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11 September 2024

Many cancer trials use the progression free survival as primary outcome measure, i.e. the length of time that a patient lives on without worsening of the disease. Various reasons can lead to censoring of the data. And differential censoring could influence the interpretation of the results. Paolo Eusebi presents visualisations that help to explore the pattern of events and reasons for censoring. Visualisations are available on the Wonderful Wednesday blog.

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Many cancer trials use the progression free survival as primary outcome measure, i.e. the length of time that a patient lives on without worsening of the disease. Various reasons can lead to censoring of the data. And differential censoring could influence the interpretation of the results. Paolo Eusebi presents visualisations that help to explore the pattern of events and reasons for censoring. Visualisations are available on the Wonderful Wednesday blog.

The basic plot for progression free survival is the survival plot using Kaplan-Meier estimates. Augmented with information on censoring this gives a great overview. An innovative way of displaying events and censoring is by stacked lollipop plot. See the panel discussing pros and cons. The next challenge is about visualising dose response in subgroups for personalized dosing. See the Wonderful Wednesday homepage for more detail.

Wonderful Wednesdays are brought to you by the Visualisation SIG. The Wonderful Wednesday team includes: Bodo Kirsch, Zachary Skrivanek, Lorenz Uhlmann, Steve Mallett, Rhys Warham, Mark Baillie, Paolo Eusebi, Martin Brown, Benjamin Lang

14 August 2024

The development of a new patient reported outcome (PRO) needs to include the interpretation of the results. It should be possible to define a minimal clinically important difference and a meaningful between-group difference. Rhys Warham is presenting ways how visualisations can support that process. They are available on the Wonderful Wednesday blog.

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The development of a new patient reported outcome (PRO) needs to include the interpretation of the results. It should be possible to define a minimal clinically important difference and a meaningful between-group difference. Rhys Warham is presenting ways how visualisations can support that process. They are available on the Wonderful Wednesday blog.

For comparing the new PRO with the gold standard eCDF plots and PDF plots can be shown overlapping or stacked. There are also many different ways to show the distribution of within the standard ratings to easily spot differences or possible inconsistencies. The next challenge is on the event pattern in a study aiming for improvement on progression free survival. See the Wonderful Wednesday homepage for more detail.

Wonderful Wednesdays are brought to you by the Visualisation SIG. The Wonderful Wednesday team includes: Bodo Kirsch, Zachary Skrivanek, Lorenz Uhlmann, Steve Mallett, Rhys Warham, Mark Baillie, Paolo Eusebi, Martin Brown, Benjamin Lang


07 August 2024

This webinar will help listeners gain a broader understanding of a recent and rapidly advancing core area of pharmaceutical drug development. The content will be broad, but will focus on clinical design and analysis strategies for advanced therapeutics such as cell/gene therapies, and strategic options to advance candidate drugs in this space.

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Avery McIntosh (Pfizer) and Oleksandr Sverdlov (Novartis)

This webinar will help listeners gain a broader understanding of a recent and rapidly advancing core area of pharmaceutical drug development. The content will be broad, but will focus on clinical design and analysis strategies for advanced therapeutics such as cell/gene therapies, and strategic options to advance candidate drugs in this space.

One of the recent advances in 21st century medicine is the emergence of gene therapies, drugs that affect the basic biology of genetic disease. The field has seen some notable setbacks in the past, but in recent years has exploded as decades of basic science have been successfully translated into the most complex biologics ever constructed, leading to regulatory approval of several gene therapy products in oncology, hematology, neurology, and ophthalmology indications. These drugs are at the apex of biological manufacturing complexity, and have the potential to be disease modifying or even curative. Evidence-based and innovative quantitative clinical development and lifecycle management strategies will be required as fixtures in the development for these unique drugs in order to reach patients in need. In this webinar we provide an overview of the history and future of gene therapies, and discuss the crucial role of the statistician in the drug development process of these drugs, with a focus on innovative trial design and analysis techniques.

A list of useful references from the presentation can be found below:
- McIntosh, Avery, and Oleksandr Sverdlov, eds. Development of Gene Therapies: Strategic, Scientific, Regulatory, and Access Considerations. CRC Press, 2024.
- Rohde, Maximilian, et al. "Practical and Statistical Considerations for the Long Term Follow‐Up of Gene Therapy Trial Participants." Clinical Pharmacology & Therapeutics 115.1 (2024): 139-146.
- McIntosh, Avery, et al. "Clinical design and analysis strategies for the development of gene therapies: considerations for quantitative drug development in the age of genetic medicine." Clinical Pharmacology & Therapeutics 110.5 (2021): 1207-1215.
- Mueller, Arne, et al. "Digital endpoints for self‐administered home‐based functional assessment in pediatric Friedreich’s ataxia." Annals of Clinical and Translational Neurology 8.9 (2021): 1845-1856.
- Hudry, Eloise, and Luk H. Vandenberghe. "Therapeutic AAV gene transfer to the nervous system: a clinical reality." Neuron 101.5 (2019): 839-862.
- Cox, Gerald F. "The art and science of choosing efficacy endpoints for rare disease clinical trials." American Journal of Medical Genetics Part A 176.4 (2018): 759-772

10 July 2024

This webinar follows up on last month's challenge on platform trial design. This time the impact of specific design changes is highlighted with effective visualisations. Bodo Kirsch is presenting examples for exploratory and explanatory visualisations. They are available on the Wonderful Wednesday blog.

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This webinar follows up on last month's challenge on platform trial design. This time the impact of specific design changes is highlighted with effective visualisations. Bodo Kirsch is presenting examples for exploratory and explanatory visualisations. They are available on the Wonderful Wednesday blog.

Exploring a huge variety of possible scenarios can be tedious. Exploratory visualisations can improve that process dramatically by using interactive parameter setting. That's what the two shiny apps of today's webinar do. Once an effect has been explored an explanatory visualisation is a powerful tool to communicate this. The next challenge is about responder definition. See the Wonderful Wednesday homepage for more detail.


Wonderful Wednesdays are brought to you by the Visualisation SIG. The Wonderful Wednesday team includes: Bodo Kirsch, Zachary Skrivanek, Lorenz Uhlmann, Steve Mallett, Rhys Warham, Mark Baillie, Paolo Eusebi, Martin Brown, Benjamin Lang.


02 July 2024

We will review how the Graduate study team interpreted the estimand framework and used its elements to cover the primary clinical question of interest. We will review the challenges we met and the solutions we implemented.

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Rachid Abbas, Angeliki Thanaspoulou, Marcel Wolbers

GRADUATE I(NCT03444870) and GRADUATE II (NCT03443973) were two global, Phase III, randomized, placebo-controlled trials assessing the efficacy and safety of gantenerumab in early Alzheimer’s disease. The GRADUATE studies were among the first pivotal trials in Alzheimer’s Disease to adopt the estimand framework and to conduct a primary analysis which is fully aligned with the targeted estimand. In this webinar we will review the key elements of the estimand framework through the experience of the Graduate study team. We will review how the Graduate study team interpreted the estimand framework and used its elements to cover the primary clinical question of interest. We will review the challenges we met and the solutions we implemented.

12 June 2024

How can visualisations help better understandtrial design? Steve Mallet is explaining some ideas based on simulations for a platform trial. The visualisations are available on the Wonderful Wednesday blog.

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How can visualisations help better understandtrial design? Steve Mallet is explaining some ideas based on simulations for a platform trial. The visualisations are available on the Wonderful Wednesday blog.

Visualisations can give a quick overview over a vast amount of design options. This can be achieved with facet plots, with interactive plots allowing to switch between the options, or even combing facets with interactivity as show in a shiny app. Also the use of different colours and line types can increase the number of displayed scenarios. For the next challenge we will look at the same data aiming to visualise three very specific aspects. See the Wonderful Wednesday homepage for more detail.

Wonderful Wednesdays are brought to you by the Visualisation SIG. The Wonderful Wednesday team includes: Bodo Kirsch, Zachary Skrivanek, Lorenz Uhlmann, Steve Mallett, Rhys Warham, Mark Baillie, Paolo Eusebi, Martin Brown


06 June 2024

We will share a brief overview of what Mobilise D is and why it is an important step stone in the development of digital biomarkers, and how Mobilise D outputs can be relevant for you. Regulatory and Analytical experts will share the overview of their involvement and their insights when working with Mobilise D consortium

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Daniel Rooks, Igor Knezevic, Wim Dartee, Arne Mueller, Julia Chernova

We will share a brief overview of what Mobilise D is and why it is an important step stone in the development of digital biomarkers, and how Mobilise D outputs can be relevant for you. Regulatory and Analytical experts will share the overview of their involvement and their insights when working with Mobilise D consortium.

29 May 2024

This webinar starts with providing an overview of surrogacy for licensing and reimbursement. This articulates the need of extensions of the SPIRIT and CONSORT statement related to surrogacy...

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Oriana Ciani (SDA Bocconi School of Management), Rod Taylor (University of Glasgow; University of South Denmark), Anthony Manyara (Bristol university; University of Glasgow), Ray Harris (Retired), Mario Ouwens (AstraZeneca).

This webinar starts with providing an overview of surrogacy for licensing and reimbursement. This articulates the need of extensions of the SPIRIT and CONSORT statement related to surrogacy. Both the process to define the extensions as well as the extensions themselves are then presented. The importance of right communication of the interpretation of surrogate outcomes to patients is articulated by a patient representative. Finally, it is shown by results from a simulation study that maturity influences the probability of success of surrogacy validation, among other factors like variation in estimated treatment effects.

15 May 2024

The event will open with an overview on drug development in women’s health from a clinician perspective. This talk is followed by talks about analysing the menstrual cycles, a novel mathematical approach to designing IVF needles and statistical challenges when planning IVF studies.

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Elizabeth Garner (Ferring Pharmaceuticals US), Christoph Gerlinger (Bayer), Radu Cimpeanu (University of Warwick), Jack Wilkinson (Manchester University).

This multidisciplinary webinar will cover the latest insights in women's health. Clinicians, applied mathematicians and statisticians will provide valuable perspectives on current challenges and opportunities in the field covering recent developments in women’s health drug development, statistical complexities of in vitro fertilization (IVF) and insights into the statistical considerations surround the menstrual cycle and menstrual bleeding measurements. 
● Opening on drug development in women’s health - Elizabeth Garner (Ferring Pharmaceuticals US)
● Menstrual cycle and Measurement of menstrual bleeding - Christoph Gerlinger (Bayer AG)
● A new flow-based design for double-lumen needles in IVF - Radu Cimpeanu (University of Warwick)
● Challenges in RCTs of in vitro fertilisation : an estimands perspective - Jack Wilkinson (Manchester University).

The event will open with an overview on drug development in women’s health from a clinician perspective. This talk is followed by talks about analysing the menstrual cycles, a novel mathematical approach to designing IVF needles and statistical challenges when planning IVF studies.

08 May 2024

In almost every study there is a flow chart to present the patient's path through the trial. What could the next level of study flow charts look like? Zak Skrivanek is presenting some new ideas. And the visualisations are available on the Wonderful Wednesday blog.

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In almost every study there is a flow chart to present the patient's path through the trial. What could the next level of study flow charts look like? Zak Skrivanek is presenting some new ideas. And the visualisations are available on the Wonderful Wednesday blog.

Sandard study flow charts are basically organised lookup tables. A true visualisation can do much more. For example colour coding or indenting boxes can help organising. Also additional information can be embedded. This can easily done in R. For patient disposition Sankey diagrams can be extremely useful. This is even more powerful if used interactively. People charts even go without explanation. See the Wonderful Wednesday homepage for more detail.

Wonderful Wednesdays are brought to you by the Visualisation SIG. The Wonderful Wednesday team includes: Bodo Kirsch, Zachary Skrivanek, Lorenz Uhlmann, Steve Mallett, Rhys Warham, Mark Baillie, Paolo Eusebi, Martin Karpefors


25 April 2024

This webinar will explore two different approaches to Correlates of Protection in vaccine development. Statistical models providing a quantitative framework for identification and validation of potential CoPs, and mechanistic models aiming to understand the biological mechanisms driving immune responses and protection.

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Dr. Erin Gabriel and Dr. Melanie Prague.

This webinar will explore two different approaches to Correlates of Protection in vaccine development. Statistical models providing a quantitative framework for identification and validation of potential CoPs, and mechanistic models aiming to understand the biological mechanisms driving immune responses and protection. By integrating these two approaches, researchers can gain better insights into the immunological factors associated with vaccine efficacy and infection protection. This webinar will include talks from two renowned speakers who will discuss the principles, applications, and challenges of both statistical and mechanistic models, contributing to a better understanding of CoPs and optimizing vaccine clinical trial design.

17 April 2024

Talks from the speakers will cover the use of R in a programming community, submitted to regulators using R, and also programming beyond R in C++ and Julia.

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Matthew Lyon, Ari Siggaard Knoph, Daniel Sabanes-Bove

Talks from the speakers will cover the use of R in a programming community, submitted to regulators using R, and also programming beyond R in C++ and Julia.

Slides
You can download Matthew's slides and Ari's slides from the 'documents' section below, and you can access Daniel's slides here.
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