new diagnostics to improve diagnosis of liver...
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Nairobi, Sept 13th-15th 2018
New diagnostics to improve diagnosis of liver disease
Francesco MARINUCCI,
Head HIV/HCV Programme
FIND
Financial disclosure
Nothing to disclose
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Outline
Intro FIND
New diagnostic to improve diagnosis of liver disease: a public health approach
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FIND – an innovative partner in diagnostic solutions for
LICs and LMICs
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FIND is a non-for-profit NGO that was founded in 2003
FIND mission: turning complex diagnostic challenges into simple solutions to overcome diseases and
transform lives in developing world
Key focus areas: TB, malaria, HCV, HIV, Fever and Anti Microbial Resistance, Neglected Tropical Diseases,
Outbreaks
Today, FIND offers a full package of support to develop and subsequently turn a diagnostic test into a
diagnostic solution
Catalyze development
•Dynamic needs definition with global stakeholders
•Scout technologies
•Support fit-for-purpose product development
Guidance of use and policy
•Define evidence needs
•Lead clinical trials
•Support the development of WHO guidelines
Accelerating access
•Collaborate with governments, MoH, different implementation partners to support rapid uptake of the developed products
•Develop locally appropriate QA plans
Shape agenda
•Measure and communicate the impact of diagnostics
•Shape diagnostics ecosystem to foster willingness to invest/pay
•Lead global discussions on emerging diagnostics
FIND approach
Working with 185 partners globally and forming coalitions, always with the end in mind
Industry
• 46 partners
Universities and Research
Institutes
• 44 partners
Clinical Trial Sites
• 32 partners
Implementing partners
• 26 partners
Advocacy
• 4 partners
Government/ multilateral agencies
• 35 partners
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New diagnostic tools for a public health approach
Nairobi, Sept 13th-15th 2018
WHO simplified testing algorithm for hep C triggered public
health response to viral hepatitis need for more appropriate tools
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E• Variability in performance
• Lack of quality-assured
RDT
• Lack of QA/QC systems
• No EQA
• No decentralized solution
• Lack of testing labs
• Long turnaround
• High cost
• Weak QA/QC systems
Unmet needs and prioritization
Reference
centre
District
hospital
Health
centre
Health
post
Community
health worker
POC viremic test for diagnostics, monitoring and/or test of cure
Optimizing existing and developing new screening tests
Integrate VH testing in HIV/TB programmes
Published TPPs N/A
DBS sampling
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Increasing affordability and access
True POC or platform-free test
FIND Hepatitis C Elimination through Access to Diagnostics
(HEAD-Start): bridging the gap between R&D and country adoption
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Area Target FIND work Timeline
Using existing tools for decentralizing HCV Dx
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Multicentre clinical evaluation conducted in 2017-2018 in 5 countries in various healthcare settings and
high risk populations including HIV-coinfected showed high sensitivity and specificity of new Xpert
Fingerstick HCV VL Cepheid GeneXpert Fingerstick HCV VL test can be used as a one-step diagnostic
solution
The possibility to detect HCV viraemia from a drop of capillary blood in one hour will facilitate
decentralization of testing and thereby expand access to care
Detection of
HCV RNA using
finger stick
whole blood
Georgia, Cameroon, Greece, US, Malaysia
11FIND study: evaluate performance in level 1-2 facilities
Needs plasma separation
Manual steps
Turnaround time 90’
Easy-to-use instrument,
small footprint
https://www.finddx.org/news/genedrive-partners-find-evaluate-molecular-diagnostic-
kit-hepatitis-c-virus-decentralised-settings/
Near-POC HCV
tests in
validation/impl
ementation:
GeneDrive
Using existing tools for decentralizing HCV Dx - CONTINUED
DBS sampling for HCV RNA test
Aim: provide HCV diagnostics in the settings with no access to laboratory infrastructure
Concept:
Advantages: ease of transport, possibility to gather with other tests, increased opportunity for HBV and HCV
testing and treatment follow-up in hard-to-reach individuals and people living in rural areas
Disadvantages: long turnaround time, high cost of testing
Need: strong dataset to allow confidence in the test performance from DBS
Trigger: manufacturers obtained analytical data on test performance from DBS, ready to contribute in kind
with test kits and training, expressed interest to submit regulatory claim for DBS
FIND activity: Design, prepare and conduct multicentre clinical trial
Validation of DBS sampling: a key step to scale up nucleic acid testing and
accelerate integration on polyvalent high-throughput platforms
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HCV RNA test
FIND Hepatitis C Elimination through Access to Diagnostics
(HEAD-Start): bridging the gap between R&D and country adoption
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Area Target FIND work Timeline
Three-pronged strategy for product development: reducing
the risks and improving the chances of success
HC
V D
IAG
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STIC
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ST D
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ELO
PM
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T
Advantages: Disadvantages:
Molecular test
• Low technical risks: high likelihood of
success
• Highest sensitivity and specificity
• Has a clear market in the US and Europe
• Cost of goods is high
• Stability of reagents (particularly,
enzymes) is often an issue
• Needs rather complicated, heavy and
costly instrumentation
Core Antigen
test on
immunoassay
platform
• Likely lower cost of goods as compared to
molecular test
• Bringing high-sensitive POC
immunoassay platform to the market that
can be possibly used to develop other
assays with high performance
requirements
• Technically challenging given sample
processing and signal amplification needs
• Cost will be higher than RDT
• Potential for integration with testing for
other diseases is not clear
Dual Ab/Ag
test on RDT
• Lowest cost
• Instrument-free or requires only simple
one-button reader device, i.e. greatest
decentralization potential
• Ag-part will have suboptimal sensitivity so
Ab-positive/Ag-negative results require
confirmatory testing
• Technically challenging given sensitivity
requirements and the necessity to
integrate sample processing step
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Aim: bring affordable and easy-to-use POC HCV diagnostic solution to decentralize HCV testing
Concept:
TPP: https://www.finddx.org/wp-content/uploads/2016/01/HCV-TPP-Report_17July2015_final.pdf
Attribute Optimal Minimal
Target operator Community workers with minimal training Healthcare workers/technicians with limited training
Sample preparationFully integrated sample-to-answer
Integrated specimen preparation; not more than 2
manual steps required (no precision volume control and
precision time steps)
Portability Small, portable or hand-held, device, ≤5 kg Small table-top device
Analytical sensitivity <200IU/mL <1000 IU/mL
Time to result ≤30 min <90 min
Assay COGS <7 USD <15 USD
POC HCV
viraemia test
Level 1-2: near-POC
Level 0: true POC
Target Product Profile for game-changing POC solutions:
what we will be able to achieve
On going process that recently moved into feasibility
studies of various technologies
Following the conclusion of an extensive Request for Proposal process on World
Hepatitis Day 2018 FIND announced the award of grants for feasibility studies
Grants for feasibility studies to be awarded to Abbott, BLINK-DX, and Diagnostics for
the Real World for the development of a molecular point-of-care (POC) test for
hepatitis C virus (HCV) RNA detection; and Chembio Diagnostics, Mologic and DCN
Diagnostics for development of an HCV core antigen rapid diagnostic test
2 other partners to develop HCV cAg assay will be announced in September 2018
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https://www.finddx.org/news/find-announces-new-wave-activities-addressing-
challenges-threatening-hepc-elimination/
FIND Hepatitis C Elimination through Access to Diagnostics
(HEAD-Start): bridging the gap between R&D and country adoption
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Area Target FIND work Timeline
Innovation also entails optimizing the use of current
tools: TREAT B score
New diagnostic score was developed using a large
dataset of African patients
Positive HBeAg and ALT level as independent
predictors of the EASL treatment eligibility
Diagnostic accuracy of the score for selecting
patients for HBV treatment was high
The score may facilitate scale-up of treatment
programs in LMICs
• Both ALT and HBeAg measurements are widely available in
LMICs
• User-friendly and may enable a task shifting
• only one blood sampling is required
• very flexible for its use i.e. the cut-off value can be adapted to the
local context
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https://www.journal-of-hepatology.eu/article/S0168-8278(18)32102-0/fulltext
Simple methods to detect liver disease at the point-of-care (POC)
are urgently needed as part of the global effort to eliminate VH
https://www.burnet.edu.au/projects/170_alt_point_of_care_diagnostic_to_detect_liver_disease
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ALT point-of-care diagnostic to detect liver disease1
• A POC test developed by Burnet Institute
spinoff company, Nanjing BioPoint Diagnostic
Technology (Nanjing BioPoint)
• Field studies on the use of the ALT test will
start in late 2017, initially in patients infected
with hepatitis C where it is important to
determine the level of liver disease to guide
appropriate antiviral therapy
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http://dfa.org/liver-function/
Low-cost, patterned paper-based, liver enzyme
diagnostic test2
Simple methods to detect liver disease at the point-of-care (POC) are urgently needed as
part of the global effort to eliminate VH - CONTINUED
• Developed by Diagnostics-For-All (DFA), non-profit
enterprise fusing biotechnology and device development
• Relevant laboratory and field studies to demonstrate the
liver function test's effective use in a low-resource setting
• Class I exempt status for its LFT-ALT testing system
• FDA Establishment Registration
• Preparing to submit for regulatory approval for Point of
Care Use (on going)
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Simple methods to detect liver disease at the point-of-care (POC) are urgently needed as
part of the global effort to eliminate VH - CONTINUED
A paper-based multiplexed transaminase test for low-cost,
point-of-care liver function testing3
• The device consists of two layers of similarly patterned
paper, a plasma separation membrane, and a laminated
cover of polyester film
• Fingerstick specimen or 30 μl of a specimen obtained by
venipuncture
• After 15 min, the AST and ALT test zones are matched to a
color “read guide” to obtain a concentration value
• Results are interpreted as being within one of three “bins”
of values
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624093/
To be effective the new tools have to be embedded into in
replicable models to achieve health impact globally
Common challenges in access, but no
one-size-fits all solutions…
…require "smart" response based on
replicable models
Access stakeholders, especially donors,
looking for effective solutions for uptake
Yet, country-specific barriers to uptake
Standard operational features dev. once
Processes developed once but tailored
to context specificities
Proven impactCost-effectiveness
& replicability
Health systems and
patient pathways
Community and
cultural contexts
E.g., technologies E.g., training kits
E.g., policy updateE.g., stakeholder
engagement plan
Thank you
Asante sana
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