Calibration and analysis of complex models: methodological development and application to explore the impact of HAART in AfricaMR/J014362/1
Lead Research Organisation:
London School of Hygiene & Tropical Medicine
Department Name: Epidemiology and Population Health
Abstract
Mathematical models are used routinely in government, the public sector, industry and academia to help predict the future and make policy decisions, such as what is the impact of ocean currents on the climate and how should we best prepare for the next flu pandemic? The usefulness of models in helping to make decision relies on how well they are can be matched to real data (model calibration) and how well we can analyse the models to find out how confident we should be about the predictions they make. In recent years models have become increasingly complex, but we don't yet have good methods to calibrate and analyse these more complicated models. The lack of these methods is a major obstacle to improving our predictions, and the policy decisions that affect all of us in the UK.
HIV/AIDS remains the leading public health problem in much of sub-Saharan Africa. While increased access to treatment for HIV (highly active anti-retroviral therapy or HAART) has successfully reduced suffering and deaths among people living with HIV/AIDS, it is unknown how best HAART can be used to reduce the number of new HIV infections. Models would help us determine the best strategy, but we need improved methods of model calibration and analysis to do this.
In this project we will develop new methods to calibrate and analyse complex individual-based stochastic models (these models are very computer-intensive as every individual is explicitly tracked through time). First we will develop two new model calibration methods specifically for stochastic models and also develop new methods that allow us to calibrate multiple models outputs at the same time (eg the number of people infected with HIV and the number of deaths from AIDS). Then we will compare these new methods with existing methods to see how they perform. We will go on to develop hybrid calibration methods that combines the strengths of our new and existing methods, to get the best of both. Finally we will apply our new methods to calibrate a complex model to data on HIV/AIDS trends in Africa, and use our fitted models to predict the impact of HAART on HIV/AIDS in Africa.
The development and evaluation of robust methods for the calibration and analysis of complex models should result in the generation of more reliable scientific evidence and better health policy and funding decisions. In addition, an effective method of assessing the likely impact of HAART should lead to better informed policies and improved public health in Africa. If the models are accurate, the benefits may include fewer people dying and being infected with HIV, alleviating the substantial social and economic burden of the epidemic as well as reducing the burgeoning costs of HIV-related health care.
An international multidisciplinary team will carry out this research. Statistical expertise is available from investigators from Durham University, Sheffield University and Cambridge University; expertise in the development and application of complex HIV models is available from investigators in the London School of Hygiene and Tropical Medicine; and virologic expertise and uniquely detailed high quality empirical data is available from MRC/UVRI in Uganda.
HIV/AIDS remains the leading public health problem in much of sub-Saharan Africa. While increased access to treatment for HIV (highly active anti-retroviral therapy or HAART) has successfully reduced suffering and deaths among people living with HIV/AIDS, it is unknown how best HAART can be used to reduce the number of new HIV infections. Models would help us determine the best strategy, but we need improved methods of model calibration and analysis to do this.
In this project we will develop new methods to calibrate and analyse complex individual-based stochastic models (these models are very computer-intensive as every individual is explicitly tracked through time). First we will develop two new model calibration methods specifically for stochastic models and also develop new methods that allow us to calibrate multiple models outputs at the same time (eg the number of people infected with HIV and the number of deaths from AIDS). Then we will compare these new methods with existing methods to see how they perform. We will go on to develop hybrid calibration methods that combines the strengths of our new and existing methods, to get the best of both. Finally we will apply our new methods to calibrate a complex model to data on HIV/AIDS trends in Africa, and use our fitted models to predict the impact of HAART on HIV/AIDS in Africa.
The development and evaluation of robust methods for the calibration and analysis of complex models should result in the generation of more reliable scientific evidence and better health policy and funding decisions. In addition, an effective method of assessing the likely impact of HAART should lead to better informed policies and improved public health in Africa. If the models are accurate, the benefits may include fewer people dying and being infected with HIV, alleviating the substantial social and economic burden of the epidemic as well as reducing the burgeoning costs of HIV-related health care.
An international multidisciplinary team will carry out this research. Statistical expertise is available from investigators from Durham University, Sheffield University and Cambridge University; expertise in the development and application of complex HIV models is available from investigators in the London School of Hygiene and Tropical Medicine; and virologic expertise and uniquely detailed high quality empirical data is available from MRC/UVRI in Uganda.
Technical Summary
Complex individual-based stochastic models are increasingly being used across science, engineering, medicine and public health. The utility of models for prediction & planning relies on how well they are calibrated to data and analysed for robustness of predictions. However, development of methods to calibrate and analyse complex stochastic models has greatly lagged behind their application, resulting in unreliable predictions and increasing the probability of incorrect policy and funding decisions
Aim
Develop and evaluate methods to calibrate and analyse complex individual-based stochastic models, and apply them to explore the impact of HAART on HIV/AIDS in Africa
Objectives
-Develop novel methods for Bayesian Emulation of stochastic models
-Comparative analysis of accuracy/efficiency of existing MCMC, ABC and novel Bayesian Emulation methods for the calibration and analysis of stochastic models
-Develop and analyse a novel hybrid model calibration strategy combining the strengths of ABC and Emulation methods
-Apply developed and analysed methods to predict the impact of HAART on HIV/AIDS in Africa
Methods
Development: Bayes linear and fully Bayesian emulation for calibration of stochastic models, and multivariate outputs
Hybrid ABC & Emulation methods for efficient generation of probabilistic statements about goodness of fit & joint estimation of posterior probability distributions
Experiments: Use new methods to estimate model parameters by calibrating model to simulated data with known 'true' parameter values, varying number and prior bias & variance of model parameters
Application: Use new methods to calibrate complex model to uniquely detailed HIV/AIDS data from African cohorts
Application/exploitation
Application within project to predict impact of HAART on HIV in Africa and engagement with international policy makers/funders to improve policy/funding decisions. Novel methods dissemination to other science areas/public sector/industry
Aim
Develop and evaluate methods to calibrate and analyse complex individual-based stochastic models, and apply them to explore the impact of HAART on HIV/AIDS in Africa
Objectives
-Develop novel methods for Bayesian Emulation of stochastic models
-Comparative analysis of accuracy/efficiency of existing MCMC, ABC and novel Bayesian Emulation methods for the calibration and analysis of stochastic models
-Develop and analyse a novel hybrid model calibration strategy combining the strengths of ABC and Emulation methods
-Apply developed and analysed methods to predict the impact of HAART on HIV/AIDS in Africa
Methods
Development: Bayes linear and fully Bayesian emulation for calibration of stochastic models, and multivariate outputs
Hybrid ABC & Emulation methods for efficient generation of probabilistic statements about goodness of fit & joint estimation of posterior probability distributions
Experiments: Use new methods to estimate model parameters by calibrating model to simulated data with known 'true' parameter values, varying number and prior bias & variance of model parameters
Application: Use new methods to calibrate complex model to uniquely detailed HIV/AIDS data from African cohorts
Application/exploitation
Application within project to predict impact of HAART on HIV in Africa and engagement with international policy makers/funders to improve policy/funding decisions. Novel methods dissemination to other science areas/public sector/industry
Planned Impact
This research should benefit society as a whole, primarily through improved understanding and prediction of complex models, and thereby improved guidance to policy makers.
Immediate beneficiaries will include the users and developers of complex models in government, the public sector, industry and academia. These users will have better methods with which to calibrate and analyse their complex models. Example beneficiaries include epidemiologists and public researchers who use models to compare different strategies to combat infection in the UK and elsewhere, and oil industry engineers who use models to provide information on where to drill exploratory wells. The former is an example where this research could have a relatively quick impact on public heath in the UK and elsewhere. The latter is an example where this research could have a direct and relatively quick impact on the UK economy. Investigators on the proposal have direct links to both groups of beneficiaries.
Direct beneficiaries also include national and international technical modelling committees who will be interested in these developments. An example includes WHO Quantitative Immunisation and Vaccines related Research Committee, on which one of the investigators sits.
This research should also benefit those who rely on information generated by models to make decisions. For example, UK governmental committees such as the UK Joint Committee on Vaccination and Immunisation (JCVI) and international body UNAIDS, both of which rely heavily on information generated by models in their decision making. These bodies would benefit from the higher quality information that could be provided if our novel methods are implemented. Investigators on the proposal are advisors to both these bodies.
The general public should benefit from the improved policy and funding decisions that can be made based on the higher quality information provided by our novel model calibration and analysis methods. They should also benefit from improved policy formation that should lead to improved health and well being, and improved resource allocation in public services.
Immediate beneficiaries will include the users and developers of complex models in government, the public sector, industry and academia. These users will have better methods with which to calibrate and analyse their complex models. Example beneficiaries include epidemiologists and public researchers who use models to compare different strategies to combat infection in the UK and elsewhere, and oil industry engineers who use models to provide information on where to drill exploratory wells. The former is an example where this research could have a relatively quick impact on public heath in the UK and elsewhere. The latter is an example where this research could have a direct and relatively quick impact on the UK economy. Investigators on the proposal have direct links to both groups of beneficiaries.
Direct beneficiaries also include national and international technical modelling committees who will be interested in these developments. An example includes WHO Quantitative Immunisation and Vaccines related Research Committee, on which one of the investigators sits.
This research should also benefit those who rely on information generated by models to make decisions. For example, UK governmental committees such as the UK Joint Committee on Vaccination and Immunisation (JCVI) and international body UNAIDS, both of which rely heavily on information generated by models in their decision making. These bodies would benefit from the higher quality information that could be provided if our novel methods are implemented. Investigators on the proposal are advisors to both these bodies.
The general public should benefit from the improved policy and funding decisions that can be made based on the higher quality information provided by our novel model calibration and analysis methods. They should also benefit from improved policy formation that should lead to improved health and well being, and improved resource allocation in public services.
Organisations
- London School of Hygiene & Tropical Medicine (Lead Research Organisation)
- Johns Hopkins Medicine (Collaboration)
- World Health Organization (WHO) (Collaboration)
- HARVARD UNIVERSITY (Collaboration)
- Amsterdam Institute for Global Health and Development (AIGHD) (Collaboration)
- Ghana Health Service (Collaboration)
- Intellectual Ventures (United States) (Collaboration)
- Johns Hopkins University (Collaboration)
- Viet Nam Government (Collaboration)
- Bill & Melinda Gates Foundation (Collaboration)
- Centers for Disease Control and Prevention (CDC) (Collaboration)
Publications
Andrianakis I
(2017)
History matching of a complex epidemiological model of human immunodeficiency virus transmission by using variance emulation.
in Journal of the Royal Statistical Society. Series C, Applied statistics
Andrianakis I
(2017)
Efficient History Matching of a High Dimensional Individual-Based HIV Transmission Model
in SIAM/ASA Journal on Uncertainty Quantification
Andrianakis I
(2015)
Bayesian history matching of complex infectious disease models using emulation: a tutorial and a case study on HIV in Uganda.
in PLoS computational biology
Biraro S
(2013)
Effect of HSV-2 on population-level trends in HIV incidence in Uganda between 1990 and 2007.
in Tropical medicine & international health : TM & IH
Cavany SM
(2018)
Transmission events revealed in tuberculosis contact investigations in London.
in Scientific reports
Cavany SM
(2017)
An evaluation of tuberculosis contact investigations against national standards.
in Thorax
Dodd PJ
(2013)
Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis.
in PloS one
Dodd PJ
(2016)
Age- and Sex-Specific Social Contact Patterns and Incidence of Mycobacterium tuberculosis Infection.
in American journal of epidemiology
Dowdy DW
(2014)
Impact and cost-effectiveness of current and future tuberculosis diagnostics: the contribution of modelling.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Fofana MO
(2014)
Population-level impact of shorter-course regimens for tuberculosis: a model-based analysis.
in PloS one
Gomez G
(2016)
Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis
in BMC Infectious Diseases
Harris RC
(2016)
Systematic review of mathematical models exploring the epidemiological impact of future TB vaccines.
in Human vaccines & immunotherapeutics
Harris RC
(2019)
Age-targeted tuberculosis vaccination in China and implications for vaccine development: a modelling study.
in The Lancet. Global health
Harris RC
(2016)
The potential impact of BCG vaccine supply shortages on global paediatric tuberculosis mortality.
in BMC medicine
HIV Modelling Consortium Treatment As Prevention Editorial Writing Group
(2012)
HIV treatment as prevention: models, data, and questions--towards evidence-based decision-making.
in PLoS medicine
Horton KC
(2016)
Sex Differences in Tuberculosis Burden and Notifications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.
in PLoS medicine
Houben RM
(2014)
Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings.
in Proceedings of the National Academy of Sciences of the United States of America
Houben RM
(2016)
TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions.
in BMC medicine
Houben RMGJ
(2016)
Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models.
in The Lancet. Global health
Knight GM
(2015)
Tuberculosis prevention in South Africa.
in PloS one
Knight GM
(2015)
The Distribution of Fitness Costs of Resistance-Conferring Mutations Is a Key Determinant for the Future Burden of Drug-Resistant Tuberculosis: A Model-Based Analysis.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Knight GM
(2014)
Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries.
in Proceedings of the National Academy of Sciences of the United States of America
McCreesh N
(2017)
Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention - a modelling study.
in BMC infectious diseases
McCreesh N
(2017)
Universal test, treat, and keep: improving ART retention is key in cost-effective HIV control in Uganda.
in BMC infectious diseases
McCreesh N
(2018)
Choice of time horizon critical in estimating costs and effects of changes to HIV programmes.
in PloS one
McCreesh N
(2016)
Coverage of clinic-based TB screening in South Africa may be low in key risk groups
in Public Health Action
McKinley T
(2018)
Approximate Bayesian Computation and Simulation-Based Inference for Complex Stochastic Epidemic Models
in Statistical Science
Menzies NA
(2016)
Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.
in The Lancet. Global health
Meunier NV
(2017)
Wildlife-livestock interactions and risk areas for cross-species spread of bovine tuberculosis.
in The Onderstepoort journal of veterinary research
Métras R
(2015)
Risk factors associated with Rift Valley fever epidemics in South Africa in 2008-11.
in Scientific reports
Nsubuga RN
(2014)
Estimation of the HIV basic reproduction number in rural south west Uganda: 1991-2008.
in PloS one
Odone A
(2014)
The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets.
in The lancet. Diabetes & endocrinology
Pretorius C
(2014)
Using the TIME model in Spectrum to estimate tuberculosis-HIV incidence and mortality.
in AIDS (London, England)
Pretorius C
(2014)
The potential effects of changing HIV treatment policy on tuberculosis outcomes in South Africa: results from three tuberculosis-HIV transmission models.
in AIDS (London, England)
Punyacharoensin N
(2016)
Effect of pre-exposure prophylaxis and combination HIV prevention for men who have sex with men in the UK: a mathematical modelling study.
in The lancet. HIV
Punyacharoensin N
(2015)
Modelling the HIV epidemic among MSM in the United Kingdom: quantifying the contributions to HIV transmission to better inform prevention initiatives.
in AIDS (London, England)
Reid A
(2015)
Accelerating progress towards tuberculosis elimination: the need for combination treatment and prevention.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Rhodes SJ
(2016)
Individual-level factors associated with variation in mycobacterial-specific immune response: Gender and previous BCG vaccination status.
in Tuberculosis (Edinburgh, Scotland)
Scarponi D
(2023)
Is neglect of self-clearance biassing TB vaccine impact estimates?
in medRxiv : the preprint server for health sciences
Description | Changed South African Govt Policy Announcement on TB screening in schools |
Geographic Reach | National |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Description | Course - Introduction to impact and economics of TB control |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Trained medical professionals in quantitative methods to use in their decision making at country and global level. |
Description | Evidence used to set WHO post-2015 Global TB Targets |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in other policy documents |
Impact | My group generated evidence that was used to set ambitious WHO post 2015 global TB targets. This should have major impact on TB financing and control policies and practice over the next 15 years. |
Description | Global Fund Distribution of Funding by Disease |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | I directly contributed to debate and the (eventual) consensus that led to an increase in proportion of funds allocated by the Global Fund to Tuberculosis. Global reach. Should increase survival and morbidity by reducing TB disease (no quantitative evidence yet) |
Description | Impact on TB control funding priorities and budget in South Africa |
Geographic Reach | National |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Impact | '2025 Global TB Targets' modelling for South Africa is influencing TB policy decisions in this countries (2014+). Where work is influencing SA Govt Budgets, Policy and Research Priorities. This work supported successful award of Global Fund Concept note and grant in 2015, and work was also used in first ever Govt/UNAIDS HIV and TB Investment Case, that supported the introduction of the first ever conditional (ie ringfenced) grant for TB and HIV in SA, and the allocation of an extra Rand500m (~£50m) to TB control by the SA Govt in 2016. |
Description | Impact on human TB vaccine development funding priorities |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Impact | My group helped demonstrate that an new TB vaccine targeted at adolescent/adults would have considerably greater early impact on the global TB epidemic, than a vaccine targeted at infants, and would be cost-effective, even with a relative low efficacy and short protection duration (Knight et al 2015). This evidence led to a major change in BMGF TB vaccine policy and was cited to support the primary new BMGF TB vaccine strategy goal: "To accelerate discovery and development of a vaccine to prevent TB infection and/or disease in adolescents and adults" (2014-2015). (url below) |
URL | https://drive.google.com/file/d/0B2K5XWn1bjpORmpHLUdoOXJFTlk/view |
Description | Input into Global Fund Steering Committee on Modeling work to inform development of the Global Fund's Strategy goals & targets, Needs Assessment and Funding Allocation |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Methods agreed with input from my group into Global Fund Steering Committee on Modeling work to inform development of the Global Fund's Strategy goals & targets, Needs Assessment and Funding Allocation (2015) were used to prevent inappropriate methods being used to assess Global Fund's strategy goals & targets, needs assessment and funding allocation in 2016+. Specifically inappropriate methods were being considered for between-country resource allocation of the Global Funds TB funds. Use of these methods was prevented. |
Description | Input into WHO Global Task Force on TB Impact Measurement Reference Methods Group |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Methods agreed with input from my group into WHO Global Task Force on TB Impact Measurement Reference Methods Group (2015) were used to determine if the WHO 2000-2015 global TB targets had been met. Published in 2015 WHO TB report. This also helped identify that TB is now the leading cause of death from an infectious disease globally, which should increase global resource allocation to TB over the next few years. |
URL | http://www.who.int/tb/publications/global_report/en/ |
Description | Led creation of 'STROBE-RDS': Reporting Guidelines for Respondent Driven Sampling Surveys |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Impact | Peer reviewed reporting guidelines have been published, have been incorporated into submission guidelines for at least two academic journals (2016), have already been cited in papers reporting findings from RDS surveys. This will increase the value of data collected using RDS. This should lead to improved health and funding decisions targeted (primarily) at the control and prevention of HIV, and later, improved survival, morbidity and quality of life, and the efficiency of health care delivery. |
URL | http://www.ncbi.nlm.nih.gov/pubmed/26112433 |
Description | Policy recommendation document to Ugandan Ministry of Health |
Geographic Reach | Africa |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Impact | We had a meeting with Uganda Ministry of Health Officials, and subsequently provided them with a policy recommendation document which they requested. We advised that adopting universal access to ART for all people living with HIV would be highly cost effective, and may be cost saving. Subsequent to this, the Uganda MoH revised its ART guidelines to recommend that ART be provided to all people living with HIV. |
Description | WHO/South African Department of Health Tuberculosis Meeting |
Geographic Reach | Africa |
Policy Influence Type | Contribution to a national consultation/review |
Impact | This and subsequent meetings lead to a change in the South Africa Govt's National Strategic Plan policy to include continuous Isoniazid Preventive Therapy (IPT) to HIV infected individuals. IPT greatly reduces mortality in HIV infected individuals. This will have a near immediate impact on survival / morbidity / quality of life in HIV+ South Africans. |
Description | Aeras project grant |
Amount | $150,000 (USD) |
Organisation | Aeras |
Sector | Charity/Non Profit |
Country | Global |
Start | 09/2012 |
End | 03/2013 |
Description | Aeras studentship grant |
Amount | $150,000 (USD) |
Organisation | Aeras |
Sector | Charity/Non Profit |
Country | Global |
Start | 05/2013 |
End | 12/2016 |
Description | BMGF Project Grant |
Amount | £2,348,811 (GBP) |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2017 |
End | 11/2019 |
Description | BMGF project grant |
Amount | £90,848 (GBP) |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 11/2016 |
End | 12/2017 |
Description | Bill and Melinda Gates Foundation: Global Health: Tuberculosis |
Amount | $2,300,000 (USD) |
Funding ID | OPP1084276 |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 03/2014 |
End | 12/2015 |
Description | Bill and Melinda Gates Foundation: Global Health: Tuberculosis |
Amount | $125,000 (USD) |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2016 |
End | 06/2019 |
Description | Bill and Melinda Gates Foundation: Global Health: Tuberculosis |
Amount | $2,000,000 (USD) |
Funding ID | OPP1110334 |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 05/2014 |
End | 09/2016 |
Description | Bill and Melinda Gates Foundation: Global Health: Tuberculosis |
Amount | $20,000 (USD) |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 07/2015 |
End | 05/2016 |
Description | Bristish Heart Foundation Fellowship |
Amount | £1 (GBP) |
Organisation | Heart Centre Foundation, Hungary |
Sector | Public |
Country | Hungary |
Start | 01/2016 |
End | 12/2019 |
Description | Improving scientific and public health decision making by developing technologies to increase use of robust methods to calibrate and analyse complex mathematical models |
Amount | £451,991 (GBP) |
Funding ID | 218261/Z/19/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2020 |
End | 12/2022 |
Description | Improving scientific and public health decision making by developing technologies to increase use of robust methods to calibrate and analyse complex mathematical models |
Amount | £494,109 (GBP) |
Funding ID | 218261/Z/19/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2020 |
End | 01/2023 |
Description | MRC Fellowship (by team member) |
Amount | £287,454 (GBP) |
Funding ID | MR/N014693/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2016 |
End | 06/2019 |
Description | MRC Project Grant |
Amount | £386,998 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2017 |
End | 02/2019 |
Description | UNITAID Reserach Grant |
Amount | £2,709,550 (GBP) |
Funding ID | 4214-LSHTM-Sept15 (PO #8477-0-600) |
Organisation | World Health Organization (WHO) |
Department | UNITAID |
Sector | Public |
Country | Switzerland |
Start | 05/2015 |
End | 06/2019 |
Description | USAID TB Treat Grant |
Amount | $1,499,000 (USD) |
Funding ID | GHN-A-OO-08-00004-00 |
Organisation | United States Agency for International Development |
Sector | Public |
Country | United States |
Start | 03/2014 |
End | 03/2016 |
Description | Wellcome Trust Fellowship |
Amount | £120,000 (GBP) |
Funding ID | 109915/Z/15/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2016 |
End | 07/2019 |
Title | TB ePAL (electronic PArticipant Locator tool) |
Description | In high density urban settings without formal address systems, identification of the place of residence of patients presenting to health centres is often challenging and inaccurate. This type of information is essential for patient follow up in the community, for disease surveillance and identification of hotspots for efficient targeting of limited healthcare resources, for research study participant follow up and mapping, and for identifying populations suitable for enrolment into vaccine clinical trials. ePAL (electronic PArticipant Locator tool) is a tablet-based tool aiming to facilitate accurate identification of place of residence of patients presenting to health centres in Blantyre, Malawi. Points of interest relevant to the community were collected using GPS from across Blantyre city by community engagement through health surveillance assistants. Preceded by an eCRF, these points of interest combined with high resolution satellite maps constitute the ePAL app, which is being placed on tablets in TB registration centres across Blantyre city. ePAL is currently being evaluated in this setting and is hoped will be the first electronic data capture of TB registrations in Malawi and an important tool embraced by the Department of Health and Malawi-Liverpool-Wellcome (MLW) research centre for mapping and follow up of TB cases and identification of populations suitable for research including clinical trials. The tool is being developed in collaboration between LSHTM (London, UK) and MLW (Blantyre, Malawi). |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | The tool itself has undergone validation for identifying place of residence of TB patients presenting at TB registration centres and the data are currently being analysed. The tool has been adapted for two other research projects at MLW: surveillance for an ongoing typhoid outbreak and a study on impact of PCV vaccines. Several other studies in Blantyre are soon to begin using ePAL. It is hoped once the tool is validated that it could be replicated in other similar settings. |
Title | History matching of complex agent based computer models using emulation |
Description | The developed method allows the calibration of multi-input, multi-output agent based computer models of high complexity. The method is based on a statistical approximation of the computer model, called the emulator, and tries to identify regions of the input space that are likely to lead to a match between the model's outputs and the calibration data. The computational efficiency of the emulator makes this method very applicable to computer models with long running times. |
Type Of Material | Computer model/algorithm |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | None yet |
URL | http://cmmid.lshtm.ac.uk/mrccalib/ |
Title | New user-friendly country-level modelling tool for TB-HIV control projections and costings |
Description | We created a user-friendly tool (a mathematical model) for TB-HIV control projections and costing. This tool is for use by country-level TB/HIV policy makers for decision making on TB control strategies and costing. It has been used in workshops at Global level by UNAIDS, the Global Fund and WHO, and at country level in South Africa, Viet Nam, Ghana, Nigeria. |
Type Of Material | Computer model/algorithm |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | It was rolled out globally in 2015. So far it has been used by my group to update the Sudan, Bangladesh and Vietnam National Strategic Plan in 2013/4 (in Sudan, a move to more decentralized provision of TB patient care), and in Ghana, Nigeria. It will be used in about ~5 more high TB burden countries in 2016. |
URL | http://www.avenirhealth.org/software-spectrum |
Description | In country modelling to support disease control policy making |
Organisation | Ghana Health Service |
Country | Ghana |
Sector | Public |
PI Contribution | Intellectual and meeting organisational input, and modelling expertise fitting models to country disease TB epidemics |
Collaborator Contribution | Intellectual and meeting organisational input, |
Impact | Ghana - altered TB disease control strategy Viet Nam - contributed to increased funding from Global Fund to TB disease control in Viet Nam |
Start Year | 2015 |
Description | In country modelling to support disease control policy making |
Organisation | Government of Vietnam |
Country | Viet Nam |
Sector | Public |
PI Contribution | Intellectual and meeting organisational input, and modelling expertise fitting models to country disease TB epidemics |
Collaborator Contribution | Intellectual and meeting organisational input, |
Impact | Ghana - altered TB disease control strategy Viet Nam - contributed to increased funding from Global Fund to TB disease control in Viet Nam |
Start Year | 2015 |
Description | TB Diagnostics Forum Modelling Workgroup |
Organisation | Amsterdam Institute for Global Health and Development (AIGHD) |
Country | Netherlands |
Sector | Private |
PI Contribution | Intellectual input to discussions on characteristics of desired target product profiles for new diagnostics |
Collaborator Contribution | JHU leads the working group. AIGHD provides scientific input. |
Impact | Publications. Target Product Profiles of new diagnostics. |
Start Year | 2012 |
Description | TB Diagnostics Forum Modelling Workgroup |
Organisation | Johns Hopkins Medicine |
Country | United States |
Sector | Hospitals |
PI Contribution | Intellectual input to discussions on characteristics of desired target product profiles for new diagnostics |
Collaborator Contribution | JHU leads the working group. AIGHD provides scientific input. |
Impact | Publications. Target Product Profiles of new diagnostics. |
Start Year | 2012 |
Description | TB Modelling and Analysis Consortium |
Organisation | Bill and Melinda Gates Foundation |
Country | United States |
Sector | Charity/Non Profit |
PI Contribution | Intellectual and meeting organisational input. This consortium funds 50% of my time and 100% of two of my group members (1 research, 1 admin). |
Collaborator Contribution | Has resulted in significant intellectual and in-kind research time of many other research groups input to my groups research (e.g. Global TB Targets work was a collaboration of 11 international research groups contributing results to this research question, largely unfunded). |
Impact | Huge amount of outputs, please see other sections of report Publications in Modelling research agenda, TB Diagnostics Impact on Policy, Govt Budgets, and Research Priorities in South Africa |
Start Year | 2012 |
Description | TB Modelling and Analysis Consortium |
Organisation | Centers for Disease Control and Prevention (CDC) |
Country | United States |
Sector | Public |
PI Contribution | Intellectual and meeting organisational input. This consortium funds 50% of my time and 100% of two of my group members (1 research, 1 admin). |
Collaborator Contribution | Has resulted in significant intellectual and in-kind research time of many other research groups input to my groups research (e.g. Global TB Targets work was a collaboration of 11 international research groups contributing results to this research question, largely unfunded). |
Impact | Huge amount of outputs, please see other sections of report Publications in Modelling research agenda, TB Diagnostics Impact on Policy, Govt Budgets, and Research Priorities in South Africa |
Start Year | 2012 |
Description | TB Modelling and Analysis Consortium |
Organisation | Harvard University |
Department | Harvard T.H. Chan School of Public Health |
Country | United States |
Sector | Academic/University |
PI Contribution | Intellectual and meeting organisational input. This consortium funds 50% of my time and 100% of two of my group members (1 research, 1 admin). |
Collaborator Contribution | Has resulted in significant intellectual and in-kind research time of many other research groups input to my groups research (e.g. Global TB Targets work was a collaboration of 11 international research groups contributing results to this research question, largely unfunded). |
Impact | Huge amount of outputs, please see other sections of report Publications in Modelling research agenda, TB Diagnostics Impact on Policy, Govt Budgets, and Research Priorities in South Africa |
Start Year | 2012 |
Description | TB Modelling and Analysis Consortium |
Organisation | Intellectual Ventures |
Country | United States |
Sector | Private |
PI Contribution | Intellectual and meeting organisational input. This consortium funds 50% of my time and 100% of two of my group members (1 research, 1 admin). |
Collaborator Contribution | Has resulted in significant intellectual and in-kind research time of many other research groups input to my groups research (e.g. Global TB Targets work was a collaboration of 11 international research groups contributing results to this research question, largely unfunded). |
Impact | Huge amount of outputs, please see other sections of report Publications in Modelling research agenda, TB Diagnostics Impact on Policy, Govt Budgets, and Research Priorities in South Africa |
Start Year | 2012 |
Description | TB Modelling and Analysis Consortium |
Organisation | Johns Hopkins University |
Department | Johns Hopkins Bloomberg School of Public Health |
Country | United States |
Sector | Academic/University |
PI Contribution | Intellectual and meeting organisational input. This consortium funds 50% of my time and 100% of two of my group members (1 research, 1 admin). |
Collaborator Contribution | Has resulted in significant intellectual and in-kind research time of many other research groups input to my groups research (e.g. Global TB Targets work was a collaboration of 11 international research groups contributing results to this research question, largely unfunded). |
Impact | Huge amount of outputs, please see other sections of report Publications in Modelling research agenda, TB Diagnostics Impact on Policy, Govt Budgets, and Research Priorities in South Africa |
Start Year | 2012 |
Description | TB Modelling and Analysis Consortium |
Organisation | World Health Organization (WHO) |
Department | Department of Control of Neglected Tropical Diseases |
Country | Global |
Sector | Public |
PI Contribution | Intellectual and meeting organisational input. This consortium funds 50% of my time and 100% of two of my group members (1 research, 1 admin). |
Collaborator Contribution | Has resulted in significant intellectual and in-kind research time of many other research groups input to my groups research (e.g. Global TB Targets work was a collaboration of 11 international research groups contributing results to this research question, largely unfunded). |
Impact | Huge amount of outputs, please see other sections of report Publications in Modelling research agenda, TB Diagnostics Impact on Policy, Govt Budgets, and Research Priorities in South Africa |
Start Year | 2012 |
Title | New user-friendly country-level tool for TB-HIV control projections and costings |
Description | We created a user-friendly tool (a mathematical model) for TB-HIV control projections and costing. This tool will be freely available for download by country-level TB/HIV policy makers for decision making on TB control strategies and costing in 2015. It has been used in workshops run by UNAIDS, the Global Fund, WHO and at country level. |
IP Reference | |
Protection | Copyrighted (e.g. software) |
Year Protection Granted | 2013 |
Licensed | Yes |
Impact | I was released globally in 2015. So far used to update Sudan, Bangladesh and Vietnam National Strategic Plan in 2013/4 (in Sudan: it led to a move to more decentralized provision of TB patient care), and in South Africa, Ghana and Nigeria. It will be used in about ~5 more high TB burden countries in 2016. |
Title | History matching of complex agent based computer models using emulation |
Description | The developed method allows the calibration of multi-input, multi-output agent based computer models of high complexity. The method is based on a statistical approximation of the computer model, called the emulator, and tries to identify regions of the input space that are likely to lead to a match between the model's outputs and the calibration data. The computational efficiency of the emulator makes this method very applicable to computer models with long running times. |
Type Of Technology | Software |
Year Produced | 2013 |
Open Source License? | Yes |
Impact | None yet |
URL | http://cmmid.lshtm.ac.uk/mrccalib/ |
Title | New user-friendly country-level modelling tool for TB-HIV control projections and costings |
Description | We created a user-friendly tool (a mathematical model) for TB-HIV control projections and costing. This tool is for use by country-level TB/HIV policy makers for decision making on TB control strategies and costing. It has been used in workshops run by UNAIDS, the Global Fund and WHO over the coming years. |
Type Of Technology | Software |
Year Produced | 2013 |
Open Source License? | Yes |
Impact | It was released globally in 2015. So far used to update the Government of Sudan, Bangladesh and Vietnam National Strategic Plan in 2013/4 (in Sudan, a move to more decentralized provision of TB patient care), South Africa, Ghana and Nigeria. It will be used in ~5 more high TB burden countries in 2016. |
URL | http://www.avenirhealth.org/software-spectrum |
Title | TB ePAL (electronic PArticipant Locator tool) |
Description | In high density urban settings without formal address systems, identification of the place of residence of patients presenting to health centres is often challenging and inaccurate. This type of information is essential for patient follow up in the community, for disease surveillance and identification of hotspots for efficient targeting of limited healthcare resources, for research study participant follow up and mapping, and for identifying populations suitable for enrolment into vaccine clinical trials. ePAL (electronic PArticipant Locator tool) is a tablet-based tool aiming to facilitate accurate identification of place of residence of patients presenting to health centres in Blantyre, Malawi. Points of interest relevant to the community were collected using GPS from across Blantyre city by community engagement through health surveillance assistants. Preceded by an eCRF, these points of interest combined with high resolution satellite maps constitute the ePAL app, which is being placed on tablets in TB registration centres across Blantyre city. ePAL is currently being evaluated in this setting and is hoped will be the first electronic data capture of TB registrations in Malawi and an important tool embraced by the Department of Health and Malawi-Liverpool-Wellcome (MLW) research centre for mapping and follow up of TB cases and identification of populations suitable for research including clinical trials. The tool is being developed in collaboration between LSHTM (London, UK) and MLW (Blantyre, Malawi). |
Type Of Technology | Webtool/Application |
Year Produced | 2014 |
Impact | The tool itself has undergone validation for identifying place of residence of TB patients presenting at TB registration centres and the data are currently being analysed. The tool has been adapted for two other research projects at MLW: surveillance for an ongoing typhoid outbreak and a study on impact of PCV vaccines. Several other studies in Blantyre are soon to begin using ePAL. It is hoped once the tool is validated that it could be replicated in other similar settings. |
Title | hmer R package |
Description | R package for implementing the history matching and model emulation calibration method |
Type Of Technology | Software |
Year Produced | 2022 |
Open Source License? | Yes |
Impact | The software is being used to calibrate an increasing number of infectious disease models |
URL | https://cran.r-project.org/web/packages/hmer/index.html |
Company Name | Avenir Healthcare Services Ltd |
Description | |
Year Established | 2013 |
Impact | Impacts are many and varied across a variety of health sectors. Impacts that my (Tuberculosis) work with them has supported includes: 1) generating country-level TB/HIV estimates for the WHO report 2013 and 2014, 3) Generating evidence for the STOPTB/WHO Tuberculosis Global Plan (2015) - global resource needs estimates, that are used to motivate for funding from international partners (Gates, Global Fund, ...) 3) Futures working with countries to develop TB/HIV National Strategic Plans in 3+ countries globally, affecting governmental TB/HIV strategies and resource allocation within these 3 countries. This is an active and growing collaboration and much more activity will happen over the next 12 months. |
Description | Emulation workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | We organised a workshop for 30 participants who attended a 1 day hands on workshop which showcased the research methodology that is being developed in this project. Special software was prepared that allowed the participants to try out the methods in their own laptops during the workshop. The workshop places were filled up within two days and there was strong encouragement for a second edition, which we plan to run in 2015. |
Year(s) Of Engagement Activity | 2014 |
URL | https://sites.google.com/site/emulationday/ |
Description | Meeting with Uganda Ministry of Health Officials |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Meeting with Uganda Ministry of Health officials involved with the HIV programme in the country, to present research findings on the potential costs and effects of different ART scale-up activities |
Year(s) Of Engagement Activity | 2016 |
Description | Newsnight lead story - PrEP for HIV in uk MSM |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | BBC Newsnight lead item. Video: Intro & WHITE, WHITE excerpts + BBC website, & many newspapers incl Guardian, Telegraph. Prep for HIV in UK MSM. Jan 15th 2016 |
Year(s) Of Engagement Activity | 2016 |
URL | https://drive.google.com/open?id=0B2K5XWn1bjpOQTJLRXpNMDBTdUU |
Description | Press release - PrEP for HIV in uk MSM |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press release taken up by many global news paper, BBC, newsnight, ... |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.lshtm.ac.uk/newsevents/news/2016/prep_drugs_could_reverse_hiv_epidemic.html |
Description | Tipping points in health and society - public workshop on uncertainty in health. |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A lot of interest, many questions and an increased awareness of the potential and limitations of public health models, and their associated uncertainty. Participants showed an appreciation of the impact of uncertainty in public health models. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.esrc.ac.uk/news-and-events/events/festival/festival-events/general-public/Tipping-Points-... |