Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
Abstract Background Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infec...
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ftdoajarticles:oai:doaj.org/article:642f3910338e40b0959dbe16b0a0d838 2023-05-15T15:18:34+02:00 Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis The WorldWide Antimalarial Resistance Network Methodology Study Group 2019-07-01T00:00:00Z https://doi.org/10.1186/s12936-019-2837-4 https://doaj.org/article/642f3910338e40b0959dbe16b0a0d838 EN eng BMC http://link.springer.com/article/10.1186/s12936-019-2837-4 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-019-2837-4 1475-2875 https://doaj.org/article/642f3910338e40b0959dbe16b0a0d838 Malaria Journal, Vol 18, Iss 1, Pp 1-14 (2019) Plasmodium falciparum Treatment efficacy study Competing risk event Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2019 ftdoajarticles https://doi.org/10.1186/s12936-019-2837-4 2022-12-31T00:51:55Z Abstract Background Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods Antimalarial studies typically report the risk of recrudescence derived using the Kaplan–Meier (K–M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K–M method (1 minus K–M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K–M curves was assessed using the log-rank test, and the equality of CIFs using Gray’s k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray’s sub-distributional hazard model. Results Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K–M approach was 0.04% (interquartile range (IQR): 0.00–0.27%, Range: 0.00–3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson’s correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30–0.46] or new infection [ρ: 0.43; 95% CI 0.35–0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K–M ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Meier ENVELOPE(-45.900,-45.900,-60.633,-60.633) Malaria Journal 18 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Plasmodium falciparum Treatment efficacy study Competing risk event Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Plasmodium falciparum Treatment efficacy study Competing risk event Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 The WorldWide Antimalarial Resistance Network Methodology Study Group Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis |
topic_facet |
Plasmodium falciparum Treatment efficacy study Competing risk event Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods Antimalarial studies typically report the risk of recrudescence derived using the Kaplan–Meier (K–M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K–M method (1 minus K–M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K–M curves was assessed using the log-rank test, and the equality of CIFs using Gray’s k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray’s sub-distributional hazard model. Results Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K–M approach was 0.04% (interquartile range (IQR): 0.00–0.27%, Range: 0.00–3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson’s correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30–0.46] or new infection [ρ: 0.43; 95% CI 0.35–0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K–M ... |
format |
Article in Journal/Newspaper |
author |
The WorldWide Antimalarial Resistance Network Methodology Study Group |
author_facet |
The WorldWide Antimalarial Resistance Network Methodology Study Group |
author_sort |
The WorldWide Antimalarial Resistance Network Methodology Study Group |
title |
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis |
title_short |
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis |
title_full |
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis |
title_fullStr |
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis |
title_full_unstemmed |
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis |
title_sort |
competing risk events in antimalarial drug trials in uncomplicated plasmodium falciparum malaria: a worldwide antimalarial resistance network individual participant data meta-analysis |
publisher |
BMC |
publishDate |
2019 |
url |
https://doi.org/10.1186/s12936-019-2837-4 https://doaj.org/article/642f3910338e40b0959dbe16b0a0d838 |
long_lat |
ENVELOPE(-45.900,-45.900,-60.633,-60.633) |
geographic |
Arctic Meier |
geographic_facet |
Arctic Meier |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 18, Iss 1, Pp 1-14 (2019) |
op_relation |
http://link.springer.com/article/10.1186/s12936-019-2837-4 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-019-2837-4 1475-2875 https://doaj.org/article/642f3910338e40b0959dbe16b0a0d838 |
op_doi |
https://doi.org/10.1186/s12936-019-2837-4 |
container_title |
Malaria Journal |
container_volume |
18 |
container_issue |
1 |
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1766348759872045056 |