Statistical inference in transmission models based on Bayesian synthesis of evidence from multiple sources

Lead Research Organisation: Medical Research Council
Department Name: UNLISTED

Abstract

Policy makers need reliable models to understand the HIV epidemic, to predict the likely future burden of disease for planning, and to predict the likely effect of preventive interventions. Current methods are not adequate to this task. Some methods fail to make use of all the available data, use it in an inconsistent way, and are inherently unable to predict the long term effect of interventions. This is because the risk of acquiring HIV at any point in time depends on how many people already have it, giving rise to dynamic ?feedback? effects. Other methods, which allow for dynamic effects and can therefore predict long term effects of interventions, are not as ?evidence-based? as would be desirable, and it is difficult to tell how accurate their predictions are.

The project builds on successful work already completed by the applicants, who have recently developed methods for estimating the incidence and prevalence of HIV in the England & Wales. These methods are designed to (a) incorporate all the available information, so that predictions are less uncertain, (b) allow the consistency of the information to be established, (c) provide a systematic analysis of the uncertainty in predictions, based on the uncertainties in the data inputs. These methods have been used in the most recent Department of Health report on the state of the HIV epidemic in the UK.

The plan now is to extend and refine these methods, so that they can incorporate HIV transmission dynamics and thus allow policy makers to assess the effects of alternative interventions. This will also allow many more sources of data to be incorporated, reducing uncertainty in prediction still further.


Although the intention is to apply this to the analysis of the HIV epidemic in the UK, the methods to be developed will be applicable to the prevention and control of any human or animal infectious disease.

Technical Summary

Reliable methods are need to predict the future course of the HIV epidemic and the effect of possible interventions. Current methods are not adequate. The earlier back-projection methods for incidence estimation has been compromised by anti-retroviral therapy. The ?Direct Method? for prevalence estimation has been shown to make inconsistent and incomplete use of the available data (Goubar, 2006). Models of incidence and prevalence alone cannot predict the long-term effect of lowering incidence because incidence and prevalence are related by feedback mechanisms. Dynamic transmission models address this issue. Here, incidence in any subgroup g depends on the prevalence of infection in each group j and the probability that members on each group j will infect susceptibles in group g. However, dynamic models are generally set out as complex systems of differential equations, and it is not possible to estimate the parameters formally from data. As a result, prediction uncertainty can only be analysed by scenario analysis.

Recently, the applicants developed an alternative approach to prevalence estimation (Goubar, 2006). This was a Bayesian multi-parameter evidence synthesis (MPES) of 6 distinct types of surveillance and survey data on HIV, to simultaneously estimate risk group size, group-specific HIV prevalence and proportion diagnosed, in each of 13 risk groups. MPES allows assessment of consistency in evidence, and propagates uncertainty in evidence correctly through to parameters and predictions. This method was used for the Department of Health?s official report on the status of the HIV epidemic in 2004. Recently we extended this model, so that instead of producing a series of annual prevalence estimates from a series of annual data ensembles, it produces estimates of rates of entry into each of the risk groups, group-specific HIV incidence and diagnosis rates.

We now propose to extend this further to incorporate the essential properties of dynamic transmission models. The main step is to re-parameterise the model, expressing incidence in each group g as a linear combination of proportion of number of infected in group j and probabilities in a contact-an-mixing matrix that individuals in group j will infect susceptibes in group g. This re-parameterisation means that information on sexual contact patterns and transmission probabilities can be combined with the core surveillance data in a single integrated analysis.

The combination of Bayesian propagation of uncertainty with dynamic modelling creates a powerful tool for evidence-based policy analysis, applicable to the dynamics and control of any human or animal infectious disease.

Publications

10 25 50
 
Description Adviser to WHO HIV modelling in Europe Group
Geographic Reach Europe 
Policy Influence Type Participation in a advisory committee
Impact Adviser to WHO HIV modelling in Europe Group
 
Description Citation in House of Lords Select Commitee
Geographic Reach National 
Policy Influence Type Citation in other policy documents
Impact Work is cited both in the Written and Oral Evidence presented by the Health Protection Agency in the House of Lords Select Committee on HIV and AIDS in the United Kingdom report entitled "No vaccine, no cure: HIV and AIDS in the United Kingdom" which can be accessed here http://www.parliament.uk/business/committees/committees-a-z/lords-select/hiv-select-committee/publications/ The references are given formally in the Oral with associated written evidence (http://www.parliament.uk/documents/lords-committees/hivaids/HIVAIDSUKev.pdf) but our work is referenced informally (as the MPES method or via the HPA's report "HIV in the United Kingdom (2010 Report)") also in the Select Committee's 1st Report (http://www.publications.parliament.uk/pa/ld201012/ldselect/ldaids/188/188.pdf)
URL http://www.parliament.uk/business/committees/committees-a-z/lords-select/hiv-select-committee/public...
 
Description Citation in the SaBTO report from the DoH Blood Donor Selection Steering Group
Geographic Reach National 
Policy Influence Type Citation in other policy documents
Impact The work on the blood donor selection criteria review is referenced in https://www.gov.uk/government/publications/donor-selection-criteria-review http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_129909.pdf In the SaBTO report, the work is referenced as Davison et al, in press, but this work has now been published here: http://onlinelibrary.wiley.com/doi/10.1111/j.1423-0410.2011.01491.x/abstract The work resulted in a change in the recommendation made by SABTO on the current donor deferral period for men who have sex with men.
URL https://www.gov.uk/government/publications/donor-selection-criteria-review
 
Description Department of Health Scientific Pandemic Influenza Advisory Committee, subgroup on Modelling (SPIM-O)
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Member of SPI-M (O) SPI-M(O) advices the Department of Health on methods of data analysis in the preparedness for and during an emerging epidemic. The goal is to reduce the impact of an epidemic.
 
Description HIV prevalence estimates
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact New methods for HIV prevalence estimates; Recognition for the MRC and the Unit; Estimates contribute to HIV testing policy in the UK; In 2011, estimates contributed to the House of Lords Select Committee on HIV/AIDS (http://www.parliament.uk/HIVSELECT). 9 annual reports 2005-present produced: https://www.gov.uk/government/publications/hiv-in-the-united-kingdom http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/1211HIVintheUK2012/ http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/1111HIVintheUK2011report/ http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/1011HIVUK2010Report/ http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/0911HIVUK2009Report/ http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/0811hivUK/ http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/0711TestingTimesHIVandSTIsReport/ http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/0611ComplexPictureUKHIVSTI/ http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/0511MappingHIVandSTIinUK2005/
URL https://www.gov.uk/government/publications/hiv-in-the-united-kingdom
 
Description Member of the National HIV incidence and resistance advisory group
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Member of the National HIV incidence and resistance advisory group.
 
Description WHO Influenza Pandemic mortality consultation group
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact International collaboration on estimating global pandemic H1N1/2009 mortality to influence future policy for pandemic preparedness. Resulted in co-authorship on publication DOI: 10.1016/S1473-3099(12)70121-4
URL http://www.who.int/influenza/surveillance_monitoring/updates/MortalityEstimates/en/
 
Description WHO, HIV incidence assay working group
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Contribution towards new methods of estimation of HIV incidence based on Seroconversion assays - Robust estimation of HIV incidence and identification of recent infection at the individual level, are crucial to design and evaluate interventions to reduce HIV transmission, with an obvious consequence on quality of life.
 
Title MPES 
Description Statistical methods to synthesise information on disease prevalence from multiple sources, e.g. for HIV and HCV. 
Type Of Material Improvements to research infrastructure 
Provided To Others? Yes  
Impact Approach and software used by other researchers and public health agencies (UK and Europe). 
URL https://www.gov.uk/hiv-overall-prevalence
 
Title Methods for disease prevalence and incidence estimation 
Description Development of methods for disease prevalence and incidence estimation, e.g. for HIV, HCV and influenza. Methods include evidence synthesis, back-calculation and transmission modelling (see software section). 
Type Of Material Improvements to research infrastructure 
Year Produced 2009 
Provided To Others? Yes  
Impact Strengthening collaboration with recognised organisations, such as WHO; ECDC; UNAIDS; Harvard School of Public Health. 
 
Description Harvard University/CDC/NIH 
Organisation Centers for Disease Control and Prevention (CDC)
Country United States 
Sector Public 
PI Contribution Scientific collaboration.
Collaborator Contribution Scientific collaboration and data provision. Epidemiological expertise and data provision. Hosted a member of my team for two months, funded by MRC Centenary Award.
Impact PMID: 19997612; 21612363 Talk at Epidemics conference 2009. Poster at Epidemics conference 2013. Paper in preparation.
Start Year 2009
 
Description Harvard University/CDC/NIH 
Organisation Fogarty International Centre
Department Division of International Epidemiology and Population Studies (DIEPS)
Country United States 
Sector Public 
PI Contribution Scientific collaboration.
Collaborator Contribution Scientific collaboration and data provision. Epidemiological expertise and data provision. Hosted a member of my team for two months, funded by MRC Centenary Award.
Impact PMID: 19997612; 21612363 Talk at Epidemics conference 2009. Poster at Epidemics conference 2013. Paper in preparation.
Start Year 2009
 
Description Harvard University/CDC/NIH 
Organisation Harvard University
Department Harvard T.H. Chan School of Public Health
Country United States 
Sector Academic/University 
PI Contribution Scientific collaboration.
Collaborator Contribution Scientific collaboration and data provision. Epidemiological expertise and data provision. Hosted a member of my team for two months, funded by MRC Centenary Award.
Impact PMID: 19997612; 21612363 Talk at Epidemics conference 2009. Poster at Epidemics conference 2013. Paper in preparation.
Start Year 2009
 
Description Health Protection Agency 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution Development/ application of statistical methods to enable a better understanding of the HIV epidemic in the UK.
Collaborator Contribution Data provision and epidemiological expertise
Impact Many scientific publications. One PhD thesis completed. Reports: - Health Protection Agency, HIV in the United Kingdom: 2009 Report, London, United Kingdom, November 2009. Available from: http://www.hpa.org.uk/Publications/InfectiousDiseases/HIVAndSTIs/0911HIVUK2009Report/ (De Angelis D, Presanis AM, contributors). - Health Protection Agency Centre for Infections HIV, HIV in the United Kingdom: 2008 report, London, United Kingdom, November 2008. Available from: http://www.hpa.org.uk/hivuk2008 (De Angelis D, Presanis A, contributors).
Start Year 2007
 
Description Health Protection Agency -Influenza 
Organisation Public Health England
Department Centre of Infectious Disease Surveillance and Control
Country United Kingdom 
Sector Public 
PI Contribution Statistical analysis and consultation Publication
Collaborator Contribution Data provision and statistical expertise
Impact PMIDs: 22042838; 21903689; 21087539, doi:10.1214/14-AOAS775 Papers under submission: Birrell PJ, Zhang X-S, Pebody RG, Gay NJ, De Angelis D. Reconstructing a spatially heterogeneous epidemic: Characterising the geographic spread of 2009 A/H1N1 infection in England (Scientific Reports) Birrell PJ, De Angelis D, Wernisch L, Tom BDM, Roberts GO, Pebody RG. Efficient real-time monitoring of an emerging influenza epidemic: how feasible? (Journal of the Royal Statistical Society (Series C))
Start Year 2009
 
Description Health Protection Agency -Influenza 
Organisation Royal College of General Practitioners
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical analysis and consultation Publication
Collaborator Contribution Data provision and statistical expertise
Impact PMIDs: 22042838; 21903689; 21087539, doi:10.1214/14-AOAS775 Papers under submission: Birrell PJ, Zhang X-S, Pebody RG, Gay NJ, De Angelis D. Reconstructing a spatially heterogeneous epidemic: Characterising the geographic spread of 2009 A/H1N1 infection in England (Scientific Reports) Birrell PJ, De Angelis D, Wernisch L, Tom BDM, Roberts GO, Pebody RG. Efficient real-time monitoring of an emerging influenza epidemic: how feasible? (Journal of the Royal Statistical Society (Series C))
Start Year 2009
 
Description Health Protection Agency UK-HIV 
Organisation Public Health England
Department Centre of Infectious Disease Surveillance and Control
Country United Kingdom 
Sector Public 
PI Contribution Statistical expertise. Publications and reports.
Collaborator Contribution Data provision and statistical expertise
Impact PMID: 21087539; 21525422; 21422986; 20962617; 19081004; 22039196; 21932033 Reports: The UK Collaborative Group for HIV and STI surveillance. 2005. Mapping the issues. HIV and other sexually transmitted infections in the United Kingdom:2005 The UK Collaborative Group for HIV and STI surveillance. 2006. A Complex picture. HIV and other sexually transmitted infections in the United Kingdom:2006 The UK Collaborative Group for HIV and STI surveillance. 2007. Testing times. HIV and other sexually transmitted infections in the United Kingdom:2007 Health Protection Agency Centre for Infections. HIV in the United Kingdom: 2008 report (www.hpa.org.uk/hivuk2008) Health Protection Agency Centre for Infections. HIV in the United Kingdom: 2009 report (www.hpa.org.uk/hivuk2009) Health Protection Agency Centre for Infections. HIV in the United Kingdom: 2010 report (www.hpa.org.uk/hivuk2010)
 
Description NATSAL 
Organisation National Centre for Social Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical modelling and expertise.
Collaborator Contribution Provision of data to contribute to evidence syntheses to estimate prevalence of HIV and HCV.
Impact HIV and HCV annual reports from Public Health England.
 
Description NATSAL 
Organisation University College London
Department School of Life and Medical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Statistical modelling and expertise.
Collaborator Contribution Provision of data to contribute to evidence syntheses to estimate prevalence of HIV and HCV.
Impact HIV and HCV annual reports from Public Health England.
 
Description WHO/Netherland/HPA 
Organisation National Institute for Public Health and Environment (RIVM)
Department Centre for Control of Infectious Diseases
Country Netherlands 
Sector Public 
PI Contribution Scientific collaboration and statistical expertise
Collaborator Contribution Data provision and scientific collaborationStatistical expertise. Publications and reports.Statistical expertise
Impact Presentations at formal meetings/Scientific presentations. Papers 21150562 Technical reports: - National Estimates of HIV Prevalence and Modelling of the HIV Epidemic in Europe. World Health Organization (WHO) Technical report, March 2010 (De Angelis D, Presanis AM, Conti S, contributors) - World Health Organization (WHO), 'Transmission dynamics and impact of pandemic influenza A (H1N1) 2009 virus' In Weekly Epidemiological Record, No. 46, 2009, 84, 477-484. Available from http://www.who.int/wer (De Angelis D, Presanis AM, contributors)
Start Year 2007
 
Description WHO/Netherland/HPA 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution Scientific collaboration and statistical expertise
Collaborator Contribution Data provision and scientific collaborationStatistical expertise. Publications and reports.Statistical expertise
Impact Presentations at formal meetings/Scientific presentations. Papers 21150562 Technical reports: - National Estimates of HIV Prevalence and Modelling of the HIV Epidemic in Europe. World Health Organization (WHO) Technical report, March 2010 (De Angelis D, Presanis AM, Conti S, contributors) - World Health Organization (WHO), 'Transmission dynamics and impact of pandemic influenza A (H1N1) 2009 virus' In Weekly Epidemiological Record, No. 46, 2009, 84, 477-484. Available from http://www.who.int/wer (De Angelis D, Presanis AM, contributors)
Start Year 2007
 
Description WHO/Netherland/HPA 
Organisation World Health Organization (WHO)
Country Global 
Sector Public 
PI Contribution Scientific collaboration and statistical expertise
Collaborator Contribution Data provision and scientific collaborationStatistical expertise. Publications and reports.Statistical expertise
Impact Presentations at formal meetings/Scientific presentations. Papers 21150562 Technical reports: - National Estimates of HIV Prevalence and Modelling of the HIV Epidemic in Europe. World Health Organization (WHO) Technical report, March 2010 (De Angelis D, Presanis AM, Conti S, contributors) - World Health Organization (WHO), 'Transmission dynamics and impact of pandemic influenza A (H1N1) 2009 virus' In Weekly Epidemiological Record, No. 46, 2009, 84, 477-484. Available from http://www.who.int/wer (De Angelis D, Presanis AM, contributors)
Start Year 2007
 
Title Swine Flu 
Description Advice and recommendations to the government through participation in advisory group 
Type Support Tool - For Fundamental Research
Current Stage Of Development Small-scale adoption
Year Development Stage Completed 2009
Development Status Under active development/distribution
Impact Revised public health advice 
 
Title MPES 
Description Bespoke evidence synthesis models for estimating disease prevalence (HIV, HCV), developed and employed by national and international public health agencies (Public Health England annually since 2006, Health Protection Scotland in 2014, Dutch National Institute of Public Health (RIVM) in 2010-11, 2014). 
Type Of Technology Software 
Year Produced 2006 
Impact Annual national estimates of HIV and HCV prevalence PHE Annual report on Hepatitis C in the UK (since 2008) See link to 2014 report: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/337115/HCV_in_the_UK_2014_24_July.pdf 
URL https://www.gov.uk/hiv-overall-prevalence
 
Description Annual WHO/ European Network Meeting for HIV/AIDS Surveillance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact Presented "Multi-parameter evidence synthesis to estimate HIV prevalence in the UK: applicability to other European countries?" at the Annual WHO meeting on HIV surveillance. Copenhagen, November 2008.
See also 2009 report: http://www.euro.who.int/en/health-topics/communicable-diseases/hivaids/publications/2010/hivaids-surveillance-in-europe-2009

Recognition for the work of the MRC and the Unit
Year(s) Of Engagement Activity 2008,2009
URL http://www.euro.who.int/__data/assets/pdf_file/0003/78564/E92851.pdf
 
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 Public/other audiences
Results and Impact Each year BSU participate in Cambridge Science Festival - members of the general public explore and discuss issues of scientific interest and concern, through a series of different events. The event also aims to raise aspirations by encouraging young people to consider a career in science, technology, engineering or mathematics.

BSU take part over two full days - 'Science Saturday' and the 'Cambridge Biomedical Campus' day. The unit presents a stand with 4 - 5 interactive activities that each communicate a basic statistical method or idea, representing one of the four research themes in the unit. Each year a new activity is developed and delivered requiring scientific input from staff across the unit. Over the two days, BSU engage with approximately 500 adults and children who visit the festival.


Raised awareness of the Unit's work in the local schools community
Very good feedback from festival attendants
Contributed to enhance the methodological quality of medical research developed by BSU staff
Contributed to enable Best Research for Best Health
Year(s) Of Engagement Activity 2007,2008,2009,2011,2012
URL http://www.cam.ac.uk/science-festival
 
Description Department of Health Scientific Pandemic Influenza Advisory Committee, subgroup on Modelling (SPIM-O) 2011 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Presentation of current relevant work at the Department of Health Scientific Pandemic Influenza Advisory Committee, subgroup on Modelling (SPIM-O). Audience included scientists and policy-makers

The work presented forms the basis of an ongoing funding application to NIHR
Year(s) Of Engagement Activity 2011
 
Description RIVM Netherlands 2009 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact 30 people attended the initial reports meeting of the RIVM (Nationa Institute for Public Heakth and the Envirnment- The Netherlands)

Initial report of results from the collaboration
Year(s) Of Engagement Activity 2009
URL http://www.rivm.nl/en
 
Description Stockholm-Euro-HIV meeting 2008 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Invited speaker at the EURO-HIV meeting in Stockholm. Talk entitled "HIV incidence estimates in the collaborating countries"

Recognition for the MRC and the unit.
Year(s) Of Engagement Activity 2008
 
Description UNAIDS Reference Group Meeting 2008 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact De Angelis D presented "Performance of different prevalence estimation tools in the Netherlands, and comparison with case reports of HIV infection" at UNAIDS Reference Group Meeting. December 2008, Amsterdam.

Recognition for the work of the MRC and the Unit.
Published report: "Estimation of the size of high risk groups and HIV prevalence in high risk groups in concentrated epidemics". Report of a meeting of the UNAIDS Reference Group on Estimates, Modelling and Projections held in Amsterdam, the Netherlands, Dec 9-10th 2008. TECHNICAL REPORT AND RECOMMENDATIONS
Year(s) Of Engagement Activity 2008
URL http://www.epidem.org/sites/default/files/reports/Final%20Report_Amsterdam2008_July%202009.pdf
 
Description WHO/ECDC/ UNAIDS Meeting 2007 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Invited speaker at WHO/ECDC/UNAIDS meeting in Amsterdam. Talk entitled "Current developments on estimation of HIV prevalence/incidence in the UK"

Recognition for the MRC and the Unit
Year(s) Of Engagement Activity 2007