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Study groups

WWARN facilitates a number of collaborative Study Groups to undertake individual patient data meta-analyses to answer specific research questions about malaria treatments and antimalarial drug resistance. Gathering and combining data sets from multiple studies increases sample sizes, so that effects, including smaller effects, and effects on sub-populations can be identified with greater certainty. Working together and combining data from different regions and populations is improving our understanding of drug resistance and strengthening global efforts to control and eventually eliminate malaria.

Vivax After Falciparum Study Group

This Study Group will explore the link between P. vivax recurrence and prior P. falciparum treatment, including increased risk of vivax parasitaemia due to acute malaria infection.

Antiretroviral Drugs to Treat HIV Infection. Credit NIAID
Antimalarial–Antiretroviral Analyses

Sub-study groups include the Artemether-Lumefantrine / ARV PK Study Group and the ACT-ARV Safety Study Group.

Small malnourished child in Darfur
ACT Malaria and Malnutrition Study Group

A pooled analysis that assessed the effect of various nutritional indicators in treatment outcome in children aged 6-59 months treated with artemisinin based combination therapies for uncomplicated P. falciparum malaria.
This group has published a first manuscript: Complex interactions between malaria and malnutrition: a systematic literature review. Das D et al. BMC Medicine. 2018 Oct 29;16(1):186. Read this news article summarising the results.

Mother with baby, Malawi. Credit: Lindsay Mgbor/Department for International Development
Subpatent Malaria and Pregnancy Outcome Study Group

The Subpatent Malaria and Pregnancy Outcome Study Group aims to explore the relationship between subpatent Plasmodium falciparum malaria infection and pregnancy outcome

Molecular Markers of Resistance in West Africa Study Group

This Study Group aims to bring together and explore the latest evidence on the prevalence of molecular markers associated with antimalarial drug resistance in West African Countries.

AS-MQ Dose Impact Study Group

A pooled analysis assessing the effect of mg/kg dosing strategies on the risk of treatment failure in patients treated with the currently recommended dose of artesunate-mefloquine (AS-MQ).
Research groups with relevant data have been contacted with data collection and curation still ongoing. Analysis will start in late 2016 and drafting publication in expected in 2018.

Credit: Penn State
Low-dose Primaquine Efficacy and Safety Study Groups

Pooled analyses of the efficacy and safety of single low-dose primaquine to interrupt P. falciparum malaria transmission.
Data collection has closed and curation is ongoing. Analysis and draft publications are planned for circulation to the Group by the June of 2017.

Woman receiving medication from nurses
AS-AQ Post-Treatment Prophylaxis Study Group

Modelling the protective effect of Artesunate-Amodiaquine (AS-AQ)
A pooled analysis to assess the post-treatment prophylactic effect of artesunate-amodiaquine (AS-AQ). The group is quantifying the duration of post-treatment prophylaxis mediated by AS-AQ and how it depends on host factors such as .
The Study Group closed in January 2014. The AS-AQ Post-Treatment Prophylaxis Study Group manuscript is under review at BMC Medicine. 

DRC Healthcare centre
Piperaquine (Cardiac) Safety Study Group

The Piperaquine Safety Study Group’s aim is to establish the evidence-base and safety profile to inform decision-making on the use and optimal dosing of dihydroartemisinin-piperaquine in all key target populations.
The study group call for contributors opened in June 2016 with a first scoping meeting held in July. Data collection is planned to close by end of 2016, with analysis due in 2018-2019.

Clinical Trials Methodology Study Group for P. falciparum

This Study Group is exploring key study design and analytical factors which affects derived clinical efficacy of antimalarials. 
Statistical analyses have commenced and preliminary results of ongoing analyses will be shared at EDCTP Forum 2016 (Lusaka, Zambia) and ASTMH 2016 (Atlanta, USA). Publications are expected in 2018.

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Finger-prick of child for malaria blood slide
DP Dose Impact Study Group

Effect of DP mg/kg dosing strategies on the risk of treatment failure
A pooled analysis to assess the impact of weight adjusted (mg/kg) dose variations of dihydroartemisinin-piperaquine (DP) on the therapeutic efficacy of both drugs combined. The Study Group assessed if the dose of piperaquine administered to patients was a risk factor for recrudescence, (recurrence of symptoms).
The Study Group closed in March 2013. A paper was published in Plos Medicine in December 2013. Results from this study group provided evidence for the revised recommendations for optimal use of artemisinin combination therapies included in the updated WHO ‘Guidelines for the Treatment of Malaria in June 2015.
Related publications:
The WorldWide Antimalarial Resistance Network (WWARN) DP Study Group (2013) The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data. PLOS Med 10(12): e1001564. doi:10.1371/journal.pmed.1001564

Mother and child in malaria clinic
AL Dose Impact Study Group

The AL Dose Impact Study Group was first established in 2011. The Study Group first met in December 2011 at the ASTMH Annual Meeting to discuss the Study Group governance and publication policy. The Study Group closed in March 2013. The latest results were presented at the 2014 ASTMH Annual Meeting in New Orleans, USA.
The artemether-lumefantrine (AL) Dose Impact Study Group found that the efficacy of the combination was lowest in young children from Asia and young underweight children from Africa, suggesting that a higher dose regimen should be evaluated in these groups. The manuscript for this Study Group was published by the Lancet Infectious Diseases in March 2015: The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data. 
Briefly, data from 66 clinical trials (n=15,529) conducted between 1998 and 2012, including eight unpublished studies and 58 published, studies representing 59 per cent of the targeted published literature on AL treatment were shared with WWARN. 61 studies (14,327 patients) were included in the final analysis. Of those patients included in the final analysis, 82.4 per cent were from Africa, 16.5 per cent from Asia and 1.1 per cent from South America.
Download a presentation from the AL Dose Impact Study Group.

ASAQ treatment
AS-AQ Dose Impact Study Group

Effect of AS-AQ mg/kg dosing strategies on the risk of treatment failure
A pooled analysis to assess the impact of weight adjusted (mg/kg) dose variations of artesunate-amodiaquine (AS-AQ) on therapeutic efficacy of both drugs combined. The Study Group assessed if the dose of amodiaquine administered to the patients was a risk factor for recrudescence(recurrence of symptoms). The results are expected to be published in the BMC Medicine at the end of March 2015.
The study group closed in March 2013. The paper was published in March 2015. 
Publiction details: 
The Worldwide Antimalarial Resistance Network (WWARN) AS-AQ Study Group. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data. BMC Medicine 2015 13:66. Published 31 March 2015 doi: 10.1186/s12916-015-0301-z.

Finger-prick for malaria blood slide
Parasite Clearance Study Group

Parasite clearance after treatment with an artemisinin monotherapy or ACT
This Study Group characterises parasite clearance stratified by location, treatment and time and to find optimal restricted sampling schemes for clearance estimation and provides baseline information on parasite clearance.
The latest study, ‘Baseline parasite clearance data in uncomplicated falciparum malaria after treatment with an artemisinin derivative alone or in combination’, has been submitted to Malaria Journal and is currently under review.
Related publications:
Flegg JA, Guerin PJ, Nosten F et al. Optimal sampling designs for estimation of Plasmodium falciparum clearance rates in patients treated with artemisinin derivatives. Malaria Journal, 2013. Doi: 10.1186/1475-2875-12-411.  PMID: 24225303
WWARN Parasite Clearance Study Group ‘Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: an individual patient data meta-analysis’ Published in Malaria Journal 2015. DOI:10.1186/s12936-015-0874-1

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