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Diagnostics: Bench to Bedside Pathway
Rosanna W Peeling Professor and Chair, Diagnostic Research Director, International Diagnostics Centre
London School of Hygiene & Tropical
Medicine
www.idx-dx.org
The Ideal Diagnostic Test
A = Affordable
S = Sensitive
S = Specific
U = User-friendly
R = Rapid and robust
E = Equipment-free
D = Deliverable
Accurate
Fast/Simple
Cheap
Pick 2 of 3!
Ease of detection
Confidence
DIRECT METHODS: Pathogen Detection
INDIRECT METHODS: Host Biomarkers
Culture Genome
detection Antigen
detection
Serology
IgM Serology
IgG
Adapted with permission from J. Cardosa
Diagnostics Methods: Ease of Detection vs Confidence in diagnosis
Time to Result:
Minutes Days/Hours
Microscopy
Diagnostics: Access vs Accuracy vs Affordability
Urban
Semi urban
Rural
Urban
Semi urban
Rural
Urban
Semi urban
Rural
Accurate ✓✓✓
Cheap×
Fast/simple×
Accurate ✓✓
Cheap ✓
Fast/simple✓
Accurate ✓
Cheap ✓✓
Fast/simple✓✓
FDA approves Oral HIV Tests
for home use, July, 2012
Source: time.com
Oct 22, 2013: European Parliament votes favourably for home use of IVDs
Performance of the oral HIV Test
Performance Measure*
Professional Use OraQuick Test Performance (2-sided 95% CI**)
Over-the-Counter OraQuick Test Performance (2-sided 95% CI**)
Minimum FDA Recommended Performance
Evaluation Results
Minimum FDA Recommended Performance
Evaluation Results
Sensitivity 98% (lower bound of the 2-sided 95% CI)
99.3% (98.4 - 99.7%)
95% (lower bound of the 2-sided 95% CI)
92.98% (86.64 – 96.92%)
Specificity 98% (lower bound of the 2-sided 95% CI)
99. 8% (99.6 – 99.9%)
95% (lower bound of the 2-sided 95% CI)
99.98% (99.90 – 100%)
* Compared to a blood based HIV test **95%CI = 95% Confidence Interval
Connectivity Solutions for Rapid Point-of-care Tests
Abbott Architect Ag/Ab Combo
Bio-Rad Ag/Ab Combo
Antibody Antigen Control
Determine Combo Ag/Ab Rapid Test
4th Generation HIV Tests
2011
2013
2010
Detect HIV-1 p24 antigen and IgM and IgG antibodies against either HIV-1 or HIV-2
Insufficient data for rapid Ag/Ab test to recommend it as 1st test in algorithm
2015 2013 2014 2016
Alere Q
Alere
LYNX Viral Load Platform
NWGHF
SAMBA VL
DDU/Cambridge
Liat™ Analyser
IQuum
EOSCAPE HIV™ Rapid RNA Assay System
Wave 80 Biosciences
Gene Xpert
Cepheid Cavidi AMP
Viral Load Assay with
BART Lumora
Truelab PCR
Molbio/bigTec Gene-RADAR
Nanobiosym
RT CPA HIV-1 Viral Load
Ustar
http://www.unitaid.eu/images/marketdynamics/publications/UNITAID-HIV_Diagnostic_Landscape-3rd_edition
Sample in-answer out
HIV Viral Load Product Pipeline
5 20 80 500-1000 Samples per shift
Sample In, Answer Out: A Multi-disease Random Access Real-time PCR Platform MTB/RIF
MRSA CT/Ng HIV Viral Load …..
Roche LIAT Analyser
IQuum (Boston) currently has FDA-approved Flu H1N1, A and B detection assays. The Liat Analyser has an internal optical system that provides 6 independent optical detection channels for real-time detection and quantification of multiple targets in each test. It can be powered by AC mains or by battery, allowing mobile use.
Roche: Liat Molecular Platform
Molecular point-of-care tests for Influenza
• ONLY molecular platform that is FDA approved as a POCT • Nucleic acid amplification system that uses a fluorescence-
based molecular signal to detect influenza A and B. • Time to result: 15min (only 2 min of “hands on” time) • Adapted to be used by non-laboratory staff • Results from a multicentre clinical evaluation (Bell et al
2014) indicate:
- 99.3% sensitivity and 98.1% specificity for Influenza A - 97.6 sensitivity and 100% specificity for Influenza B
- Sensitivities of 73.2% and 82.3% have ben reported in other studies
Alere i Influenza A&B (Alere, San Diego, CA, USA)
Alere i Influenza A&B test:
STI Multiplex Molecular BioChip Array
• Chlamydia trachomatis
• Neisseria gonorrhoea
• Herpes simplex I
• Herpes simplex II
• Treponema pallidum
• Trichomonas vaginalis
• Mycoplasma hominis
• Mycoplasma genitalium
• Ureaplasma urealyticum
• Haemophilus ducreyi
25 ul sample, 22 assays per biochip, 45 samples and 4 calibrators per run
Nanotechnologies
Nanowire technology: From a finger-pricked sample of blood, this device can detect in 20 min: - malaria parasites - distinguish malaria species - malaria drug resistance
Nanodot technology:
Diagnostic Targets
Product Prototype
Lab & field evaluation
Test adoption
Policy and guidelines for use
Proof of Principle
Technology platform
Diagnostics: Bench to Bedside Pathway
Regulatory Approval: 2-5 years
Valley of Death:
Target Product Profile
Policy & Uptake 5-7 years
R & D: 2-10 years; $ 10-100 million
Diagnostic Targets
Product Prototype
Lab & field evaluation
Test adoption
Policy and guidelines for use
Proof of Principle
Technology platform
Overcoming Challenges along the Diagnostics Bench to Bedside Pathway
Regulatory science to keep up with technological innovation;
Harmonized Regulation
Target Product Profile
Define product standards/ target product profiles
Standardise/ publish evaluation protocols
Set up networks of evaluation sites pre-approved for standardised protocols
Share resources: Biobank Targets Reagents
Accelerate policy development through modelling health impact and cost-effectiveness
Product profile of HIV/Syphilis Dual Tests
Purpose/use setting
Screen for HIV and Syphilis in clinics Screen for HIV and Syphilis in clinics
Screen for HIV and Syphilis in clinics
Specimen Serum/Plasma/Whole Blood
(10-20uL) S/P/WB
(1 drop, approx.30-40uL) S/P/WB
(1 drop, approx.30-40uL)
Test time 15-20min. >20min
+ sample preparation 15-20min
+ sample preparation
#Operator steps
3 3 4
Performance HIV: 100%/100%
SYP : 100%/99.1%
99.8%/99.7% 94.4%/100%
99.1-100%/99.6-100% 95.7-100%/98.2-100%
Price($)
$1.50
$3.50
$2.50 - 3.00
Standard Diagnostics, Inc.
BIOLINE HIV/Syphilis Duo
MedMira Multiplo TP/HIV Antibody Test
Chembio DPP® HIV-Syphilis Assay