Xpert MTB/RIF -Operational Research Initiatives 2/Langley - Xpert...Introduction Operational...

Xpert MTB/RIF - Operational Research InitiativesXpert MTB/RIF - Operational Research Initiatives

GLI Partners Meeting – 18th April 2012

Ivor Langley (LSTM) & Afrânio Kritski (Rede-TB)

Agenda

� Introduction

� Example Initiatives

� Virtual Implementation - Ivor Langley, LSTM

2

� Prove-IT pragmatic trial in Brazil - Afrânio Kritski, Rede-TB

� Acknowlegements

Introduction

Operational research1 projects are conducted with the aim of

1. Improving programme performance and outcomes2. Assessing the feasibility, effectiveness or impact of new

strategies or interventions on TB control

3

strategies or interventions on TB control3. Collecting data to guide policy recommendations on specific

interventions

1 Priorities in Operational Research to Improve Tuberculosis Care and Control, World Health Organisation (2011),

ISBN 978 92 4 154825 0

Introduction – Operational Research

Process and Scope

DEFINEthe problem & questions to

be addressed

DESIGNthe study and agree the

analysis to be conducted

Impact/

effectiveness

Observational

Qualitative

Interventional

Quantitative

Feasibility

4

analysis to be conducted

DOthe change, collect the data,

and complete the analysis

DISSEMINATEthe results and learning’s

from the study and analysis

Research

Across settings

Qualitative Quantitative

Routine

Setting Specific

Local Global

Introduction - Two Example Studieswork in progress

PROVE-IT, BrazilPragmatic controlled trial of Xpert & LPA for drug sensitivity testing

Impact & Effectiveness

Interventional

Virtual ImplementationModelling of TB diagnostic tools

including Xpert MTB/RIF

Impact & Effectiveness

Observational

5

Interventional

Qualitative & Quantitative

Across a number of settings in Brazil

Local with Global Implications

Observational

Quantitative

Across many settings with example from Tanzania

Global Implications

Data on

new

diagnostics

in Context B

Data on

current

diagnostics

in Context A

Virtual Implementation of new TB diagnosticsprojecting impacts

6

Impacts of

new

diagnostics

in Context A

in Context Bin Context A

Virtual Implementation – DEFINEusing the Impact Assessment Framework (IAF)

Patients Health System Community

EFFICACY

- How well does

it work?

Impact

Assessment

Framework2

How many more TB treatments

required? Will it reduce

wastage – false positive?

What is the increase in

patients diagnosed

and cured?

7

EQUITY

- Who benefits

and why?

SCALE-UP

- Impacts of

national rollout?

HEALTH SYSTEM

- Operational

effects?

HORIZON SCANNING

- How does it compare

to other technologies?

2 Mann G, Squire SB, Bissell K, Eliseev P, Du Toit E, Hesseling A, et al. (2010), Beyond accuracy: creating a

comprehensive evidence base for TB diagnostic tools. Int J Tuberc Lung Dis. 2010; 14(12): 1518-24.

Do HIV+ patients benefit? Will

it benefit the poor? Will drug

resistant patients benefit?How much will it cost? What is the affect on the

number of samples collected? Will it overcome

bottlenecks or just move them on? Where to

place the new test in the diagnostic algorithm

What will the impact be on

TB incidence and

prevalence?

How many patients will

benefit if rolled out? Where to start? How much will it

cost? Is it cost effective?

How will staff be

impacted?Will it reduce patient visits

and waiting time? How

much quicker will patients

be treated?

Will it mean more

patients seek diagnosis?

What if? - New test performance

changes, targeted differently,

numbers grow or fall?

Will it contribute to achieving

the 2015/ 2050 millennium

development goals for TB?

Virtual Implementation – DEFINEunderstanding the process

8

The model needed to be:-

A. Sufficiently detailed - to take account of the complex interactions that affect outcomes, cause bottlenecks, and limit capacity

B. 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’.

C. Flexible- so the effects of many new and existing diagnostics options and contexts can be

Virtual Implementation - DESIGNthe key requirements

9

C. Flexible- so the effects of many new and existing diagnostics options and contexts can be modelled. Also enabling ‘what if?’ questions to be addressed.

D. 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

E. Powerful – to enable many iterations of the process to be rapidly completed e.g. simulating 5-10 years of TB diagnosis in under an hour of real time

F. Comprehensive – to model both the shorter term operational characteristics of the process and the longer term disease transmission impacts

Virtual Implementation – DESIGNthe conceptual model4

Patient & Health System Impacts

Turnaround timeDefault Rates

10

Transmission Impacts

TB Incidence

4Lin HH, Langley I, Mwenda R, et al. (2011), A modelling framework to support the selection and implementation of new

tuberculosis diagnostic tools. Int J Tuberc Lung Dis 15(8):996–1004, doi:10.5588/ijtld.11.0062

DIAGONSTIC CENTRE CURRENT PERFORMANCE

Annual Smear Positive TB Cases 255

Annual Smear Negative TB Cases 64

Annual Retreatment Cases 91

HIV+ rate in TB cases 42.0%

Proportion of new suspects Smear Poitive 11.6%

Virtual Implementation – DOthe model development - INPUTS

11

EXCEL WORKBOOK

DIAGNOSTIC DEMAND MATRIX DISTRICT1 Parameters marked in yellow must be input

SMEAR +ve -ve -ve -ve -ve Default N0.

X-RAY No Yes Yes No Diagnosis Seeking

TREATMENT Yes Yes Yes No No No TOTAL

NEW/

RETREAT HIV

NEW +ve 95 0 39 789 0 163 1,086

-ve 160 0 25 1,090 0 225 1,500

TOTAL 255 0 64 1,879 0 388 2,586

RETREAT +ve 38 2 40

-ve 53 3 56

TOTAL 91 5 96

PATIENT CATEGORY

�Assumptions validated with experts,

published literature, and subject to

sensitivity analysis e.g.

� Accuracy (Sensitivity and Specificity

of each test)

� TB suspect and treatment default

rates

� Diagnostic processes and

treatment times

� Costing information

The Diagnostic

Options

A detailed model

was developed

using the

WITNESS

Simulation

Virtual Implementation – DOthe model development – Diagnostic Centre

12

Simulation

Software. Patients

are modelled

through each

process from

Health Clinics into

a TB Diagnostic

Centre and through

to Treatment where

appropriate.

Sputum samples are

modelled through the lab

process. The lab model

shows a schematic of the

process and includes

microscopy and Xpert

MTB/RIF with flows

defined for each sample

Virtual Implementation – DOthe model development – Diagnostic Lab

13

defined for each sample

by rules defined in an

input data files

Lab technicians and assistants as well as

clinical staff are modelled as resources

EXCEL WORKBOOK

LAB TESTS COMPLETED

TOTAL

Year TB Positive TB Negative TB Positive TB Negative TB Positive TB Negative

RIF Sensitive RIF Resistant RIF Se nsitive RIF Re sistant RIF Sensitive RIF Resistant RIF Sensitive RIF Resistant No. +ve rate No. +ve rate RIF+% No. +ve rate No. +ve rate No. +ve rate RIF+% No. +ve rate No. +ve rate No. +ve rate No. +ve rate RIF+% No. +ve rate

QTR1 0 0 0 10386 0 49503 255 0 0 697 0 0 0 216 1440 0 0.0% 60144 17.3% 0.4% 60144 17.3% 0 0.0% 697 100.0% 0.0% 697 100.0% 1656 13.0% 1656 13.0% 60841 18.2% 0.4% 64153 17.9%

QTR2 0 0 0 24552 5 106444 495 0 0 2107 0 0 0 834 15114 0 0.0% 131496 18.7% 0.4% 131496 18.7% 0 0.0% 2107 100.0% 0.0% 2107 100.0% 15948 5.2% 15948 5.2% 133603 20.0% 0.4% 165499 17.1%

QTR3 0 0 0 37385 14 158436 606 0 0 3168 0 0 0 1270 47234 0 0.0% 196441 19.0% 0.3% 196441 19.0% 0 0.0% 3168 100.0% 0.0% 3168 100.0% 48504 2.6% 48504 2.6% 199609 20.3% 0.3% 296617 14.5%

QTR4 0 0 0 49067 14 213168 630 0 0 4393 0 0 0 1601 86032 0 0.0% 262879 18.7% 0.2% 262879 18.7% 0 0.0% 4393 100.0% 0.0% 4393 100.0% 87633 1.8% 87633 1.8% 267272 20.0% 0.2% 442538 12.8%

QTR1 1 0 0 62480 24 269317 635 0 0 5134 0 0 0 2205 121671 0 0.0% 332456 18.8% 0.2% 332456 18.8% 0 0.0% 5134 100.0% 0.0% 5134 100.0% 123876 1.8% 123876 1.8% 337590 20.0% 0.2% 585342 12.3%

QTR2 1 0 0 74887 34 324382 760 0 0 6354 0 0 0 2615 157839 0 0.0% 400063 18.7% 0.2% 400063 18.7% 0 0.0% 6354 100.0% 0.0% 6354 100.0% 160454 1.6% 160454 1.6% 406417 20.0% 0.2% 727325 11.9%

QTR3 1 0 0 87870 34 377930 770 0 0 7774 23 0 0 3321 194110 0 0.0% 466604 18.8% 0.2% 466604 18.8% 0 0.0% 7797 100.0% 0.3% 7797 100.0% 197431 1.7% 197431 1.7% 474401 20.2% 0.2% 869263 11.8%

QTR4 1 0 0 102091 34 433179 785 0 0 8483 23 0 0 4222 230341 0 0.0% 536089 19.1% 0.2% 536089 19.1% 0 0.0% 8506 100.0% 0.3% 8506 100.0% 234563 1.8% 234563 1.8% 544595 20.3% 0.2% 1013721 11.7%

QTR1 2 0 0 115591 48 484988 920 0 0 9733 23 0 0 4618 268971 0 0.0% 601547 19.2% 0.2% 601547 19.2% 0 0.0% 9756 100.0% 0.2% 9756 100.0% 273589 1.7% 273589 1.7% 611303 20.5% 0.2% 1158481 11.6%

QTR2 2 0 0 127988 48 538919 1075 0 0 10494 23 0 0 5072 308890 0 0.0% 668030 19.2% 0.2% 668030 19.2% 0 0.0% 10517 100.0% 0.2% 10517 100.0% 313962 1.6% 313962 1.6% 678547 20.4% 0.2% 1306471 11.4%

QTR3 2 0 0 140463 53 594255 1225 0 0 11719 23 0 0 5622 346138 0 0.0% 735996 19.1% 0.2% 735996 19.1% 0 0.0% 11742 100.0% 0.2% 11742 100.0% 351760 1.6% 351760 1.6% 747738 20.4% 0.2% 1451258 11.3%

QTR4 2 0 0 153045 154 648647 1245 0 0 12807 28 0 0 6464 382143 0 0.0% 803091 19.1% 0.2% 803091 19.1% 0 0.0% 12835 100.0% 0.2% 12835 100.0% 388607 1.7% 388607 1.7% 815926 20.3% 0.2% 1593140 11.2%

QTR1 3 0 0 164943 154 705334 1351 0 0 14257 28 0 0 7456 419160 0 0.0% 871782 18.9% 0.2% 871782 18.9% 0 0.0% 14285 100.0% 0.2% 14285 100.0% 426616 1.7% 426616 1.7% 886067 20.2% 0.2% 1739299 11.2%

QTR2 3 0 0 178772 154 760360 1764 0 0 15463 28 0 0 7679 456421 0 0.0% 941050 19.0% 0.2% 941050 19.0% 0 0.0% 15491 100.0% 0.2% 15491 100.0% 464100 1.7% 464100 1.7% 956541 20.3% 0.2% 1884741 11.1%

QTR3 3 0 0 191521 154 814517 1885 0 0 16257 28 0 0 8203 493090 0 0.0% 1008077 19.0% 0.2% 1008077 19.0% 0 0.0% 16285 100.0% 0.2% 16285 100.0% 501293 1.6% 501293 1.6% 1024362 20.3% 0.2% 2026948 11.1%

QTR4 3 0 0 204459 159 871736 1995 0 0 17192 28 0 0 8790 532752 0 0.0% 1078349 19.0% 0.2% 1078349 19.0% 0 0.0% 17220 100.0% 0.2% 17220 100.0% 541542 1.6% 541542 1.6% 1095569 20.2% 0.2% 2178653 11.0%

QTR1 4 0 0 217244 164 924028 2207 0 0 18054 67 0 0 9523 571113 0 0.0% 1143643 19.0% 0.2% 1143643 19.0% 0 0.0% 18121 100.0% 0.4% 18121 100.0% 580636 1.6% 580636 1.6% 1161764 20.3% 0.2% 2323036 11.0%

QTR2 4 0 0 228348 265 976900 2371 0 0 18925 67 0 0 10005 607374 0 0.0% 1207884 18.9% 0.2% 1207884 18.9% 0 0.0% 18992 100.0% 0.4% 18992 100.0% 617379 1.6% 617379 1.6% 1226876 20.2% 0.2% 2461634 10.9%

QTR3 4 0 0 242159 270 1034796 2620 0 0 20136 67 0 0 10872 643168 0 0.0% 1279845 18.9% 0.2% 1279845 18.9% 0 0.0% 20203 100.0% 0.3% 20203 100.0% 654040 1.7% 654040 1.7% 1300048 20.2% 0.2% 2608128 10.9%

QTR4 4 0 0 254456 270 1091989 2890 0 0 21615 67 0 0 11381 678982 0 0.0% 1349605 18.9% 0.2% 1349605 18.9% 0 0.0% 21682 100.0% 0.3% 21682 100.0% 690363 1.6% 690363 1.6% 1371287 20.2% 0.2% 2752013 10.9%

QTR1 5 0 0 267876 314 1146738 3024 0 0 22882 67 0 0 12315 716280 0 0.0% 1417952 18.9% 0.2% 1417952 18.9% 0 0.0% 22949 100.0% 0.3% 22949 100.0% 728595 1.7% 728595 1.7% 1440901 20.2% 0.2% 2898091 10.9%

QTR2 5 0 0 281302 381 1199144 3139 0 0 24070 67 0 0 13186 754661 0 0.0% 1483966 19.0% 0.2% 1483966 19.0% 0 0.0% 24137 100.0% 0.3% 24137 100.0% 767847 1.7% 767847 1.7% 1508103 20.3% 0.2% 3043797 10.9%

QTR3 5 0 0 293099 588 1252241 3163 0 0 25438 72 0 0 13573 795412 0 0.0% 1549091 19.0% 0.2% 1549091 19.0% 0 0.0% 25510 100.0% 0.3% 25510 100.0% 808985 1.7% 808985 1.7% 1574601 20.3% 0.2% 3192571 10.8%

QTR4 5 0 0 305602 588 1307122 3299 0 0 26692 72 0 0 13992 831971 0 0.0% 1616611 18.9% 0.2% 1616611 18.9% 0 0.0% 26764 100.0% 0.3% 26764 100.0% 845963 1.7% 845963 1.7% 1643375 20.3% 0.2% 3335301 10.8%

QTR1 6 0 0 317096 588 1361429 3342 0 0 28007 72 0 0 14734 868367 0 0.0% 1682455 18.9% 0.2% 1682455 18.9% 0 0.0% 28079 100.0% 0.3% 28079 100.0% 883101 1.7% 883101 1.7% 1710534 20.2% 0.2% 3476736 10.8%

QTR2 6 0 0 329929 602 1414999 3453 0 0 29308 72 0 0 15278 905074 0 0.0% 1748983 18.9% 0.2% 1748983 18.9% 0 0.0% 29380 100.0% 0.2% 29380 100.0% 920352 1.7% 920352 1.7% 1778363 20.2% 0.2% 3619067 10.8%

QTR3 6 0 0 343320 607 1473276 3462 0 0 30327 77 0 0 15879 941842 0 0.0% 1820665 18.9% 0.2% 1820665 18.9% 0 0.0% 30404 100.0% 0.3% 30404 100.0% 957721 1.7% 957721 1.7% 1851069 20.2% 0.2% 3766511 10.8%

QTR4 6 0 0 357437 708 1524412 3572 0 0 31088 77 0 0 16581 980609 0 0.0% 1886129 19.0% 0.2% 1886129 19.0% 0 0.0% 31165 100.0% 0.2% 31165 100.0% 997190 1.7% 997190 1.7% 1917294 20.3% 0.2% 3911674 10.8%

QTR1 7

QTR2 7

QTR3 7

QTR4 7

QTR1 8

QTR2 8

QTR3 8

QTR4 8

QTR1 9

QTR2 9

QTR3 9

QTR4 9

QTR1 10

QTR2 10

QTR3 10

QTR4 10

TREATMENT MONITORING TOTALGene Xpert Micrsoscopy

MicroPositive Negative Positive Negative Micro GX

GeneXpert Micrsoscopy NEW SUSPECTS RETREAT

Total Micro

NEW SUSPECTS RETREAT TREATMENT MONITORING TOTAL

Micrsoscopy

GX GX TotalTotal Micro

LAB TESTS COMPLETED

TOTAL



QTR1 0 0 0 10386 0 49503 255 0 0 697 0 0 0 216 1440 0 0.0% 60144 17.3% 0.4% 60144 17.3% 0 0.0% 697 100.0% 0.0% 697 100.0% 1656 13.0% 1656 13.0% 60841 18.2% 0.4% 64153 17.9%

QTR2 0 0 0 24552 5 106444 495 0 0 2107 0 0 0 834 15114 0 0.0% 131496 18.7% 0.4% 131496 18.7% 0 0.0% 2107 100.0% 0.0% 2107 100.0% 15948 5.2% 15948 5.2% 133603 20.0% 0.4% 165499 17.1%

QTR3 0 0 0 37385 14 158436 606 0 0 3168 0 0 0 1270 47234 0 0.0% 196441 19.0% 0.3% 196441 19.0% 0 0.0% 3168 100.0% 0.0% 3168 100.0% 48504 2.6% 48504 2.6% 199609 20.3% 0.3% 296617 14.5%

QTR4 0 0 0 49067 14 213168 630 0 0 4393 0 0 0 1601 86032 0 0.0% 262879 18.7% 0.2% 262879 18.7% 0 0.0% 4393 100.0% 0.0% 4393 100.0% 87633 1.8% 87633 1.8% 267272 20.0% 0.2% 442538 12.8%

QTR1 1 0 0 62480 24 269317 635 0 0 5134 0 0 0 2205 121671 0 0.0% 332456 18.8% 0.2% 332456 18.8% 0 0.0% 5134 100.0% 0.0% 5134 100.0% 123876 1.8% 123876 1.8% 337590 20.0% 0.2% 585342 12.3%

QTR2 1 0 0 74887 34 324382 760 0 0 6354 0 0 0 2615 157839 0 0.0% 400063 18.7% 0.2% 400063 18.7% 0 0.0% 6354 100.0% 0.0% 6354 100.0% 160454 1.6% 160454 1.6% 406417 20.0% 0.2% 727325 11.9%

QTR3 1 0 0 87870 34 377930 770 0 0 7774 23 0 0 3321 194110 0 0.0% 466604 18.8% 0.2% 466604 18.8% 0 0.0% 7797 100.0% 0.3% 7797 100.0% 197431 1.7% 197431 1.7% 474401 20.2% 0.2% 869263 11.8%

QTR4 1 0 0 102091 34 433179 785 0 0 8483 23 0 0 4222 230341 0 0.0% 536089 19.1% 0.2% 536089 19.1% 0 0.0% 8506 100.0% 0.3% 8506 100.0% 234563 1.8% 234563 1.8% 544595 20.3% 0.2% 1013721 11.7%

QTR1 2 0 0 115591 48 484988 920 0 0 9733 23 0 0 4618 268971 0 0.0% 601547 19.2% 0.2% 601547 19.2% 0 0.0% 9756 100.0% 0.2% 9756 100.0% 273589 1.7% 273589 1.7% 611303 20.5% 0.2% 1158481 11.6%

QTR2 2 0 0 127988 48 538919 1075 0 0 10494 23 0 0 5072 308890 0 0.0% 668030 19.2% 0.2% 668030 19.2% 0 0.0% 10517 100.0% 0.2% 10517 100.0% 313962 1.6% 313962 1.6% 678547 20.4% 0.2% 1306471 11.4%

QTR3 2 0 0 140463 53 594255 1225 0 0 11719 23 0 0 5622 346138 0 0.0% 735996 19.1% 0.2% 735996 19.1% 0 0.0% 11742 100.0% 0.2% 11742 100.0% 351760 1.6% 351760 1.6% 747738 20.4% 0.2% 1451258 11.3%

QTR4 2 0 0 153045 154 648647 1245 0 0 12807 28 0 0 6464 382143 0 0.0% 803091 19.1% 0.2% 803091 19.1% 0 0.0% 12835 100.0% 0.2% 12835 100.0% 388607 1.7% 388607 1.7% 815926 20.3% 0.2% 1593140 11.2%

QTR1 3 0 0 164943 154 705334 1351 0 0 14257 28 0 0 7456 419160 0 0.0% 871782 18.9% 0.2% 871782 18.9% 0 0.0% 14285 100.0% 0.2% 14285 100.0% 426616 1.7% 426616 1.7% 886067 20.2% 0.2% 1739299 11.2%

QTR2 3 0 0 178772 154 760360 1764 0 0 15463 28 0 0 7679 456421 0 0.0% 941050 19.0% 0.2% 941050 19.0% 0 0.0% 15491 100.0% 0.2% 15491 100.0% 464100 1.7% 464100 1.7% 956541 20.3% 0.2% 1884741 11.1%

QTR3 3 0 0 191521 154 814517 1885 0 0 16257 28 0 0 8203 493090 0 0.0% 1008077 19.0% 0.2% 1008077 19.0% 0 0.0% 16285 100.0% 0.2% 16285 100.0% 501293 1.6% 501293 1.6% 1024362 20.3% 0.2% 2026948 11.1%

QTR4 3 0 0 204459 159 871736 1995 0 0 17192 28 0 0 8790 532752 0 0.0% 1078349 19.0% 0.2% 1078349 19.0% 0 0.0% 17220 100.0% 0.2% 17220 100.0% 541542 1.6% 541542 1.6% 1095569 20.2% 0.2% 2178653 11.0%

QTR1 4 0 0 217244 164 924028 2207 0 0 18054 67 0 0 9523 571113 0 0.0% 1143643 19.0% 0.2% 1143643 19.0% 0 0.0% 18121 100.0% 0.4% 18121 100.0% 580636 1.6% 580636 1.6% 1161764 20.3% 0.2% 2323036 11.0%

QTR2 4 0 0 228348 265 976900 2371 0 0 18925 67 0 0 10005 607374 0 0.0% 1207884 18.9% 0.2% 1207884 18.9% 0 0.0% 18992 100.0% 0.4% 18992 100.0% 617379 1.6% 617379 1.6% 1226876 20.2% 0.2% 2461634 10.9%

QTR3 4 0 0 242159 270 1034796 2620 0 0 20136 67 0 0 10872 643168 0 0.0% 1279845 18.9% 0.2% 1279845 18.9% 0 0.0% 20203 100.0% 0.3% 20203 100.0% 654040 1.7% 654040 1.7% 1300048 20.2% 0.2% 2608128 10.9%

QTR4 4 0 0 254456 270 1091989 2890 0 0 21615 67 0 0 11381 678982 0 0.0% 1349605 18.9% 0.2% 1349605 18.9% 0 0.0% 21682 100.0% 0.3% 21682 100.0% 690363 1.6% 690363 1.6% 1371287 20.2% 0.2% 2752013 10.9%

QTR1 5 0 0 267876 314 1146738 3024 0 0 22882 67 0 0 12315 716280 0 0.0% 1417952 18.9% 0.2% 1417952 18.9% 0 0.0% 22949 100.0% 0.3% 22949 100.0% 728595 1.7% 728595 1.7% 1440901 20.2% 0.2% 2898091 10.9%

QTR2 5 0 0 281302 381 1199144 3139 0 0 24070 67 0 0 13186 754661 0 0.0% 1483966 19.0% 0.2% 1483966 19.0% 0 0.0% 24137 100.0% 0.3% 24137 100.0% 767847 1.7% 767847 1.7% 1508103 20.3% 0.2% 3043797 10.9%

QTR3 5 0 0 293099 588 1252241 3163 0 0 25438 72 0 0 13573 795412 0 0.0% 1549091 19.0% 0.2% 1549091 19.0% 0 0.0% 25510 100.0% 0.3% 25510 100.0% 808985 1.7% 808985 1.7% 1574601 20.3% 0.2% 3192571 10.8%

QTR4 5 0 0 305602 588 1307122 3299 0 0 26692 72 0 0 13992 831971 0 0.0% 1616611 18.9% 0.2% 1616611 18.9% 0 0.0% 26764 100.0% 0.3% 26764 100.0% 845963 1.7% 845963 1.7% 1643375 20.3% 0.2% 3335301 10.8%

QTR1 6 0 0 317096 588 1361429 3342 0 0 28007 72 0 0 14734 868367 0 0.0% 1682455 18.9% 0.2% 1682455 18.9% 0 0.0% 28079 100.0% 0.3% 28079 100.0% 883101 1.7% 883101 1.7% 1710534 20.2% 0.2% 3476736 10.8%

QTR2 6 0 0 329929 602 1414999 3453 0 0 29308 72 0 0 15278 905074 0 0.0% 1748983 18.9% 0.2% 1748983 18.9% 0 0.0% 29380 100.0% 0.2% 29380 100.0% 920352 1.7% 920352 1.7% 1778363 20.2% 0.2% 3619067 10.8%

QTR3 6 0 0 343320 607 1473276 3462 0 0 30327 77 0 0 15879 941842 0 0.0% 1820665 18.9% 0.2% 1820665 18.9% 0 0.0% 30404 100.0% 0.3% 30404 100.0% 957721 1.7% 957721 1.7% 1851069 20.2% 0.2% 3766511 10.8%

QTR4 6 0 0 357437 708 1524412 3572 0 0 31088 77 0 0 16581 980609 0 0.0% 1886129 19.0% 0.2% 1886129 19.0% 0 0.0% 31165 100.0% 0.2% 31165 100.0% 997190 1.7% 997190 1.7% 1917294 20.3% 0.2% 3911674 10.8%

QTR1 7

QTR2 7

QTR3 7

QTR4 7

QTR1 8

QTR2 8

QTR3 8

QTR4 8

QTR1 9

QTR2 9

QTR3 9

QTR4 9

QTR1 10

QTR2 10

QTR3 10

QTR4 10




Total Micro


Micrsoscopy


LAB TESTS COMPLETED

TOTAL



QTR1 0 0 0 10386 0 49503 255 0 0 697 0 0 0 216 1440 0 0.0% 60144 17.3% 0.4% 60144 17.3% 0 0.0% 697 100.0% 0.0% 697 100.0% 1656 13.0% 1656 13.0% 60841 18.2% 0.4% 64153 17.9%

QTR2 0 0 0 24552 5 106444 495 0 0 2107 0 0 0 834 15114 0 0.0% 131496 18.7% 0.4% 131496 18.7% 0 0.0% 2107 100.0% 0.0% 2107 100.0% 15948 5.2% 15948 5.2% 133603 20.0% 0.4% 165499 17.1%

QTR3 0 0 0 37385 14 158436 606 0 0 3168 0 0 0 1270 47234 0 0.0% 196441 19.0% 0.3% 196441 19.0% 0 0.0% 3168 100.0% 0.0% 3168 100.0% 48504 2.6% 48504 2.6% 199609 20.3% 0.3% 296617 14.5%

QTR4 0 0 0 49067 14 213168 630 0 0 4393 0 0 0 1601 86032 0 0.0% 262879 18.7% 0.2% 262879 18.7% 0 0.0% 4393 100.0% 0.0% 4393 100.0% 87633 1.8% 87633 1.8% 267272 20.0% 0.2% 442538 12.8%

QTR1 1 0 0 62480 24 269317 635 0 0 5134 0 0 0 2205 121671 0 0.0% 332456 18.8% 0.2% 332456 18.8% 0 0.0% 5134 100.0% 0.0% 5134 100.0% 123876 1.8% 123876 1.8% 337590 20.0% 0.2% 585342 12.3%

QTR2 1 0 0 74887 34 324382 760 0 0 6354 0 0 0 2615 157839 0 0.0% 400063 18.7% 0.2% 400063 18.7% 0 0.0% 6354 100.0% 0.0% 6354 100.0% 160454 1.6% 160454 1.6% 406417 20.0% 0.2% 727325 11.9%

QTR3 1 0 0 87870 34 377930 770 0 0 7774 23 0 0 3321 194110 0 0.0% 466604 18.8% 0.2% 466604 18.8% 0 0.0% 7797 100.0% 0.3% 7797 100.0% 197431 1.7% 197431 1.7% 474401 20.2% 0.2% 869263 11.8%

QTR4 1 0 0 102091 34 433179 785 0 0 8483 23 0 0 4222 230341 0 0.0% 536089 19.1% 0.2% 536089 19.1% 0 0.0% 8506 100.0% 0.3% 8506 100.0% 234563 1.8% 234563 1.8% 544595 20.3% 0.2% 1013721 11.7%

QTR1 2 0 0 115591 48 484988 920 0 0 9733 23 0 0 4618 268971 0 0.0% 601547 19.2% 0.2% 601547 19.2% 0 0.0% 9756 100.0% 0.2% 9756 100.0% 273589 1.7% 273589 1.7% 611303 20.5% 0.2% 1158481 11.6%

QTR2 2 0 0 127988 48 538919 1075 0 0 10494 23 0 0 5072 308890 0 0.0% 668030 19.2% 0.2% 668030 19.2% 0 0.0% 10517 100.0% 0.2% 10517 100.0% 313962 1.6% 313962 1.6% 678547 20.4% 0.2% 1306471 11.4%

QTR3 2 0 0 140463 53 594255 1225 0 0 11719 23 0 0 5622 346138 0 0.0% 735996 19.1% 0.2% 735996 19.1% 0 0.0% 11742 100.0% 0.2% 11742 100.0% 351760 1.6% 351760 1.6% 747738 20.4% 0.2% 1451258 11.3%

QTR4 2 0 0 153045 154 648647 1245 0 0 12807 28 0 0 6464 382143 0 0.0% 803091 19.1% 0.2% 803091 19.1% 0 0.0% 12835 100.0% 0.2% 12835 100.0% 388607 1.7% 388607 1.7% 815926 20.3% 0.2% 1593140 11.2%

QTR1 3 0 0 164943 154 705334 1351 0 0 14257 28 0 0 7456 419160 0 0.0% 871782 18.9% 0.2% 871782 18.9% 0 0.0% 14285 100.0% 0.2% 14285 100.0% 426616 1.7% 426616 1.7% 886067 20.2% 0.2% 1739299 11.2%

QTR2 3 0 0 178772 154 760360 1764 0 0 15463 28 0 0 7679 456421 0 0.0% 941050 19.0% 0.2% 941050 19.0% 0 0.0% 15491 100.0% 0.2% 15491 100.0% 464100 1.7% 464100 1.7% 956541 20.3% 0.2% 1884741 11.1%

QTR3 3 0 0 191521 154 814517 1885 0 0 16257 28 0 0 8203 493090 0 0.0% 1008077 19.0% 0.2% 1008077 19.0% 0 0.0% 16285 100.0% 0.2% 16285 100.0% 501293 1.6% 501293 1.6% 1024362 20.3% 0.2% 2026948 11.1%

QTR4 3 0 0 204459 159 871736 1995 0 0 17192 28 0 0 8790 532752 0 0.0% 1078349 19.0% 0.2% 1078349 19.0% 0 0.0% 17220 100.0% 0.2% 17220 100.0% 541542 1.6% 541542 1.6% 1095569 20.2% 0.2% 2178653 11.0%

QTR1 4 0 0 217244 164 924028 2207 0 0 18054 67 0 0 9523 571113 0 0.0% 1143643 19.0% 0.2% 1143643 19.0% 0 0.0% 18121 100.0% 0.4% 18121 100.0% 580636 1.6% 580636 1.6% 1161764 20.3% 0.2% 2323036 11.0%

QTR2 4 0 0 228348 265 976900 2371 0 0 18925 67 0 0 10005 607374 0 0.0% 1207884 18.9% 0.2% 1207884 18.9% 0 0.0% 18992 100.0% 0.4% 18992 100.0% 617379 1.6% 617379 1.6% 1226876 20.2% 0.2% 2461634 10.9%

QTR3 4 0 0 242159 270 1034796 2620 0 0 20136 67 0 0 10872 643168 0 0.0% 1279845 18.9% 0.2% 1279845 18.9% 0 0.0% 20203 100.0% 0.3% 20203 100.0% 654040 1.7% 654040 1.7% 1300048 20.2% 0.2% 2608128 10.9%

QTR4 4 0 0 254456 270 1091989 2890 0 0 21615 67 0 0 11381 678982 0 0.0% 1349605 18.9% 0.2% 1349605 18.9% 0 0.0% 21682 100.0% 0.3% 21682 100.0% 690363 1.6% 690363 1.6% 1371287 20.2% 0.2% 2752013 10.9%

QTR1 5 0 0 267876 314 1146738 3024 0 0 22882 67 0 0 12315 716280 0 0.0% 1417952 18.9% 0.2% 1417952 18.9% 0 0.0% 22949 100.0% 0.3% 22949 100.0% 728595 1.7% 728595 1.7% 1440901 20.2% 0.2% 2898091 10.9%

QTR2 5 0 0 281302 381 1199144 3139 0 0 24070 67 0 0 13186 754661 0 0.0% 1483966 19.0% 0.2% 1483966 19.0% 0 0.0% 24137 100.0% 0.3% 24137 100.0% 767847 1.7% 767847 1.7% 1508103 20.3% 0.2% 3043797 10.9%

QTR3 5 0 0 293099 588 1252241 3163 0 0 25438 72 0 0 13573 795412 0 0.0% 1549091 19.0% 0.2% 1549091 19.0% 0 0.0% 25510 100.0% 0.3% 25510 100.0% 808985 1.7% 808985 1.7% 1574601 20.3% 0.2% 3192571 10.8%

QTR4 5 0 0 305602 588 1307122 3299 0 0 26692 72 0 0 13992 831971 0 0.0% 1616611 18.9% 0.2% 1616611 18.9% 0 0.0% 26764 100.0% 0.3% 26764 100.0% 845963 1.7% 845963 1.7% 1643375 20.3% 0.2% 3335301 10.8%

QTR1 6 0 0 317096 588 1361429 3342 0 0 28007 72 0 0 14734 868367 0 0.0% 1682455 18.9% 0.2% 1682455 18.9% 0 0.0% 28079 100.0% 0.3% 28079 100.0% 883101 1.7% 883101 1.7% 1710534 20.2% 0.2% 3476736 10.8%

QTR2 6 0 0 329929 602 1414999 3453 0 0 29308 72 0 0 15278 905074 0 0.0% 1748983 18.9% 0.2% 1748983 18.9% 0 0.0% 29380 100.0% 0.2% 29380 100.0% 920352 1.7% 920352 1.7% 1778363 20.2% 0.2% 3619067 10.8%

QTR3 6 0 0 343320 607 1473276 3462 0 0 30327 77 0 0 15879 941842 0 0.0% 1820665 18.9% 0.2% 1820665 18.9% 0 0.0% 30404 100.0% 0.3% 30404 100.0% 957721 1.7% 957721 1.7% 1851069 20.2% 0.2% 3766511 10.8%

QTR4 6 0 0 357437 708 1524412 3572 0 0 31088 77 0 0 16581 980609 0 0.0% 1886129 19.0% 0.2% 1886129 19.0% 0 0.0% 31165 100.0% 0.2% 31165 100.0% 997190 1.7% 997190 1.7% 1917294 20.3% 0.2% 3911674 10.8%

QTR1 7

QTR2 7

QTR3 7

QTR4 7

QTR1 8

QTR2 8

QTR3 8

QTR4 8

QTR1 9

QTR2 9

QTR3 9

QTR4 9

QTR1 10

QTR2 10

QTR3 10

QTR4 10




Total Micro


Micrsoscopy


LAB TESTS COMPLETED

TOTAL



QTR1 0 0 0 10386 0 49503 255 0 0 697 0 0 0 216 1440 0 0.0% 60144 17.3% 0.4% 60144 17.3% 0 0.0% 697 100.0% 0.0% 697 100.0% 1656 13.0% 1656 13.0% 60841 18.2% 0.4% 64153 17.9%

QTR2 0 0 0 24552 5 106444 495 0 0 2107 0 0 0 834 15114 0 0.0% 131496 18.7% 0.4% 131496 18.7% 0 0.0% 2107 100.0% 0.0% 2107 100.0% 15948 5.2% 15948 5.2% 133603 20.0% 0.4% 165499 17.1%

QTR3 0 0 0 37385 14 158436 606 0 0 3168 0 0 0 1270 47234 0 0.0% 196441 19.0% 0.3% 196441 19.0% 0 0.0% 3168 100.0% 0.0% 3168 100.0% 48504 2.6% 48504 2.6% 199609 20.3% 0.3% 296617 14.5%

QTR4 0 0 0 49067 14 213168 630 0 0 4393 0 0 0 1601 86032 0 0.0% 262879 18.7% 0.2% 262879 18.7% 0 0.0% 4393 100.0% 0.0% 4393 100.0% 87633 1.8% 87633 1.8% 267272 20.0% 0.2% 442538 12.8%

QTR1 1 0 0 62480 24 269317 635 0 0 5134 0 0 0 2205 121671 0 0.0% 332456 18.8% 0.2% 332456 18.8% 0 0.0% 5134 100.0% 0.0% 5134 100.0% 123876 1.8% 123876 1.8% 337590 20.0% 0.2% 585342 12.3%

QTR2 1 0 0 74887 34 324382 760 0 0 6354 0 0 0 2615 157839 0 0.0% 400063 18.7% 0.2% 400063 18.7% 0 0.0% 6354 100.0% 0.0% 6354 100.0% 160454 1.6% 160454 1.6% 406417 20.0% 0.2% 727325 11.9%

QTR3 1 0 0 87870 34 377930 770 0 0 7774 23 0 0 3321 194110 0 0.0% 466604 18.8% 0.2% 466604 18.8% 0 0.0% 7797 100.0% 0.3% 7797 100.0% 197431 1.7% 197431 1.7% 474401 20.2% 0.2% 869263 11.8%

QTR4 1 0 0 102091 34 433179 785 0 0 8483 23 0 0 4222 230341 0 0.0% 536089 19.1% 0.2% 536089 19.1% 0 0.0% 8506 100.0% 0.3% 8506 100.0% 234563 1.8% 234563 1.8% 544595 20.3% 0.2% 1013721 11.7%

QTR1 2 0 0 115591 48 484988 920 0 0 9733 23 0 0 4618 268971 0 0.0% 601547 19.2% 0.2% 601547 19.2% 0 0.0% 9756 100.0% 0.2% 9756 100.0% 273589 1.7% 273589 1.7% 611303 20.5% 0.2% 1158481 11.6%

QTR2 2 0 0 127988 48 538919 1075 0 0 10494 23 0 0 5072 308890 0 0.0% 668030 19.2% 0.2% 668030 19.2% 0 0.0% 10517 100.0% 0.2% 10517 100.0% 313962 1.6% 313962 1.6% 678547 20.4% 0.2% 1306471 11.4%

QTR3 2 0 0 140463 53 594255 1225 0 0 11719 23 0 0 5622 346138 0 0.0% 735996 19.1% 0.2% 735996 19.1% 0 0.0% 11742 100.0% 0.2% 11742 100.0% 351760 1.6% 351760 1.6% 747738 20.4% 0.2% 1451258 11.3%

QTR4 2 0 0 153045 154 648647 1245 0 0 12807 28 0 0 6464 382143 0 0.0% 803091 19.1% 0.2% 803091 19.1% 0 0.0% 12835 100.0% 0.2% 12835 100.0% 388607 1.7% 388607 1.7% 815926 20.3% 0.2% 1593140 11.2%

QTR1 3 0 0 164943 154 705334 1351 0 0 14257 28 0 0 7456 419160 0 0.0% 871782 18.9% 0.2% 871782 18.9% 0 0.0% 14285 100.0% 0.2% 14285 100.0% 426616 1.7% 426616 1.7% 886067 20.2% 0.2% 1739299 11.2%

QTR2 3 0 0 178772 154 760360 1764 0 0 15463 28 0 0 7679 456421 0 0.0% 941050 19.0% 0.2% 941050 19.0% 0 0.0% 15491 100.0% 0.2% 15491 100.0% 464100 1.7% 464100 1.7% 956541 20.3% 0.2% 1884741 11.1%

QTR3 3 0 0 191521 154 814517 1885 0 0 16257 28 0 0 8203 493090 0 0.0% 1008077 19.0% 0.2% 1008077 19.0% 0 0.0% 16285 100.0% 0.2% 16285 100.0% 501293 1.6% 501293 1.6% 1024362 20.3% 0.2% 2026948 11.1%

QTR4 3 0 0 204459 159 871736 1995 0 0 17192 28 0 0 8790 532752 0 0.0% 1078349 19.0% 0.2% 1078349 19.0% 0 0.0% 17220 100.0% 0.2% 17220 100.0% 541542 1.6% 541542 1.6% 1095569 20.2% 0.2% 2178653 11.0%

QTR1 4 0 0 217244 164 924028 2207 0 0 18054 67 0 0 9523 571113 0 0.0% 1143643 19.0% 0.2% 1143643 19.0% 0 0.0% 18121 100.0% 0.4% 18121 100.0% 580636 1.6% 580636 1.6% 1161764 20.3% 0.2% 2323036 11.0%

QTR2 4 0 0 228348 265 976900 2371 0 0 18925 67 0 0 10005 607374 0 0.0% 1207884 18.9% 0.2% 1207884 18.9% 0 0.0% 18992 100.0% 0.4% 18992 100.0% 617379 1.6% 617379 1.6% 1226876 20.2% 0.2% 2461634 10.9%

QTR3 4 0 0 242159 270 1034796 2620 0 0 20136 67 0 0 10872 643168 0 0.0% 1279845 18.9% 0.2% 1279845 18.9% 0 0.0% 20203 100.0% 0.3% 20203 100.0% 654040 1.7% 654040 1.7% 1300048 20.2% 0.2% 2608128 10.9%

QTR4 4 0 0 254456 270 1091989 2890 0 0 21615 67 0 0 11381 678982 0 0.0% 1349605 18.9% 0.2% 1349605 18.9% 0 0.0% 21682 100.0% 0.3% 21682 100.0% 690363 1.6% 690363 1.6% 1371287 20.2% 0.2% 2752013 10.9%

QTR1 5 0 0 267876 314 1146738 3024 0 0 22882 67 0 0 12315 716280 0 0.0% 1417952 18.9% 0.2% 1417952 18.9% 0 0.0% 22949 100.0% 0.3% 22949 100.0% 728595 1.7% 728595 1.7% 1440901 20.2% 0.2% 2898091 10.9%

QTR2 5 0 0 281302 381 1199144 3139 0 0 24070 67 0 0 13186 754661 0 0.0% 1483966 19.0% 0.2% 1483966 19.0% 0 0.0% 24137 100.0% 0.3% 24137 100.0% 767847 1.7% 767847 1.7% 1508103 20.3% 0.2% 3043797 10.9%

QTR3 5 0 0 293099 588 1252241 3163 0 0 25438 72 0 0 13573 795412 0 0.0% 1549091 19.0% 0.2% 1549091 19.0% 0 0.0% 25510 100.0% 0.3% 25510 100.0% 808985 1.7% 808985 1.7% 1574601 20.3% 0.2% 3192571 10.8%

QTR4 5 0 0 305602 588 1307122 3299 0 0 26692 72 0 0 13992 831971 0 0.0% 1616611 18.9% 0.2% 1616611 18.9% 0 0.0% 26764 100.0% 0.3% 26764 100.0% 845963 1.7% 845963 1.7% 1643375 20.3% 0.2% 3335301 10.8%

QTR1 6 0 0 317096 588 1361429 3342 0 0 28007 72 0 0 14734 868367 0 0.0% 1682455 18.9% 0.2% 1682455 18.9% 0 0.0% 28079 100.0% 0.3% 28079 100.0% 883101 1.7% 883101 1.7% 1710534 20.2% 0.2% 3476736 10.8%

QTR2 6 0 0 329929 602 1414999 3453 0 0 29308 72 0 0 15278 905074 0 0.0% 1748983 18.9% 0.2% 1748983 18.9% 0 0.0% 29380 100.0% 0.2% 29380 100.0% 920352 1.7% 920352 1.7% 1778363 20.2% 0.2% 3619067 10.8%

QTR3 6 0 0 343320 607 1473276 3462 0 0 30327 77 0 0 15879 941842 0 0.0% 1820665 18.9% 0.2% 1820665 18.9% 0 0.0% 30404 100.0% 0.3% 30404 100.0% 957721 1.7% 957721 1.7% 1851069 20.2% 0.2% 3766511 10.8%

QTR4 6 0 0 357437 708 1524412 3572 0 0 31088 77 0 0 16581 980609 0 0.0% 1886129 19.0% 0.2% 1886129 19.0% 0 0.0% 31165 100.0% 0.2% 31165 100.0% 997190 1.7% 997190 1.7% 1917294 20.3% 0.2% 3911674 10.8%

QTR1 7

QTR2 7

QTR3 7

QTR4 7

QTR1 8

QTR2 8

QTR3 8

QTR4 8

QTR1 9

QTR2 9

QTR3 9

QTR4 9

QTR1 10




Total Micro


Micrsoscopy


Virtual Implementation – DOthe model development – OUTPUTS

14

Data is output to an Excel Workbook every

Quarter in line with the World Health

Organisation requirements for trials of TB

diagnostics

QTR1 10

QTR2 10

QTR3 10

QTR4 10

Testing approach in Tanzania.

Measure CountPopulation 44million

Virtual Implementation – DOthe model development – Calibration in Tanzania

15

Health Facility CountCentral TB Reference Lab 1

Zonal Laboratories 2

Regions 27

Districts 168

TB Laboratories >900

Sources Basra Doulla , Ministry of Health, Dar es Salaam, Tanzania

Population 44million

New TB cases per year 80k p.a.

TB cases Treated 64k p.a.

HIV+% in TB Incidence 47%

Treatment Cure Rate 87%

SET-UP

16

SET-UP

17

Virtual Implementation – DOthe options to be considered

A. Base Case – ZN Microscopy – with 2 samples

B. LED Fluorescence Microscopy

C. Same Day Fluorescence Microscopy

18

D. Xpert MTB/RIF as secondary test for HIV+, Smear-ve new TB suspects- part of current Xpert trials in Tanzania (a. 10% HIV status known, b. 90% HIV status known)

E. Xpert MTB/RIF as primary test for HIV+ new TB suspects – (a. 10% HIV+ status known, b. 90% HIV+ status known)

F. Full rollout of Xpert MTB/RIF to all new TB suspects

Virtual Implementation – DOthe example results - DRAFT

19


20


21

Virtual Implementation – DOthe example results – Cost Effectiveness & Sustainability

Rank

by cost

(High-

Low)

Site A

Currently

using ZN

Microscopy

Site B

Currently

using LED

Fluor.

Microscopy

Incremental

Health

System

Costs

($k p.a.)

1 Xpert for all Xpert for all 79.3

2 Xpert for all Xpert -HIV+ 72.1

22

3 Xpert -HIV+ Xpert for all 54.7

4 Xpert for all No Change 53.3

5 Xpert -HIV+ Xpert -HIV+ 47.9

6 Xpert -HIV+ No Change 29.1

7 LED Fluor. Xpert for all 26.5

8 LED Fluor. Xpert -HIV+ 19.3

9 LED Fluor. No Change 0.5


Rank

by cost

(High-

Low)

Site A

Currently

using ZN

Microscopy

Site B

Currently

using LED

Fluor.

Microscopy

DALY’s

averted

per year

Incremental

Health

System

Costs

($k p.a.)

1 Xpert for all Xpert for all 1,983 79.3

2 Xpert for all Xpert -HIV+ 1,654 72.1

23

3 Xpert -HIV+ Xpert for all 1,606 54.7

4 Xpert for all No Change 1,220 53.3

5 Xpert -HIV+ Xpert -HIV+ 1,277 47.9

6 Xpert -HIV+ No Change 843 29.1

7 LED Fluor. Xpert for all 1,162 26.5

8 LED Fluor. Xpert -HIV+ 833 19.3

9 LED Fluor. No Change 399 0.5


Rank

by cost

(High-

Low)

Site A

Currently

using ZN

Microscopy

Site B

Currently

using LED

Fluor.

Microscopy

DALY’s

averted

per year

Incremental

Health

System

Costs

($k p.a.)

1 Xpert for all Xpert for all 1,983 79.3

2 Xpert for all Xpert -HIV+ 1,654 72.1

24

3 Xpert -HIV+ Xpert for all 1,606 54.7

4 Xpert for all No Change 1,220 53.3 XIneffective due to no

benefit over No.5

5 Xpert -HIV+ Xpert -HIV+ 1,277 47.9

6 Xpert -HIV+ No Change 843 29.1 XIneffective due to no

benefit over No.7

7 LED Fluor. Xpert for all 1,162 26.5

8 LED Fluor. Xpert -HIV+ 833 19.3

9 LED Fluor. No Change 399 0.5


Rank

by cost

(High-

Low)

Site A

Currently

using ZN

Microscopy

Site B

Currently

using LED

Fluor.

Microscopy

DALY’s

averted

per year

Incremental

Health

System

Costs

($k p.a.)

ICER

to base

case ($)

ICER(2)

to the next

effective

intervention

($)

1 Xpert for all Xpert for all 1,983 79.3 40.0 65.1

2 Xpert for all Xpert -HIV+ 1,654 72.1 43.6 361.8

25

3 Xpert -HIV+ Xpert for all 1,606 54.7 34.0 20.6

4 Xpert for all No Change 1,220 53.3 43.6 XIneffective due to no

benefit over No.5

5 Xpert -HIV+ Xpert -HIV+ 1,277 47.9 37.5 185.8

6 Xpert -HIV+ No Change 843 29.1 34.5 XIneffective due to no

benefit over No.7

7 LED Fluor. Xpert for all 1,162 26.5 22.8 21.9

8 LED Fluor. Xpert -HIV+ 833 19.3 23.1 43.3

9 LED Fluor. No Change 399 0.5 1.2 1.2


Rank

by cost

(High-

Low)

Site A

Currently

using ZN

Microscopy

Site B

Currently

using LED

Fluor.

Microscopy

DALY’s

averted

per year

Incremental

Health

System

Costs

($k p.a.)

ICER

to base

case ($)

ICER(2)

to the next

effective

intervention

($)

Comment

(ICER threshold of

$150 per DALY

averted)

1 Xpert for all Xpert for all 1,983 79.3 40.0 65.1Cost effective $79k

pa

2 Xpert for all Xpert -HIV+ 1,654 72.1 43.6 361.8Ineffective due to

high ICER(2)

26

high ICER(2)

3 Xpert -HIV+ Xpert for all 1,606 54.7 34.0 20.6


benefit over No.5

5 Xpert -HIV+ Xpert -HIV+ 1,277 47.9 37.5 185.8Ineffective due to

high ICER(2)


benefit over No.7

7 LED Fluor. Xpert for all 1,162 26.5 22.8 21.9

8 LED Fluor. Xpert -HIV+ 833 19.3 23.1 43.3

9 LED Fluor. No Change 399 0.5 1.2 1.2


Rank

by cost

(High-

Low)

Site A

Currently

using ZN

Microscopy

Site B

Currently

using LED

Fluor.

Microscopy

DALY’s

averted

per year

Incremental

Health

System

Costs

($k p.a.)

ICER

to base

case ($)

ICER(2)

to the next

effective

intervention

($)

Comment

(ICER threshold of

$150 per DALY

averted)

1 Xpert for all Xpert for all 1,983 79.3 40.0 65.1Cost effective $79k

pa

2 Xpert for all Xpert -HIV+ 1,654 72.1 43.6 361.8Ineffective due to

high ICER(2)

27

high ICER(2)

3 Xpert -HIV+ Xpert for all 1,606 54.7 34.0 20.6Cost effective $55k

pa


benefit over 5

5 Xpert -HIV+ Xpert -HIV+ 1,277 47.9 37.5 185.8Ineffective due to

high ICER(2)


benefit over No.7

7 LED Fluor. Xpert for all 1,162 26.5 22.8 21.9Cost effective $27k

pa

8 LED Fluor. Xpert -HIV+ 833 19.3 23.1 43.3Cost effective $19k

pa

9 LED Fluor. No Change 399 0.5 1.2 1.2 Cost effective $1k pa

� IMPACT ASSESSMENT IN TANZANIA

� Of scale-up of the options

� Of the proposed Xpert MTB/RIF implementations in the 5 diagnostic centres (supporting Tanzanian staff to conduct their own evaluations)

� WIDER APPLICATION

Virtual Implementation – DOINGthe next steps

28

� Apply the models to other settings e.g. Malawi

� Develop models for MDR-TB diagnosis e.g. Brazil

� Local

� Presentation to a forum of policy makers in Tanzania

� Pier reviewed publications

� Concept Paper4

� Results orientated paper – Health Journal

Virtual Implementation – DISSEMINATIONthe next steps

29

� Results orientated paper – Health Journal

� Methodology orientated publications – Management Science

� International Conferences

� Union conferences

� Post Graduate Courses

� Guidelines

� Modelling guidelines

4Lin HH, Langley I, Mwenda R, et al. (2011), A modelling framework to support the selection and implementation of new

tuberculosis diagnostic tools. Int J Tuberc Lung Dis 15(8):996–1004, doi:10.5588/ijtld.11.0062

Summary

� Virtual implementation of options for TB diagnostics :-

• is a practical and effective approach

• engages policy makers in validation and questioning

• enables complex interactions to be taken into account

30

• enables complex interactions to be taken into account

• provides comprehensive information on impacts that can be useful in policy decisions

PROVEPROVE--ITITPPolicy RRelevant OOutcomes from VValidating EEvidence on

IImpacT

PROVE-IT, BRAZIL – Afrânio Kritski

31

of Xpert MTB/RIF and Line Probe Assay

on Presumptive Diagnosis of DR-TB in Brazil

REDE-TB: Afranio Kritski, Martha Oliveira, Monica Kramer, Claudia Vater, Fatima

Carparo, Jose Ueleres Braga

The Union: Anne Detjen, Paula Fujiwara

MRC UK: Patrick Phillips

LSTM: Bertie Squire, Ivor Langley, Kerry Millington

GOAL: To evaluate Xpert MTB/RIF, Line Probe Assay (LPA), and

MGIT960, performance for DR/MDR TB diagnosis in

different provinces with distinct epidemiological and

health systems backgrounds in order to identify which

one(s) will be most appropriate for the Brazilian public

PROVE-IT in Brazil - DEFINE

32

one(s) will be most appropriate for the Brazilian public

health system (SUS)

To determine the most appropriate we need to

understand effects/impacts of the change

PROVE-IT in Brazil - DEFINEA Framework for Impact Assessment for New Diagnostics2

Layer of Assessment Kinds of question(s) being answered

Layer 1: EFFECTIVENESS

How well does it work?

Layer 2: EQUITY

- Who benefits and why?

33

Layer 3: HEALTH SYSTEM

- Operational effects?

Layer 4: SCALE UP

Impacts of national rollout?

Layer 5: HORIZON SCANNING

- How does it compare to

other technologies?



PROVE-IT in Brazil - DEFINEA Framework for Impact Assessment for New Diagnostics2

Layer of Assessment Kinds of question(s) being answered

Layer 1: EFFECTIVENESS

How well does it work?

• Time from sputum collection to detect DR/MDR-TB cases and to start the

appropriate DR-TB treatment

• Proportion smear conversion rate at 2 months

• Proportion culture conversion rate at 6 months

• All-cause mortality

Layer 2: EQUITY

- Who benefits and why?

• Costs to the patients (by poverty status/income)

• Who is benefiting? – Subgroup analyses: poor/non-poor, men/women, adults

•Time from sputum collection to detect DR/MDR-TB cases and to start the

appropriate DR-TB treatment - PRIMARY OUTCOME

•Proportion culture conversion rate at 6 months - SECONDARY OUTCOME

34

- Who benefits and why? • Who is benefiting? – Subgroup analyses: poor/non-poor, men/women, adults

HIV+/HIV-, inpatients vs. outpatients.

Layer 3: HEALTH SYSTEM

- Operational effects?

• Costs to the health system (per case started on appropriate regimen)

• Lab system requirements (infrastructure, HR, procurement, quality assurance etc)

• Clinical system requirements

• HR and training requirements

• Patient management requirements (drugs, treatment facilities etc)

Layer 4: SCALE UP

Impacts of national rollout?

• Projection of data from Layers for national scale-up.

• Projection of likely impact on transmission

Layer 5: HORIZON SCANNING

- How does it compare to

other technologies?

• Comparison of LPA/GeneXpert/MGIT960 impact with models of impact expected

from other new tools/approaches and packages of tools/approaches.



PROVE-IT in Brazil - DESIGNa pragmatic, cluster-randomised, implementation trial

Site 4

35

Site 2Site 3

Site 1

Site2

MG

IT

train

in

Implementation9 mths

follow-up6 mths

LP

A

train

in


follow-up6 mths

Site

1

Xp

ert

train

i


follow-up6 mths

MG

IT

train

i


follow-up6 mths

PROVE-IT in Brazil - DESIGNa pragmatic, cluster-randomised, crossover design

36

Site

3

MG

IT

train

in

g


follow-up6 mths

Xp

ert

train

in


follow-up6 mths

Site

4

LP

A

train

i

ng Implementation

9 mthsfollow-up6 mths

MG

IT

train

i


follow-up6 mths

LP

A

train

in 9 mths 6 mths

Implementation

– e.g. Site 4, 1st 9

months a) Site accounts

– health

system costs

b) Routine

registers


37

LJ and DST (PM/MGIT)LPA

registers

(clinical & lab)

c) Subset of

patients –

patients costs

Expected ~3 days

Implementation –

e.g. Site 1, 2nd 9

monthsa) Site accounts –

health system

costs

b) Routine

registers


38

LJ and DST (PM/MGIT)MGIT 960

registers

(clinical & lab)

c) Subset of

patients –

patients costs

Expected ~15 days

Implementation

– e.g. Site 3, 1st 9

months

a) Site accounts

– health

system costs

b) Routine


39

LJ and DST (PM/MGIT)MTB/RIF

b) Routine

registers

(clinical &

lab)

c) Subset of

patients –

patients

costs

Expected ~2 days

1. Inclusion criteria - DR/MDR TB suspects presenting witha) TB in the past

i. Suspected re-treatment failure or

ii. Smear positive at 2 months

b) Without previous TB treatment

i. HIV positive or

ii. Close contact with MDR-TB case or

iii. Homeless or

PROVE-IT in Brazil - DESIGNinclusion criteria and data collection

40

iii. Homeless or

iv. Inmates/assylum/penitentiary

2. DR/MDR TB patients at each site and during each phase interviewed for to

collect cost and socio-economic data

3. Health system costs collected across all sites for each intervention

4. Active involvement of community through Community Advisory Boards

(CAB’s) at all stages in all sites

Policy transfer anaysis will interview:

• Laboratory professionals

• Physicians that take care of DR-TB suspects

• Other health care professionals that are part of the local health teams

• Representatives of Community Advisory Board

PROVE-IT in Brazil - DESIGNPolicy Transfer Analysis

41

• Representatives of Community Advisory Board

• Managers of TB Reference Hospitals

• Managers of Health Services (Unified Health System / SUS)

Objective:

To derive constructive lessons that will be applicable for future activity in

introducing /piloting/modifying other new diagnostics.

1. Baseline (Feb – September 2011 – 4 sites and sentinel Units)

• Rio de Janeiro (x2), São Paulo, Ceará

• Total number of patients enrolled at implementation phase: 269

• Excluded: 11

• Included: 258

• Required numbers to power trial – 630 over 7months

PROVE-IT in Brazil – DObase line recruitment

42

• Required numbers to power trial – 630 over 7months

2. Problem: Low recruitment of eligible patients

3. Strategies adopted for increasing recruitment

• Added sites and sentinel Units

• Ongoing discussion in Municipalities to increase engagement.

PROVE-IT in Brazil – DOincreased sites

Site 4

Site 6 (Added)

PARÁSite 8 (?)

43

Site 7 (?)

Site 3

Site 2

Site 1

Site 5 (Added)

Results: Number of eligible DR TB suspects have increased

Site 3: Reference Center Helio Fraga Site 1: Clemente Ferreira Institute

1414

16

7780

90

PROVE-IT in Brazil – DOrecruitment since intervention

44

1

6

3

5

14

0

2

4

6

8

10

12

14

Dec Jan Feb March April

6 5 48

77

0

10

20

30

40

50

60

70

Nov Dec Jan Feb March

N a

bs

1. Recruitment ongoing to first intervention

2. Switch to second intervention August 2012 – December 2012

3. Complete recruitment to second intervention - April 2013

PROVE-IT in Brazil – DOING/DISSEMINATION

45

4. Ongoing patient, health system, and policy transfer data collection throughout intervention

5. Complete Analysis September 2013

6. Publish results 2014

Acknowledgment

� USAID� YaDiul Mukadi

� Tanzania NTLP� Dr Saidi Egwaga

� Basra Doulla

� The Union (Treat-TB)

� Liverpool School of Tropical Medicine

� Bertie Squire

� Kerry Millington

� National Taiwan University� Hsien-Ho Lin

46

� I.D. Rusen

� Anne Detjen

� Paula Fujiwara

� MRC UK� Patrick Phillips

� Harvard School of Public Health

� Ted Cohen

� Megan Murray

� Lanner Group� Geoff Hook

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