Unit 10 MC Malaria RDT QA

The US Agency for International Development (USAID) funded MalariaCare under the terms of Cooperative Agreement No. AID-OAA-A-12-00057. The information provided in this presentation does not necessarily reflect the views or positions of USAID or the US Government.

TOT: Refresher Training for Malaria Diagnostics

Learning Unit 10: Quality Assurance of Malaria RDTs

Outline

2

• RDT implementation overview • Product testing • Lot testing • Field quality assurance and quality control

• RDT job-aids and training

Learning Objectives

3

On completion of this module, participants will be able to: 1.Demonstrate an understanding of the process used in the Malaria RDT WHO Product Testing programme, including:

- Inclusion criteria for manufacturers- Testing against parasite positive and

negative panels 2.Describe the WHO-FIND Lot Testing programme including:

- Why lot testing is necessary- What tests are performed and how to use

the programme3.Explain how community-level QA/QC contributes to maintaining good quality RDT testing by health workers 4.Know the importance of health worker training and the use of appropriate Job Aids

RDT Implementation: Effort and outcomes

4

Good manufacture

Good procurement

Quality control

Training and

supervision

•Save resources•Reduce pressure to drug resistance

• Reduce mortality• Early referral

• Assess impact• Enable planning• Guide elimination

Accurate malaria diagnosis

Know true malaria rates and results

of interventions

Rational use of anti-malarial

drugs (e.g. ACT)

Early recognition

and management of other diseases

Product testing

Lot testing

Job-aids and training

Quality control of malaria RDT results

5

Product Testing

Lot Testing

Job-aids and Training

Field QA/QCPositive control

wells2011

Available

Now

Available

Manufacturer panels

Round 1 (May 2008-9)Round 2 (April 2009-10)Round 3 (April 2010-11)

Available to manufacturers andtest developers through WHO/TDR

Product testing

6

• Evaluates malaria RDTs to produce comparative performance data to guide procurement and use

• Data relevant to performance in all endemic countries

• Forms basis of WHO RDT procurement recommendations

• Starting point for choosing a product: assurance that product can perform sufficiently well

Product testing results

7

Performance against 200 and 2000 para/µL P. falciparum samples

www.wpro.who.int/sites/rdt

False positive rates

Detection rates (Panel detection Score – PDS)

Invalid rate

Laboratory trials vs. field trials: Why base procurement on laboratory-based results?

8

• Product testing in laboratory:– Can control quality of testing, and parasite density

– Direct comparison of many tests on same samples(e.g. PT Round 1: 40 products, > 30000 tests, >130000 bits of data)

9

• Field trials:– Can only compare a few tests,

– Parasite density can not be controlled (therefore, require very high sample population to achieve statistically-significant differences in test performance at different levels of parasite density

– Require PCR as reference standard, as RDTs may out-perform microscopy, in some settings

– Very expensive to do properly

10

• Why do field trials?– Useful for assessing specific questions such as ease of use, use of results, use in pregnancy etc

– Answering local questions on sensitivity in specific populations (rather than primarily comparison of tests)

– On-going monitoring (later…)

Lot testing

11

Product Testing

Lot Testing



wells2011

Available

Now

Available

Manufacturer panels


Laboratories performing lot testing

12

Collection and testing site Specimen characterizationGlobal specimen bankGlobal lot-testing site

2006: 41 lots2007: 81 lots2008: 167 lots2009: 196 lots (? 15% of public sector

procurement)

A ‘lot’ is usually about 40000 RDTs

HTD

CDC

UL IPB

RITMIPC

AMI

IHRDCIPM

DMR

CIDEIM

IMT

KEMRIEHNRI

UCAD

Why lot test?

13

• Lot-lot variation noted in most products

• Ensure no damage during transport to country

• Need to convince clinicians / users / regulatory authorities that tests are working

Lot testing requests

14

• WHO-FIND lot testing programme:

• Testing available at no charge through the WHO-FIND network, but sending institution/programme covers cost of RDT shipment to lot-testing lab

• At least 2 weeks prior notice to arrange for testingLot test request form,

obtained fromWHO and FIND: [email protected] nora.champouillon@finddiag

nostics.org

Lot testing procedure

15

Procurement

Release to field

200 para/ul x22000 para/uL x1

x28

Negative x10Report in 5 wk days

200 para/ul x22000 para/uL x1

x6

Negative x2

Report every 6 months

125 Pf RDTs

Country programme

Lot testing lab

Requirements:• 125 Pf RDTs• 175 Pf-pan RDTs

Failures:• Follow re-testing algorithm• Confirm at second lab

End of shelf life

Incubate

Algorithm for lot testing of RDTs

16

QC panels (A & B)PASS

QC panels (A & B) FAIL

discard QC panels

QC panels (A, B, C, D)FAIL

discard QC panels

Test RDTS with more recently prepared QC

panels (If available)(return to top)

If no panel, send RDTS to

confirmatory laboratory

FAIL1) Send out preliminary fail

report2) send RDTS to

confirmatory laboratory

Confirmatory resultsPASS

Confirmatory resultsFAIL

PASS Review Level 1

Laboratory

PASSsend PASS report

report

FAILSend FAIL


Results suggest two possibilities:1) When prepared QC panels (A&B) had a slightly lower parasite concentration than panels (C&D)2) QC panels (A&B) may have lost some sensitivity since intial

preparation,, but Ag concentration is still adequate enough to be detected by

stock RDTs

QC panels (A,B,C,D)PASS

RDTs tested withPanel A (Pf or Pv): 2 x 200 p/µL, 1 x 5000 p/µL

Panel B (Pf or Pv): 2 x 200 p/µL, 1 x 5000 p/µLPanel C & D For initial testing. 1 x Negative control

Repeat testing with new QC panels (C & D)

QC panels (C & D) FAIL

QC panels (C & D) PASS


PASS100%

FAILless than 100%

Check QC panels (A & B) areOK with stock RDTS

Check QC panels (A & B) areOK with stock RDTS

Lot test results from (excerpt)

17

% PASS, RITM, IPC, EHNRI lot-testing results (2007-2009)

18

Low failure rate reflects the fact that only 15% of public sector RDTs are being tested, from specific procurers with good procurement policy, and nearly all are products with good performance in product testing

Routine lot-testing

All lot-testing

Future of lot testing

19

• Recombinant antigen lot testing panels

• Stable panels for use at country level

• Available for use in all country programmes

• Accepted common standard for programmes and industry 1 2 3 4 5

6 7 8 9 10Antigen concentration

Antigen types

Field QA/QC

20

Product Testing

Lot Testing



wells2011

Available

Now

Available

Manufacturer panels


Community-level QA/QC of RDT use and quality

21

• On-site monitoring and supervision1. Check-lists for clinic review

(including waste disposal, storage, record-keeping etc)

2. Observed RDT preparation (following steps of job-aid)

3. Testing against ‘proficiency panels’ of RDT results (photographic quizzes or real RDTs)

4. Review of workplace and safety

• Periodic / focal checking of RDT sensitivity– e.g. Cross-checking against expert

microscopy in sentinel sites (such as those existing for drug efficacy monitoring)

Future of Community level QC: Positive Control Wells

22

• Positive control wells:– Under development by WHO, FIND and partners– Field implementation trials plannedDried

antigen

Water added Contents

placed on RDT

Plastic wells containing stable manufactured parasite antigen, to be diluted with water and placed on an RDT, giving a positive test line if the RDT has good ‘sensitivity’

Quality control of malaria RDTs

23

Product Testing

Lot Testing



wells2011

Available

Now

Available

Manufacturer panels


Job-aids and training- Zambia

24

Access material: http://www.wpro.who.int/sites/rdt/using_rdts/training/main.htm

http://www.finddiagnostics.org/programs/malaria/find_activities/rdt-job-aids/ QAP, Zambia MoH, WHO, FIND, Malaria

Consortium

- Job-aidSuite of products freely downloaded and assistance for adaptation provided- Proficiency tests - Photographic

result guide - Training manual

2007, Zambia (QAP, URC, Zambia NMCP, WHO, TDR)

25

61%

72%

81%86%

90%96%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Test prep RDT reading

Package directions Job aid only Job aid + training

Harvey SA, et al. Improving community health worker use of malaria rapid diagnostic tests in Zambia: package instructions, job aid and job aid-plus-training. Malar J. 2008 Aug 22;7:160

• Blood safety

• Accuracy• Consisten

cy

Job-aids and training- Zambia12 month follow-up

26

• High retention rates• Good adherence despite low parasite prevalence <5% (currently

being quantified)• Scores for test preparation and interpretation higher after 12

months than at initial training

Zambia NMCP, Malaria Consortium, URC, FIND, WHO, TDR

3 mos (n=62)

6 mos (n=60)

12 mos (n=59)

Mean 87.9% 90.6% 93.4%Median 88.9% 88.9% 94.4%

3 mos (n=62) 6 mos (n=60)

12 mos (n=59)

Mean 88.9% 94.0% 97.0%Median 87.5% 100 % 100%

Use of results in the field…

27

• not always brilliant…• Reyburn et al. 2007 (Tanzania)

– “More than 90% of prescriptions for antimalarial drugs in low-moderate transmission settings were for patients for whom a test requested by a clinician was negative for malaria.”

• Bisoffi et al. 2009 (Burkina Faso)– “In the dry season, 80.8% and 79.8% of patients with a

negative RDT were nevertheless diagnosed and treated for malaria …. an exceedingly and unexpectedly low compliance with the negative test result”.

• …. but successful elsewhere. Why??

Minimum Country Implementation Plan for national programs, funding agencies

28

Timeline for implementation

RDT introduction

Programme planning and managementRegulatory issues

Monitoring and

evaluation

Training and communication

Quality assurance

RDT procurement

and logistics

Couresy: MoH Uganda, WHO

Summary

29

• Buy well:– RDTs vary widely in performance. Products with good sensitivity, specificity, stability are avaialble

• Confirm quality at purchase– Lot-testing of all lots. RDTs are biological tests, and subject to variation in quality at manufacture

• Confirm performance in typical storage conditions– Compare against high-quality microscopy, in selected sites in typical conditions\

• Ensure good preparation and interpretation– Monitor health worker performance

30

• Confirming and demonstrating good performance will:

– Save lives through correct diagnosis and treatment

– Gain and maintain trust of clinicians, health workers and community

– Maintain NMCP morale

Seeing is believing: we need to make the QA programme prominent so that clinicians and patients know that these tests can be relied on. Diagnostic QA is an indispensible part of the malaria programme budget.

Unit 10 MC Malaria RDT QA

Documents

Transcript of Unit 10 MC Malaria RDT QA