answering key questions on malaria drug delivery: 8 years of research
TRANSCRIPT
Prof David SchellenbergLondon School of Hygiene & Tropical Medicine
Prof David SchellenbergLondon School of Hygiene & Tropical Medicine
Prof David SchellenbergLondon School of Hygiene & Tropical Medicine
The ACT Consortium
Goal: Develop and evaluate mechanisms to improve ACT delivery
ACCESS
TARGETING
SAFETY
QUALITY
Formative research, cluster randomised trials, cohort and
descriptive studies, impact evaluations, economic and
anthropological studiesACT Consortium 2007-2016
25 projects 10 countries
20+ institutions
What is ACT?•Artemisinin-based Combination Treatment•The recommended treatment for uncomplicated malaria caused by Plasmodium falciparum
ACT now for a malaria-free worldhttps://vimeo.com/109480993
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Access to ACT among African children <5 years with confirmed malaria
WHO World Malaria Report 2014
Getting ACTs to people who need themAppropriate diagnostic strategies are needed
wherever patients seek care
The Private Sector
Pharmacies, shops, mobile street vendors
Most malaria treatments are obtained from the private sector in some countries
• Eg DRC 85%, Nigeria 95% • Nigeria + DRC had 1/3 of all African malaria cases in 2006
Subsidies for ACTs can enhance access• E.g. novel financing mechanisms such as the Affordable
Medicines Facility for malaria (AMFm)
A Balancing Act
ACCESS
TARGETING
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Targeting of ACTs
Private retail sector, TanzaniaBriggs M et al (2014) PLoS ONE 9(4): e94074.
Fever patients attending private retail outlets in Tanzania
• 70% of those infected did not get ACTs
• 80% of those receiving ACTs were not infected
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The need for targeting ACTs: Tanzanian Health Facilities
Low prevalence (Mbeya)
Medium prevalence (Mwanza)
No diagnostic testing
Medium prevalence (Mtwara)
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The Goal
www.actconsortium.org/VennGeneratorTool
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Rapid Diagnostic Tests (RDTs)
Point of care diagnostic
No laboratory or electricity needed, minimum training
Based on antigen capture: 2 main types
• HRP-2 – persists (weeks)after cure
• LDH – negative ~2 days after cure
Access & Targeting Studies
1. UGANDAPublic health facilities(part of HF ‘enhancement’ trial)
2.+3. UGANDAHBMFDrug shops(comparing with no RDT)
4. TANZANIAPublic health facilities(Observing MoH scale-up)
7. ZANZIBARPublic health facilities(observational)
6. AFGHANISTANPublic health facilities(IRT & cluster trials of RDT vs standard care)
9. TANZANIAPublic health facilities(+peer group training; patient intervention)
8. GHANAPublic health facilities(observational safety & health outcomes)
15. GHANAPublic health facilities(IRT RDT vs standard)
5a. CAMEROONPublic health facilities(enhanced training)
5b. NIGERIAPublic & Private(enhanced training; community intervention)
IRT = Individually Randomised Trial
Ugandan community health workers, RDTs & ACTs
Control group:Symptom-based diagnosis
Intervention group:RDT-guided treatment
High Transmission
Low Transmission
no ACT
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Antibiotic prescription by RDT result
RDTs available
Positive Negative Not tested
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*0
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Per
cent
age
RDT arms
Positive
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Per
cent
age
RDT arms
Negative
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Per
cent
age
RDT arms
Not tested
Mapping causes of non-malaria febrile illness in malaria-endemic areas
www.wwarn.org/surveyor/NMFI
A collaboration with WWARN/Oxford and several other partners
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ACT Consortium research:
Our 25 studies in 10 countries address ACT:
Access
Targeting
Safety
Quality
Drug SafetyIndividual trials are often insufficiently powered to detect rare side effects
With widespread programmatic implementation of ACTs,need to consolidate safety profiles
ACT Consortium studies sought to address questions on:
•High-risk groups including children subjected to repeat dosing
•Safety in people with HIV, including those on anti-retrovirals
Data Capture Tools• Formative research to develop a range of tools
– Non-clinician & clinicians – Active follow-up & spontaneous reports– Adults & children
Data flow in drug safety repository
Signal Detection (Data Mining
Tool)
Centralised Safety Database
ADR repository
Additional Participant data
ID
SAEs/AEs
Data
Entry
Additional denominator
data
Liverpool SG/CSP
DSR Liverpool
Send electronically or by fax on continuous basis
Descriptive analysis & signal
investigation/ confirmation
Batch Data Upload at pre-defined intervals
ACT Ex
Comm
Assessment for causality, severity, coding (MedDRA, WHO)
Research sites (direct or via PV co-ordinator)
Conversion of trial files to compatible file format
Data output (emerging
signals)
DSMBs PIs
Reports
Dissemination
DSMB/ Sponsor
No new safety concerns have been identified
Safety repository is available for wider use
www.actconsortium.org/drugsafetydatabase
Future work on drug safetyOnline resource for pharmacovigilance work in collaboration with The Global Health Network (TGHN)
•Link to safety reports and tools from ACT Consortium and other sites with open-access material relevant for global community•Invite experts for interviews, topical discussions•Survey membership to informfurther resources
Website launch planned for May 2016
• Review training opportunities & identify eLearning needs, for collaborative development
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ACT Consortium research:
Our 25 studies in 10 countries address ACT:
Access
Targeting
Safety
Quality
Fake antimalarials?Can health professionals and patients assume that the medicines that
they are prescribing and taking are of good quality?
10,000 packets of ACTs 3 independent laboratories
6 endemic countries
RESULTS
Country (date of sampling) Brands Falsified Substandard
Rwanda (2008) 1 0 found 6.2%
Cambodia (2010) 21 0 found 31.3%
Ghana-Kintampo (2011) 31 0 found 37.0%
Tanzania (2010) 37 0 found 12.0%
Tanzania (2011) 46 0 found 2.2%
Nigeria-Enugu Metropolis (2013) 131 1.2% 6.6%
Nigeria-Ilorin city (2013) 77 0.8% 7.7%
Equatorial Guinea-Bioko Island (2014) 142 7.4% 1.6%
Distribution of Active Pharmaceutical Ingredients (APIs) in ACTs in Tanzania
Compared with stated amount, one or more APIs outside
85-115% for 12.1% samples(30.6% outside 90-110%)
% o
f ant
imal
aria
ls
Active Pharmaceutical Ingredient (%)
Am J Trop Med Hyg 2015: doi:10.4269/ajtmh.14-0544
Process Evaluations in Operational Research
If a strategy doesn’t work, make sure the evaluation can show where it broke down.
If it does work, identify
components critical to success!
A B L A C K
B O X
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RESOURCES
●Resources in English, French and Portuguese
www.actconsortium.org
Our multidisciplinary teams developed, piloted, delivered & evaluated training resources…
…now available to those responsible for developing health communication & training about malaria diagnosis & treatment
Listening to Your Audience: Qualitative Research in Malaria Interventions
Dr Clare Chandler