Global Landscape ofof 

POC Tests and Their UptakePOC Tests and Their Uptake

Rosanna W PeelingProfessor and Chair, Diagnostic ResearchProfessor and Chair, iagnostic Research

London School of Hygiene & Tropical Medicine

Global Landscape of POC Tests and their Uptake

• Diagnostic landscape in the

p p

• Diagnostic landscape in the developing world

• The promise of Point‐of‐Care tests to improve global healthimprove global health

• Challenges in uptake• Challenges in uptake 

• The way forwardy

Diagnostics Landscape in the Developing World

• Lack of accessAlthough high‐quality diagnostics are available for many infectious g g q y g ydiseases, they are neither affordable nor accessible to patients in the developing world 

• Lack of investmentLittle industry interest in developing quality diagnostics for diseases prevalent in the developing world, due to a perceived lack of return for investment, and lack of investment by MOHs

• Lack of regulatory oversightLack of regulatory oversightTests are often sold and used without evidence of effectiveness, discouraging companies with quality products from competing

• Lack of quality standards for test evaluationsClaimed accuracy on product inserts often misleading

Inequity of Access to DiagnosticsThe  2004  Health  Development  Report  cited  the  lack  of  access  and 

unaffordability as two major reasons why services fail

Distance to Nearest Medical Facility forthe Poorest 5th of the population: Pregnant women with syphilis

Country Distance (km)

Benin 7.5Bolivia 11.8

% who access ANC

% who access ANC

75%

50%Chad 22.9Haiti 8.0Madagascar 15.5Niger 26.9Tanzania 4 7

early in pregnancy% tested

for syphilis

50%

25%Tanzania 4.7Uganda 4.7Zimbabwe 8.6

Selected from the 2004 World Health Report, p.22%

treated

% giventest results 18%

15%

Balance between Access and Performance of Diagnostics

Source: Foundation for Innovative New Diagnostics (FIND)

Lack of Regulatory Oversight for Diagnostics

In Vitro Diagnostic Devices Regulation ByIn Vitro Diagnostic Devices

Regulated

In Vitro Diagnostic Devices Regulation By Region

No52%

Yes48%

Yes No No 11 9 5 2 2 15

Yes 4 9 4 14 3 7

AFRO AMRO EMRO EURO SEARO WPRO

TDR survey 2002

How Good are Dengue Rapid Tests?

Test Claimed Accuracy(%)

S S

WHO Evaluation (%)

S SSens Spec

Core 100 100Diazyme NS NS

Sens Spec

23 9918 98Diazyme NS NS

GlobaleMed 80 >99Minerva NS NS

18 9863 699 100

PanBio 70 100Standard 93 100

65 9822 99

Tulip 100 100 6 99

Blacksell et al Clin Infect Dis 2006;42:1127Blacksell et al. Clin Infect Dis 2006;42:1127

ASSURED Tests I Gl b l H l hto Improve Global Health

A = affordableS = sensitive S = specificU = user‐friendly R = rapid and robustE = equipment‐free D = deliverable

The Promise of POC Tests

Disease  Population Sens/Spec(%)

Potential Impact(%)

ALRI  Children <5 yrs 

95/85 Save ~405,000 lives

HIV Infants <12 90/90 Save 2 5 million DALYs if 100%HIV  Infants <12 months 

90/90 Save 2.5 million DALYs if 100% access to treatment 

Malaria  Children <5 yrs

90/90 Save 2.2 million DALYS and prevent 447 million unnecessary treatmentyrs  447 million unnecessary treatment

TB  Symptomatic  85/97  Save ~400,000 livesSyphilis  prenatal 86/72 Save 201,000 DALYS, avert 215,000 

tillbi thstillbirthsCt/Ng  Sex workers 85/90 Save ~4 million DALYs, avert 16.5 

million new cases and prevent 212 000 HIV212,000 HIV  cases

 Urdea M et al Nature 2006

RPR vs. Rapid Tests C TSp

• Can be used to distinguish active from past treated infection and for t t f

• Treponemal antibodies persist for years – measure of exposure

test of cure

• Serum/plasma

• Needs laboratory facility

• Whole blood/serum/plasma

• Can be done in primary health care• Needs laboratory facility& trained personnel

• Test only takes 8 min. but patients often need to return for results and

Can be done in primary health care settings

• Results in 10-20 min and treatment given at same visitoften need to return for results and

treatment

• Reagent needs refrigeration

g

• Test kits can be transported and stored at room temperature

• False negative results due to prozone effect

stored at room temperature

• No prozone effect

Rapid Tests for SyphilisRapid Tests for SyphilisProcedure:1. Use dropper provided, dispense 1 drop of serum/whole blood to sample well S 2. Add 2 drops of diluent buffer to sample well S3 R d l f 15 i3. Read results after 15 minutes

C TS Negative

C TS Positive

C TS Invalid

Validating Rapid Syphilis Testsg p yp• Lab-based evaluation of 9 tests in 8 countries

• Field trials of 4 rapid tests in 4 countries

h i l d l• Mathematical models to:– Estimate impact– Estimate cost-effectiveness of different strategies for g

introduction

• 7 tests with acceptable performance included in WHO Bulk7 tests with acceptable performance included in WHO Bulk Procurement Scheme at $ .19 – 1.00

Laboratory based Evaluation of Rapid Syphilis Tests(China, Gambia, Haiti, Russian Federation, South Africa, Sri Lanka, Tanzania, USA)

Test whole blood Sensitivity(%)* Specificity %)*

( , , , , , , , )

Fujireibio Espline, Japan - 98 93Determine, UK + 97 94

CTK Bi t h USA 96 95CTK Biotech, USA - 96 95

Standard Bioline, KOREA + 95 95

Qualpro Syphicheck II, INDIA + 95 94

Pacific Biotech Bioline, THAI. - 93 97

Diesse Syphilis Fast, ITALY - 86 93

(Omega VisiTect UK + 85 98)

* Performance in serum compared to TPHA/TPPA

(Omega VisiTect, UK + 85 98)

Herring et al STI 2006; 82 Suppl V: v7 12Herring et al. STI 2006; 82 Suppl V: v7-12

Field Evaluation of Rapid Syphilis Testsat Sites in Brazil, China, Haiti & Tanzania

Test SpecimenSensitivity* (%) Specificity* (%)

, ,

Abbott Determine serum 89-100 96-98whole blood 60-89 98-99

St d d Bi li 91 100 96 99Standard Bioline serum 91-100 96-99whole blood 86-100 98-99

Qualpro Syphicheck serum 67-98 98-99Q p ypwhole blood 64-84 98-100

Omega VisiTect serum 84-98 98-99whole blood 73 96 99 100

* Performance vs. TPPA

whole blood 73-96 99-100

Mabey et al STI 2006; 82 Suppl V: v13-16Mabey et al. STI 2006; 82 Suppl V: v13-16

Cost‐effectiveness of Antenatal Screening Using Rapid Syphilis Tests: Mwanza, Tz

Cost effecti eness of sing rapid tests depends on• Cost‐effectiveness of using rapid tests depends on: – Cost of rapid tests – Sensitivity of rapid test for high titre active syphilis (RPR>8)

• Rapid tests need to be < US$ 0.63 to be as cost‐effective as RPRRPR

• Cost‐effectiveness of RPR decreases by 25‐65% if 20‐40% of did t t f th i t t ltwomen did not return for their test results

Vickerman et al STI 2006;82:Suppl V; pp

Screening Using Rapid Syphilis Tests is Cost‐effectiveCost effective

• Cost of antenatal screening in Haiti using rapid tests:– Programme costs: 46% for test, 42% labour, 7% supplies, 6% for others 

including treatment)– $2.15 per woman screened vs $1.43 for RPR 

ff $ / f $ / f– Cost‐effectiveness: $10/DALY for urban and $7/DALY for rural areas– Cost/adverse outcome prevented: $108‐218

• Compares favourably with other child health interventions

• Rapid test is the preferred strategy as long as test sensitivity isRapid test is the preferred strategy as long as test sensitivity is >70% and return rate for 1st FU visit for RPR is >75%

Schackman et al PLoS Med May 2007Schackman et al PLoS Med May 2007

Increasing Access to Syphilis Screening

Goal:To reduce the burden associated with syphilis in the developing world through increased access to screeningdeveloping world through increased access to screening

Objectives:

1. To assess the feasibility of increasing access to antenatal screening using a Same Day Testing and Treatment Strategy (STAT)

2. To determine the cost-effectiveness of introducing quality-. o dete e t e cost e ect ve ess o t oduc g qua tyassured rapid syphilis testing into existing services for PMTCT/other prenatal services or high risk populations

Table 2. Study settings for Rapid Syphilis Test Introduction

U d /Study Settings Brazil China Haiti Peru Tanzania Uganda/Zambia

Income ranking Upper middle Middle Low Lower

middle Low Low

Prenatal: - no PMTCT - with PMTCT

x

x

x

x x

x

High Risk ( )gpopulations x x (some)

Remote communities x x

Health system-Health systemwide introduction

x x

Target population: 380,000 pregnant womenEstimated adverse pregnancy outcomes averted: 14,000Communities: 57,250 in Brazil; 250,000 in HaitiHigh risk population: 28,500 in China

Rapid Test Project in Brazil

Rapid Syphilis Test Introduction & S i bl Ad iSustainable Adoption

Policy Technical Aspects of ImplementationAdvocacy

Procurement &GuidelinesSt t Stock management

Quality control of Tests &Quality assurance of Testing

Guidelines

T t S l ti

Status quo, identify barriers,design strategies, estimate potential

Cost Implications

Training& Training of Trainers

Q y gTest Selection p

impact & costs

Implementation:Cost-effective Strategies for Test introduction

Monitoring / Evaluation

Links to disease surveillance to validate impact

Generic Tool Kit for Use of Rapid Syphilis Tests

Advocacy

Policy platform: generic process for translating research findings into policy and practice; engagement with regulatoryfindings into policy and practice; engagement with regulatory authorities

Data collection and management, including cost data

Questionnaire to capture barriers to introduction

Setting up Quality Assurance/Quality Control systems

Training in Procurement/stock management

Training and Training-of-Trainers packages for test useTraining and Training of Trainers packages for test use

Study monitoring tools

W b b d I t ti th ti l d l t di tWeb based Interactive mathematical models to predict potential impact and cost-effectiveness of strategies for introduction

Buy-in: Introduction & Sustainability• AdvocacyAdvocacy

– Define disease burden, problems with status quo and what is needed to improve it, the attributable benefit of introducing new tool (such as a rapid test) e g lives saved orintroducing new tool (such as a rapid test) e.g. lives saved or morbidity prevented, cost-effectiveness of strategies for tool introduction

• Policy and Guidelines– Accrue evidence needed for development or change of

policy– implications of policy or policy change: determine fiscal and

human resources

S r eillance• Surveillance– ability to monitor disease trends as an attributable benefit of

test introduction– Links to STI surveillance?Links to STI surveillance?– What is reported and what is the mechanism?

Ensuring the Quality of Diagnostics• Procurement

– Selecting the best test that is fit for purpose– Based on test performance evaluations

• Quality during transport and storageQuality during transport and storage– Lot testing and periodic checks on test performance

• Quality of testing P fi i f t ti– Proficiency of testing

Genomics

Translation Research Pathway for Appropriate Diagnostics

Proteomics

PathogenesisEpidemiology Quality Standards for Host Immune

Response

Animal models

Regulatory Approval

Diagnostic Targets

Product Prototype

Lab & field evaluations

Test adoption

Test introduction: implementation research

Proof of PrincipleProduct

SpecificationsTechnology platform

Microscopy

serology

MicrofluidicsDiagnostics used appropriately to improve health outcomes

Nanotechnolgyto improve health outcomes