London Area Symposium: Statistical Innovations in Clinical Trials at Amgen (Uxbridge) in collaboration with Cytel.
Speakers are Peter Colman (UCB) Cyrus Mehta (Cytel), James Wason (MRC Biostatistics Unit, Cambridge), Kevin Carroll (kjcstatistics)
To view the slides from this meeting please click here.
London Area Symposium: Statistical Innovations in Clinical Trials at Amgen (Uxbridge) in collaboration with Cytel
Speakers are Peter Colman (UCB) Cyrus Mehta (Cytel), James Wason (MRC Biostatistics Unit, Cambridge), Kevin Carroll (kjcstatistics)
9am Arrival and Coffee
9:30am – 11am : Statistical and Operational Challenges of VALOR, an Adaptive Phase-3 Trial for Acute Myeloid Leukemia. Cyrus Mehta, Cytel Inc.
The recently completed VALOR trial comparing vosaroxin to cytarabine in acute myeloid leukemia (ASH 2014) accrued 711 patients, and comprises the largest body of evidence for AML from a randomized phase 3 clinical trial. This adaptive event driven trial was designed with an interim analysis that allowed for early efficacy stopping, early futility stopping, unblinded sample size re-estimation, or continuation as planned. The sample size re-estimation option was implemented. We will present top-line results from the trial and discuss the operational, regulatory and statistical challenges that were faced along the way. To our knowledge this is the first phase 3 confirmatory oncology trial in which unblinded sample size re-estimation was implemented.
Cyrus Mehta is President and co-founder of Cytel Corporation and Adjunct Professor of Biostatistics, Harvard University. Cytel is a leading provider of software and services for the design, interim monitoring and implementation of adaptive clinical trials. Dr. Mehta consults extensively with the biopharmaceutical industry on group sequential and adaptive design, offers workshops on these topics, and serves on data monitoring and steering committees for trials in many therapeutic areas including oncology, cardiology, neurology and metabolic disease. He has led the development of the StatXact, LogXact and East software packages that are widely used in the biopharmaceutical industry and at academic research centers. He publishes his methodological research in leading statistics journals and is a past co-winner of the George W. Snedecor Award from the American Statistical Association. He is a Fellow of the American Statistical Association and an elected member of the International Statistical Institute. He was named Mosteller Statistician of the Year by the Massachusetts Chapter of the American Statistical Association in 2000, and Outstanding Zoroastrian Entrepreneur by the World Zoroastrian Chamber of Commerce in 2002.
11am-11:15am – Coffee break
11:15am – 12:45am: Innovative Considerations on a Phase 2a Dose-Finding Strategy Using Bayesian Methods and MCP-Mod. James Wason (MRC Biostatistics Unit, Cambridge, UK), Julian Zhou (Roche Products, Shanghai, China)
Early phase clinical trials in patients who are currently on treatments may be difficult to recruit for. Owing to this limited availability of patients they often require the use of smaller numbers of patients and more innovative statistical methods. Often single agents, developed for the same disease of interest are not sufficient and may need be used in combination to be effective. Appropriate decsisions may also have to be made for doses, treatment duration and combinations with other compounds.
The plan for the twelve-week phase 2a study in one such population will involve an early futility look at week 2 based on a biomarker, using Bayesian posterior probabilities. This will be followed by using MCP-Mod at the end of study on a clinical response, in order to investigate the dose response.
At week 2, a biomarker is measured to see if there is a clinically meaningful effect at the target for appropriated doses. If not then new doses may need to be added. The posterior probability of the meaningful effect will be used in the decision criteria.
At the end of the study MCP-Mod will be used in order to investiagate the dose response. MCP-Mod involves pre-specifying candidate dose-reponse models followed by statistical testing for dose-response signal whilst controlling the type I error. The best fitting model is then selected, and the target dose estimated, which is then recommended for phase 2b and phase 3 studies. The method has been qualified by the EMA as an efficient method of dose finding.
Simulations have been conducted to investigate the futility and dose finding decisions in phase 2a and understand the operating characteristics, and comparisons made to a traditional dose finding paradigm, which might involve fewer doses compared to a control using pairwise comparisons.
Dr James Wason is a senior investigator statistician at the MRC Biostatistics unit (BSU) in Cambridge. He has been there since doing his Ph.D. in 2006. Since 2009 he has worked in the BSU’s Hub for Trials Methodology Research, directed by Adrian Mander. His main research interests are adaptive designs for clinical trials, efficient analysis of composite endpoints, and the use of biomarkers in clinical trials. He is also the co-lead of the MRC Hub for Trials Methodology’s stratified medicine working group.
12:45 noon- 1:45pm – Lunch
1:45pm – 3:15pm: Defining, Understanding and Communicating Decision Criteria in Early Clinical Development. Peter Colman (UCB)
It is not uncommon to investigate multiple indicators of potential clinical efficacy in an early study in patients. A broad swathe of biomarkers may be nominated to ensure that evidence of activity on the projected biochemical pathway is acquired and additional biomarkers may indicate the precursors of clinical benefit. Registration endpoints, surrogates thereof or less-qualified biomarkers of efficacy may also be captured. The number of endpoints may easily exceed the number of subjects in the study and so it is vital that the properties of any decisions are well understood and consistently communicated. We discuss one approach which elicits views on the combinations of results that would be considered positive or encouraging and seeks to assess the likely false-positive rates associated with the consequent decision criteria. We illustrate the ideas with some real examples.
Peter spent the first 29 years of his statistical career with Pfizer at their UK research site in Sandwich. During this time he worked in Animal Health, Clinical Pharmacology and Early Clinical Development. He also experienced a phase III project for 6 months. For several years, he led a group of statisticians focussing on PK-PD Modelling & Simulation, Genetics, Clinical Technology and Outcomes Research. He returned to mainstream, hands-on project work and also contributed to a number of European collaborations (e.g. IMI SAFE-T). In 2011, upon closure of the Sandwich site, Peter moved to AZ at Alderley Park, where he worked on safety data and as a manager of statisticians in the oncology and anti-infectives area. He joined the UCB early development statistics team at UCB in 2013 where he contributes to the design of studies in the immunology and neuroscience areas. In his spare time he plays classical double bass and he is currently the chair of Maidstone Orchestral Society.
3:15pm – 3:30pm – Coffee Break
3:30pm – 5pm: Tackling Real Problems in Multi Regional Clinical Trials. Kevin Carroll (KJCStatistics)
MRCTs are an increasingly necessary feature of modern drug development. In areas like diabetes and cardiovascular disorders, or early adjuvant oncologic disease settings, or where there is a regulatory requirement to rule out small, but important safety issues such as in the ongoing cluster of trials investigating long acting beta agonists in the treatment of asthma, the demand for very large trials drives the need for MRCTs. Such trials are needed to provide the power to address the underlying hypothesis of interest, but can only do so under the assumption of no true regional heterogeneity. This talk will address the implications of true regional differences in MRCTs and will illustrate the real statistical and regulatory challenges faced by reference to recent case studies, including the 18,000 patient ‘PLATO’ trial in acute coronary syndromes.
Kevin Joseph Carroll, PhD, CStat, CSci, Honorary Senior Lecturer Medical Statistics is an Independent Statistical Consultant and owner of KJCStatistics Ltd. Kevin has 26 years drug development of experience across all trial phases and multiple therapeutic areas including Oncology, CV, Metabolism, Respiratory, CNS and GI. Most recently Kevin held the positions of VP Statistics and Chief Statistician at AstraZeneca Pharmaceuticals and Expert Statistician with Boehringer-Ingelheim. Kevin has extensive experience in the design, conduct, analysis and reporting of clinical trials. As a Consultant, Kevin has gained experience in helping both small and large pharma and biotech companies tackle statistical issues in development, including the application of innovative statistical approaches to trial design and analysis and regulatory product license applications. This includes the use of Bayesian decision-based designs to expedite effective decision making, and the use of complex staged designs in pivotal Phase II/III and Phase III trials to expedite overall development times. Kevin retains a strong technical interest in areas such as parametric survival modelling, group sequential analysis, adaptive designs and large outcomes trial design, and a growing interest in the statistical issues associated with health economic analyses and network meta-analyses.
PSI New Starters Half-Day Networking Event
An opportunity to meet statisticians from across the pharmaceutical industry in a relaxed and informal setting. An exciting program of events and a chance to work in small groups on a data analysis challenge. Lunch provided.
A Non-PSI Event - Protecting confidentiality and privacy in clinical trial and medical data sets
We are increasingly living in a data driven world. Data are collected in many different ways for a variety of purposes. As such, concerns around protecting the privacy of individuals have increased in recent times.
A PSI Training Course - Practical Approaches to Designing Adaptive Clinical Trials
This hands-on course will provide a deep dive into 4 software packages used to design adaptive clinical trials.
The course will start by providing a general overview of adaptive designs, explaining the different type of adaptations possible and the benefits of each design. Following this, participants will be given the opportunity to have a go at designing trials in R (using RPACTS), EAST, FACTS, and nQuery.
PSI Training Course - Bayesian Practical Course using R and SAS
This practical training course will give a deep dive into performing Bayesian analyses in R and SAS. It is aimed at statisticians who need to be able to conduct Bayesian analyses as part of their day to day work. By the end of the course participants will be able to conduct their own analyses.
This webinar will address operational issues of paramount importance within the healthcare industry with a view to using statistics for the benefit of patients. In attending this webinar, you'll hear more about work being conducted to address some operational issues we face in the health care industrys e.g. patient rectuitment, drug supply and meeting NHS 18 week targets.
PSI Toxicology SIG workshop – 16th and 17th March 2020
The Toxicology SIG provides a forum for statisticians working in regulatory/investigative toxicology, as well as most other pre-clinical areas, to discuss issues and interact with one another.
This 1.5-day workshop will involve approximately 20 statisticians, focusing on discussions around “best practice” in the statistical analysis of various data types.
The afternoon of Day 1 will include a 4.5 hour Bayesian training course focused towards applications in toxicology/pre-clinical, provided by Prof. Dr. Katja Ickstadt and is included in the workshop fee.
The cost will be £270 including VAT per delegate, inclusive of food and one night’s accommodation (and the training course). The workshop is being held at the Crowne Plaza Hotel, Heathrow.
The agenda and topics that will be discussed are yet to be finalised, but please get in touch with email@example.com if you have suggestions. Full details will be circulated in the coming weeks.
This course is aimed at Statisticians and Programmers experienced in SAS, but little or no experience with R.
An Introduction to R studio and the R language, statistical graphics, programming statistical models, simulations and more…
Non-proportional hazards and applications in immuno-oncology
Designs of clinical trials with time to event primary endpoints usually rely on hazards being constant over time. A major challenge in immuno-oncology is the delayed onset of benefit with such therapies and the presence of non-proportional hazards. The impact of this needs to be accounted for in sample size calculations, analysis methodology and reporting. At this meeting, we will examine possible strategies to handle such features, which may not be fully known when the trial is initiated.
The ITIT course will take 25 delegates new to the industry on a complete drug development experience from discovery to marketing. They will visit 6 companies from October 2020 to July 2021 to learn about 6 topics from experts in their field. The ITIT course will have 3 sessions in continental Europe and 3 - 4 sessions in the UK. It promises to be a truly memorable course.