rapid diagnostic tests (rdts) for malaria

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