Weyer - Review of WHO TB diagnostics policy development 1/Weyer - Review of WHO TB... ·...

Review of WHO TB diagnostics Review of WHO TB diagnostics

1 |

Karin Weyer

Laboratories, Diagnostics and Drug Resistance Unit

Review of WHO TB diagnostics

policy development


policy development

GLI Meeting: Les Pensièrees, Annecy, France : 17 -19

Review of WHO TB diagnostics Review of WHO TB diagnostics

Karin Weyer

Laboratories, Diagnostics and Drug Resistance Unit


policy development


policy development

19 April 2012

Outline

• WHO TB diagnostics policy formulation process

• Current WHO-endorsed TB diagnostics/approaches

• Policy transfer and uptake

• Policy impact

Policy innovation • Policy innovation

Outline

WHO TB diagnostics policy formulation process

endorsed TB diagnostics/approaches

Identifying the needfor policy change

Reviewing the evidence

WHO TB diagnostics polic

• WH

• Partners (researchers, industry, etc)

• Body of evidence available

• Commissioning of systematic reviews

• QU

• Meta

• Experts, methodologists, end

• Guidelines Review CommitteeConvening an Expert Group

Assessing policy proposal

and recommendations

Formulating and

disseminating policy

• Guidelines Review Committee

• GRADE process for evidence synthesis

• Strategic and Technical Advisory Group

• Endorsement/revision/addition

• Advise to WHO to proceed/not with policy

• Guidelines Review Committee

• Dissemination to Member States

• Promotion with stakeholders & funders

• Phased implementation & scale

policy formulation process

HO strategic monitoring of country needs

Partners (researchers, industry, etc)

Body of evidence available

Commissioning of systematic reviews

UADAS or other diagnostic accuracy tool

Meta-analyses (where feasible)

Experts, methodologists, end-users

Guidelines Review CommitteeGuidelines Review Committee

GRADE process for evidence synthesis

Strategic and Technical Advisory Group

Endorsement/revision/addition

Advise to WHO to proceed/not with policy

Guidelines Review Committee

Dissemination to Member States

Promotion with stakeholders & funders

Phased implementation & scale-up plan

GRADE evaluation

Clear separation:

• Recommendationstrong or conditional/optional/weak (for or against an intervention)– Benefits and downsides, values and preferences, impact, resource use

balanced with

*Grades of Recommendation Assessment,

balanced with

• Quality of evidence

⊕⊕⊕⊕ (High), ⊕⊕⊕�(Moderate), ⊕⊕��

– Methodological quality of evidence– Likelihood of bias– By outcome and across outcomes

• GRC review cycle 3 to 5 years

GRADE evaluation

/optional/weak (for or against an intervention)Benefits and downsides, values and preferences, impact, resource use

with

ssessment, Development and Evaluation

with

��(Low), ⊕��(Very low)

Methodological quality of evidence

Example of GRADE for

1. Xpert MTB/RIF should be used as the initia

of having MDR-TB or HIV-associated TB. (

2. Xpert MTB/RIF may be considered as a follow

where MDR-TB or HIV is of lesser concern, especially in further testing of smear

negative specimens. (Conditional recomme

implications)

Remarks:

6

Remarks:

These recommendations apply to the use of Xpert MTB/RIF

decontaminated specimens). Data on the utility of Xpert

limited;

These recommendations support the use of one sputum specimen for diagnostic testing

that multiple specimens increase the sensitivity of Xpert

These recommendations also apply to children, based on the generalisation of data from adults and

acknowledging the limitations of microbiological diagnosis of TB (including MDR

Access to conventional microscopy, culture and DST is still needed

surveys and/or surveillance, and for recovering isolate

including second-line anti-TB drugs).

Example of GRADE for Xpert MTB/RIF

nitial diagnostic test in individuals suspected

associated TB. (Strong recommendation)

MTB/RIF may be considered as a follow-on test to microscopy in settings

TB or HIV is of lesser concern, especially in further testing of smear-

mmendation, acknowledging major resource

6

MTB/RIF in sputum specimens (including pellets from

Xpert MTB/RIF in extra-pulmonary specimens are still

one sputum specimen for diagnostic testing, acknowledging

Xpert MTB/RIF but have major resource implications;

, based on the generalisation of data from adults and

acknowledging the limitations of microbiological diagnosis of TB (including MDR-TB) in children;

Access to conventional microscopy, culture and DST is still needed for monitoring of therapy, for prevalence

lates for drug susceptibility testing other than rifampicin

Outline




• Policy impact


Outline



Acceleration

• Tools development: At least 20stages of development and evaluation in last 10 years

• WHO policy formulation*- 2007 : New SS+ case definition, two

culture, rapid speciation- 2008 : Line probe assay- 2008 : Line probe assay- 2009 : LED microscopy, ‘same-day diagnosis’, selected non

commercial culture and drug susceptibility testing methods- 2010 : Xpert MTB-RIF- 2011 : IGRAs, commercial serodiagnostics

• Access to new diagnostics and and EXPAND-TB)

*Available at: http://www.who.int/tb/dots/laboratory/policy/en

Acceleration

st 20 new technologies in various stages of development and evaluation in last 10 years

New SS+ case definition, two-specimen approach, liquid culture, rapid speciation

day diagnosis’, selected non-commercial culture and drug susceptibility testing methods

serodiagnostics

and laboratory strengthening (GLI

http://www.who.int/tb/dots/laboratory/policy/en

Tools/methods not recommended

• Evidence base too weak, to be reassessed

– 2009: Sputum processing methods

– 2009: TLA method for rapid DST

– 2010: LPA for XDR-TB – 2010: LPA for XDR-TB

• ‘Negative’ policy (do-not

– 2011: Commercial serodiagnostics

– 2011: IGRAs (high TB or HIV burden settings)

Tools/methods not recommended

Evidence base too weak, to be reassessed

Sputum processing methods

TLA method for rapid DST

not-use)

Commercial serodiagnostics

IGRAs (high TB or HIV burden settings)

Diagnostics pipelineDiagnostics pipeline

Policy pipeline 2012

• Laboratory biosafety

– Procedure (risk)-based, minimum requirements

• Guidance on drug susceptibility testing

– Update on 2008 guidance– Update on 2008 guidance

• LPA update

– New 2nd-line LPA (XDR)

• Evaluation of new technologies

– LAMP assay

Policy pipeline 2012

based, minimum requirements

Guidance on drug susceptibility testing

guidanceguidance

line LPA (XDR)

Evaluation of new technologies

Outline




• Policy impact


Outline



Surveillance

Reference methods

Network supervision

Tools in tiered heath services

National

Reference

Level

Central

Reference

Level

Case finding

TreatmentDistrict &

Sub-district Level

Community Level

District &

Sub-district Level

Community LevelScreening

Referral

Tools in tiered heath services

National

Reference

Level

Central

Reference

Level

District &

district Level

Community Level

District &

district Level

Community Level

Year Technology

Before 2007ZN microscopy

Solid Culture

early diagnosis & care smear-negative TB rapid resistance detection

Tools in combination

2007Liquid Culture / DST

Rapid speciation

2008Line Probe Assay

(1st line, Rif & INH)

2009LED-based FM

2009

In house DST

(MODS, CRI, NRA)

2010

Xpert MTB/RIF

(TB, R resistance

Technology Turnaround timeSensitivity

gain

ZN microscopy

Solid Culture

2-3 days

30-60 daysBaseline

negative TB rapid resistance detection

Tools in combination

Liquid Culture / DST

Rapid speciation15-30 days

+10% compared

to LJ

Line Probe Assay

(1st line, Rif & INH)2-4 days S+ only

based FM 1-2 days+10% compared

to ZN

In house DST

(MODS, CRI, NRA)15-30 days 1st line only

MTB/RIF

resistance)100 minutes

+40% compared

to ZN

Tools in different algorithms

One size no longer fits all

Tools in different algorithms

One size no longer fits all

Policy uptake at country level

• Rapid uptake

– SS+ case definition

• Limited or no uptake

– Two-specimen strategy

– Same-day-diagnosis – Same-day-diagnosis

– Non-commercial culture and DST methods

• Gradual uptake

– LED microscopy

– Liquid culture and DST

– Rapid speciation

– Line probe assay

Policy uptake at country level (1)

commercial culture and DST methods


HIGH TB BURDEN

HIGH MDR-TB BURDEN

GLOBAL

Source: 2011 WHO TB Control Report



Policy uptake at country level (

HIGH TB BURDEN

HIGH MDR-TB BURDEN

GLOBAL




Outline




• Policy impact


Outline



Policy impact (1)

460 GXP machines and 591,450

procured in 47 countries

Dec 2010 Dec 2011

Policy impact (1)

460 GXP machines and 591,450 Xpert MTB/RIF cartridges

procured in 47 countries

2011

Policy impact (2)

First ’negative’ policy guidance by WHO

Unprecedented p

Policy impact (2)

First ’negative’ policy guidance by WHO

d political commitment by India

Outline




• Policy impact


Outline



Guidance documents

• GLI Roadmap, Tools Set, Accreditation Guide

• WHO Policy Framework for Im

• WHO Fact Sheets

• ‘How to’ documents and online tracking

• Xpert MTB/RIF Rapid Implementation Document• Xpert MTB/RIF Rapid Implementation Document

• Xpert MTB/RIF Checklist

• Xpert MTB/RIF Website and Online Data Collection Tool

Guidance documents

Roadmap, Tools Set, Accreditation Guide

or Implementing TB Diagnostics

‘How to’ documents and online tracking

MTB/RIF Rapid Implementation DocumentMTB/RIF Rapid Implementation Document

Online Data Collection Tool

GRADE evolution for TB Diagnostics

• Refined quality assessment tools

• Refined statistical methodology for meta

• Standardised proxies for patient

• Cost-effectiveness modeling

• But: Test-specific recommendations necessary• But: Test-specific recommendations necessary

• Different technologies, targets, performance characteristics

GRADE evolution for TB Diagnostics

Refined quality assessment tools (eg. QUADAS-2)

Refined statistical methodology for meta-analyses

proxies for patient- and public health impact

modeling

specific recommendations necessaryspecific recommendations necessary

Different technologies, targets, performance characteristics

Dynamic policy refinement

New product successfully implemented in routine diagnostic services in early implementers’ laboratories in high disease endemic countries

Dynamic policy refinement

New product successfully implemented in routine diagnostic services in early implementers’ laboratories in high disease endemic countries

New technology rolled out in high disease endemic countries

Acknowledgements

• WHO/STB/TBL staff

C Gilpin, F Mirzayev, W van Gemert, J Iragena

• Systematic reviewers

K Steingart, A Cattamanchi, J MetcaA Zwerling, M Pai, A Date

• GRADE Working Group Chair: Holger

• Expert Group members

• WHO STAG members

• Funding: USAID, WHO, TDR, TREATTB/The Union

• FIND: Evaluation studies and reports

Acknowledgements

C Gilpin, F Mirzayev, W van Gemert, J Iragena

etcalf, A Detjen, R Menzies, L Rangaka,

Holger Schünemann

Funding: USAID, WHO, TDR, TREATTB/The Union

FIND: Evaluation studies and reports

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