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Rapid Diagnostic Tests (RDTs) for Malaria. Bryan Ranger & Rafa Rahman USAID Global Health, Center for Accelerating Innovation and Impact (CII) USAID HESN, MIT Comprehensive Initiative on Technology Evaluation (CITE). Outline. Introduction to HESN, CITE, and CII Our work Future. - PowerPoint PPT Presentation
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Bryan Ranger & Rafa RahmanUSAID Global Health, Center for Accelerating Innovation and Impact (CII)
USAID HESN, MIT Comprehensive Initiative on Technology Evaluation (CITE)
Rapid Diagnostic Tests (RDTs) for Malaria
• Introduction to HESN, CITE, and CII• Our work• Future
Outline
3S
suitability
scalabilitysustainability
Comprehensive Initiative for Technology Evaluation (CITE)
• Evaluate technological solutions to development challenges and poverty relief.
• “Consumer reports” for development.
Comprehensive Initiative for Technology Evaluation (CITE)
Source: Jarrod Goentzel, CITE
Comprehensive Initiative for Technology Evaluation (CITE)
Define/Refine Comprehensive 3S
Methodology
Conduct 3S Evaluation
Product Evaluation
Pipeline
Product Catalog
Suitability Design Principles
Evaluation Reports
Design Challenges
Scalability Design Principles
Scientific Knowledge
Case Studies
Spring class with 14
students
Student interns
working with Mercy Corps,
UNICEF, USAID, etc.
Pilot in Uganda with 3
students
Preliminary catalog
developed in spring by
students
Sustainability Design Principles
• Identify state of the art practices
• Catalyze innovation
• Scaling for impact
Goal: promote innovative, business minded approaches to accelerate ‐impact against some of the world’s most important health challenges.
Development Introduction ScaleProblem Definition and
Vision
Product Design
Research and Development
Operational Planning for Uptake
Launch and Uptake Execution
Product Introduction Lifecycle & 3S Model
3S
suitability
scalabilitysustainability
Define Technology Focus
Defined which technology categories we will focus on:
• Rapid diagnostic tests (RDT’s) for malaria• Family planning
Considerations for narrowing technology categories:• Mutual interest between CITE and CII• Available information (in-house expertise,
CITE intern placement)• USAID strategic focus areas• UN and WHO goals• Suitable for evaluation
Development Introduction ScaleProblem Definition and
Vision
Product Design
Research and Development
Operational Planning for Uptake
Launch and Uptake Execution
Problem Definition & Product Design Case Studies
3S
suitability
scalabilitysustainability
• Case Study 1: Malaria Rapid Diagnostic Tests • Case Study 2: Intrauterine Devices
Part 1: Defining the Problem• Prevalence
– Geographic– At-risk populations
• Financial Burden• Pathology
– Plasmodium species– Spread and life cycle– Symptoms– Reasons for at-risk groups– Treatment
• Diagnosis– Diagnostic Technologies
• Microscopy• Fluorescence Microscopy• Polymerase Chain Reaction• Serology
Part 1: Defining the Problem
Part 1: Defining the ProblemPrevalence
Source: CDC, 2008
• Timely and appropriate treatment• Decrease chance of transmission• Reduced exposure to unnecessary drugs• Conserve drugs• Lessen likelihood of drug resistant species
development
Benefits of a Good Diagnostic Test
Part 1: Defining the ProblemDiagnostic Pipeline
Source: UNITAID
Parasite Presence, Species, Density
Part 1: Defining the ProblemMicroscopy
Source: CDC
Part 1: Defining the ProblemIntroduction of Rapid Diagnostic Tests (RDTs)
• Immunochromatographic strip (ICS)• Suitable to low-resource settings• Technology developed in 1981• First product in 1994• Increased funding and uptake in early 2000s
Part 1: Defining the ProblemUse of Diagnostics
• Confusing array• Mistrust due to sensitivity concerns
Over 200 Products
Part 1: Defining the ProblemProliferation of RDT Industry
Product Testing
Lot Testing
End-User Testing
WHO
Part 1: Defining the ProblemHow It WorksSAMPLEADDITION TEST BAND CONTROL
BAND
IMMUNOCHROMATOGRAPHIC STRIP (ICS)
TEST CONTROL
TEST CONTROL
GOLD PARTICLE OR LIPOSOME
LABEL
TEST CONTROL
TEST CONTROL
TEST CONTROL
TEST CONTROL
Product Design Factors
Product Design Factors
Antigen Selection
Sensitivity &
Specificity
Cost
Ease-of-use
Speed
Stability
Antigen HRP-2 pLDH Aldolase
Species
P. falciparum specific X X
Pan-specific (all species) X X
P. vivax specific X
Part 1: Defining the Problem1. Antigen Selection
Source: UNICEF
sensitivity specificity
Part 1: Defining the Problem2. Sensitivity & Specificity
• Sensitivity – percent positive detection out of true-positive sample
• Specificity – percent negative detection out of true-negative sample
Part 1: Defining the Problem3. Cost
• Decrease– 2006: $0.65 to $2.50
• Pan-specific cost 40% more than P. falciparum-only– 2010: $0.51 for P. falciparum-specific and $0.69 for
combination– Currently: ~$0.45 for P. falciparum, $0.65 for
combination– Some bids below $0.30
• Manufacturing & packaging
Source: Mary Anne Fisher, BD
Part 1: Defining the Problem4. Ease-of-use
• Dipstick, Card, Cassette, Hybrid
Source: A. MoodySource: Mary Anne Fisher, BD
Part 1: Defining the Problem5. Speed
• 15-20 minutes• Balance speed and sensitivity
• End-user issues with timing
Part 1: Defining the Problem6. Stability
• Excellent compared to other methods• Heat, humidity concerns
“Although receiving significant attention, stability has ‘turned out to
be a complete non-issue.’” -Dr. Larry Barat, PMI
`
Product Design Factors
Antigen Selection
-3 currently in use-HRP-2 detecting is
most sensitive
Sensitivity & Specificity-Future products
might benefit from higher sensitivity at
low parasitemia
Cost-Declining costs
-May not be sustainable
Ease-of-use
-Trend from dipsticks to cassettes
Speed-Has remained ~15
minutes
Stability-Previous heat and humidity concerns-Not a major issue
Part 1: Defining the ProblemRemaining Challenges
• Adherence to test results• Unaddressed populations• Non-falciparum detection quality• Persisting antigenemia
Part 1: Defining the ProblemConclusion
RDTs fill suitability gap in malaria diagnostics
Development Introduction ScaleProblem Definition and
Vision
Product Design
Research and Development
Operational Planning for Uptake
Launch and Uptake Execution
3S
suitability
scalabilitysustainability
Part 1: Defining the ProblemFuture
New gold standard?
Development Introduction ScaleProblem Definition and
Vision
Product Design
Research and Development
Operational Planning for Uptake
Launch and Uptake Execution
`Landscape & Analysis Project
3S
suitability
scalabilitysustainability
• Phase 1: Collect data on selected technological categories
• Phase 2: Perform analysis (coverage and uptake plots to illustrate product introduction and scale, etc.)
Data Collection:Summary of Sources
• WHO– World Malaria Report (includes country profiles)– Evaluations of RDT Products– Roll Back Malaria Initiative
• President’s Malaria Initiative (PMI) & USAID Deliver Project– Malaria Operational Plans, Country Profiles
• The Global Fund to Fight AIDS, Tuberculosis and Malaria
• UNICEF (in progress)
WHO Data(From Malaria Report 2012)
Possible metrics to analyze coverage
• Questions to consider:– How has coverage of RDT changed over time?– How has scale-up of RDT coincided with microscopy?
WHO Data(From Malaria Report 2012)
= Start of PMI involvement
1998 2000 2002 2004 2006 2008 2010 20120
2,000,000
4,000,000
6,000,000
8,000,000
10,000,000
12,000,000
Total Cases Confirmed by either RDT or Microscopy by year (African PMI-focus countries)
Total Cases confirmed with RDT (PMI-focus countries)
Total Cases confirmed with microscopy (PMI-focus countries)
Year
Num
ber o
f Cas
es
WHO Data(From Malaria Report 2012)
1998 2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80Cambodia
Year
Perc
ent
2000 2002 2004 2006 2008 2010 20120
20
40
60
80
100
120Sierra Leone
Year
Perc
ent
• Conclusion: RDTs appear to be replacing microscopy in some countries
WHO Data(From Malaria Report 2012)
2003 2004 2005 2006 2007 2008 2009 2010 2011 20120
10
20
30
40
50
60Ghana
Year
Perc
ent
2004 2005 2006 2007 2008 2009 2010 2011 20120
10
20
30
40
50
60
Angola
Year
Perc
ent
• Conclusion: Similar trend in some PMI-focus countries, but more future time points needed
= Start of PMI involvement
WHO Data(From Malaria Report 2012)
1998 2000 2002 2004 2006 2008 2010 20120
20
40
60
80
100
120Madagascar
Year
Perc
ent
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 20120
102030405060708090
100Niger
Year
Perc
ent
• Conclusion: Rapid uptake of RDTs in many countries
= Start of PMI involvement
WHO Data(From Malaria Report 2012)
1998 2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90Burundi
Year
Perc
ent
2004 2005 2006 2007 2008 2009 2010 2011 20120
102030405060708090
100Liberia
Year
Perc
ent
• Conclusion: Despite general trends, every country has its own story to tell
= Start of PMI involvement
Conclusions from WHO Data
RDTs seem to be more scalable, and in some places replacing older technology
Development Introduction ScaleProblem Definition and
Vision
Product Design
Research and Development
Operational Planning for Uptake
Launch and Uptake Execution
3S
suitability
scalabilitysustainability
Procurement of RDTs
Possible metric to analyze coverage
• Questions to consider:– How has coverage of RDT changed over time?– What products have been procured?– Have countries started procuring RDTs for themselves?
2005 2006 2007 2008 2009 2010 2011 2012 20130
10,000,000
20,000,000
30,000,000
40,000,000
50,000,000
60,000,000
70,000,000
Total Procurement of RDTs (African PMI-focus Countries)
Year
Amou
nt P
rocu
red
Procurement of RDTs
0
1,000,000
2,000,000
3,000,000
4,000,000
5,000,000
6,000,000
7,000,000
Num
ber of Malaria Cases Confirm
ed by RDT [WHO
]
Procurement of RDTs – Angola Example
2005 2006 2007 2008 2009 2010 2011 2012 20130
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
1,800,000
Procurement - Angola
PMIGlobal FundAngola National Malaria Program
Year
Proc
urem
ent
• Angola has begun to procure RDTs on its own, with procurement plans up to 2015 [Source: Angola Global Fund Round 10 Proposal]
Orgenics Clearview Orchid Paracheck ICT SD Bioline Premier FirstResponse
AccessBio CareStart CTK OnSite0
5,000,000
10,000,000
15,000,000
20,000,000
25,000,000
30,000,000
35,000,000
40,000,000
45,000,000
50,000,000
Number of Each RDT Product Purchased by Global Fund(Africa PMI-Focus Countries, All years)
RDT Product
Tota
l Pro
cure
d (A
ll Ye
ars)
Procurement of RDTs - Products
Source: Global Fund
Procurement of RDTs – Amount Spent
Source: Global Fund
Angola
DRC
Ethiopia
Ghana
GuineaKen
yaLib
eria
Madaga
scar
Malawi
Mozambique
Nigeria
Rwanda
Senega
l
Tanzan
ia
Uganda
Zambia
Zimbab
we0
2,000,000
4,000,000
6,000,000
8,000,000
10,000,000
12,000,000
14,000,000
Amount Spent on RDT Procurement by Global Fund (African PMI-focus countries)
Country
Amou
nt (U
SD)
Difference between purchase order date and actual delivery date
Difference between scheduled delivery date and actual delivery date
Average ± SD 129 ± 87 3 ± 82
(min, max) (1,475) (-233,278)
• Large variance in time between scheduled and actual delivery date
Procurement of RDTs
Source: Global Fund
Conclusions from Procurement Data
Scalability: No lag between RDT procurement and confirmed cases
Sustainability: Some countries have started to procure RDTs
Potential issues: many products (no standard), large variance in time between scheduled and actual delivery
Development Introduction ScaleProblem Definition and
Vision
Product Design
Research and Development
Operational Planning for Uptake
Launch and Uptake Execution
3S
suitability
scalabilitysustainability
• Explored suitability, scalability and sustainability of RDTs [CITE]
• Considered our work in context of product uptake timeline [CII]
Overall Conclusions
Development Introduction ScaleProblem Definition and
Vision
Product Design
Research and Development
Operational Planning for Uptake
Launch and Uptake Execution
3S
suitability
scalabilitysustainability
RDT Product
Price Antigens Detected
Sensitivity at ____ parasites/ul
Specificity at ____ parasites/ul
Format Speed Stability Number of units procured
Countries with implement-ation
Product A
Product B
Future Work
• Combine our case study projects to create powerful evaluation tool for RDTs
• Possible format:
Acknowledgements
USAID• Joe Wilson• Callie Raulfs-Wang• Dave Milestone• Larry Barat• Amit Mistry
CITE• Christine Pilcavage• Derek Brine
Becton Dickinson• Mary Anne Fisher
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