Methods and applications in the management of heart and lung diseases

Lead Research Organisation: MRC Biostatistics Unit

Abstract

This programme includes work on the understanding of chronic disease onset and progression, with applications to cardiothoracic medicine and surgery. We aim to develop realistic models, so that methods for assessment of disease models and model comparisons are important. With an understanding of the disease process we can identify promising new treatments. We will be involved in clinical trials of new diagnostic tools for suspected heart disease and of treatments for management of angina. In these trials treatments will be evaluated in terms of survival, quality of life and costs.Treatment policy decisions are based on combining information from randomised trials with other information, such as registers of patients and epidemiological studies. Because randomised trials are carried out over a short time period, in a particular group of patients, or in a different country, we often need to extrapolate findings beyond trials. This involves careful modelling, with transparent and defensible assumptions, which should be subject to sensitivity analysis. Examples will be: to provide guidelines for the use of heart valves for patients of different ages, and for the use of mechanical pumps for end-stage heart failure.

Technical Summary

Current and future research builds on progress made in 2001-06 and continues to be heavily funded by, and relevant to, research at Papworth Hospital. Future work can be split into 5 major categories: effectiveness and cost-effectiveness studies; the use of the utility measure EQ-5D in cardiovascular research; transplantation research; a decision analytic approach to aortic valve replacement; and statistical methods. Previous effectiveness and cost-effectiveness studies highlighted some questions regarding the estimation strategies in health economic assessment, such as: how much is lost by ignoring the covariance structure in a two-stage approach to estimation of cost-effectiveness compared with simultaneously estimating model parameters and cost-effectiveness summaries? Can we improve estimates of lifetime treatment effects by focussing on cause-specific mortality? Is a model based on mixtures a more accurate representation of cost data? These questions will be explored using both secondary analysis of previous trial data and results from trials that will complete follow-up in the next 2-3 years. It is clear that cost-effectiveness is crucially dependent on elicitation of utilities. We plan a major review of the EQ-5D utility measure, currently recommended by NICE, to evaluate its use in cardiovascular research. Studies in transplantation focus on the optimal methods for allocating organs and for the use of VADs and continued modelling of chronic dysfunction. A further application of multistate models is a decision analytic approach to allocation of mechanical or tissue valves, according to patient characteristics, for aortic valve replacement. Informal graphical methods and formal statistical tests for assessing fit of multistate models are not well established. We plan to make a major contribution to work in this area, by providing a strategy for model criticism and model choice, and by incorporating methods into the msm software.

Publications

10 25 50
 
Description Inflammation on lung cancer staging provided to NICE appraisal
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
 
Description Member of Various Data Monitoring and Ethics Committees including MARS, QUARTZ and SERCA gene LVAD pilot study
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description NCG advisor on use of Ventricular Assist Devices as a bridge to transplantation
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact NCG advisor on use of Ventricular Assist Devices as a bridge to transplantation
 
Description MRC BSU Early Career Centenary Award-Sweeting
Amount £30,000 (GBP)
Organisation University of Cambridge 
Department MRC Biostatistics Unit
Sector Academic/University
Country United Kingdom
Start 01/2012 
End 01/2013
 
Description MRC BSU Early Career Centenary Award-Thom
Amount £22,000 (GBP)
Organisation University of Cambridge 
Department MRC Biostatistics Unit
Sector Academic/University
Country United Kingdom
Start 06/2012 
End 06/2013
 
Description MRC BSU Early Career Centenary Award-Wheeler
Amount £10,000 (GBP)
Organisation University of Cambridge 
Department MRC Biostatistics Unit
Sector Academic/University
Country United Kingdom
Start 06/2012 
End 06/2013
 
Description NIHR Clinical Trials Fellowship
Amount £135,244 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 09/2009 
End 09/2013
 
Description Papworth
Amount £100,000 (GBP)
Organisation Royal Papworth Hospital NHS Foundation Trust 
Sector Public
Country United Kingdom
Start 06/2006 
End 09/2013
 
Title A series of Health Technology Assessments 
Description A series of Health Technology Assessments: Nurse Practitioners, Implantable Cardioverter Defibrillators, Ventricular Assist devices and diagnostic methods in coronary artery disease. 
Type Of Material Data analysis technique 
Year Produced 2006 
Provided To Others? Yes  
Impact Substantial media interest in nurse practitioner roles, ICD work in NICE appraisal and VAD work used in NCG commissioning 
 
Title Diagnostic methods for multistate models 
Description Diagnostic methods for multistate models 
Type Of Material Data analysis technique 
Year Produced 2007 
Provided To Others? Yes  
Impact Makes diagnostic methods accessible in this context 
 
Title Hierarchical and other flexible models for understanding unusual performance in health care providers 
Description Hierarchical and other flexible models for understanding unusual performance in health care providers 
Type Of Material Data analysis technique 
Year Produced 2007 
Provided To Others? Yes  
Impact Published in high impact journals 
 
Title Large body of collaborative work introducing rigorous statistical methods into areas with traditionally poor evaluation 
Description Large body of collaborative work introducing rigorous statistical methods into areas with traditionally poor evaluation eg surgical trials and evaluation of extended nursing roles 
Type Of Material Data analysis technique 
Year Produced 2006 
Provided To Others? Yes  
Impact Publications in high impact journals 
 
Title Methods for extrapolating survival patterns using external data 
Description Methods for extrapolating survival patterns using external data 
Type Of Material Data analysis technique 
Year Produced 2006 
Provided To Others? Yes  
Impact Used in NCG evaluation of implantable verntricular assist devices and to assess the impact of novel preservation devices in transplantation 
 
Title R software for calculating the goodness of fit statistics for multistate models 
Description R software for calculating the goodness of fit statistics for multistate models 
Type Of Material Improvements to research infrastructure 
Year Produced 2007 
Provided To Others? Yes  
Impact Makes the methods practicable 
 
Title Understanding structural uncertainty and model averaging in health economic analysis using information criteria 
Description Understanding structural uncertainty and model averaging in health economic analysis using information criteria 
Type Of Material Data analysis technique 
Year Produced 2009 
Provided To Others? Yes  
Impact Emerging collaborations with York University 
 
Title WinBUGS code for cost-effectiveness modelling 
Description The model code contains a new BUGS function, CE(), for calculating the expected cost and effectiveness from a Markov model in terms of multinomial logistic regression parameters (baseline log odds for the state on the next day, and log odds ratios for covariates governing the transition probabilities). This allows the complex matrix multiplications involved in the cost-effectiveness calculation to be performed very quickly, compared to writing them in BUGS model code. 
Type Of Material Data analysis technique 
Year Produced 2010 
Provided To Others? Yes  
Impact Notable impact has not yet been established 
 
Title msm package 
Description msm: Multi-state Markov and hidden Markov models in continuous time 
Type Of Material Data analysis technique 
Year Produced 2010 
Provided To Others? Yes  
Impact Ongoing maintainance of the msm R package for continuous-time Markov and hidden Markov modelling. Product used under GNU General Public License. 
 
Description Addenbrooke's 
Organisation Addenbrooke's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Statistical expertise
Collaborator Contribution Provinding data and general collaboration
Impact PMID: 20098281; PMID: 20538027; PMID: 21079553; PMID: 19224513; PMID: 19681825; PMID: 21449941; PMID: 21079553; PMID: 20861803; PMID: 20098281; PMID: 20538027
 
Description BSU 
Organisation University of Cambridge
Department MRC Biostatistics Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution Modelling development (mixture models in cognitive analysis)
Collaborator Contribution Project leader
Impact - Presentation given in ISCB conference (Ottawa, Canada, Aug 2011) PMID: 21602487; PMID: 21969987; PMID: 20383261; PMID: 19654169; PMID: 19912172 DOI: 10.1177/0962280211419645 Papers submitted/ in preparation: - Estimation of life expectancy in lung transplantation. Journal of the Royal Statistical Society Series A/C. - Cause-specific survival extrapolation for cost-effectiveness studies. Applied Statistics Journal.
Start Year 2010
 
Description Bristol Heart Institute 
Organisation Bristol Heart Institute
Country United Kingdom 
Sector Hospitals 
PI Contribution Statistical modelling of heart valves surgery
Collaborator Contribution Data provision and clinical input
Impact PMID: 20956488
Start Year 2008
 
Description Brunel University 
Organisation Brunel University London
Department Health Economics Research Group
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical expertise
Collaborator Contribution Provided Health economics expertise
Impact PMIDs: 20525323; PMID: 20109189; PMID: 19941657; PMID: 20525323; PMID: 20109189 Paper submitted/in preparation: Effectiveness and Cost-effectiveness of Endobronchial and Endoscopic Ultrasound relative to Surgical Staging in Potentially Resectable Lung Cancer: Results from the ASTER Randomised Controlled Trial. Journal of Health Technology Assessment (2011)
 
Description HPA 
Organisation Public Health England
Department Centre of Infectious Disease Surveillance and Control
Country United Kingdom 
Sector Public 
PI Contribution Statistical modelling of HPV vaccination strategies
Collaborator Contribution Joint research
Impact Publications in preparation
Start Year 2010
 
Description MRC Cancer Cell Unit / CCHSR 
Organisation Medical Research Council (MRC)
Country United Kingdom 
Sector Public 
PI Contribution Models screening and treatment of Barrett's oesophagus
Collaborator Contribution Intellectual contribution, data provisionJoint research
Impact Paper submitted/ in preparation: - Population health benefits and cost-effectiveness of endoscopic and non-endoscopic Cystosponge screening for Barrett's oesophagus. Submitted to Bristish Medical Journal (October 2011) - Cause-specific survival extrapolation for cost-effectiveness studies. Applied Statistics Journal (2011)
Start Year 2009
 
Description MRC Cancer Cell Unit / CCHSR 
Organisation University of Cambridge
Department Cambridge Institute of Public Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Models screening and treatment of Barrett's oesophagus
Collaborator Contribution Intellectual contribution, data provisionJoint research
Impact Paper submitted/ in preparation: - Population health benefits and cost-effectiveness of endoscopic and non-endoscopic Cystosponge screening for Barrett's oesophagus. Submitted to Bristish Medical Journal (October 2011) - Cause-specific survival extrapolation for cost-effectiveness studies. Applied Statistics Journal (2011)
Start Year 2009
 
Description Missing data in crossover trials 
Organisation Newcastle University
Department School of Mathematics and Statistics
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical and clinical knowledge, dataset, supervision of post-doc
Collaborator Contribution Statistical and technical expertise, direct supervision of post doc
Impact Paper in preparation. Small NIHR grant to support post doc in Newcastle.
Start Year 2012
 
Description Multi-state models in analysis of routine health records 
Organisation Polytechnic University of Milan
Country Italy 
Sector Academic/University 
PI Contribution Expertise
Collaborator Contribution Project lead and data
Impact Two publications, one more planned
Start Year 2013
 
Description National trial in transplantation 
Organisation Newcastle University
Department Newcastle Clinical Trials Unit (NCTU)
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise
Collaborator Contribution Research leading
Impact N/A
Start Year 2010
 
Description Papworth Hospital 
Organisation Research and Development Unit Papworth
Country United Kingdom 
Sector Public 
PI Contribution Statistical expertise
Collaborator Contribution Clinical research studies
Impact PMID: 20385666; PMID: 19930784; PMID: 18057060; PMID: 20525323; PMID: 20109189; PMID: 19465626; PMID: 20188594; PMID: 20148816; PMID: 20555263; PMID: 19941657; PMID: 19486222; PMID: 19188504; PMID: 20956488; PMID: 21790520; PMID: 21247984; PMID: 20188594; PMID: 20956488; PMID: 20971234; PMID: 21095311; PMID: 20148816; PMID: 20555263 DOI: 10.1016/S0140-6736(11)61144-6 Paper in press: Two year multicentre, randomised, double blind, placebo controlled trial assessing the effect of weekly Ridesronate on bone mineral density in adults with cystic fibrosis. Journal of Cystic Fibrosis 2011 epub ahead of print. Five papers in preparartion/ Submitted (2011): - Impact of different measuring techniques on T staging of lung cancer on multidetector computed tomography. Journal of Thoracic Imaging. - Euroscore II. European Journal of Cardiothoracic Surgery. - The impact of a bedside computerised information system on the adequacy of nutritional support in critically ill cardiothoracic patients. Clinical journal - Prolonged critical care and subsequent psychological distress: a matched-cohorts study in cardiac surgical patients. Clinical journal - Epithelial mesenchymal transition commences early during the progression of squamous perneoplasia of the lung. Journal of Thoracic Oncology.
 
Description Research Discontinuity Designs for post trial assessment of effectiveness 
Organisation University College London
Department Department of Statistical Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Member of study steering group
Collaborator Contribution Advice brought to steering group
Impact Inaugural meeting attended.
Start Year 2013
 
Description Society for Cardiothoracic Surgery 
Organisation Society for Cardiothoracic Surgery in Great Britain and Ireland (SCTS)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Statistical modelling
Collaborator Contribution Data provision
Impact Add pubs!
Start Year 2006
 
Description UK Transplant 
Organisation NHS Blood and Transplant (NHSBT)
Country United Kingdom 
Sector Public 
PI Contribution Statistical expertise
Collaborator Contribution Provinding data and general collaboration
Impact PMID: 19656145; PMID: 21343871 DOI: 10.1016/S0140-6736(11)61144-6
 
Description Use of routine datasets to inform health care provision and patient outcomes 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution Collaborative work
Collaborator Contribution Collaborative work
Impact Two papers
Start Year 2013
 
Description York University 
Organisation University of York
Department Centre for Health Economics (CHE)
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical expertise
Collaborator Contribution Provided Health Economics expertise
Impact PMID: 21602487 One successful grant.
Start Year 2009
 
Description Cafe Scientifique Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Around 80 people attended this event. The talk sparked interesting questions and discussion afterwards

Staff member interviewed and podcast. For listening podcast please see: http://www.thenakedscientists.com/HTML/podcasts/specials/cafe-scientifique/
Year(s) Of Engagement Activity 2011
URL http://www.cambridgecafescientifique.com/
 
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 Public/other audiences
Results and Impact Demonstrated some statistical principles in BSU exhibits at Cambridge Science Festival. The practical activities were very well received by a young audience and and accompanying adults.
Prepared exhibition in 2011. Around 300 children and accompanying adults visited the BSU/HNR joint stand.

Raised awareness of the work of the Unit in the local schools community, strenghten networking with other MRC Units
Year(s) Of Engagement Activity 2007,2008,2009,2011,2012
URL http://www.cam.ac.uk/science-festival
 
Description School science talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Schools
Results and Impact School science talk

Raised awareness of the work of the Unit in the local schools community
Year(s) Of Engagement Activity 2008