Evidence synthesis, health economic modelling, and randomised trials

Lead Research Organisation: MRC Biostatistics Unit

Abstract

In order to inform health care policy decisions about the effectiveness of medical interventions, all the available evidence should be accumulated. However the studies that contribute to the evidence are not always free from bias, or do not directly address the policy question of interest. We are developing methods to encompass these aspects by down-weighting the evidence from less rigorous or less relevant studies. Another component of our work relates to providing generic statistical techniques for evaluating cost-effectiveness from clinical trial data. While such analyses are informative, they are based on limited follow-up, and health economic modelling is required to address the issue of long term cost-effectiveness. We are working on ways in which the parameters needed for these models can be estimated, and how the uncertainty associated with the assumed model structure can be assessed. We are using examples in screening and treatment for abdominal aortic aneurysms, a major cause of death in elderly men, to explore these issues. Another way to obtain better information is to collate the data on individual participants from all the contributing studies. In the context of novel factors related to the risk of cardiovascular disease, we are providing statistical methodology to address whether these factors have a causal role and how much they add to the prediction of disease risk. Finally we are undertaking long term follow-up of the major UK trials of aortic aneurysm screening and treatment, and evaluating the use of the internet in health promotion.

Technical Summary

This programme focuses on key areas related to clinical and health policy decision making where methodological development is required. These include methods for evidence synthesis and long term health economic modelling. We also maintain our involvement in selected randomised trials with important policy implications. Specifically, we are developing our work in four main areas: Generic bias modelling in evidence synthesis: We are developing methods that encompass the rigour and relevance of component studies in systematic reviews, by applying additive components of variance informed by empirical data or prior judgement. Health economic modelling: We are undertaking research into methods for cost-effectiveness analysis of multicentre studies and cluster randomised trials. We are also developing generic methods relevant to long-term health economic modelling, for assessing model fit and external validation, structuring sensitivity analyses, model averaging, and encompassing model uncertainty. Individual participant data meta-analyses: We provide statistical guidance for major meta-analyses of the prospective studies of cardiovascular risk markers, addressing issues of regression dilution bias for aetiological associations and the cost-effectiveness of measuring additional factors to predict disease risk. Randomised trials: We focus on continued follow-up in the major UK trials of aortic aneurysm screening and endovascular treatment, and trials of health promotion delivered via the internet.

Publications

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Ballantyne C. (2007) Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA(2) and cardiovascular diseases in EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION

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Bowden J (2008) Unbiased estimation of selected treatment means in two-stage trials. in Biometrical journal. Biometrische Zeitschrift

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Bowden J (2010) Modelling multiple sources of dissemination bias in meta-analysis. in Statistics in medicine

 
Description Impact on UK national AAA screening programme
Geographic Reach Asia 
Policy Influence Type Citation in other policy documents
Impact Helped to develop the basis for the UK National AAA screening programme. High profile paper in BMJ (PMID: 19553269) with associated press coverage
URL http://europepmc.org/abstract/MED/19553269
 
Description Invited participant at NICE Methods Review Workshop, London: "Identifying subgroups and exploring heterogeneity in decision making".
Geographic Reach Asia 
Policy Influence Type Participation in advisory committee
Impact Development of revised methodological guidelines for NICE
 
Description Invited participant at UK National Screening Committee Working Group on abdominal aneurysm screening, London.
Geographic Reach Asia 
Policy Influence Type Participation in advisory committee
Impact Invited participant at UK National Screening Committee Working Group on abdominal aneurysm screening, London. ; UK national screening programme initiated
 
Description National Screening Committee recommendation for AAA screening
Geographic Reach Asia 
Policy Influence Type Citation in other policy documents
Impact http://www.screening.nhs.uk/aaa
URL http://www.screening.nhs.uk/aaa
 
Description PHSRN dissemination workshop
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Guideline Title Screening for Abdominal Aortic Aneurysm: Recommendation Statement
Description Recommendation for AAA screening
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact International recognition of the value of national systematic screening programmes for AAA; Initiation of UK national screening programme
URL http://annals.org/article.aspx?articleid=718158
 
Description MRC Hubs for Trial Methodology Research (HTMR)
Amount £1,773,176 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2009 
End 07/2014
 
Description NIHR HTA Project Grant 08/30/02 The growth and rupture rate of small abdominal aortic aneurysms: implications for population re-screening intervals
Amount £200,000 (GBP)
Funding ID HTA/08/30/02 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 07/2009 
End 07/2011
 
Description NIHR Project Grant- COPD
Amount £217,626 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 07/2011 
End 07/2015
 
Description NIHR Project Grant- SHEAR
Amount £4,059 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2011 
End 06/2013
 
Description NIHR-HTA-CanTalk
Amount £4,555 (GBP)
Funding ID HTA/09/33/02 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 06/2011 
End 06/2014
 
Description NIHR-Project Grant Diabetes
Amount £61,810 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2011 
End 06/2016
 
Title Cost-effectiveness Analysis 
Description Novel methods for undertaking cost-effectiveness analysis based on cause specific mortality to increase precision of estimates 
Type Of Material Technology assay or reagent 
Year Produced 2008 
Provided To Others? Yes  
Impact Improved methodology which is generally applicable 
 
Title Developing methods for joint modelling 
Description Developing methods for joint modelling of longitudinal and time-to-event data with application to aneurysm growth and rupture 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact Papers published 
 
Title Developing methods for predicting monitoring intervals 
Description Developing methods for predicting monitoring intervals with application to the AAA national screening programme 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact Papers published 
 
Title Development of Bayesian methods for both design and analysis of cluster randomised trials 
Description Development of Bayesian methods for both design and analysis of cluster randomised trials 
Type Of Material Technology assay or reagent 
Year Produced 2006 
Provided To Others? Yes  
Impact International recognition 
 
Title Development of flexible statistical methods for cost-effectiveness analysis 
Description Development of flexible statistical methods for cost-effectiveness analysis 
Type Of Material Technology assay or reagent 
Year Produced 2006 
Provided To Others? Yes  
Impact Major uptake of these methods by both researchers and practitioners 
 
Title Methods for investigating and describing heterogeneity in meta-analysis 
Description Methods for investigating and describing heterogeneity in meta-analysis 
Type Of Material Technology assay or reagent 
Year Produced 2006 
Provided To Others? Yes  
Impact Major impact in the way meta-analyses are undertaken and reported 
 
Title Software for randomisation-based estimate of efficacy in attenders 
Description Software for randomisation-based estimate of efficacy in attenders published in a generic format for use by others in publicly available software 
Type Of Material Technology assay or reagent 
Year Produced 2006 
Provided To Others? Yes  
Impact Kim LG, White IR. Compliance-adjusted intervention effects in survival data. Stata J. 2004 4(3): 227-34 
 
Title Structural uncertainty in health economic evaluation 
Description Novel method for encompassing structural uncertainty in health economics for evaluations such as those used by NICE 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact Improved methodology with direct policy relevance 
 
Title Validation of long term health economic models 
Description PMID 19206080 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact Appreciation of the problems of validating long term health economic models 
URL http://europepmc.org/abstract/MED/19206080
 
Description AAA repair trials 
Organisation Imperial College London
Department Department of Surgery and Cancer
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical supervision and oversight of the trials and their interpretation
Collaborator Contribution Co-ordinated the major UK trials of aneurysm repair
Impact PMIDs 17362572; 17244392; 17514695; 17514693; 17514666; 17572116; 17876749; 19118733; 19464199; 20542161; 20602502; 20395842; 20382983; 20382982; 20096611; 20184048
 
Description Alcohol intervention trial 
Organisation University College London
Department Research Department of Primary Care & Population Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical supervision and oversight of the trial
Collaborator Contribution Co-ordinated internet trial of alcohol reduction for heavy drinkers
Impact PMIDs 17963483; 19403465 Paper accepted for publication: Khadjesari Z, Murray E, Kalaitzaki E, White IR, McCambridge J, Thompson SG, Wallace P, Godfrey C. Impact and costs of incentives to reduce attrition from follow-up in online trials: Two randomised controlled trials. Journal of Medical Internet Research, August 2010.
Start Year 2007
 
Description COPD 
Organisation University College London
Department Division of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Provide statistical support for the design and analysis of the trial
Collaborator Contribution Providing data and intellectual input
Impact None as yet
Start Year 2011
 
Description CanTalk 
Organisation University College London
Department Neuroscience, Physiology & Pharmacology
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical input
Impact None as yet
Start Year 2011
 
Description Diabetes e-health intervention trial 
Organisation University College London
Department Research Department of Primary Care & Population Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical input
Impact None as yet
Start Year 2011
 
Description Emerging Risk Factors Collaboration 
Organisation University of Cambridge
Department Department of Public Health and Primary Care
Country United Kingdom 
Sector Academic/University 
PI Contribution Developing statistical methods appropriate for summarising results from multiple epidemiological studies
Collaborator Contribution Individual participant data on 1 million people from 100 epidemiological studies, providing a rich source of aetiological and risk prediction problems in a high profile area
Impact PMIDs 19903920; 19622820; 19222087; 19222086; 17876711; 17785713; 17301621; 20609967; 20452521; 20439481; 20031199; 19903920 Papers accepted for publication: - PROMIS Study Group (Saleheen D, Soranzo N, Thompson SG, Danesh J et al). Genetic determinants of major blood lipids in Pakistanis compared with Europeans. Circulation: Cardiovascular Genetics, May 2010. - Thompson SG, Kaptoge S, White IR, Wood AM, Perry PL, Danesh J; Emerging Risk Factors Collaboration. Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies. International Journal of Epidemiology, May 2010 [Epub ahead of print].
 
Description Extended follow-up of the MASS Randomised Trial of Aortic Aneurysm Screening 
Organisation St Richard's Hospital
Department Scott Research Unit
Country United Kingdom 
Sector Hospitals 
PI Contribution Statistical responsibility for the MASS Trial
Collaborator Contribution Coordination and management of the MASS Trial
Impact Publications
 
Description RESCAN 
Organisation Brunel University London
Department Health Economics Research Group
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical analysis and project leadership
Collaborator Contribution Scientific collaborationScientific collaboration
Impact PMIDs: 20952216; 20494541; 20952216; 21412998; 21834127 Papers accepted for publication: - Sweeting MJ, Thompson SG. Making predictions from complex longitudinal data, with application to planning monitoring intervals in a national screening programme. Journal of the Royal Statistical Society (Series A, Statistics in Society), May 2011
Start Year 2009
 
Description RESCAN 
Organisation Imperial College London
Department Department of Surgery and Cancer
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical analysis and project leadership
Collaborator Contribution Scientific collaborationScientific collaboration
Impact PMIDs: 20952216; 20494541; 20952216; 21412998; 21834127 Papers accepted for publication: - Sweeting MJ, Thompson SG. Making predictions from complex longitudinal data, with application to planning monitoring intervals in a national screening programme. Journal of the Royal Statistical Society (Series A, Statistics in Society), May 2011
Start Year 2009
 
Description SHEAR 
Organisation University College London
Department Division of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical guidance
Impact None as yet
Start Year 2011
 
Title AAA Screening 
Description The MASS trial results led to the implementation of a national screening programme for AAA 
Type Diagnostic Tool - Imaging
Current Stage Of Development Wide-scale adoption
Year Development Stage Completed 2010
Development Status Under active development/distribution
Clinical Trial? Yes
Impact NA 
 
Description AMgen meeting 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Health professionals
Results and Impact Research overview meeting with Amgen Pharmaceuticals

None as yet
Year(s) Of Engagement Activity 2011
 
Description Abdominal aortic aneurysms: from randomised trials to a national screening policy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Invited speaker at NICE workshop: Evidence Synthesis and Public Health: "Abdominal aortic aneurysms: from randomised trials to a national screening policy".

Recognition for the MRC and the Unit
Year(s) Of Engagement Activity 2008
 
Description Addenbrookes Biomedical Research Centre Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact About hundred people attended talks and discussed posters

Networking
Year(s) Of Engagement Activity 2009
 
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 Quintessential 'Counting for Health' 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact Policy relevant topical examples in 'Counting for Health' were used to illustrate how cost-effectiveness is worked out for screening programmes

Recognition for the MRC and the Unit
Year(s) Of Engagement Activity 2009