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
Comprehensive Initiative for
Technology Evaluation (CITE)
• Evaluate technological
solutions to
development challenges
and poverty relief.
suitability
• “Consumer reports” for
development.
3S
sustainability
scalability
Comprehensive Initiative
Initiative for
for
Comprehensive
Technology Evaluation (CITE)
Technology Evaluation (CITE)
Student
interns
working with
Mercy Corps,
UNICEF,
USAID, etc.
Spring class
with 14
students
Product Catalog
Scientific
Knowledge
Case
Studies
Product
Evaluation
Pipeline
Define/Refine
Comprehensive 3S
Methodology
Evaluation
Reports
Conduct 3S
Evaluation
Design
Challenges
Suitability Design Principles
Scalability Design Principles
Sustainability Design Principles
Source: Jarrod Goentzel, CITE
Preliminary
catalog
developed
in spring by
students
Pilot in
Uganda
with 3
students
Goal: promote innovative, business‐minded approaches to accelerate
impact against some of the world’s most important health challenges.
• Identify state of the art
practices
• Catalyze innovation
• Scaling for impact
Product Introduction Lifecycle & 3S Model
Development
Introduction
Scale
Problem Definition and
Vision
suitability
Product Design
Research and
Development
Operational Planning for
Uptake
Launch and Uptake
Execution
3S
sustainability
scalability
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
Problem Definition &
Product Design Case Studies
Development
Introduction
Scale
Problem Definition and
Vision
suitability
Product Design
Research and
Development
Operational Planning for
Uptake
3S
sustainability
scalability
Launch and Uptake
Execution
• Case Study 1: Malaria Rapid Diagnostic Tests
• Case Study 2: Intrauterine Devices
Part
1:
Defining
the
Problem
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
Prevalence
Part 1: Defining the Problem
Source: CDC, 2008
Benefits of a Good Diagnostic Test
•
•
•
•
•
Timely and appropriate treatment
Decrease chance of transmission
Reduced exposure to unnecessary drugs
Conserve drugs
Lessen likelihood of drug resistant species
development
Diagnostic
Pipeline
Part 1: Defining the Problem
Source: UNITAID
Microscopy
Part 1: Defining the Problem
Parasite Presence, Species, Density
Source: CDC
Introduction of Rapid Diagnostic Tests
Part 1: Defining
(RDTs)the Problem
•
•
•
•
•
Immunochromatographic strip (ICS)
Suitable to low-resource settings
Technology developed in 1981
First product in 1994
Increased funding and uptake in early 2000s
Use
of
Diagnostics
Part 1: Defining the Problem
Proliferation
of
RDT
Industry
Part 1: Defining the Problem
Over 200 Products
• Confusing array
• Mistrust due to sensitivity concerns
WHO
Product
Testing
Lot
Testing
End-User
Testing
How
It
Works
CONTROL
Part 1: Defining the Problem
SAMPLE
ADDITION
TEST BAND
BAND
IMMUNOCHROMATOGRAPHIC STRIP (ICS)
TEST
CONTROL
TEST
CONTROL
GOLD
PARTICLE OR
LIPOSOME
LABEL
TEST
CONTROL
TEST
CONTROL
TEST
CONTROL
TEST
CONTROL
Product
Design
Factors
Antigen
Selection
Sensitivity
&
Specificity
Stability
Product
Design
Factors
Speed
Cost
Ease-ofuse
1.
Antigen
Selection
Part 1: Defining the Problem
Antigen
HRP-2
pLDH
X
X
Aldolase
Species
P. falciparum
specific
Pan-specific (all
species)
X
P. vivax specific
X
Source: UNICEF
X
2.
Sensitivity
&
Specificity
Part 1: Defining the Problem
• Sensitivity – percent positive detection out of
true-positive sample
• Specificity – percent negative detection out of
true-negative sample
3.
Cost
Part 1: Defining the Problem
• 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
4.
Ease-of-use
Part 1: Defining the Problem
• Dipstick, Card, Cassette, Hybrid

Source: Mary Anne Fisher, BD
Source: A. Moody
5.
Speed
Part 1: Defining the Problem
• 15-20 minutes
• Balance speed and sensitivity
• End-user issues with timing
6.
Stability
Part 1: Defining the Problem
• 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
Antigen
Selection
`
-3 currently in use
-HRP-2 detecting is
most sensitive
Sensitivity &
Specificity
Stability
-Previous heat and
humidity concerns
-Future products
might benefit from
higher sensitivity at
low parasitemia
-Not a major issue
Product
Design
Factors
Cost
Speed
-Declining costs
-Has remained ~15
minutes
-May not be
sustainable
Ease-ofuse
-Trend from dipsticks
to cassettes
Remaining
Challenges
Part 1: Defining the Problem
•
•
•
•
Adherence to test results
Unaddressed populations
Non-falciparum detection quality
Persisting antigenemia
Conclusion
Part 1: Defining the Problem
Development
Introduction
Scale
Problem Definition and
Vision
suitability
Product Design
Research and
Development
Operational Planning for
Uptake
3S
sustainability
scalability
Launch and Uptake
Execution
RDTs fill suitability gap in malaria diagnostics
Future
Part 1: Defining the Problem
New gold standard?
Landscape & Analysis
Project
`
Development
Introduction
Scale
Problem Definition and
Vision
suitability
Product Design
Research and
Development
Operational Planning for
Uptake
3S
sustainability
scalability
Launch and Uptake
Execution
• 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)
Total Cases Confirmed by either RDT or Microscopy by year
(African PMI-focus countries)
12,000,000
10,000,000
Number of Cases
8,000,000
Total Cases confirmed with RDT (PMI-focus
countries)
6,000,000
Total Cases confirmed with microscopy (PMI-focus
countries)
4,000,000
= Start of PMI involvement
2,000,000
0
1998
2000
2002
2004
2006
Year
2008
2010
2012
WHO Data
(From Malaria Report 2012)
Cambodia
Sierra Leone
120
80
70
100
60
Percent
Percent
80
60
40
50
40
30
20
20
0
2000
10
2002
2004
2006
Year
2008
2010
2012
0
1998
2000
2002
2004
2006
2008
2010
Year
• Conclusion: RDTs appear to be replacing microscopy
in some countries
2012
WHO Data
(From Malaria Report 2012)
Ghana
60
60
50
50
40
40
Percent
Percent
Angola
30
30
20
20
10
10
0
2004
2005
2006
2007
2008
Year
2009
2010
2011
2012
0
2002
2004
2006
2008
2010
Year
= Start of PMI involvement
• Conclusion: Similar trend in some PMI-focus
countries, but more future time points needed
2012
WHO Data
(From Malaria Report 2012)
Madagascar
Niger
100
120
90
100
80
70
Percent
Percent
80
60
40
50
40
30
20
20
0
1998
60
10
2000
2002
2004
2006
2008
2010
2012
0
2002
2004
2006
2008
2010
Year
Year
= Start of PMI involvement
• Conclusion: Rapid uptake of RDTs in many countries
2012
WHO Data
(From Malaria Report 2012)
Burundi
90
80
70
Percent
Percent
60
50
40
30
20
10
0
1998
2000
2002
2004
2006
2008
2010
2012
100
90
80
70
60
50
40
30
20
10
0
2004
Liberia
2005
2006
2007
2008
2009
2010
2011
Year
Year
= Start of PMI involvement
• Conclusion: Despite general trends, every country
has its own story to tell
2012
Conclusions from WHO Data
Development
Introduction
Scale
Problem Definition and
Vision
suitability
Product Design
Research and
Development
Operational Planning for
Uptake
3S
sustainability
Launch and Uptake
Execution
RDTs seem to be more scalable, and in some
places replacing older technology
scalability
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?
Procurement of RDTs
70,000,000
7,000,000
60,000,000
6,000,000
50,000,000
5,000,000
40,000,000
4,000,000
30,000,000
3,000,000
20,000,000
2,000,000
10,000,000
1,000,000
0
2005
2006
2007
2008
2009
Year
2010
2011
0
2012
Number of Malaria Cases Confirmed by RDT [WHO]
Amount Procured
Total Procurement of RDTs
(African PMI-focus Countries)
2013
Procurement of RDTs – Angola Example
Procurement - Angola
1,800,000
1,600,000
1,400,000
Procurement
1,200,000
1,000,000
PMI
800,000
Global Fund
Angola National Malaria Program
600,000
400,000
200,000
0
2005
2006
2007
2008
2009
2010
2011
2012
2013
Year
• Angola has begun to procure RDTs on its own, with procurement plans
up to 2015 [Source: Angola Global Fund Round 10 Proposal]
Procurement of RDTs - Products
Number of Each RDT Product Purchased by Global Fund
(Africa PMI-Focus Countries, All years)
50,000,000
45,000,000
Total Procured (All Years)
40,000,000
35,000,000
30,000,000
25,000,000
20,000,000
15,000,000
10,000,000
5,000,000
0
Orgenics Clearview
Orchid Paracheck
ICT
SD Bioline
Premier
FirstResponse
AccessBio CareStart
CTK OnSite
RDT Product
Source: Global Fund
Procurement of RDTs – Amount Spent
Amount Spent on RDT Procurement by Global Fund
(African PMI-focus countries)
14,000,000
12,000,000
Amount (USD)
10,000,000
8,000,000
6,000,000
4,000,000
2,000,000
0
Country
Source: Global Fund
Procurement of RDTs
Average ± SD
(min, max)
Difference
between purchase
order date and
actual delivery
date
Difference
between scheduled
delivery date and
actual delivery
date
129 ± 87
3 ± 82
(1,475)
(-233,278)
• Large variance in time between scheduled and
actual delivery date
Source: Global Fund
Conclusions from Procurement Data
Development
Introduction
Scale
Problem Definition and
Vision
suitability
Product Design
Research and
Development
Operational Planning for
Uptake
3S
sustainability
scalability
Launch and Uptake
Execution
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
Overall Conclusions
Development
Introduction
Scale
Problem Definition and
Vision
suitability
Product Design
Research and
Development
Operational Planning for
Uptake
3S
sustainability
Launch and Uptake
Execution
• Explored suitability, scalability and
sustainability of RDTs [CITE]
• Considered our work in context of product
uptake timeline [CII]
scalability
Future Work
• Combine our case study projects to create powerful evaluation
tool for RDTs
• Possible format:
RDT
Product
Product A
Product B
Price
Antigens
Detected
Sensitivity
at ____
parasites/
ul
Specificity
at ____
parasites/
ul
Format
Speed
Stability
Number
of units
procured
Countries
with
implement
-ation
Acknowledgements
•
•
•
•
•
USAID
Joe Wilson
Callie Raulfs-Wang
Dave Milestone
Larry Barat
Amit Mistry
CITE
• Christine Pilcavage
• Derek Brine
Becton Dickinson
• Mary Anne Fisher