1. Trials Methodology Research at
University of Birmingham
Professor Lucinda (Cindy) Billingham
Professor of Biostatistics
Director, MRC Midland Hub for Trials Methodology Research
Director of Statistics, Cancer Research UK Clinical Trials Unit
University of Birmingham
BCCT Showcase, University of Birmingham
November 27th 2013

2. The Need for Trials
Methodology Research
Users
Change
Clinical
Practice
Evidence
Synthesis
Pre-trial
Development
Add-on
translational
studies
Established
expertise
New areas
Trial Analysis
Change
Clinical
Practice
Trial
Conduct
Phase I, II, III
Trial Set-Up
and Design

3. MRC Network of Hubs for Trials
Methodology Research (HTMR)
All-Ireland Hub
led by Professor Mike Clarke
Dr Adrian Mander
www.methodologyhubs.mrc.ac.uk

4. Structure of the Midland Hub
University of Birmingham
College of Medical and Dental Sciences
School of Cancer Sciences
Cancer Research
UK Clinical Trials
Unit (CRCTU)
Birmingham
Clinical Trials
Unit (BCTU)
School of Health and Population Sciences
Primary Care
Clinical Sciences
Unit
Public Health,
Epidemiology &
Biostatistics Unit
Health
Economics Unit
Birmingham Centre for Clinical Trials (BCCT)
Billingham
Wheatley
Johnson
[Stocken]
Gray
[Ives]
Calvert
Delaney
Freemantle
Hobbs
Wilson
(Draper)
Deeks
Lilford
Zeegers
[Girling]
[Riley]
[Hemming]
Bryan
[Barton]
[Coast]
(Al-Janabi)
Billingham
Wheatley
Deeks
[Ives]
Calvert
Draper
Lilford
Deeks
Girling
Hemming
Lilford
Riley
Coast
[Barton]
Director: Professor Lucinda Billingham
Deputy Director: Dr Richard Riley
[Key collaborators who are active MHTMR researchers & MHTMR Management Group members]
(Key collaborators who are supervisors for MHTMR PhD projects)

5. Midland Hub Resources (2009-2014)
Director (60%)
Day-to-day management; support and mentorship
to RFs and PhD students; ensure successful
delivery Hub programme; networking
12 Hub Investigators
Supervision and development of research projects
and contributions to training and advisory service
3 Research Fellows
Methodological research projects
Project grant applications
Provision and coordination of advice facility
Training and support to PhD students
1 Senior
Administrator
Support Director, Investigators, Research Fellows
Support training programme and PhD students
Organise Hub meetings and events
5 PhD Students
Methodological development
Plus other affiliated RFs and PhD students

6. Mission Statement of the Midland Hub
‘The mission of the MRC Midland Hub for
Trials Methodology Research is to be a
centre of excellence for trials methodology
research, providing researchers
undertaking trials with appropriate and
innovative methodology for design,
conduct, analysis and reporting, thereby
improving the quality of trials and
ultimately patient care.’
Research Programme
Training Programme
Advice, Support and Dissemination Function

7. Qualitative research methods
Decision modelling
Economic evaluation
Evaluations of Service Delivery and
Policy Interventions
(Lilford, Girling, Hemming)
Cluster trials and stepped-wedge designs
Improving the Quality of Consent
to Trials
(Draper)
Joint modelling of longitudinal and event data
Trials in Rare Diseases
(Wheatley, Billingham)
Statistical modelling of time-to-event data
Early Phase Clinical Trials
(Billingham in collaboration
with O’Quigley)
Systematic reviews and meta-analysis methods
Stratified Medicine and Test Evaluation
(Riley, Deeks)
Bayesian methods
Outcome Measures for Trials
(Calvert, Coast, Billingham)
General clinical trial design, conduct and analysis
Key Research Themes in Midland Hub

8. Some Highlights
• Patient-reported outcomes (PRO): international collaboration to develop
the CONSORT PRO and improve standards of reporting
– Calvert M, Blazeby J, Altman D et al; Reporting of patient-reported outcomes in
randomised trials: the CONSORT PRO extension; JAMA 2013
• Stratified medicine: review to establish methodological standards for
evaluating predictive biomarkers
– Malottki K, Biswas M, Deeks J, Riley R, Craddock C, Johnson P, Billingham L;
Stratified medicine in European Medicines Agency licensing: a systematic review of
predictive biomarkers; on review with BMJ Open
– Billingham L, Deeks J, Riley R, Malottki K, Middleton G, Morton D, Craddock C;
Stratified medicine: methods for evaluating predictive biomarkers for treatment of
cancer; Grant submission to Cancer Research UK Population Research Committee
Nov 2013
• Implementing improved methodology for early phase trials in cancer in
CRCTU
– Craddock C, Yap C et al; A phase I/II trial of combined 5-azacitidine and lenalidomide
salvage therapy in patients with acute myeloid leukaemia who relapse after allogenic
stem cell transplantation; funded by Leukaemia and Lymphoma Research

9. Some Highlights (cont)
• Implementing novel designs to enable practice-changing trials in rare
cancers
– Funding for trials with novel designs in paediatric oncology run by Childrens Cancer
Trials Team in CRCTU (led by Wheatley)
– Funding from CRUK for phase III trial in penile cancer (Billingham in collaboration with
International Rare Cancers Initiative and ICR Trials Unit)
• Enhancing results of an NIHR funded trial run at BCTU that failed to
recruit using Bayesian methods
– Morris RK, Malin GL, Quinlan-Jones E, Middleton LJ, Hemming K, Burke D, Daniels JP,
Khan K, Deeks J, Kilby MD; Percutaneous vesicoamniotic shunting versus conservative
management for fetal lower urinary tract obstruction (PLUTO): a randomised trial;
Lancet 2013
• Influencing decisions of the National Research Ethics Service regarding
patient information for trials
– Kirkby HM, Calvert M, McManus RJ, Draper H; Informing potential participants about
research; observational study with an embedded randomised controlled trial; PloS one
2013

10. Looking to the Future
• Funding for the Midland Hub will cease on May 31st 2014
• The development of the Midland Hub established a
team of researchers involved in trials methodology and
– facilitated some important research projects that
should benefit trials practitioners in the future
– established an infrastructure from which to continue
as a centre of excellence for trials methodology
research into the future within BCCT