis 
     Course runs from: 10:00 – 17:30 (registration from 9:30) on Day 1 
                                      09:00 – 16:30 on Day 2.

     

    Registration

     
    Early Bird (Up To & Including 24th April)  After 24th April
    PSI Member £495 + VAT £595 + VAT
    Non-Member £570 + VAT (This includes PSI membership for 2019) £670 + VAT (This includes PSI membership for 2019)

    Please click here to register.

    Registration costs include lunch and refreshments. PSI are holding a limited number of hotel rooms on 21st and 22nd May which will be allocated on a first come first served basis. Please contact psi@mci-group.com to reserve a room. Rooms are charged at £109.00 inc VAT per room including breakfast.
  • PSI Conference 2019

    Dates: 02 – 05 Jun, 2019

    PSI are pleased to announce that the countdown to the 2019 Conference has begun! The theme for the conference is “Data Driven Decision Making in Medical Research”.  The 2019 PSI Conference will take place at the Queen Elizabeth II Centre (QEII), London, from 2nd to 5th June 2019.

    Registration will open in November 2018, with the early bird deadline for registrations on the 20th March 2019.

    The conference will consist of a variety of plenary and parallel sessions, as well as breakout discussion sessions, workshops, a poster session and the Annual General Meeting. Please note that the conference will run over three full days from Monday to Wednesday, with an optional half day training course on the  Sunday afternoon (can booked during registration at an additional cost). 

    Sessions will include early phase innovative trial design, industry best practice - 10 years on, statistical issues in safety drug labelling, model based dose finding designs, an update from Transcelerate and much more, with speakers from industry, academia and regulatory agencies.  A draft agenda will be released later this year.

    Abstract submissions for the 2019 Conference are now open! We welcome abstracts on any subject but are interested in the following topics; decision making, bayesian topics within early or late phase, causal inference, future trends, pre-clinical statistics, patient reported outcomes, and patient-centric data. To view the full list of topics and for information on how to submit an abstract, click here

    Finally, sponsorship and exhibition opportunities are already ongoing. Thank you to those who have already signed up. We will be allocating exhibition spaces in the order in which exhibitors sign-up, so get in early to secure the best spot!

    Should your company be interested in the sponsorship opportunities available, please contact Alex Currie (alexander.8.currie@gsk.com) or Chris Watton (chris@wattonhall.com).

    We hope you will join us in building on the huge success of this year’s event in Amsterdam, to make the 2019 Conference in London an even greater event!

    Kate Taylor

    PSI Conference Chair

    For more information on the conference, please click here.

  • Statistical Issues in Regulatory Submissions: Learning from the MHRA experience.

    Dates: 10 Jun, 2019

    Based on the MHRA experience from hundreds of scientific advice meetings with industry and contributions to CHMP scientific advice, this one-day course will provide valuable insights to the most talked about methodological challenges facing applicants. The course will cover key statistical aspects that need to be considered for successful trial design across clinical development.

    The course is suitable for:

    • Statisticians working in clinical trials in industry and academia
    • Clinicians and clinical trials staff who wish to expand their knowledge on the key statistical concepts that impact licensing

    Registration fees: £575 + VAT

    Further details and registration here:  https://mhrastatistics.co.uk/home  

    Engage in the conversation #MHRAStats


  • PSI Toxicology SIG Webinar "Pig-A Assay":

    Dates: 18 – 18 Jun, 2019

    18 June 2019 14:00-15:00

    The in vivo Pig-a gene mutation assay is based on the endogenous X-linked Pig-a gene (phosphatidylinositol N-acetylglucosaminyltransferase, subunit A).

    The Pig-a gene codes for an N-acetyl glucosamine transferase that is involved in the biosynthesis of Glycosyl phosphatidyl inositol (GPI) anchor for tethering a variety of mammalian cell surface protein markers. A single mutation in the Pig-a gene results in loss of the GPI anchor and the GPI-tethered protein markers and can be detected by fluorescent antibodies against the surface markers and flow cytometric analysis to quantify marker deficient cells.

    The Pig-a assay has been evaluated internationally and the data generated to date indicate that it is sensitive, robust and has high reproducibility and transferability. With this in mind, Working Groups of the International Workshop on Genotoxicity Testing (IWGT) and HESI Genetic Toxicology Technical Committee (GTTC) have been working towards the development of an OECD testing guideline for performing the Pig-a assay in rodents, which will allow the Pig-a assay to be used for regulatory assessments in drug development.

    Current guidance for the assessment of DNA reactive (mutagenic) impurities in pharmaceuticals (ICH M7(R1)) has already suggested the use of the Pig-a assay to investigate the in vivo relevance of in vitro mutagens (Ames positive).

    This webinar is free to attend, to register please click here.

  • Introduction to Bayesian Statistics

    Dates: 25 – 26 Jun, 2019

    Presented by: Ros Walley, Foteini Strimenopoulou & Phyllis Smetana

     
    At the end of the course attendees will:
    • Understand the motivation for Bayesian designs and the meaning of the Bayesian terminology including the differences between the frequentist and Bayesian methods 
    • Learn the basics of constructing a prior distribution
      Know the impact of priors on the results and how to summarise the posterior distribution
    • Understand how Bayes methods can be used to improve decision making.
    • Know some of the practical aspects (including software choices) of Bayesian design implementation.
    The course will focus on the practical implementation of the background and practicalities of Bayesian design, analysis and reporting and will not go into deep statistical methodology or software coding. Examples and practical exercises are used throughout to aid understanding and interaction. References will be to give the attendee links to the statistical formulae and other reading.

    Although not essential, it would be useful for attendees to bring a laptop with either SAS or R installed, so that they can join in with the practical workshops rather than just watch.

    The following topics will be covered:

    • Informative vs Vague Priors
    • Construction of Priors
    • Documentation of Priors
    • Posteriors
    • Credible Intervals
    • Prior-data conflict
    • Decision rules
    • Simulation and MCMC
    • Checks for convergence
    • Types of software to run Bayesian analyses
     
    Course runs from: 10:00 – 17:30 (registration from 9:30) on Day 1 and 
                                     09:00 – 16:45 on Day 2.
    Click here to download the flyer.

    Registration

      Early Bird (Up To & Including 24th May)   After 24th May
    PSI Member  £495 + VAT £595 + VAT
    Non-Member £590 + VAT (This includes PSI membership for 2019) £690 +  VAT (This includes PSI membership for 2019)
    Click here to register.
  • Introduction To Industry Training Course 2019

    Dates: 01 Oct, 2019

    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!


    NEXT COURSE STARTS OCTOBER 2019,
    Final dates to be confirmed

    PSI Member: £1,050 + VAT
    Non-Member: £1,145 + 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.

     PLEASE CLICK HERE TO VIEW THE FLYER

    CLICK HERE TO DOWNLOAD THE APPLICATION FORM

    For further information contact:

    Alex Godwood & Zelie Bailes

    Sosei Heptares 
    Steinmetz Building
    Granta Park
    Cambridge 
    CB21 6DG
    United Kingdom

     

       Email: Alex.Godwood@SoseiHeptares.com ; zelie.a.bailes@gsk.com