Methodological Issues in the Assessment of Antimalarial Drug Treatment: Analysis of 13 Studies in Eight African Countries from 2001 to 2004.

Hdl Handle:
http://hdl.handle.net/10144/17734
Title:
Methodological Issues in the Assessment of Antimalarial Drug Treatment: Analysis of 13 Studies in Eight African Countries from 2001 to 2004.
Authors:
Guthmann, J P; Pinoges, L; Checchi, F; Cousens, S; Balkan, S; Van Herp, M; Legros, D; Olliaro, P
Journal:
Antimicrobial Agents and Chemotherapy
Abstract:
The objectives of these analyses were to assess the feasibility of the latest WHO recommendations (28-day follow-up with PCR genotyping) for the assessment of antimalarial drug efficacy in vivo and to examine how different statistical approaches affect results. We used individual-patient data from 13 studies of uncomplicated pediatric falciparum malaria conducted in sub-Saharan Africa, using chloroquine (CQ), sulfadoxine/pyrimethamine (SP), or amodiaquine (AQ). We assessed the use effectiveness and test performance of PCR genotyping in distinguishing recurrent infections. In analyzing data, we compared (i) the risk of failure on target days (days 14 and 28) by using Kaplan-Meier and per-protocol evaluable patient analyses, (ii) PCR-corrected results allowing (method 1) or excluding (method 2) new infections, (iii) and day 14 versus day 28 results. Of the 2,576 patients treated, 2,287 (89%) were evaluable on day 28. Of the 695 recurrences occurring post-day 14, 650 could be processed and 584 were resolved (PCR use effectiveness, 84%; test performance, 90%). The risks of failure on day 28 with Kaplan-Meier and evaluable-patient analyses tended to be generally close (except in smaller studies) because the numbers of dropouts were minimal, but attrition rates on day 28 were higher with the latter method. Method 2 yielded higher risks of failure than method 1. Extending observation to 28 days produced higher estimated risks of failure for SP and AQ but not for CQ (high failure rates by day 14). Results support the implementation of the current WHO protocol and favor analyzing PCR-corrected outcomes by Kaplan-Meier analysis (which allows for dropouts) and retaining new infections (which minimizes losses).
Affiliation:
Epicentre, 8 rue Saint Sabin, 75011 Paris, France. jguthmann@epicentre.msf.org
Publisher:
Published by American Society for Microbiology
Issue Date:
Nov-2006
URI:
http://hdl.handle.net/10144/17734
DOI:
10.1128/AAC.01618-05
PubMed ID:
16954313
Language:
en
ISSN:
0066-4804
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorGuthmann, J P-
dc.contributor.authorPinoges, L-
dc.contributor.authorChecchi, F-
dc.contributor.authorCousens, S-
dc.contributor.authorBalkan, S-
dc.contributor.authorVan Herp, M-
dc.contributor.authorLegros, D-
dc.contributor.authorOlliaro, P-
dc.date.accessioned2008-02-07T16:10:58Z-
dc.date.available2008-02-07T16:10:58Z-
dc.date.issued2006-11-
dc.identifier.citationMethodological Issues in the Assessment of Antimalarial Drug Treatment: Analysis of 13 Studies in Eight African Countries from 2001 to 2004. 2006, 50 (11):3734-9 Antimicrob. Agents Chemother.en
dc.identifier.issn0066-4804-
dc.identifier.pmid16954313-
dc.identifier.doi10.1128/AAC.01618-05-
dc.identifier.urihttp://hdl.handle.net/10144/17734-
dc.description.abstractThe objectives of these analyses were to assess the feasibility of the latest WHO recommendations (28-day follow-up with PCR genotyping) for the assessment of antimalarial drug efficacy in vivo and to examine how different statistical approaches affect results. We used individual-patient data from 13 studies of uncomplicated pediatric falciparum malaria conducted in sub-Saharan Africa, using chloroquine (CQ), sulfadoxine/pyrimethamine (SP), or amodiaquine (AQ). We assessed the use effectiveness and test performance of PCR genotyping in distinguishing recurrent infections. In analyzing data, we compared (i) the risk of failure on target days (days 14 and 28) by using Kaplan-Meier and per-protocol evaluable patient analyses, (ii) PCR-corrected results allowing (method 1) or excluding (method 2) new infections, (iii) and day 14 versus day 28 results. Of the 2,576 patients treated, 2,287 (89%) were evaluable on day 28. Of the 695 recurrences occurring post-day 14, 650 could be processed and 584 were resolved (PCR use effectiveness, 84%; test performance, 90%). The risks of failure on day 28 with Kaplan-Meier and evaluable-patient analyses tended to be generally close (except in smaller studies) because the numbers of dropouts were minimal, but attrition rates on day 28 were higher with the latter method. Method 2 yielded higher risks of failure than method 1. Extending observation to 28 days produced higher estimated risks of failure for SP and AQ but not for CQ (high failure rates by day 14). Results support the implementation of the current WHO protocol and favor analyzing PCR-corrected outcomes by Kaplan-Meier analysis (which allows for dropouts) and retaining new infections (which minimizes losses).en
dc.language.isoenen
dc.publisherPublished by American Society for Microbiology-
dc.rightsArchived on this site with permission and copyright by the American Society for Microbiologyen
dc.subject.meshAfricaen
dc.subject.meshAmodiaquineen
dc.subject.meshAntimalarialsen
dc.subject.meshChild, Preschoolen
dc.subject.meshChloroquineen
dc.subject.meshClinical Trials as Topicen
dc.subject.meshDrug Combinationsen
dc.subject.meshFemaleen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshMalariaen
dc.subject.meshMaleen
dc.subject.meshPyrimethamineen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshRisken
dc.subject.meshSulfadoxineen
dc.subject.meshTreatment Outcomeen
dc.titleMethodological Issues in the Assessment of Antimalarial Drug Treatment: Analysis of 13 Studies in Eight African Countries from 2001 to 2004.en
dc.contributor.departmentEpicentre, 8 rue Saint Sabin, 75011 Paris, France. jguthmann@epicentre.msf.orgen
dc.identifier.journalAntimicrobial Agents and Chemotherapyen

Related articles on PubMed

All Items in MSF are protected by copyright, with all rights reserved, unless otherwise indicated.