Hub in Trials Methodology Research (MRC Biostatistics Unit, Cambridge)

Lead Research Organisation: MRC Biostatistics Unit

Abstract

In clinical trials, the choice of which treatment a participant receives is decided by a random process. Such trials provide the foundation for deciding what medical interventions work, and in whom, and inform patient choice and clinical decision making. In order to be effective, however, trials must be well designed, well run, and well analysed and reported. The Hub in Trial Methodology Research based at the MRC Biostatistics Unit in Cambridge will develop and promote the use of efficient and state-of-the-art methods for trials. It will work with the existing extensive clinical trial research networks in Cambridge and East Anglia to support good practice in trials in specific clinical areas (for example in cancer, paediatrics, dementia, brain sciences, arthritis, and primary care). Trials will range from early proof-of-concept studies to large pragmatic trials of healthcare interventions. The proposed formation of the Hub has received an enthusiastic response from a large number of potential collaborators and networks in Cambridge and the local region. The Hub will also evaluate the cost-effectiveness of proposed interventions, to inform health policy decisions. In particular, it will investigate statistical problems involved in trial designs, and in the analysis and interpretation of the trial results. Methodological development and support are needed to improve study design, to run trials more efficiently, and to ensure that they are as informative as possible for both clinical and health policy decision making. Methodological development must also take advantage of new medical technologies (for example in imaging, in genetics, in pharmacology and drug targeting) so that new cost-effective treatments are identified efficiently and brought into medical practice.

Technical Summary

The Hub based at the MRC Biostatistics Unit (BSU) will:

1. Establish an internationally competitive research programme in clinical trials methodology that adds new strengths and capacity to the Unit ? for example in early phase trials, adaptive trials, or genetics-related trials;

2. Focus primarily on statistical issues in trial design, analysis, interpretation and decision making, rather than the mechanics of trial conduct;

3. Interact with and enhance the existing methodological expertise in the Unit, that focuses on missing data and causal analysis, Bayesian methods, clustering in trials, design issues, meta-analysis, and health economic assessment;

4. Establish strong collaborations especially with relevant research groups in Cambridge and the local region that undertake clinical trials, ranging from early phase trials, through pragmatic phase III and implementation trials, to cost-effectiveness evaluations;

5. Provide added value to the Unit?s current collaborations in trials by maintaining some of Tony Johnson?s roles as he retires, including those with a number of clinical trials units, and by increasing capacity for involvement in trials in new areas ? for example in cancer, imaging, and brain sciences;

6. Establish a training and dissemination programme for methodology in clinical trials, aligned to its research interests and those of the existing Unit.

BSU?s current collaborations in practical trials are very selective. Such involvement is usually motivated by the need for statistical expertise that exists in the Unit, by the need to develop new methodology, or by the continuation of research programmes in particular clinical areas. The Hub will be able greatly to expand BSU?s trials-related research by providing methodological support to a much wider range of trials, by extending the range of methodological research, by increasing dissemination of methodological advances, and by being proactive in developing additional collaborations. From initial contacts in the local region, there is extensive and enthusiastic support for collaboration with such a source of methodological expertise, and the clear potential to enhance many applied research programmes involving trials by ensuring robust design, efficient conduct, and high-class analysis.

Publications

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Cook N (2010) A phase 2 study of vatalanib in metastatic melanoma patients. in European journal of cancer (Oxford, England : 1990)

 
Description HTA Award - Epilepsy
Amount £53,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2013 
End 06/2016
 
Description Industrial CASE studentship - GSK
Amount £90,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 07/2013 
End 07/2016
 
Description Industrial CASE studentship - Philips Research UK
Amount £89,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 07/2013 
End 07/2016
 
Description MRC BSU Early Career Centenary Award- McCallum
Amount £12,000 (GBP)
Organisation University of Cambridge 
Department MRC Biostatistics Unit
Sector Public
Country United Kingdom
Start 07/2012 
End 07/2013
 
Description MRC BSU Early Career Centenary Award- Wason
Amount £8,000 (GBP)
Organisation University of Cambridge 
Department MRC Biostatistics Unit
Sector Public
Country United Kingdom
Start 07/2012 
End 07/2013
 
Description Research Collaboration with MRC HNR
Amount £23,888 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 06/2013 
End 06/2015
 
Title Admissible design 
Description Stata program 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact NA 
 
Title Continuous 2 stage design 
Description adaptation of Simon 2-stage design for continuous outcomes 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Research still ongoing 
 
Title Continuous reassessment method 
Description R package to implement various designs of the continuous reassessment method in Phase I trials 
Type Of Material Improvements to research infrastructure 
Year Produced 2011 
Provided To Others? Yes  
Impact None as yet 
 
Title Designs for Phase 1 combination trials 
Description Bayesian adaptive designs for Phase 1 combination trials 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact None as yet 
 
Title H1-optimality designs 
Description Novel study design 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact publication in preparation 
 
Title Minimax designs 
Description R software programme 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact N/A 
 
Title Simon 2 stage design 
Description Stata program 
Type Of Material Improvements to research infrastructure 
Year Produced 2009 
Provided To Others? Yes  
Impact unknown 
 
Description ALD 
Organisation University of Cambridge
Department Department of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical expertise and design
Collaborator Contribution Shared dataset
Impact Publication in preparation
Start Year 2011
 
Description BAMMOS 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom 
Sector Public 
PI Contribution Paper drafting and addressing reviews comments.
Collaborator Contribution Provide data and research questionsProvide data and research questionsProvide data and research questions
Impact PMID: 21186183; PMID: 21255448; PMID: 21383837 Workshop given in 2009
Start Year 2007
 
Description BAMMOS 
Organisation University of Cambridge
Department MRC Biostatistics Unit
Country United Kingdom 
Sector Public 
PI Contribution Paper drafting and addressing reviews comments.
Collaborator Contribution Provide data and research questionsProvide data and research questionsProvide data and research questions
Impact PMID: 21186183; PMID: 21255448; PMID: 21383837 Workshop given in 2009
Start Year 2007
 
Description BAMMOS 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom 
Sector Multiple 
PI Contribution Paper drafting and addressing reviews comments.
Collaborator Contribution Provide data and research questionsProvide data and research questionsProvide data and research questions
Impact PMID: 21186183; PMID: 21255448; PMID: 21383837 Workshop given in 2009
Start Year 2007
 
Description Cambridge Cancer Trials Centre 
Organisation Addenbrooke's Hospital
Department Cambridge Cancer Trials Centre
Country United Kingdom 
Sector Hospitals 
PI Contribution Statistical expertise
Collaborator Contribution Statistical expertise
Impact PMID: 20800475; PMID: 21239164; PMID: 21835398; PMID: 21847130 doi:10.1038/nature10251
Start Year 2009
 
Description FISH 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom 
Sector Public 
PI Contribution Design and analysis of study
Collaborator Contribution Publications in preparation
Impact Publications in preparation
Start Year 2008
 
Description Horizon Data Sharing agreement 
Organisation AstraZeneca
Department Statistics & Informatics
Country United Kingdom 
Sector Private 
PI Contribution We submitted methodological research ideas
Collaborator Contribution They provided the data
Impact None so far
Start Year 2013
 
Description Improving outcomes in adults with epilepsy and intellectual disability 
Organisation University of Cambridge
Department Department of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical design and analysis of a trial
Collaborator Contribution The psychiatry motivation of the study
Impact It has just started so no outputs yet
Start Year 2013
 
Description MAMS 
Organisation Lancaster University
Department Department of Mathematics and Statistics
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical expertise
Collaborator Contribution Statistical expertise
Impact Grant application. One paper submitted and currently under revision: Wason, J.M.S. and Jaki T. Optimal design of multi-arm multi-stage trials. Biometrics (2011)
Start Year 2011
 
Description Non-linear modelling 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom 
Sector Public 
PI Contribution Novel modelling
Collaborator Contribution Advanced modelling
Impact PMID: 21042021; PMID: 20980653 Paper in preparation
Start Year 2008
 
Description Polypill 
Organisation University of Cambridge
Department Cambridge Institute of Public Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical design and analysis
Collaborator Contribution Grant holders
Impact N/A
Start Year 2011
 
Description WRAP 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom 
Sector Public 
PI Contribution statistical design and future analysis
Collaborator Contribution The motivation and running the trial
Impact None yet
Start Year 2013
 
Description Weightwatchers 
Organisation Medical Research Council (MRC)
Department MRC Human Nutrition Research Unit
Country United Kingdom 
Sector Public 
PI Contribution Design and analysis of Weightwatchers trials
Collaborator Contribution Publications in preparation
Impact PMID: 21906798 (paper widely covered by national and international media) Publications currently in preparation
Start Year 2007
 
Description Big Bang Eastern Fair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The Fair had over 1000 pupils (Schools from around the region (Bedfordshire, Cambridgeshire, Essex, Hertfordshire, Norfolk and Suffolk), >130 teachers, and >100 volunteers from STEM (Science, Technology, Engineering & Maths) industry and research across the region. Over 100 school STEM projects were exhibited by the children.
More than 150 children visited our exhibit.

N/A
Year(s) Of Engagement Activity 2011
 
Description Big Bang Fair London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Over 250 school children and adults visited the exhibit "Are you really what you eat?"

Radio interviews
Invitation to participate in Big Bang Fair East (Duxford)
Year(s) Of Engagement Activity 2011
 
Description Cambridge Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Schools
Results and Impact Helped man the Unit's display for the festival

Raised awareness of the work of the Unit in the local school community
Year(s) Of Engagement Activity 2007,2008,2009,2010,2011
 
Description Cambridge Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Schools
Results and Impact Helped man the Unit's display for Cambridge Science Festival

Raised awareness of the Unit's work in the local schools community
Year(s) Of Engagement Activity 2007,2008,2009,2011
 
Description Statistical analysis for weight-loss trial (WRAP) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Programme Leader Track, Adrian Mander, was co-author on peer-review publication in The Lancet on weight-loss trial (published April 2017). Paper received various local and national press attention, including article in The Guardian
Year(s) Of Engagement Activity 2017
URL https://www.theguardian.com/lifeandstyle/2017/may/04/give-overweight-patients-a-year-of-weight-loss-...