Upcoming Events

WEBINAR: Pragmatic randomized trials: a conceptual introduction;

Dr Merrick Zwarenstein and Ms Alison Howie, University of Western Ontario, Canada.

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7th TRIALS METHODOLOGY SYMPOSIUM IRELAND  & UK (Online)

The future of clinical trials: people, projects, purpose, place

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4th, 5th and 6th October 2021

Hosted by HRB-TMRN (UCD) & MRC/NIHR-TMRP

Dr Alan Phillips, Senior Director, Biostatistics, ICON Clinical Research.

Tuesday 2nd November at 2.00pm (GMT) 

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For many years there has been a consensus among the Clinical Research community that ITT analysis represents the correct approach for the vast majority of trials. Recent worldwide regulatory guidance for pharmaceutical industry trials has allowed discussion of alternatives to the ITT approach to analysis; different treatment effects can be considered which may be more clinically meaningful and more relevant to patients and prescribers.

The key concept is of a trial “estimand”, a precise description of the estimated treatment effect. The strategy chosen to account for patients who discontinue treatment or take alternative medications which are not part of the randomised treatment regimen are important determinants of this treatment effect. One strategy to account for these events is treatment policy, which corresponds to an ITT approach. Alternative equally valid strategies address what the treatment effect is if the patient actually takes the treatment or does not use specific alternative medication.  There is no single right answer to which strategy is most appropriate, the solution depends on the key clinical question of interest.

The estimands framework discussed in the new guidance has been particularly useful in the context of the current COVID-19 pandemic and has clarified what choices are available to account for the impact of COVID-19 on clinical trials.  Specifically, an ITT approach addresses a treatment effect that may not be generalisable beyond the current pandemic.

Dr. Alan Phillips is Senior Director Biostatistics providing consultancy services to the Pharmaceutical Industry. Prior to this role, he was Vice President Head of Biostatistics for ICON Clinical Research where he directed and managed the global biostatistics resources based in US, Europe and Asia Pac.  With over 35 years of experience in biostatistics, Dr. Phillips has extensive knowledge of clinical trials, statistical methodology and world wide statistical regulatory requirements.  Prior to joining ICON, Dr. Phillips was with Wyeth Research for over 12 years and served as Senior Director, Clinical Biostatistics. Subsequently Dr Phillips has both CRO and Pharma experience.

Dr Phillips has experience of regulatory submissions in Biosimilars (Rituximab, Herception), CNS (depression, insomnia, Generalized Anxiety Disorder), Cardiovascular (Hypertension), Oncology (Breast Cancer) and Women’s Health (Hormone Replacement Therapy, Oral Contraceptives). Dr. Phillips frequently represents sponsors at US and EU scientific advisory and approval meetings.

Dr. Phillips received his B.Sc. degree in mathematics from the University of Exeter and his Ph.D. in statistics from the University of Birmingham.  He has published in a number of areas including adaptive trial designs, patient recruitment modelling, regulatory statistical challenges (eg missing data, multiplicity), sample size estimation, and statistical principals for clinical trials.  Dr. Phillips is affiliated with the Royal Statistical Society (RSS) and Statisticians in the Pharmaceutical Industry (PSI). In 2012, Dr Phillips was made an Honorary member of PSI in recognition of his scientific contributions to the organisation. Dr Phillips is also an Adjunct Associate Professor at University College Dublin and visiting Senior Lecturer at King’s College.

Kate Edgar, PhD student in Medical Statistics, London School of Hygiene and Tropical Medicine.

10th November – 12.00pm GMT

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In large multicentre trials in diverse settings, there is uncertainty about the need to adjust for centre variation in design and analysis. A key distinction is the difference between variation in outcome (independent of treatment) and variation in treatment effect. Through re-analysis of the CRASH-2 trial (2010), this study clarifies when and how to use multi-level models for multicentre studies with binary outcomes. The trial data had a hierarchical structure, with patients nested in hospitals which in turn are nested within countries. Reanalysis of CRASH-2 trial data assessed treatment effect and both patient and centre level baseline covariates as fixed effects in logistic regression models. Random effects were included to assess where there was variation between countries, and between centres within countries, both in underlying risk of death and in treatment effect. It is important to distinguish between underlying variation in outcomes and variation in treatment effects; the former is common but the latter is not. Stratifying randomisation by centre overcomes many statistical problems and including random intercepts in analysis may increase power and decrease bias in mean and standard error estimates.

Kate completed the MSc in Medical Statistics at LSHTM in 2019.  As part of an NIHR fellowship she stayed there as a Research Assistant in the Medical Statistics department, working with Professor Linda Sharples on multi-level models and subgroup analysis.  Since then she has started a PhD at LSHTM, using causal mediation analysis to investigate a trial of Hospital at home vs. hospital care for older persons.

International Clinical Trials Methodology Conference 2022 will take place from 3rd – 6th October 2022 at Harrogate Convention Centre, Harrogate, Yorkshire, UK.

ICTMC 2022 promises to be a unique opportunity for those working in clinical trials to meet and discuss the current issues within trials and trials methodology.

ICTMC is the leading international platform for researchers and practitioners to present the very latest in trials methodology research. The meeting also offers valuable networking and training opportunities, with over 750 delegates from 22 countries attending in 2019.

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