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Ivor Langley, Liverpool School of Tropical Medicine, UK Hsien-Ho Lin, National Taiwan University
Agenda
Background Tuberculosis diagnostics - Some challenges and opportunities - How can modelling help? Virtual implementation What is it? - Operational modelling - Transmission modelling - Linking operational and transmission models
Virtual Implementation Case Study from Tanzania Next Steps
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
McNerney R, and Daley P (2011), Towards a point-of-care test for active tuberculosis: obstacles and opportunities, March 2011 | Volume 9 www.nature.com/reviews/micro 3 Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
SPEED OF DIAGNOSIS Many visits required to provide sputum samples, receive diagnosis, and commence treatment Leads to high diagnostic default rate MDR-TB diagnosis will take a lot longer ~2-4 months
At end of intermediate phases if smear Positive Test For Drug Resistance and put on MDR -TB Treatment if found
Treatment Monitoring
TB Diagnostic Centre
Home
Home
Return Home
TB Cure
Health Clinic
TB Suspect
Home
Smear Positive
TB Diagnostic Centre
Smear Negative
No TB Found
Return Home
Home
Home
Return Home
TB Diagnostic Centre
Receive Diagnosis
Home
Return Home
TB Diagnostic Centre
Provide Sputum Sample 2
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
GeneXpert MTB/RIF
Sensitivity 80-95% Specificity 98-99% Turnaround <12hrs Cost per test $10-$17 Time per test ~2hrs Extra Investment $9k-18k
Point of Care?
Sensitivity ? Specificity ? Turnaround <1hr Cost per test ? Time per test ? Extra Investment ?
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Small PM, Pai M. (2010), Tuberculosis diagnosis - time for a game change. N Engl J Med. 2010; 363(11): 1070-1.
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
to identify the most effective, sustainable, and appropriate TB diagnostic technology and algorithm for each individual context
. by projecting the impacts on patients, the health system, and the community.
Frank Cobelens, Susan van den Hof, Madhukar Pai, S. Bertel Squire, Andrew Ramsay, Michael E. Kimerling (2012); 7 Which New Diagnostics for Tuberculosis, and When?, National Taiwan of InfectiousNTLP Tanzania Liverpool School of Tropical Medicine, The Journal University, and Diseases, DOI: 10.1093/infdis/jis188
Patients
What is the increase in patients diagnosed and cured? Do HIV+ patients benefit? Will it benefit the poor? Will drug resistant patients benefit? Will it reduce patient visits and waiting time? How much quicker will patients be treated? How many patients will benefit if rolled out?
Health System
How many more TB treatments required? Will it reduce wastage false positive?
Community
What if? - New test performance changes, targeted differently, numbers grow or fall?
* Mann G, Squire SB, Bissell K, Eliseev P, Du Toit E, Hesseling A, et al. (2010), Beyond accuracy: creating a 8 comprehensiveevidence base for TB diagnostic tools. Int J University,Lung Dis. 2010; 14(12): 1518-24. Liverpool School of Tropical Medicine, National Taiwan Tuberc and NTLP Tanzania
Critical evidence is provided by : Laboratory Tests Demonstration Studies Explanatory Trials (Does it work?) Pragmatic Trials (Does it work in normal practice in a particular context?)
Modelling (Virtual Implementation) complements trials by applying the evidence to other contexts to predict impacts
Projecting patient effects across a wide spectrum of measures Projecting health system effects and costs Projecting impacts of scale-up Assessing cost effectiveness and sustainability Projecting TB incidence and other transmission impacts
SB. Squire, ARC. Ramsay, S. van den Hof, KA. Millington, I. Langley, G. Bello, A. Kritski, A. Detjen, R. Thomson, F. Cobelens, GH. Mann, Making innovations accessible to the poor through implementation research, INT J TUBERC LUNG DIS 15(7):862870, doi:10.5588/ijtld.11.0161 Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
Berkeley Madonna
Katsaliaki K, Mustafee N (2010), Applications of simulation within the healthcare context. Journal of the Operational 10 Research Society. 2010; doi:10.1057/ University, and NTLP Tanzania Liverpool School of Tropical Medicine, National Taiwanjors.2010.20mall PM,
TB patients home
3. Further sample required or not TB D. Results B. Results A. Sputum sample for testing 5. Start TB treatment Sputum Collection and Diagnosis 9. Continuation of treatment
6. Return home with treatment 7. Return for next batch of medication LEGEND Solid Green Lines Individuals with suspected TB Dash/Dot Red Lines -.-.Patients being treated for TB Dash Blue Lines - - Sputum sample pathways
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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The operational component of virtual implementation is:A. B. C. D. E. Detailed - to take account of the complex interactions that affect outcomes, cause bottlenecks,
and limit capacity
Visual- to give a representation of the operation that enables non modellers (e.g. policy
makers) to engage with the modelling and assist in its validation not a black box.
new and existing diagnostics options and contexts can be modelled. Also enabling what if? questions to be addressed.
Output rich - so outcomes can be analysed using readily available database and statistical
tools e.g. matching the WHO output requirements for monitoring implementations of Xpert MTB/RIF
Powerful to enable many iterations of the process to be rapidly completed e.g. simulating 510 years of TB diagnosis in under an hour of real time
SB. Squire, ARC. Ramsay, S. van den Hof, KA. Millington, I. Langley, G. Bello, A. Kritski, A. Detjen, R. Thomson, F. Cobelens, GH. Mann, Making innovations accessible to the poor through implementation research, Int J Tuberc Ling Dis 12 Liverpool School 15(7):862870, doi:10.5588/ijtld.11.0161 NTLP Tanzania of Tropical Medicine, National Taiwan University, and
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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SET-UP
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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affect transmission
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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Diagnostic accuracy is only one step in the whole diagnostic pathway In order to understand the transmission impact of a new tool, we have to understand the operational context where it is implemented
Dowdy DW, Cattamanchi A, Steingart KR, Pai M (2011), Is Scale-Up Worth It? Challenges in Economic Analysis 17 of Diagnosticof Tropical Medicine, National Taiwan University, 8(7): e1001063 Liverpool School Tests for Tuberculosis. PLoS Med and NTLP Tanzania
Sensitivity
Lin HH, Langley I, Mwenda R, et al. (2011), A modelling framework to support the selection and implementation of new 18 tuberculosis diagnostic tools. Int J Tuberc Lung Dis 15(8):9961004, doi:10.5588/ijtld.11.0062 Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
What will be the impact of new TB diagnostics on HIV epidemiology? -- Do we care? Better survival of TB-HIV co-infected patients Increased HIV prevalence Increased cost from expenditure on antiretroviral therapy?
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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A Isp S Lf Ls Isn
TB disease States
HIV R
HIV + CD4>350
Test + will treat
Sick2
Sick1
Health center
Sputu m exam
Result s
Test +
Treat
LTFU
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120 100 80 60 40
project
Characteristics of diagnostics
Health system context
TB/HIV epidemiology
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Output
OPERATIONAL MODEL Patient & Health System Effects
Input
Input
Output
Combining the outputs to calculate the Incremental Cost Effectiveness Ratio (ICER)
Lin HH, Langley I, et al. (2011), A modelling framework to support the selection and implementation of new tuberculosis 22 diagnostic tools. Int J TubercMedicine, National Taiwan University, and NTLP Tanzania Liverpool School of Tropical Lung Dis 15(8):9961004, doi:10.5588/ijtld.11.0062
Tell the future -- The future is molded by unpredictable events. -- Models seek to simplify a complex world. -- Comparisons are usually more useful than precise point estimates. Tell us which sets of assumptions are right -- Models can use different sets of assumptions to make different projections, but cannot tell which projections are the right ones. Make decisions for people -- Decision-making is a political process; models seek only to bring evidence into that process, and highlight where assumptions are being made.
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ZN Microscopy
LED Fluorescence
LED Same Day New TB Cures Xpert for Sm- HIV+ & Retreat Retreat TB Cures MDR-TB
Treatment Fail
Xpert for HIV+ and retreat Untreated TB
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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0.00 ZN Microscopy
2.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00
LED Fluorescence
Xpert for Sm- HIV+ & Retreat Xpert for Sm- HIV+ Known & Retreat Xpert for HIV+ and retreat Xpert for HIV+ known and retreat Xpert full roll-out
Start TB Treatment
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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LED Fluorescence
Xpert for Sm- HIV+ & Retreat Test+ve TB Test-ve TB Xpert for Sm- HIV+ Known & Retreat MDR-TB
Xpert full roll-out 0 5000 10000 15000 20000 25000 30000 35000 40000 45000 50000
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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Decline in TB incidence
4.0% 2.4%
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6000
4000 2000 0 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
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A measure of the cost effectiveness of a new intervention which enables interventions to be compared and prioritised. ICER = Incremental costs of the intervention Incremental DALYs averted
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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$200
Xpert for Smknown HIV+
25720
$150
Xpert for known HIV+
32426
NOTE: The size of the circle and the number in the circle represent the benefits measured in DALY's averted per year of the new tool relative to LED fluorescence microscopy (Benefit)
$100
$50
LED
LED
72098
161622
$0
60445
-$500,000
$500,000
$1,500,000
$2,500,000
$3,500,000
$4,500,000
-$50
Additional Annual Cost to Health Service (Sustainable?)
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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Virtual Implementation
the next steps Tanzania Finalise analysis of scale-up of the options including additional ART costs and sensitivity analysis Consider which centres should be priority for Xpert implementation and which algorithms Implement virtual implementation tool in the NTLP Wider Application Apply the models to other settings Develop models for MDR-TB diagnosis Publications Peer reviewed publication Brochure Treat TB Symposium 15th November- 5pm Conf Hall 1
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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Acknowledgment
USAID Ya Diul Mukadi Tanzania NTLP Saidi Egwaga Basra Doulla Raymond Shirima Riziki Kisonga Malawi MOH Reuben Mwenda The Union (Treat-TB) I.D. Rusen Anne Detjen
Liverpool School of Tropical Medicine Bertie Squire Kerry Millington Harvard School of Public Health Ted Cohen Megan Murray Lanner Group Geoff Hook
Liverpool School of Tropical Medicine, National Taiwan University, and NTLP Tanzania
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ANY QUESTIONS?
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