PSI Respiratory One Day Meeting

VENUE Roche Products Limited 6 Falcon Way Shire Park Welwyn Garden City Al7 1TW

PSI One Day Meeting: The Innovative, Challenging and Diversified World of Respiratory Disease

During this one day meeting, PSI aims to cover a wide range of respiratory diseases and design considerations when working in this therapeutic area. We hope that sharing between different areas; will stimulate interesting discussion and an opportunity to knowledge share.

Respiratory diseases, where we are and where we want to be in clinical science and medicines development: unmet needs, challenges and opportunities

Abstract: A brief overview of respiratory diseases, with a more detailed characteristics of selected indications (focusing on asthma, COPD and IPF) will be given at the start of the presentation. An overview of unmet needs and challenges in overcoming them, both from the clinical and the medicines development points of view, will follow. Some of the challenges are disease specific while some of them are relevant across indications, if not beyond the area of respiratory, which will be reflected in the talk. An overview of "where we are and where we want to be" for the discussed indications, and respiratory medicine, will follow.   

Janusz Kaminski (Roche)

Associate Group Clinical Director, Product Development Immunology, Infectious Diseases and Ophthalmology (PD I2O), Welwyn Garden City. Janusz is a physician with approximately 20 years of professional experience spanning careers in academia, clinical medicine and pharmaceutical industry.

Statistical input into improving data quality: the impact on respiratory endpoints in a COPD trial

Abstract: Large, global late phase studies often involve huge amounts of data of varying quality. Data frequently needs cleaning up prior to locking the database, a responsibility typically lying with data management. The ability to look at multiple extracts of data while the study is ongoing and blinded has enabled us to develop novel methods for increasing the confidence in data quality.

In COPD trials, outcomes such as rate of decline of FEV1 can be heavily influenced by outliers. Looking at these in a visual way emphasises the importance of ensuring that these outliers are genuine data points. Similarly, when rates of respiratory tract exacerbations are an endpoint, recording duplicate or overlapping events will alter results. Prior to this work clinicians would spend time looking through vast amounts of data. This talk will present a variety of Patient Profile review tools that has made clinical review a quick and easy process stressing the importance of these data on our endpoints. We attempt to assess the value of statistical input on the data management processes.

Nick Cowans (Veramed)

Nick has been working as a Statistician at Veramed since September 2013, where he has been primarily involved in a large Phase IIIb clinical trial. During this time he has developed his skills in R and SAS programming as well as his knowledge in the respiratory therapeutic area. Nick has 9 years’ experience as a research assistant within a group focused on developments in prenatal screening.  During this time he developed strong statistical skills to build upon his biochemistry and pharmacology background.  He was able to acquire experience and expertise in statistical analysis, report writing and communication of data through published papers and presentations at conferences and meetings. Nick holds an MSc in Statistics (University of Sheffield), an MSc in Pharmacology (Kings College London) and a BSc in Biochemistry (Imperial College London).

Abigail Fuller (Veramed)

Since November 2012, Abby has been working as a Statistician at Veramed, where she has been primarily involved in a large, global Phase IIIb clinical study. During this time she has developed her skills in SAS programming, applying statistical methods, RAP writing and study management, as well as her knowledge in the respiratory therapeutic area. She gained an interest in the industry after completing a placement year working at Amgen in Oncology and went on to study an MSc in Statistics with Applications in Medicine (University of Southampton) after completing her BSc in Mathematics and its Applications (Cardiff University). She is a SAS Certified Base Programmer (SAS Institute)

CDISC Asthma Therapeutic Area Data Standards User Guide - Yes, it is interesting!

Abstract: CDISC has developed industry-wide data standards enabling the harmonization of clinical data and streamlining research processes from protocol (study plan) through analysis and reporting. In December 2013, the Therapeutic Area Data Standards User Guide (TAUG) for Asthma was released in order to improve standardization of Asthma studies. The TAUG describes the most common data needed for asthma studies, so that those handling the data (e.g., data managers, statisticians, programmers) understand the data and can apply standards appropriately. Descriptions include the clinical situations from which the data arise and the reasons these data are relevant for asthma. The TAUG also strives to define research concepts unambiguously, so that consistent terminology can be used in asthma studies to enable aggregation and comparison of data across studies and drug programs.

This presentation provides an overview of the information that exists within the standard along with a couple of specific examples, with the objective being to show that the data standards work produced by CDISC should be of interest and of use to study statisticians working within the asthma therapeutic area.

Paul Terrill

Paul Terrill is a Consultant Statistician working for CROS NT, an international Contract Research Organization specialized in clinical data services. Paul started his career working as a statistician in the agrochemical industry at Jealott’s Hill, Berkshire before becoming a statistical trainer for SAS. He moved into the pharmaceutical industry in 2005 and primarily provides support to biotech and small pharmaceutical companies who lack in-house statistical expertise. In addition to providing advice on study design,  analysis and interpretation he is involved in a team responsible for developing and governing standards that apply to clinical trial datasets. 

Paul holds a BSc in Applied Mathematics and Statistics from the University of Wales, Aberystwyth and a PhD in Statistics from the University of Kent, Canterbury

Reflections on the methodological issues associated with the CHMP guideline on the evaluation of medicinal products for treatment of bacterial infections (CPMP/EWP/558/95 rev 2)

Abstract: This talk will focus on the methodological issues associated with the bacterial infections guideline. In particular the design of non-inferiority studies including defining an appropriate non-inferiority margin. Also alternative study designs that might be used when it is not feasible to conduct at least one adequately powered randomised controlled clinical trial will be discussed

Dr David Wright (MHRA)

Dr David Wright has worked at the MHRA for 15 years and is an Expert Statistical Assessor and Deputy Manager of the Statistics and Pharmacokinetics Unit. He coordinated MHRA scientific advice for over 5 years and is now the Chair of the review committee that approves advice letters. He is the chair of the CHMP  Biostatistics Working Party . David writes assessment reports on methodological aspects of licensing applications for CHM and CHMP, advises companies on methodological aspects of their clinical development programme via national and CHMP scientific advice, and is involved in writing methodological guidelines for CHMP. Before joining the MHRA David was a Lecturer in Medical Statistics at University College London.

Clinical trial design and analyses considerations for the clinical development of a molecularly target agent (AZD9291) for patients with advanced NSCLC

Abstract: Non-Small Cell Lung Cancer is estimated to be the most common cause of death from cancer worldwide. Molecularly targeted agents are an important area of clinical research for the development of therapies appropriate to treat these patients. AZD9291 is a highly selected molecularly targeted therapy which is currently in clinical development. The talk will cover the design of the clinical programme for AZD9291 to meet the specific area of unmet medical in this field, focusing on phase II studies with registration intent and including the analyses considerations for the evaluation of clinical benefit in this setting

Rachael Lawrance (AZ)

I am currently a Principal Statistician at AstraZeneca leading sta AZD9291 which is in late-stage clinical development in advanced NSCLC. I have worked on the design and the analyses of studies with registration intent for a molecularly targeted indication (EGFR T790M resistance mutation). I have worked various oncology and respiratory projects in different stages of clinical development (including IRESSA for treatment of NSCLC, and a phase II programme in rheumatoid arthritis). Prior to working in clinical development I worked as a statistical geneticist on various projects, including Symbicort (COPD)

Respiratory Device Development and the PBE method

Abstract: The development of a respiratory device is a challenging and dynamic process.  In-vitro assessments are typically performed within the Pharmaceutical arena to evaluate the impact of device changes during development.   Regulatory bodies recommend a number of statistical tests to assess such changes, including the population bioequivalence (PBE) method.  The purpose of this talk is to give a brief overview of the development of a respiratory device, and to share some of the recent statistical debates ongoing about the PBE method.

Misbah Ahmed (GSK)

Misbah Ahmed is a statistician at GlaxoSmithKline, currently based in Stevenage.  She joined GSK in 2009 after completing her MSc in Statistics at UCL.  She has spent the majority of her career at GSK supporting the CMC (Chemistry, Manufacturing and Control) aspects of regulatory dossiers within the Respiratory therapeutic area, including inhaled products recently launched by GSK.  She now supports early phase clinical trials, currently working on proof of concept studies in COPD, focusing on the statistical modelling of novel correlated endpoints measured through imaging techniques.

Clinical Development Challenges in Idiopathic Pulmonary Fibrosis

Abstract: Idiopathic Pulmonary Fibrosis (IPF) is a severe, debilitating disease with a prognosis worse than most forms of cancer. Despite recently approved therapies an unmet need still exists. Development of clinical study designs in the rapidly changing landscape of IPF has been dynamic in the extreme.  Switching between monotherapy and combination treatments, from very early readouts on PD markers to futility interims on "halfway" endpoints, from positive risk taking via borrowing data to old school conservatism, an IPF statistician's life is...interesting.  By discussing the disease related considerations and design challenges, we aim to give a picture of the evolving treatment paradigm for IPF

Andy Kenwright (Roche)

Andy has been a statistician in the industry for 22 years, starting in pre-clinical and moving through the CRO world to become head of stats at two small CROs in Norfolk & Newcastle where he dabbled in medical writing and PK analysis also. He joined Roche in 2008. Since then he has helped bring treatment to children with unmet need in severe forms of rheumatoid arthritis and become a specialist in pediatric clinical development. He has taken the lead on clinical development programs in osteo and rheumatoid arthritidies, pulmonary fibrosis and influenza at Roche and is too busy with work and children to have interesting hobbies anymore

Statistical Analysis in the UBIOPRED Consortium

Abstract: U-BIOPRED (Ubiased BIOmarkers in PREDiction of respiratory disease outcomes) is a research project using information and samples from adults and children, to learn about different types of asthma and to ensure better diagnosis and treatment for each person. 

A consortium of pharmaceutical companies, biotechnology companies, hospitals and universities, drawn from Europe and North America, joined forces in this Innovative Medicines Initiative.  There were a total of 1025 study participants, representing the spectrum of health to severe asthma, across all ages.  Detailed health-assessment and questionnaire data were gathered, together with blood, sputum, urine and lung-biopsy samples, with the aim of stratifying the disease and obtaining predictive biomarkers.  Aruna will discuss some of the key statistical issues encountered in this endeavour, and describe how they were addressed.

Aruna

Aruna has an MSc in statistics and a PhD in biostatistics.  She started her career working as a lecturer in the USA, before returning to the UK to work in biotech, then the pharmaceutical industry.  She now works as a consultant biostatistician, and her many roles include that of Chief Statistician for the UBIOPRED Consortium.