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Composite endpoints for malaria case-management: not simplifying the picture?

Cairns ME, Leurent B, Milligan PJ - Malar. J. (2014)

Bottom Line: Rapid diagnostic tests (RDTs) for infection with Plasmodium spp. offer two main potential advantages related to malaria treatment: 1) ensuring that individuals with malaria are promptly treated with an effective artemisinin-based combination therapy, and 2) ensuring that individuals without malaria do not receive an anti-malarial they do not need (and instead receive a more appropriate treatment).However combining correct management of positives and negatives into a single summary measure can be misleading.Two graphical approaches to help understand case management performance are illustrated.

View Article: PubMed Central - PubMed

Affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. matthew.cairns@lshtm.ac.uk.

ABSTRACT
Rapid diagnostic tests (RDTs) for infection with Plasmodium spp. offer two main potential advantages related to malaria treatment: 1) ensuring that individuals with malaria are promptly treated with an effective artemisinin-based combination therapy, and 2) ensuring that individuals without malaria do not receive an anti-malarial they do not need (and instead receive a more appropriate treatment). Some studies of the impact of RDTs on malaria case management have combined these two different successes into a binary outcome describing 'correct management'. However combining correct management of positives and negatives into a single summary measure can be misleading. The problems, which are analogous to those encountered in the evaluation of diagnostic tests, can largely be avoided if data for patients with and without malaria are presented and analysed separately. Where a combined metric is necessary, then one of the established approaches to summarise the performance of diagnostic tests could be considered, although these are not without their limitations. Two graphical approaches to help understand case management performance are illustrated.

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Related in: MedlinePlus

Biggerstaff method for comparing case-management strategies. The blue diamond shows the positive management rate plotted against 1- negative management rate for the control group in [19]. The red square shows the estimate of PMR and 1- NMR for the enhanced training group. Dotted red lines show equivalent PMR and NMR. The upper left rectangle (upward shading) shows the region where a strategy would be considered superior both in term of NMR and PMR; the lower right quadrant (downward shading) shows the region where a new strategy would be considered inferior in terms of NMR and PMR. The solid black line shows the line of constant likelihood ratio for positives, and the dashed black line shows the line of constant likelihood ratio for negatives. The blue shaded area shows the region where an alternative strategy would be considered superior on the basis of higher LR+ and lower LR-, as discussed in Biggerstaff [18].
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Fig1: Biggerstaff method for comparing case-management strategies. The blue diamond shows the positive management rate plotted against 1- negative management rate for the control group in [19]. The red square shows the estimate of PMR and 1- NMR for the enhanced training group. Dotted red lines show equivalent PMR and NMR. The upper left rectangle (upward shading) shows the region where a strategy would be considered superior both in term of NMR and PMR; the lower right quadrant (downward shading) shows the region where a new strategy would be considered inferior in terms of NMR and PMR. The solid black line shows the line of constant likelihood ratio for positives, and the dashed black line shows the line of constant likelihood ratio for negatives. The blue shaded area shows the region where an alternative strategy would be considered superior on the basis of higher LR+ and lower LR-, as discussed in Biggerstaff [18].

Mentions: Biggerstaff [18] describes a graphical approach to compare diagnostic tests using the likelihood ratios, which could be used to compare different case-management strategies. An example using data from a recent trial to improve adherence to malaria treatment guidelines [19] is shown in Figure 1. In the control group, 208/278 patients with malaria received an ACT (PMR = 74.8%); but only 38/239 negative patients did not receive an ACT (NMR = 15.9%). In the group given enhanced training, 363/498 patients with malaria received an ACT (PMR = 72.9%), and 527/759 negatives were not treated (NMR = 69.4%). Thus the main change was an improvement in the management of negatives, at the cost of a slight fall in the correct management of positives. When a new strategy falls in the upper left quadrant or lower right quadrant (as defined by the lines of equivalent PMR and NMR to the reference strategy), the new strategy is clearly superior or clearly inferior, respectively. When a new strategy falls into the bottom left or upper right quadrant, whether this is preferred will depend on how much of a decrease in NMR or PMR can be compensated by an increase in the other rate. According to the method proposed by Biggerstaff, any combination of PMR and NMR that lies above the lines for the LR+ and LR- (the area shaded blue in Figure 1) would be considered ‘superior’ on the basis of the likelihood ratios. However, a case management strategy with a higher LR+ and lower LR- will not systematically be preferred, because different importance may be attached to failure to treat positives, or the incorrect treatment of negatives.Figure 1


Composite endpoints for malaria case-management: not simplifying the picture?

Cairns ME, Leurent B, Milligan PJ - Malar. J. (2014)

Biggerstaff method for comparing case-management strategies. The blue diamond shows the positive management rate plotted against 1- negative management rate for the control group in [19]. The red square shows the estimate of PMR and 1- NMR for the enhanced training group. Dotted red lines show equivalent PMR and NMR. The upper left rectangle (upward shading) shows the region where a strategy would be considered superior both in term of NMR and PMR; the lower right quadrant (downward shading) shows the region where a new strategy would be considered inferior in terms of NMR and PMR. The solid black line shows the line of constant likelihood ratio for positives, and the dashed black line shows the line of constant likelihood ratio for negatives. The blue shaded area shows the region where an alternative strategy would be considered superior on the basis of higher LR+ and lower LR-, as discussed in Biggerstaff [18].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4300677&req=5

Fig1: Biggerstaff method for comparing case-management strategies. The blue diamond shows the positive management rate plotted against 1- negative management rate for the control group in [19]. The red square shows the estimate of PMR and 1- NMR for the enhanced training group. Dotted red lines show equivalent PMR and NMR. The upper left rectangle (upward shading) shows the region where a strategy would be considered superior both in term of NMR and PMR; the lower right quadrant (downward shading) shows the region where a new strategy would be considered inferior in terms of NMR and PMR. The solid black line shows the line of constant likelihood ratio for positives, and the dashed black line shows the line of constant likelihood ratio for negatives. The blue shaded area shows the region where an alternative strategy would be considered superior on the basis of higher LR+ and lower LR-, as discussed in Biggerstaff [18].
Mentions: Biggerstaff [18] describes a graphical approach to compare diagnostic tests using the likelihood ratios, which could be used to compare different case-management strategies. An example using data from a recent trial to improve adherence to malaria treatment guidelines [19] is shown in Figure 1. In the control group, 208/278 patients with malaria received an ACT (PMR = 74.8%); but only 38/239 negative patients did not receive an ACT (NMR = 15.9%). In the group given enhanced training, 363/498 patients with malaria received an ACT (PMR = 72.9%), and 527/759 negatives were not treated (NMR = 69.4%). Thus the main change was an improvement in the management of negatives, at the cost of a slight fall in the correct management of positives. When a new strategy falls in the upper left quadrant or lower right quadrant (as defined by the lines of equivalent PMR and NMR to the reference strategy), the new strategy is clearly superior or clearly inferior, respectively. When a new strategy falls into the bottom left or upper right quadrant, whether this is preferred will depend on how much of a decrease in NMR or PMR can be compensated by an increase in the other rate. According to the method proposed by Biggerstaff, any combination of PMR and NMR that lies above the lines for the LR+ and LR- (the area shaded blue in Figure 1) would be considered ‘superior’ on the basis of the likelihood ratios. However, a case management strategy with a higher LR+ and lower LR- will not systematically be preferred, because different importance may be attached to failure to treat positives, or the incorrect treatment of negatives.Figure 1

Bottom Line: Rapid diagnostic tests (RDTs) for infection with Plasmodium spp. offer two main potential advantages related to malaria treatment: 1) ensuring that individuals with malaria are promptly treated with an effective artemisinin-based combination therapy, and 2) ensuring that individuals without malaria do not receive an anti-malarial they do not need (and instead receive a more appropriate treatment).However combining correct management of positives and negatives into a single summary measure can be misleading.Two graphical approaches to help understand case management performance are illustrated.

View Article: PubMed Central - PubMed

Affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. matthew.cairns@lshtm.ac.uk.

ABSTRACT
Rapid diagnostic tests (RDTs) for infection with Plasmodium spp. offer two main potential advantages related to malaria treatment: 1) ensuring that individuals with malaria are promptly treated with an effective artemisinin-based combination therapy, and 2) ensuring that individuals without malaria do not receive an anti-malarial they do not need (and instead receive a more appropriate treatment). Some studies of the impact of RDTs on malaria case management have combined these two different successes into a binary outcome describing 'correct management'. However combining correct management of positives and negatives into a single summary measure can be misleading. The problems, which are analogous to those encountered in the evaluation of diagnostic tests, can largely be avoided if data for patients with and without malaria are presented and analysed separately. Where a combined metric is necessary, then one of the established approaches to summarise the performance of diagnostic tests could be considered, although these are not without their limitations. Two graphical approaches to help understand case management performance are illustrated.

Show MeSH
Related in: MedlinePlus