Rapid Diagnostic Tests (RDTs) for Malaria

1. Rapid Diagnostic Tests (RDTs) for Malaria Bryan Ranger & RafaRahman USAID Global Health, Center for Accelerating Innovation and Impact (CII) USAID HESN, MIT Comprehensive Initiative on Technology Evaluation (CITE)

2. Outline • Introduction to HESN, CITE, and CII • Our work • Future

3. Comprehensive Initiative for Technology Evaluation (CITE) • Evaluate technological solutions to development challenges and poverty relief. • “Consumer reports” for development.

4. Comprehensive Initiative for Technology Evaluation (CITE) Comprehensive Initiative for Technology Evaluation (CITE) Product Catalog Preliminary catalog developed in spring by students Student interns working with Mercy Corps, UNICEF, USAID, etc. Scientific Knowledge Case Studies Evaluation Reports Product Evaluation Pipeline Pilot in Uganda with 3 students Define/Refine Comprehensive 3S Methodology Conduct 3S Evaluation Spring class with 14 students Design Challenges Suitability Design Principles Scalability Design Principles Sustainability Design Principles Source: Jarrod Goentzel, CITE

5. 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

6. Product Introduction Lifecycle & 3S Model Development Introduction Scale Problem Definition and Vision Product Design Research and Development Operational Planning for Uptake Launch and Uptake Execution

7. 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

8. Problem Definition & Product Design Case Studies Development Introduction Scale Problem Definition and Vision Product Design Research and Development Operational Planning for Uptake • Case Study 1: Malaria Rapid Diagnostic Tests • Case Study 2: Intrauterine Devices Launch and Uptake Execution

9. 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

10. Prevalence Part 1: Defining the Problem Source: CDC, 2008

11. 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

12. Diagnostic Pipeline Part 1: Defining the Problem Source: UNITAID

13. Microscopy Part 1: Defining the Problem Parasite Presence, Species, Density Source: CDC

14. Introduction of Rapid Diagnostic Tests (RDTs) Part 1: Defining 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

15. Use of Diagnostics Part 1: Defining the Problem

16. Proliferation of RDT Industry Part 1: Defining the Problem • Confusing array • Mistrust due to sensitivity concerns Over 200 Products WHO

17. How It Works Part 1: Defining the Problem SAMPLEADDITION CONTROLBAND TEST BAND IMMUNOCHROMATOGRAPHIC STRIP (ICS)

18. CONTROL TEST

19. TEST CONTROL GOLD PARTICLE OR LIPOSOME LABEL

20. TEST CONTROL

21. TEST CONTROL

22. TEST CONTROL TEST CONTROL

25. 1. Antigen Selection Part 1: Defining the Problem Source: UNICEF

26. 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 specificity sensitivity

27. 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

28. 4. Ease-of-use Part 1: Defining the Problem • Dipstick, Card, Cassette, Hybrid  Source: A. Moody Source: Mary Anne Fisher, BD

29. 5. Speed Part 1: Defining the Problem • 15-20 minutes • Balance speed and sensitivity • End-user issues with timing

30. 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

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32. Remaining Challenges Part 1: Defining the Problem • Adherence to test results • Unaddressed populations • Non-falciparum detection quality • Persisting antigenemia

33. Conclusion Part 1: Defining the Problem Development Introduction Scale Problem Definition and Vision Product Design Research and Development Operational Planning for Uptake Launch and Uptake Execution RDTs fill suitability gap in malaria diagnostics

34. Future Part 1: Defining the Problem New gold standard?

35. Landscape & Analysis Project ` Development Introduction Scale Problem Definition and Vision Product Design Research and Development Operational Planning for Uptake • Phase 1: Collect data on selected technological categories • Phase 2: Perform analysis (coverage and uptake plots to illustrate product introduction and scale, etc.) Launch and Uptake Execution

36. 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)

37. 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?

38. WHO Data (From Malaria Report 2012) = Start of PMI involvement

39. WHO Data (From Malaria Report 2012) • Conclusion: RDTs appear to be replacing microscopy in some countries

40. WHO Data (From Malaria Report 2012) • Conclusion: Similar trend in some PMI-focus countries, but more future time points needed = Start of PMI involvement

41. WHO Data (From Malaria Report 2012) • Conclusion: Rapid uptake of RDTs in many countries = Start of PMI involvement

42. WHO Data (From Malaria Report 2012) • Conclusion: Despite general trends, every country has its own story to tell = Start of PMI involvement

43. Conclusions from WHO Data RDTs seem to be more scalable, and in some places replacing older technology Development Introduction Scale Problem Definition and Vision Product Design Research and Development Operational Planning for Uptake Launch and Uptake Execution

44. 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?

45. Procurementof RDTs Number of Malaria Cases Confirmed by RDT [WHO]

46. Procurementof RDTs – Angola Example • Angola has begun to procure RDTs on its own, with procurement plans up to 2015 [Source: Angola Global Fund Round 10 Proposal]

47. Procurementof RDTs - Products Source: Global Fund

48. Procurementof RDTs – Amount Spent Source: Global Fund

49. Procurementof RDTs • Large variance in time between scheduled and actual delivery date Source: Global Fund

50. 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 Scale Problem Definition and Vision Product Design Research and Development Operational Planning for Uptake Launch and Uptake Execution