Hub in Trials Methodology Research (MRC Biostatistics Unit, Cambridge)
Lead Research Organisation:
MRC Biostatistics Unit
Department Name: UNLISTED
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.
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.
People |
ORCID iD |
Publications
Aston LM
(2010)
No difference in the 24-hour interstitial fluid glucose profile with modulations to the glycemic index of the diet.
in Nutrition (Burbank, Los Angeles County, Calif.)
Ban M
(2010)
A non-synonymous SNP within membrane metalloendopeptidase-like 1 (MMEL1) is associated with multiple sclerosis.
in Genes and immunity
Bluck LJ
(2011)
Bayesian hierarchical methods to interpret the (13)C-octanoic acid breath test for gastric emptying.
in Digestion
Bowden J
(2011)
Individual patient data meta-analysis of time-to-event outcomes: one-stage versus two-stage approaches for estimating the hazard ratio under a random effects model.
in Research synthesis methods
Bowden J
(2011)
Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics.
in BMC medical research methodology
Bowden J
(2012)
Identifying combined design and analysis procedures in two-stage trials with a binary end point.
in Statistics in medicine
Browning LM
(2012)
Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish.
in The American journal of clinical nutrition
Chatfield M
(2009)
The Skillings-Mack test (Friedman test when there are missing data).
in The Stata journal
Cook N
(2010)
A phase 2 study of vatalanib in metastatic melanoma patients.
in European journal of cancer (Oxford, England : 1990)
Corrie PG
(2012)
A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications.
in British journal of cancer
Cresswell L
(2011)
Assessment of joint symmetry in arthritis.
in Statistics in medicine
Da Costa TH
(2010)
How much human milk do infants consume? Data from 12 countries using a standardized stable isotope methodology.
in The Journal of nutrition
Dwan K
(2011)
Comparison of protocols and registry entries to published reports for randomised controlled trials.
in The Cochrane database of systematic reviews
International Multiple Sclerosis Genetics Consortium
(2011)
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
in Nature
Jebb SA
(2011)
Primary care referral to a commercial provider for weight loss treatment versus standard care: a randomised controlled trial.
in Lancet (London, England)
Low L
(2009)
DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer.
in Human gene therapy
Mander AP
(2012)
Admissible two-stage designs for phase II cancer clinical trials that incorporate the expected sample size under the alternative hypothesis.
in Pharmaceutical statistics
Mander AP
(2010)
Two-stage designs optimal under the alternative hypothesis for phase II cancer clinical trials.
in Contemporary clinical trials
Moodie Z
(2010)
Response definition criteria for ELISPOT assays revisited.
in Cancer immunology, immunotherapy : CII
Prynne CJ
(2009)
Diet and glycosylated haemoglobin in the 1946 British birth cohort.
in European journal of clinical nutrition
Rimmer Y
(2011)
Accelerated BEP: a phase I trial of dose-dense BEP for intermediate and poor prognosis metastatic germ cell tumour.
in British journal of cancer
Sawcer S
(2012)
Risk in complex genetics: "all models are wrong but some are useful".
in Annals of neurology
Sawcer S
(2010)
What role for genetics in the prediction of multiple sclerosis?
in Annals of neurology
Siervo M
(2010)
Acute effects of hyperglycaemia on asymmetric dimethylarginine (ADMA), adiponectin and inflammatory markers (IL-6, hs-CRP) in overweight and obese women with metabolic syndrome.
in British journal of biomedical science
Simmonds MC
(2011)
Meta-analysis of time-to-event data: a comparison of two-stage methods.
in Research synthesis methods
| 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 | Public |
| 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 | Public |
| 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 | Academic/University |
| 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 | Academic/University |
| 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 | Public |
| 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 Group |
| Country | United Kingdom |
| Sector | Academic/University |
| 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 | Academic/University |
| 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 | Academic/University |
| 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 | Academic/University |
| 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 Group |
| Country | United Kingdom |
| Sector | Academic/University |
| 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 Group |
| Country | United Kingdom |
| Sector | Academic/University |
| 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 Group |
| Country | United Kingdom |
| Sector | Academic/University |
| 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 Group |
| Country | United Kingdom |
| Sector | Academic/University |
| 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 | 2007,2008,2009,2010,2011,2012 |
| 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-... |