Getting to Zero TB Deaths,

New Infections, Stigma and

Discrimination

Colleen Daniels

Global Forum of Xpert MTB/RIF Implementers

April 17, 2013

Why advocacy for roll-out

of new diagnostic tools for

TB?

Duba, 5 years old

Papua New Guinea

Duba, 7 months into treatment

• Diagnosed using

GeneXpert

• Duba had drug resistant

TB

TAG & Sentinel Project We Can Heal, 2013

Mass community mobilisation to increase

access to quality treatment and care, increase

global and national funding, R&D spending,

combat stigma, harmful trade policies…

Community Engagement in TB

Community participation in TB research

through creating research awareness, clinical

trial participation, encourage recruitment &

retention, trial design & oversight >> CABs

Community Engagement in TB

Goals of the TB CAB • Interact strategically with developers of TB

drugs, diagnostics, and vaccines at key moments

in the development process

• Influence research and roll-out decisions of

developers from a community perspective

• Learn about the priorities and plans of the TB

research world, then activate TB CAB members’

networks to educate them and build an advocacy

platform to influence the TB research community

Goals of the TB CAB

• Bring special attention to neglected populations

e.g. pediatrics, TB/HIV coinfection, IDUs

• Drive good quality research and

accelerate/support regulatory approval processes

• Interact with TB research funders and

policymakers to drive development and uptake of

new TB tools.

Key advocacy issues taken on

• Urging Cepheid, the developers of the GeneXpert

rapid TB diagnostic, to make the price of its

machines and cartridges affordable in the high TB

burden settings where it is needed

• Reviewing a protocol synopsis for a new clinical

trial that combines multiple novel anti-TB

compounds

• Expanding responsible pre-approval access to

new TB drugs in late-stage clinical trials for patients

with few or no treatment alternatives

Key advocacy issues taken on

• Advocating for regulatory harmonization between

regulatory authorities to simplify the TB drug

development pathway

• Encouraging sponsors of TB drug candidates in

late-stage development to conduct necessary drug-

drug interaction studies, to ensure their co-

administration is safe, as they will likely be used in

combination post-approval.

Diagnostics: Vision

• True point of care

• Instrument-free

• Electricity-free

• Doesn’t need cold chain

• Fast results (<30m)

• Sensitive (>95%) / Specific (>95%)

• Affordable

• Useful in children, people with HIV

Universal Drug Susceptibility Testing

• Need different tests for diagnosis and DST

• Point of care test that can allow tailored

treatment options

• Able to detect resistance

• GeneXpert only screens for Rif resistance

• For proper treatment and cure - DST (for

all drugs in armamentarium) is going to be

needed

689w w w.exp ert-reviews.c om

Special Report

(TPPs) specific to TB NAAT are currently

under development by various aid and donor

organizations, and are expected to provide

clearer quantitative guidelines and possibly

more stringent or additional requirements to

ensure acceptable performance and sustainable

implementation. Recent discussions amongst

key stakeholders in high-burden countries

such as India [22,23] may result in country-

specific criteria. Additional requirements have

been articulated related to external quality

assurance, remote connectivity and electronic

result reporting [24–26] . However, no definitive

TPP for a POC NAAT is available to date,

and a single TPP that fits the diverse spectrum

of targeted countries and healthcare levels is

probably unattainable. Such uncertainties are

challenging for developers, and complicate

device performance assessment required for

adoption.

TB NAAT process overview

Sample collection, preprocessing &

alternate sample types

Pulmonary TB is diagnosed from sputum, a viscous and hetero-

geneous matrix, which is difficult to collect and manipulate. In

peripheral primary care settings, sputum is not routinely collected,

and is often of poor quality, consisting more of saliva than being

a lower respiratory tract specimen. Obtaining an appropriate

specimen is critical, since even the best assay performed on

inadequate specimens will generate false-negative results, which

Types of testing Health system levels

Fraction of patients

seen at given level

veillance 5%

25%

10%

60%

Figure 1. Healthcare access pyramid for tuberculosis control in the developing

world.

Reproduced with permission from [103] .

A

D

B

E

C

F

Figure 2. Levels of laboratory infrastructure in high tuberculosis-burden countries. (A) Tuberculosis testing in a district hospital

with biosafety precautions entailing a simple dead air box. (B) Open sample processing at a crowded bench in a peripheral laboratory.

(C) Community-level healthcare provider and (D) vehicle for ambulatory patient care. (E) Storage of laboratory supplies and (F) bio-

hazardous waste disposal exemplify logistical challenges of clinical diagnostics in low-resource settings.

Photographs provided courtesy of Gerard Cangelosi, Tanya Ferguson and PATH.

Image (C) is reprinted with permission from [19].

Nuc leic a c id testing fo r TB a t the p o int-o f-c a re in hig h -b urd en c ountries

Health care access

Current Situation • Four NAAT-based technologies on/coming

to market

Test Sponsor Technology

Ustar UStar Biotechnologies Ltd. (China)

NAAT

VereMTB™ Lab-on-Chip Veredus Laboratories (Singapore)

NAAT

UltraFast LabChip System Nanobiosys (Korea) NAAT

INFINITI® MTB Assay Autogenomics (USA) NAAT

Diagnostic algorithms,

implementation • Algorithm development needs to take into

account user perspective

• Bringing in new technologies

– India – slow implementation GeneXpert

– Countries waiting for TrueNat, GeneDrive –

cheaper?

– What happens to people with TB when

implementation does not occur?

Central Tibetan

Administration • Delek Hospital

– Diagnosis increasing detection of

drug resistance TB

– Sustainability & funding?

• Cure rate 80% MDR-TB (INH/Rif)

• 60% quinolone/injectable

resistance

– Power supply an issue – lost 8 tests

in two days due to power outage

($17 X 8 = $136 not including time,

resources, patient impact)

The case of India

• Serology ban in June 2012 (Gazette order) – In July labs

in Punjab were still doing serology – private labs said to

use IGRA instead, but this is much more expensive and

also ineffective for diagnosing active TB

• WHO policy explicitly indicates that IGRAs should NOT

be used to diagnose active TB

• Shameful Qiagen (Cellestis) still marketing test in India

2011 TB R&D investments witnessed an 82% increase

over 2005 levels, but only 3% growth since 2010

Total TB R&D Funding: 2005-2011

$700,000,000

$525,000,000

$350,000,000

$175,000,000

$0

2005 2006 2007 2008 2009 2010

$357,426,170

$417,824,708

$473,920,682 $491,476,917

$619,209,536 $630,446,462

2011

$649,648,183

Annual Global Plan Research Funding Targets

vs. 2011 Investments

$800,000,000

$600,000,000

$400,000,000

$200,000,000

$0

Fundamental

research

New

diagnostics

New

drugs

New

vaccines

$420,000,000

$340,000,000

$740,000,000

$380,000,000

$80,000,000

Operational

research

Global Plan Annual Targets 2011 Investments

$120,361,419

$55,043,541 $95,446,326 $84,140,175

$250,038,877

South Africa • Expenditure on TB R&D is insignificant

relative to disease burden

– Small relative to total R&D expenditure

– Cost of treating TB in excess of $588 million

per year

– Calculation on return on investment – R&D

spending should be at least $92 million

annually

Walwyn Health Research Policy and Systems 2013, 11:10

• After decades of neglect for TB R&D we have

now built the architecture to develop new drugs,

vaccines and diagnostics that together would

eliminate TB.

• We are on the cusp of getting the tools we need

• Now is not the time to cut R&D investment

• Now is not the time to slow implementation of

current tools

• Now is not the time to exclude civil society

A Call to Action

We commit to zero TB Deaths

1. TB is preventable and curable

2. No reason for anyone to die from TB

other than lack of political will

3. Every country in the world has the

potential to reach zero TB deaths

Thanks to:

Wim Vandevelde, Chair TB CAB

Mark Harrington

TB CAB Members

TAG TB Team

Compassionate care

In My Own Words: An introduction to my teachings and philosophy.

HH Dalai Lama

"if one is sick and being treated at the hospital by a doctor who

evinces a warm human feeling, one feels at ease; and the doctor's

desire to give the best possible care is itself curative, irrespective

of the degree of his or her technical skill. On the other hand, if

one's doctor lacks human feeling and displays an unfriendly

expression, impatience or casual disregard, one will feel anxious,

even if he or she is the most highly qualified doctor and the disease

has been correctly diagnosed and the right medication prescribed.

Inevitably, patients' feelings make a difference with respect to the

quality and completeness of their recovery."