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Analysing malaria drug trials on a per individual or a per clone basis: a comparison of methods

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Analysing malaria drug trials on a per individual or a per clone basis : a comparison of methods. / Jaki, Thomas; Parry, Alice; Winter, Katherine et al.

In: Statistics in Medicine, Vol. 32, No. 17, 30.07.2013, p. 3020-3038.

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Jaki T, Parry A, Winter K, Hastings I. Analysing malaria drug trials on a per individual or a per clone basis: a comparison of methods. Statistics in Medicine. 2013 Jul 30;32(17):3020-3038. Epub 2012 Dec 19. doi: 10.1002/sim.5706

Author

Jaki, Thomas ; Parry, Alice ; Winter, Katherine et al. / Analysing malaria drug trials on a per individual or a per clone basis : a comparison of methods. In: Statistics in Medicine. 2013 ; Vol. 32, No. 17. pp. 3020-3038.

Bibtex

@article{0a8669e77d414f6192817ab9b38b602d,
title = "Analysing malaria drug trials on a per individual or a per clone basis: a comparison of methods",
abstract = "There are a variety of methods used to estimate the effectiveness of antimalarial drugs in clinical trials, invariably on a per-person basis. A person, however, may have more than one malaria infection present at the time of treatment. We evaluate currently used methods for analysing malaria trials on a per-individual basis and introduce a novel method to estimate the cure rate on a per-infection (clone) basis. We used simulated and real data to highlight the differences of the various methods. We give special attention to classifying outcomes as cured, recrudescent (infections that never fully cleared) or ambiguous on the basis of genetic markers at three loci. To estimate cure rates on a per-clone basis, we used the genetic information within an individual before treatment to determine the number of clones present. We used the genetic information obtained at the time of treatment failure to classify clones as recrudescence or new infections. On the per-individual level, we find that the most accurate methods of classification label an individual as newly infected if all alleles are different at the beginning and at the time of failure and as a recrudescence if all or some alleles were the same. The most appropriate analysis method is survival analysis or alternatively for complete data/per-protocol analysis a proportion estimate that treats new infections as successes. We show that the analysis of drug effectiveness on a per-clone basis estimates the cure rate accurately and allows more detailed evaluation of the performance of the treatment.",
keywords = "clone, cure rate, malaria, per-clone, per individual",
author = "Thomas Jaki and Alice Parry and Katherine Winter and Ian Hastings",
year = "2013",
month = jul,
day = "30",
doi = "10.1002/sim.5706",
language = "English",
volume = "32",
pages = "3020--3038",
journal = "Statistics in Medicine",
issn = "0277-6715",
publisher = "John Wiley and Sons Ltd",
number = "17",

}

RIS

TY - JOUR

T1 - Analysing malaria drug trials on a per individual or a per clone basis

T2 - a comparison of methods

AU - Jaki, Thomas

AU - Parry, Alice

AU - Winter, Katherine

AU - Hastings, Ian

PY - 2013/7/30

Y1 - 2013/7/30

N2 - There are a variety of methods used to estimate the effectiveness of antimalarial drugs in clinical trials, invariably on a per-person basis. A person, however, may have more than one malaria infection present at the time of treatment. We evaluate currently used methods for analysing malaria trials on a per-individual basis and introduce a novel method to estimate the cure rate on a per-infection (clone) basis. We used simulated and real data to highlight the differences of the various methods. We give special attention to classifying outcomes as cured, recrudescent (infections that never fully cleared) or ambiguous on the basis of genetic markers at three loci. To estimate cure rates on a per-clone basis, we used the genetic information within an individual before treatment to determine the number of clones present. We used the genetic information obtained at the time of treatment failure to classify clones as recrudescence or new infections. On the per-individual level, we find that the most accurate methods of classification label an individual as newly infected if all alleles are different at the beginning and at the time of failure and as a recrudescence if all or some alleles were the same. The most appropriate analysis method is survival analysis or alternatively for complete data/per-protocol analysis a proportion estimate that treats new infections as successes. We show that the analysis of drug effectiveness on a per-clone basis estimates the cure rate accurately and allows more detailed evaluation of the performance of the treatment.

AB - There are a variety of methods used to estimate the effectiveness of antimalarial drugs in clinical trials, invariably on a per-person basis. A person, however, may have more than one malaria infection present at the time of treatment. We evaluate currently used methods for analysing malaria trials on a per-individual basis and introduce a novel method to estimate the cure rate on a per-infection (clone) basis. We used simulated and real data to highlight the differences of the various methods. We give special attention to classifying outcomes as cured, recrudescent (infections that never fully cleared) or ambiguous on the basis of genetic markers at three loci. To estimate cure rates on a per-clone basis, we used the genetic information within an individual before treatment to determine the number of clones present. We used the genetic information obtained at the time of treatment failure to classify clones as recrudescence or new infections. On the per-individual level, we find that the most accurate methods of classification label an individual as newly infected if all alleles are different at the beginning and at the time of failure and as a recrudescence if all or some alleles were the same. The most appropriate analysis method is survival analysis or alternatively for complete data/per-protocol analysis a proportion estimate that treats new infections as successes. We show that the analysis of drug effectiveness on a per-clone basis estimates the cure rate accurately and allows more detailed evaluation of the performance of the treatment.

KW - clone

KW - cure rate

KW - malaria

KW - per-clone

KW - per individual

U2 - 10.1002/sim.5706

DO - 10.1002/sim.5706

M3 - Journal article

VL - 32

SP - 3020

EP - 3038

JO - Statistics in Medicine

JF - Statistics in Medicine

SN - 0277-6715

IS - 17

ER -