Table 4.
Relative importance of variable parameters ranked for the nine treatment regimens, using Wald, log likelihood, and odds ratio statistics in logistic regression, with drug failure as the outcomea
| Drug | Variableb | Rank | Wald statistic | Change in −2 log likelihood | Significance (P value) | Odds ratio (95% CI) |
|---|---|---|---|---|---|---|
| Chloroquine | P0 | 7 | 7.029 | 7.112 | 0.008 | 1.122 (1.031-1.223) |
| a | 2 | 478.113 | 2,358.325 | 0.000 | 264.216 (160.274-435.566) | |
| k | 5 | 324.825 | 640.959 | 0.000 | 10.762 (8.311-13.935) | |
| n | 6 | 274.542 | 487.471 | 0.000 | 0.134 (0.105-0.169) | |
| IC50 | 3 | 394.607 | 1,075.476 | 0.000 | 25.467 (18.504-35.052) | |
| Vd | 4 | 387.435 | 1,046.712 | 0.000 | 24.438 (17.777-33.595) | |
| V | 1 | 508.018 | 5,903.412 | 0.000 | 0.000 (0.000-0.000) | |
| Constant | 522.451 | 0.000 | ||||
| Chloroquine plus artesunate | P0 | 9 | 17.670 | 18.283 | 0.000 | 1.227 (1.116-1.350) |
| a | 2 | 388.052 | 2,044.336 | 0.000 | 321.885 (181.216-571.748) | |
| CQ k | 5 | 231.727 | 420.421 | 0.000 | 8.185 (6.244-10.729) | |
| CQ n | 6 | 221.282 | 386.808 | 0.000 | 0.145 (0.113-0.188) | |
| CQ IC50 | 3 | 321.878 | 827.574 | 0.000 | 21.178 (15.172-29.562) | |
| CQ Vd | 4 | 316.659 | 788.882 | 0.000 | 19.629 (14.142-27.246) | |
| CQ V | 1 | 417.353 | 5,279.992 | 0.000 | 0.000 (0.000-0.000) | |
| AS k | 7 | 43.178 | 46.965 | 0.000 | 1.812 (1.518-2.164) | |
| AS n | 12 | 0.002 | 0.002 | 0.965 | 1.004 (0.842-1.196) | |
| AS IC50 | 10 | 2.786 | 2.804 | 0.094 | 1.162 (0.974-1.385) | |
| AS Vd | 11 | 0.842 | 0.842 | 0.359 | 1.085 (0.911-1.292) | |
| AS V | 8 | 40.981 | 44.564 | 0.000 | 0.555 (0.464-0.665) | |
| Constant | 430.377 | 0.000 | ||||
| Lumefantrine | P0 | 7 | 19.198 | 20.130 | 0.000 | 1.293 (1.152-1.450) |
| a | 2 | 267.100 | 1,461.201 | 0.000 | 415.911 (201.797-857.206) | |
| k | 3 | 243.528 | 821.347 | 0.000 | 56.223 (33.895-93.259) | |
| n | 6 | 27.154 | 29.445 | 0.000 | 0.546 (0.435-0.686) | |
| IC50 | 5 | 77.610 | 96.781 | 0.000 | 2.955 (2.322-3.760) | |
| Vd | 4 | 82.145 | 101.599 | 0.000 | 2.957 (2.339-3.739) | |
| V | 1 | 289.468 | 5,334.075 | 0.000 | 0.000 (0.000-0.000) | |
| Constant | 295.124 | 0.000 | ||||
| Lumefantrine plus artesunate | P0 | 9 | 19.811 | 21.134 | 0.000 | 1.331 (1.173-1.509) |
| a | 2 | 232.508 | 1,150.943 | 0.000 | 251.521 (123.598-511.845) | |
| LF k | 3 | 186.486 | 485.514 | 0.000 | 22.058 (14.149-34.388) | |
| LF n | 8 | 24.768 | 27.014 | 0.000 | 0.535 (0.418-0.684) | |
| LF IC50 | 7 | 28.178 | 31.114 | 0.000 | 1.977 (1.537-2.543) | |
| LF Vd | 6 | 39.783 | 44.971 | 0.000 | 2.317 (1.784-3.008) | |
| LF V | 1 | 257.517 | 4,257.815 | 0.000 | 0.000 (0.000-0.000) | |
| AS k | 4 | 62.142 | 75.273 | 0.000 | 2.872 (2.209-3.733) | |
| AS n | 11 | 0.596 | 0.598 | 0.440 | 0.908 (0.712-1.159) | |
| AS IC50 | 10 | 8.165 | 8.342 | 0.004 | 1.387 (1.108-1.735) | |
| AS Vd | 12 | 0.351 | 0.352 | 0.553 | 1.070 (0.855-1.340) | |
| AS V | 5 | 52.110 | 62.342 | 0.000 | 0.398 (0.310-0.511) | |
| Constant | 263.643 | 0.000 | ||||
| Lumefantrine plus artemether | P0 | 9 | 17.670 | 18.283 | 0.000 | 1.227 (1.116-1.350) |
| a | 2 | 388.052 | 2,044.336 | 0.000 | 321.885 (181.216-571.748) | |
| LF k | 5 | 231.727 | 420.421 | 0.000 | 8.185 (6.244-10.729) | |
| LF n | 6 | 221.282 | 386.808 | 0.000 | 0.145 (0.113-0.188) | |
| LF IC50 | 3 | 321.878 | 827.574 | 0.000 | 21.178 (15.172-29.562) | |
| LF Vd | 4 | 316.659 | 788.882 | 0.000 | 19.629 (14.142-27.246) | |
| LF V | 1 | 417.353 | 5,279.992 | 0.000 | 0.000 (0.000-0.000) | |
| AR k | 7 | 43.178 | 46.965 | 0.000 | 1.812 (1.518-2.164) | |
| AR n | 12 | 0.002 | 0.002 | 0.965 | 1.004 (0.842-1.196) | |
| AR IC50 | 10 | 2.786 | 2.804 | 0.094 | 1.162 (0.974-1.385) | |
| AR Vd | 11 | 0.842 | 0.842 | 0.359 | 1.085 (0.911-1.292) | |
| AR V | 8 | 40.981 | 44.564 | 0.000 | 0.555 (0.464-0.665) | |
| Constant | 430.377 | 0.000 | ||||
| Mefloquine | P0 | 7 | 1.469 | 1.477 | 0.224 | 1.083 (0.952-1.232) |
| a | 2 | 176.479 | 761.123 | 0.000 | 110.263 (55.093-220.680) | |
| k | 3 | 80.146 | 116.012 | 0.000 | 4.264 (3.104-5.858) | |
| n | 6 | 12.501 | 13.263 | 0.000 | 0.613 (0.468-0.804) | |
| IC50 | 5 | 13.256 | 13.883 | 0.000 | 1.581 (1.236-2.023) | |
| Vd | 4 | 17.108 | 18.392 | 0.000 | 1.840 (1.378-2.456) | |
| V | 1 | 202.508 | 3,128.261 | 0.000 | 0.000 (0.000-0.000) | |
| Constant | 206.623 | 0.000 | ||||
| Mefloquine plus artesunate | P0 | 9 | 1.538 | 1.548 | 0.213 | 1.093 (0.950-1.258) |
| a | 2 | 159.869 | 668.108 | 0.000 | 87.176 (43.613-174.254) | |
| MQ k | 3 | 45.487 | 55.621 | 0.000 | 2.867 (2.111-3.894) | |
| MQ n | 8 | 3.920 | 3.971 | 0.046 | 0.750 (0.564-0.997) | |
| MQ IC50 | 5 | 12.613 | 13.441 | 0.000 | 1.633 (1.246-2.142) | |
| MQ Vd | 7 | 6.892 | 7.086 | 0.008 | 1.480 (1.104-1.983) | |
| MQ V | 1 | 187.344 | 2,676.097 | 0.000 | 0.000 (0.000-0.000) | |
| AS k | 4 | 22.465 | 25.146 | 0.000 | 2.006 (1.504-2.675) | |
| AS n | 11 | 0.088 | 0.088 | 0.767 | 0.959 (0.726-1.266) | |
| AS IC50 | 10 | 0.646 | 0.647 | 0.421 | 0.896 (0.686-1.171) | |
| AS Vd | 12 | 0.020 | 0.020 | 0.887 | 0.980 (0.744-1.292) | |
| AS V | 6 | 11.547 | 12.206 | 0.000 | 0.625 (0.476-0.819) | |
| Constant | 192.601 | 0.000 | ||||
| Piperaquine | P0 | 7 | 12.093 | 12.306 | 0.000 | 1.163 (1.068-1.266) |
| a | 2 | 405.719 | 1,147.304 | 0.000 | 27.102 (19.659-37.363) | |
| k | 5 | 268.650 | 446.987 | 0.000 | 6.565 (5.242-8.222) | |
| n | 6 | 96.420 | 111.102 | 0.000 | 0.416 (0.349-0.495) | |
| IC50 | 4 | 324.886 | 666.386 | 0.000 | 11.141 (8.572-14.480) | |
| Vd | 3 | 331.315 | 667.546 | 0.000 | 10.928 (8.447-14.138) | |
| V | 1 | 514.197 | 4,464.531 | 0.000 | 0.000 (0.000-0.000) | |
| Constant | 543.153 | 0.000 | ||||
| Piperaquine plus DHA | P0 | 8 | 13.759 | 14.059 | 0.000 | 1.181 (1.082-1.290) |
| a | 2 | 374.163 | 1,074.747 | 0.000 | 28.157 (20.077-39.488) | |
| PQ k | 5 | 231.611 | 376.353 | 0.000 | 5.928 (4.714-7.455) | |
| PQ n | 6 | 90.066 | 104.273 | 0.000 | 0.411 (0.342-0.494) | |
| PQ IC50 | 4 | 283.653 | 533.022 | 0.000 | 8.900 (6.901-11.479) | |
| PQ Vd | 3 | 298.725 | 566.776 | 0.000 | 9.691 (7.491-12.539) | |
| PQ V | 1 | 470.841 | 4,087.798 | 0.000 | 0.000 (0.000-0.000) | |
| DHA k | 9 | 13.447 | 13.705 | 0.000 | 1.364 (1.155-1.609) | |
| DHA n | 12 | 0.000 | 0.000 | 0.988 | 0.999 (0.844-1.181) | |
| DHA IC50 | 11 | 0.077 | 0.078 | 0.781 | 0.977 (0.828-1.152) | |
| DHA Vd | 10 | 1.920 | 1.928 | 0.165 | 1.123 (0.953-1.322) | |
| DHA V | 7 | 19.808 | 20.370 | 0.000 | 0.693 (0.590-0.815) | |
| Constant | 499.203 | 0.000 |
a
Chloroquine, mefloquine, and lumefantrine were all given alone and with artesunate, in addition to artemether-lumefantrine. Dosages are in accordance with WHO guidelines(Table 1). The sample size for each drug regimen was 10,000 patients, and overall failure rates are given in Table 2.
b
P0, parasite number at time of treatment; a, parasite growth rate; k, terminal elimination rate constant; n, slope of the dose-response curve; IC50, concentration at which 50% of maximal killing occurs; Vd, volume of distribution; V, maximal drug killing rate.