Point of Care diagnostics: South Africa’s experienceLesley Scott

Department of Molecular Medicine and HaematologyUniversity of the Witwatersrand,

and the National Priority Program, NHLSJohannesburg, South Africa

POC WHO, IAS satellite 30th June 2013

A perspective on South Africa’s Testing volumes• Total Population over 50 Million at last census• Estimated 5.7 million HIV infected individuals of which 1.9 million are

receiving ARV therapy. HIV continues to drive these testing needs.• Currently Conduct approximately ~ 4 million CD4 tests annually, 2

million viral loads and currently 360 000 EID assays• 3rd highest TB cases, 20% worlds reported HIV‐associated TB cases

and 4th largest reported numbers of MDR. • over 1.4 million GeneXpert tests (2012), smear microscopy load ~5

million smears in 2012, 1.2 million TB cultures in 2012• 30-40% of all public health sector laboratory expenditure for HIV and

TB• Universal testing for HIV and screening for TB – the primary

objectives being to ensure that all citizens know their HIV and TB status, and to prevent new HIV and TB infections (NSP: 2012/2013-2016/2017) . Increase testing requirements

NSP, 2012 http://www.doh.gov.za/docs/stratdocs/2012/NSPsum.pdf

• Over 7636 health facilities• 54 different categories of facility• 45% urban, 45% rural, 0.7% peri-

urban• Over 3515 ARV clinics

NDOH Healthcare Facilities

New guidelines:On ART: CD4 only at 12 monthsPre-ART: CD4 every 6 months2013/2014: 14 million HCT – 2,166 855 (14%)

expected HIV positive and require CD4.

Target to initiate 500 000, thus 1 CD4 at 12 months.

Residual 1,666 855 with CD4 >350c/ul will be monitored 6 monthly (ie 3,333 711 CD4 tests).

Total CD4 for 2013/14 = 6,000 566: significant scale up

256 NHLS labs ~80% population (public sector)

Evaluations of POC CD4 Count Within Comprehensive Interventions: linkage to care!!

• Recently completed pilot evaluations (no comparison arms):− HBCT-Plus (Home based counseling and testing, POC CD4 count, facilitated

referrals, and follow up home visits) 86% initiated ART ≤ 3months in rural KZN [16]

− RAP (“Rapid Initiation of Antiretroviral Therapy in Pregnancy”) 97% initiated ART (91% on same day) in Cape Town [17]

• Randomized controlled trials now underway− Grand Challenges Canada RCT (“Investigating the feasibility of

implementation of multi-disciplinary point-of-care testing in an HIV treatment clinic using a randomised controlled trial”)

− RapIT (“Rapid Initiation of Antiretroviral Therapy to Promote Early HIV/AIDS Treatment in South Africa”)

• Others?

Courtesy Syndey Rosen, NDoH/NHLS POC workshop Pretoria, 24-15 th June 2013Health Economics and Epidemiology Research Office

Wits Health Consortium University of the Witwatersrand

HERO2

Feasibility of implementing multi-disciplinary point-of care (POC) testing in an active HIV treatment

clinic ( PI: Wendy Stevens )

Grand Challenges Canada

(POC implementation award, 2011-2014)

• CD4, Creatinine, ALT, Hb, TB (VL, CryAG)• Develop a “POCT package”• Perform randomized controlled trial (POC vs SOC “2010

guidelines”)• Determine costing• Recommend policy

Findings• Clinic space to perform “multiple POCT” is variable and limited.• POCT requires its own checklist within quality ISO, CLSI and SANAS

guidelines : pre-analytical, analytical and post analytical; equipment, safety, storage, waste, test QC, EQA, operator certification, training.• SOP’s to include quick reference charts.• Training both central and “on-site” test witnessing: more emphasis placed on

computer literacy (GeneXpert experience)• A “starter kit” (measuring cylinder, squeegee bottle, spill kit, order charts etc to

introduce GCLP into clinics.• Health system strengthening required for daily clinic workflow issues• 69% HIV patients require multiple POCT (>3/visit).

3%

27%

7%

24%12%

24%

3%

Incidents experienced in clinics (June 12 - May 13)

Clinic flooded

Clinic stock shortages

No water/electricity

No eligible patients

POC instrument failures

Clinic staff shortages

Change in guidelines

Nurses perform multiple POC, daily QC and EQA as accurately as laboratory testing.

Multiple POC’s (CD4, Hb, ALT, Creat) could be performed accurately on 1 finger stick (8% required >1 finger stick).

100% of patients said they prefer either one (65.5%) or two finger sticks (34.5%) over a venepuncture specimen. 68.8% would be willing to have up to 3 finger

sticks before having a blood draw. • Earliest time a POCT performed was 09:30,

(median11:00 and the latest 12:24). • Median time taken from the time the nurse

started the first POCT to the time taken to start the last POCT varied depending on the number and type of tests requested. • When CD4 requested, tests took ~1hr47min, • No CD4 requested, ~6min - 14minutes. These

time measurements did not include acting on result or any connectivity.

-200-150-100

-500

50100150200250300

0 200 400 600 800 1000

Refe

renc

e -PI

MA

CD4

Reference CD4

CD4 reference vs PIMA CD4 using whole blood EDTA

-100

010

020

030

0D

iffer

ence

: Pre

dica

te -

PIM

A

0 500 1000 1500Predicate CD4

diff1 diff2

Human resources

CLINIC DUTIES• Patient registration• History taking• Physical exam• Counselling• Rapid testing (HIV,

pregnancy)• Phlebotomy – lab tests• Treatment• Return visit booking

POC DUTIES (pre-analytical, analytical, post-analytical)

• Additional finger prick/venepuncture• Sample labelling• Instrument QC testing• Instrument maintenance• Testing:

• ALT, Creat, lactacte, Hb: <2minutes• PIMA = 20 minutes• Xpert MTB/RIF =2 hours

• Result recording/printing/reporting• External quality assessment (EQA)• Infection control• Spill cleaning• Waste disposal• Additional skills:

• Phlebotomy• Testing performed from blood tubes

(pipetting skills)• Additional duties:

• Operator certification and on-going monitoring

• Managing test failures, instrument downtime

• Stock control• Specimen storage

+Who will perform POCT?Task Shifting – management of task shifting from lab staff to clinical staffRegulation and certification around scope of work?

N=3000

HCT/PICT

HIV PositiveHIV Negative

PIMA

CD4> 350 CD4< 350

ALTTB screening

(questionnaire) Hemoglobin

NegativePositive

GeneXpert

Creatinine

SOC participants

Consent and Finger-stick x1

Venipuncture: HIV test confirmation +PIMA in POC

Use stored blood from tests above

Sputum

POC participants

Adherence counseling

ART start (same day)

Venipuncture

Adherence counseling

TB screening

Return in one week

CD4<350

Adherence counseling

ART start 1-4 weeks later

Follow up for 6 or 12 months

N=1000

N=480 N=480

N=316

N=50

N=316 N= 288

CD4>350

RCT at 3 remote PHC

Outcome measures• Primary: Proportion of patients retained in care at 6/12 and 12/12• Secondary:

• Time taken from HCT to initiation of ART in both arms• Proportion of patients in each arm experiencing an OI (including TB)

in the follow-up period• Proportion of patients experiencing treatment interruptions in each

group• Determine cost effectiveness of POC testing vs Standard of Care

(SOC)

GC

C R

B O

sih

10

Category POC SOC P-value

Initiation 112 74 0.01

Mean CD4 values if less than 350

194.6 cells/mm3 166.4 cells/mm3

TB symptoms present 132 (52.4%) 123 (55.9%)

Time to initiation (Mean) 4.1 days 16.9 days

Time to initiation (Median) 1 day 20 days

As per 2010 guidelines

Preliminary results before study end (dedicated staff)

Turnaround times

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

80.000

days

1 da

y

2 da

ys

3 da

ys

4 da

ys

5 -1

5 da

ys

16 -

30

31 -

50

51-1

00

>100

Perc

enta

ge

Sample collected from clinic to received at laboratory (n=1638)Sample received at laboratory to result printed (n=1638)Result printed at laboratory to stamped at clinic (n=1611)*

75% of specimens are collected (once/day courier) from the clinic and received at laboratory within one day;

85% lab tests completed by lab within one day;

72% printed results stamped in the clinic within one day.

Patient initiated SOC

TAT: 3 clinics North West Province• Patient initiated day 1 with POC , same day 72% lab results returned to clinic• POC placement with staff versus treatment guideline timeline change to initiate day 1 or day

7 to compliment clinic work flow.

Without connectivity in clinics, POCT will lose National data

Laboratory information system (LIS): instant data stream to central “powerhouse data repository”

Result reporting

Billing

Program M&ECentral data warehouse

National data

Beyond the LIS: Our experience at POC:Manual entry transcription errors• Both clinic sites had transcription errors (1%;

n=5/480):• Incorrect assay result recorded• Assay result recorded under incorrect test.

Increasing access to results:SMS printers

• SMS printers to improve turn-around-time of results back to facilities from the labs

• Beneficial in remote, far-reaching areas where no internet access is available

• SMS is automatically generated from the lab’s LIS • Result printed on paper and to be stored in patient’s file• Initial roll-out in 2009:

• Currently 1990 SMS printers in the field nationwide (~4500 DoH facilities)

• Services available for: CD4 Count, HIV VL, EID, GeneXpert TB and TB Microscopy.

Dashboard

Centralised data for decentralised testing

POC Device #1

POC Device #2

POC Device #3

POC Device #4

Host LIS/HIS

Universal POC Devices Interface Program / Data Management System

HL7/ASTM/POCT1-A

Bi-directional Communication

POCT1-A ASTM HL7 Proprietar

y

Feasibility of multi-disciplinary Point-of-Care Testing

Available Options for Connectivity

Product Instrument Interfacing

Training and Certification

QC and instr.

Management

Patient History

Result Managemen

t

Clinical Information

Visit Managemen

t

AegisPOC Extensive Yes Yes Yes Yes No No

POCcelerator Extensive Yes Yes Yes Yes No No

Cobas IT Limited Yes Yes No Yes No No

Identicare Development No No Yes Yes No Yes

Therapy Edge

None No No Yes Yes Yes Yes

eKAPA None No No Yes Yes Yes Yes

Instrument and Data Management

Patient Management

PIMA connectivity:

• PIMA modem required for FTP-PUSH• LIS mechanism can be developed to interface results from CSV file• Two components: Dashboard and Middleware Solutions• Dashboard contains a small subset of the full features of the

middleware solutions• Dashboard is unlinked from patient information • Dashboards are instrument / manufacturer specific• Middleware solutions are vendor & instrument neutral.

Dashboard Middleware

Cepheid/NHLS Remote Monitoring • Operational dashboard for real-time monitoring of results, errors, resistance and positivity rates

• Pre-configured on all newly installed GeneXperts

User Workshop held 5-9th November to improve usability and facilitate design changes, Johannesburg

Current GeneXpert Placements

Testing centres: 175Analysers: 242Clinic placements: 20Gx4: 77Gx16-8: 1Gx16: 162GX48: 1GX80-48: 1

Phase 2

Phase 3

National policyRoll out March 2011, testing at smear microscopy labs>1mil tests to date.Gx at POC: NTCM=too costly,2 ½ staff required for 15 patients same day treatment

POCT not an easy decision for South Africa

• Both a national policy and legal framework required.• NDoH/NHLS combined POCT workshop (24-25th June

2013): output to form a national advisory body to focus on POCT.• POCT “an extension of the lab tiered network”• Focus on CD4, Cryptococcal antigen testing <100CD4 cells/ul • Investigate POCT for NCD’s • Determine the place of VL• Address lack of regulation issues• Address connectivity as a critical component for quality POCT• Combine efforts on modeling the place and cost for POCT.• Address gaps in research – especially linkage to care (HIV and

TB) and improve health systems.

Totally Centralised model (4hr)

22www.mapplace.co.uk© Selective Analytics 2012

Solution:15 LabsNo POC

Solution: 127 Labs 190 POC

Decentralised model (1hr)

Models for implementation

Proposed CD4 service delivery model• NHLS CD4 testing

laboratories (Red),

• Proposed community laboratories (Green),

• POC/mini-lab sites (Yellow)

• in reference to the NDOH clinics (blue)

In the interim: 62 CD4 labs – current footprint

Is South Africa ready for (multiple) POCT?

• Clinic space is varied and limited• Nurses can perform multiple POCT duties but time is

limited. Need a new cadre of POCT staff • More studies needed:

• Full economic costing • Cost-effectiveness (incl. multiple POCT)• Cost of deployment and logistics• Cost of quality assurance• Address economic scale and new guidelines: Hb, ALT, cr, CD4 at

once for 7 day initiation• Same day initiation impact (HCT + adherence + LTH + HIV

resistance) yet unknown: takes more than a rapid CD4 count

Acknowledgments

• National Department of Health • NHLS National Priority Program staff (led by Prof Wendy Stevens and Dr. Leigh Berrie• NHLS POCT working group• GCC team and clinical partners• Funders: Clinton Foundation, CDC, PEPFAR, Grand Challenges Canada• Professor Scott and R&D Development team• South African Cryptococcal Screening Programme: Nelesh Govender• HERO: Professor Sydney Rosen, Dr. Lawrence Long, Kate Schnippel• Connectivity working group (Brad Cunningham)• CD4 working team (Prof. Debbie Glencross), viral load (Dr. Sergio. carmona)• Special thanks to Trevor Peter, Maurine Murtagh, Rosanna Peeling, Tim Tucker, • Ilesh Jani. Mozambique program