Diagnostics: Bench to Bedside Pathway

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1 Diagnostics: Bench to Bedside Pathway Rosanna W Peeling Professor and Chair, Diagnostic Research Director, International Diagnostics Centre London School of Hygiene & Tropical Medicine

2 The Ideal Diagnostic Test A = Affordable S = Sensitive S = Specific U = User-friendly R = Rapid and robust E = Equipment-free Accurate Fast/Simple Cheap Pick 2 of 3! D = Deliverable

3 Diagnostics Methods: Ease of Detection vs Confidence in diagnosis Confidence DIRECT METHODS: Pathogen Detection INDIRECT METHODS: Host Biomarkers Microscopy Culture Genome detection Antigen detection Serology IgM Serology IgG Ease of detection Time to Result: Days/Hours Minutes Adapted with permission from J. Cardosa

4 Diagnostics: Access vs Accuracy vs Affordability Urban Urban Urban Semi urban Semi urban Semi urban Rural Rural Rural Accurate Cheap Fast/simple Accurate Cheap Fast/simple Accurate Cheap Fast/simple

5 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

6 Performance of the oral HIV Test Performance Measure* Sensitivity Specificity Professional Use OraQuick Test Performance (2-sided 95% CI**) Minimum FDA Evaluation Recommended Results Performance 98% (lower bound of the 2-sided 95% CI) 98% (lower bound of the 2-sided 95% CI) 99.3% ( %) 99. 8% ( %) Over-the-Counter OraQuick Test Performance (2-sided 95% CI**) Minimum FDA Evaluation Recommended Results Performance 95% (lower bound of the 2- sided 95% CI) 95% (lower bound of the 2- sided 95% CI) 92.98% ( %) 99.98% ( %) * Compared to a blood based HIV test **95%CI = 95% Confidence Interval

7 Connectivity Solutions for Rapid Point-of-care Tests

8 4 th Generation HIV Tests Abbott Architect Ag/Ab Combo 2010 Control Antigen Antibody Bio-Rad Ag/Ab Combo 2011 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 Determine Combo Ag/Ab Rapid Test 2013

9 HIV Viral Load Product Pipeline Sample in-answer out SAMBA VL DDU/Cambridge Alere Q Alere EOSCAPE HIV Rapid RNA Assay System Wave 80 Biosciences Liat Analyser IQuum Molbio/bigTec Gene Xpert Cepheid Truelab PCR Cavidi AMP RT CPA HIV-1 Viral Load Ustar Gene-RADAR Nanobiosym LYNX Viral Load Platform NWGHF Viral Load Assay with BART Lumora

10 Sample In, Answer Out: A Multi-disease Random Access Real-time PCR Platform MTB/RIF MRSA CT/Ng HIV Viral Load Samples per shift

11 Roche: Liat Molecular Platform 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.

12 Molecular point-of-care tests for Influenza Alere i Influenza A&B test: ONLY molecular platform that is FDA approved as a POCT Nucleic acid amplification system that uses a fluorescencebased 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: % sensitivity and 98.1% specificity for Influenza A 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)

13 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

14 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:

15 Diagnostics: Bench to Bedside Pathway R & D: 2-10 years; $ million Regulatory Approval: 2-5 years Target Product Profile Diagnostic Targets Technology platform Product Prototype Proof of Principle Lab & field evaluation Policy and guidelines for use Test adoption Valley of Death: Policy & Uptake 5-7 years

16 Overcoming Challenges along the Diagnostics Bench to Bedside Pathway Regulatory science to keep up with technological innovation; Harmonized Regulation Diagnostic Targets Target Product Profile Technology platform Product Prototype Proof of Principle Lab & field evaluation Policy and guidelines for use Test adoption Define product standards/ target product profiles Share resources: Biobank Targets Reagents Standardise/ publish evaluation protocols Set up networks of evaluation sites pre-approved for standardised protocols Accelerate policy development through modelling health impact and cost-effectiveness

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20 Product profile of HIV/Syphilis Dual Tests Standard Diagnostics, Inc. BIOLINE HIV/Syphilis Duo MedMira Multiplo TP/HIV Antibody Test Chembio DPP HIV-Syphilis Assay 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 Performance HIV: 100%/100% SYP : 100%/99.1% 99.8%/99.7% 94.4%/100% %/ % %/ % Price($) $1.50 $3.50 $