yeung_oct202011

Shunmay Yeung and Yoel Lubell LSHTM & Mahidol-Oxford Research Unit

Recap from WHO/GFATM meeting last year  Ongoing work  Moving forward 

◦ RDTs in context ◦ Incorporating cost of resistance ◦ Other FIRDTs

Clinical practice Uptake

Antimalarials Cost

Adherence to test results Treatment of nonmalarial illness

Effectiveness

Accuracy Cost

Durability

HRP2/pLDH

Epidemiological circumstances Access to health facilities

Availability

RDTs

Context

Costeffectiveness of parasitological confirmation

Analytical choices Perspective (societal e.g. resistance) Scope

Lubell, Y., H. Reyburn, et al. (2008). "The impact of response to the results of diagnostic tests for malaria: cost-benefit analysis." BMJ 336(7637): 202-5.

Possible limitation of most RDT models – confound parasite prevalence with cause of illness

Shillcutt, S., C. Morel, et al. (2008). "Cost-effectiveness of malaria diagnostic methods in subSaharan Africa in an era of combination therapy." Bulletin of the World Health Organization 86(2): 101-11

Assumptions and context: • Assume full adherence • RDT negatives are assumed to receive an effective antibiotic • Co-infection is cause of illness

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174 facilities (public/private/medicine retailers) 938 exit interviews with patients (fever or received antimalarial) ACTs available in 72% (n=121) Microscopy available in 91% of public (n=36) and 100% of private (n=43) but only 35% and 45% of patients had test respectively Overall 73% received an antimalarial, 51% received ACT Only 29% (22-36%) were actually parasitaemic (by research RDT) Treatment did not differ significantly by test or test result

(Mangham L et al. Malaria prevalence and treatment of febrile patients at health facilities and medicine retailers in Cameroon - TMIH In press)

◦ Exploring the impact and cost of introducing RDTs in different settings: health centres, private sector and community health workers (Uganda, Cameroon, Ghana, Cambodia, Afghanistan, Tanzania) ◦ Design and evaluation of interventions to enhance quality of case management and the uptake and adherence to RDT results. Interventions include enhanced training of health workers, supportive supervision and school-based interventions. ◦ Aetiology studies of non-malarial febrile illness (Tanzania and Afghanistan)

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1) RDTs are being brought into a social context, wherever that is, and that social research has been used to understand this in ACTc studies, with implications for the design of supporting packages to aid uptake and appropriate use of the tests

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2) The introduction/use of RDTs ends up being complex in whatever setting they are brought into, because of the intended supporting interventions and other local facilitators/barriers to their use. This means that causality and generalisability of 'what works' is challenging methodologically and social insights are essential to unpicking mechanisms of change in order to draw useful conclusions.

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Customers exiting private outlets after buying antimalarials Mean WTP

◦ For RDT = UGX1067 (US$0.53) ◦ For ACT = UGX3661 (US $1.82) ◦ For ACT following a positive test = UGX4128 (US$2.05) (Hansen K et al, submitted)

Procurement and official sales prices  RDT Procurement price = $0.45 - $0.60 per test  Original wholesale price = US$2.20 for box of 10 tests ($0.22 per test)  In 2009 wholesale price dropped to US$0.50 for box of10 tests  RRP for RDT = US$0.24 per test (compared to RRP of US$0.61for adult dose of ACT)

(Yeung et al, Malarial Journal 2011)

RDTs in context  Determinants of uptake and adherence  Modelling effectiveness and costeffectiveness of RDTs: ◦ Epidemiological setting (prevalence, PF/PV ◦ Health care infrastructure ◦ Treatment seeking behaviour

Antimalarials and antibiotic resistance have by and large been treated as externalities, excluding one of the primary aims and benefits of the diagnostic process  As long as diagnostics are higher or similarly priced to treatments they will appear far less cost-effective than they should and offer little incentive for their use  Should the costs of resistance be accounted for formally in CEAs? 

Incidence

MAP project WHO Malaria Report

Health outcomes

Resistance

Literature review

WWARN database

Consumption DHS

Outlet surveys

Delphi survey

Cost of resistance

Cost of treatment AQUAMAT Literature review

Nigeri a CQ

Zimbabw e CQ

Malaw i SP

Tanzan ia SP

Rwanda AQ

Tanzan ia AQ

Consumption adult doses/ 100,000

36,87 8

16,326

28,74 8

25,162

3243

3888

Deaths/100,000 associated with resistance

74.2

54.9

97

120

6.7

19.7

Cost of resistance per treatment

$8.5

$13.8

$13.9

$18.6

$7.5

$19.4

For illustrative purposes ONLY!

£8.0 £7.0 £6.0

Empirical rX

£5.0

Parasitology directed rX

£4.0

Empirical rX with cost of resistance

£3.0

Parasitology directed rX with cost of resistance

£2.0 £1.0 £0.0 1%

10%

20% 30% 40% 50% 60% 70% 80% Prevalence of parasitaemia in febrile patients

90%

100%

R=resistant to drug A S=sensitive to drug A

Fail

Behaviour factors

Asymptomatic

Drug factors

Not treated (ntr) Cure Adherence

Access to treatment and treatment seeking behaviour Not infected

Cure rates

Infected Monotherapy (trA)

Inoculation rate

Gametocyte switching rate

Cure

Fail

Symptomatic Parasite density

Vector factors

Fail

Combination therapy (trAB) Cure

“Infectiousness�

Parasite Parasite Parasite clearance Parasite clearanc Parasite Parasite clearance times clearance eclearanc times clearance times times e times times

Private

Blood test

A

Cost of diagnosis and drugs

No blood test A+B Blood test Public

No blood test

None/Other

R0 nontreat

Not treated Not infected

R0 res1

Population

A Infected

Treated

R0 res2 R0 sen R0 res1

A+B Coverage rate

Private

Blood test

A

No blood test A+B Blood test Public

No blood test

None/Other

R0 res2 R0 sen

Diagnosis rate Cost of diagnosis

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CEAs on the use of malaria and other RDTs in combination

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RDTs for markers of severity/bacterial illness

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Disease specific diagnostics. Multiplex tests

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Ultimate goal: A platform merging epidemiology of fever maps with cost-effectiveness models.