Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria
Abstract Background Treatments for uncomplicated falciparum malaria should have high cure rates. The World Health Organization has recently set a target cure rate of 95% assessed at 28 days. The use of more effective drugs, with longer periods of patient follow-up, and parasite genotyping to disting...
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ftdoajarticles:oai:doaj.org/article:7d11be1fe60c47048ca6c5d02c02a446 2023-05-15T15:14:22+02:00 Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria Stepniewska Kasia White Nicholas J 2006-12-01T00:00:00Z https://doi.org/10.1186/1475-2875-5-127 https://doaj.org/article/7d11be1fe60c47048ca6c5d02c02a446 EN eng BMC http://www.malariajournal.com/content/5/1/127 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-5-127 1475-2875 https://doaj.org/article/7d11be1fe60c47048ca6c5d02c02a446 Malaria Journal, Vol 5, Iss 1, p 127 (2006) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2006 ftdoajarticles https://doi.org/10.1186/1475-2875-5-127 2022-12-31T04:59:45Z Abstract Background Treatments for uncomplicated falciparum malaria should have high cure rates. The World Health Organization has recently set a target cure rate of 95% assessed at 28 days. The use of more effective drugs, with longer periods of patient follow-up, and parasite genotyping to distinguish recrudescence from reinfection raise issues related to the design and interpretation of antimalarial treatment trials in uncomplicated falciparum malaria which are discussed here. Methods The importance of adequate follow-up is presented and the advantages and disadvantages of non-inferiority trials are discussed. The different methods of interpreting trial results are described, and the difficulties created by loss to follow-up and missing or indeterminate genotyping results are reviewed. Conclusion To characterize cure rates adequately assessment of antimalarial drug efficacy in uncomplicated malaria requires a minimum of 28 days and as much as 63 days follow-up after starting treatment. The longer the duration of follow-up in community-based assessments, the greater is the risk that this will be incomplete, and in endemic areas, the greater is the probability of reinfection. Recrudescence can be distinguished from reinfection using PCR genotyping but there are commonly missing or indeterminate results. There is no consensus on how these data should be analysed, and so a variety of approaches have been employed. It is argued that the correct approach to analysing antimalarial drug efficacy assessments is survival analysis, and patients with missing or indeterminate PCR results should either be censored from the analysis, or if there are sufficient data, results should be adjusted based on the identified ratio of new infections to recrudescences at the time of recurrent parasitaemia. Where the estimated cure rates with currently recommended treatments exceed 95%, individual comparisons with new regimens should generally be designed as non-inferiority trials with sample sizes sufficient to determine adequate ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 5 1 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Stepniewska Kasia White Nicholas J Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Treatments for uncomplicated falciparum malaria should have high cure rates. The World Health Organization has recently set a target cure rate of 95% assessed at 28 days. The use of more effective drugs, with longer periods of patient follow-up, and parasite genotyping to distinguish recrudescence from reinfection raise issues related to the design and interpretation of antimalarial treatment trials in uncomplicated falciparum malaria which are discussed here. Methods The importance of adequate follow-up is presented and the advantages and disadvantages of non-inferiority trials are discussed. The different methods of interpreting trial results are described, and the difficulties created by loss to follow-up and missing or indeterminate genotyping results are reviewed. Conclusion To characterize cure rates adequately assessment of antimalarial drug efficacy in uncomplicated malaria requires a minimum of 28 days and as much as 63 days follow-up after starting treatment. The longer the duration of follow-up in community-based assessments, the greater is the risk that this will be incomplete, and in endemic areas, the greater is the probability of reinfection. Recrudescence can be distinguished from reinfection using PCR genotyping but there are commonly missing or indeterminate results. There is no consensus on how these data should be analysed, and so a variety of approaches have been employed. It is argued that the correct approach to analysing antimalarial drug efficacy assessments is survival analysis, and patients with missing or indeterminate PCR results should either be censored from the analysis, or if there are sufficient data, results should be adjusted based on the identified ratio of new infections to recrudescences at the time of recurrent parasitaemia. Where the estimated cure rates with currently recommended treatments exceed 95%, individual comparisons with new regimens should generally be designed as non-inferiority trials with sample sizes sufficient to determine adequate ... |
format |
Article in Journal/Newspaper |
author |
Stepniewska Kasia White Nicholas J |
author_facet |
Stepniewska Kasia White Nicholas J |
author_sort |
Stepniewska Kasia |
title |
Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria |
title_short |
Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria |
title_full |
Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria |
title_fullStr |
Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria |
title_full_unstemmed |
Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria |
title_sort |
some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria |
publisher |
BMC |
publishDate |
2006 |
url |
https://doi.org/10.1186/1475-2875-5-127 https://doaj.org/article/7d11be1fe60c47048ca6c5d02c02a446 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 5, Iss 1, p 127 (2006) |
op_relation |
http://www.malariajournal.com/content/5/1/127 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-5-127 1475-2875 https://doaj.org/article/7d11be1fe60c47048ca6c5d02c02a446 |
op_doi |
https://doi.org/10.1186/1475-2875-5-127 |
container_title |
Malaria Journal |
container_volume |
5 |
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1 |
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1766344830095458304 |