Reduced Exposure to Calcineurin Inhibitors in Renal Transplantation
2007 · paper · Clinical trials
A randomized trial of 1645 kidney-transplant recipients comparing four immunosuppressive regimens. Low-dose tacrolimus with daclizumab, mycophenolate and steroids gave higher kidney function, less acute rejection and better graft survival than the low-dose cyclosporine, low-dose sirolimus or standard-dose cyclosporine regimens.
1 finding
Substance Figure 1 legend gives safety population sizes of 384, 408, 403 and 380 (total 1575). This is smaller than the ITT total of 390+399+401+399 = 1589, although ITT is defined as a subset of the safety population ("received at least one dose of a study drug and underwent transplantation").
- p. 5 Figure 1 legend
included 384 patients in the stan-dard-dose cyclosporine group, 408 patients in the low-dose cyclosporine group, 403 patients in the low-dose tacrolimus group, and 380
- p. 5 Figure 1 boxes
390 Received treatment and transplantation
- p. 4 Statistical Analysis
a safety population (patients who received at least one dose of a study drug) and an inten-tion-to-treat population (patients who received at least one dose of a study drug and underwent transplantation)
Only the authors can say what is right here.
Judge's note: The Methods on p4 define safety as at least one dose, and ITT as at least one dose plus transplantation, so ITT ⊆ safety. Figure 1 boxes (p5) give 390/399/401/399 who received treatment and transplantation. The legend gives safety Ns that are smaller in total, and the Table 3 headers use 384/408/403/380. Analysis by treatment actually received could move patients between arms but cannot shrink the total. The paper gives no explanation.
Second check: another model agreed
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10 minor (typos and the like; most checked by the judge only)
Reference or label Table 2 row "Mean calculated GFR — ml/min¶" gives the unit as ml/min, while footnote ¶ defines the MDRD quantity as "estimated GFR (ml/min/1.73 m2)".
- p. 8 Table 2, secondary end point row
Mean calculated GFR — ml/min¶
- p. 8 Table 2 footnote ¶
estimated GFR (ml/min/1.73 m2) = 186 ×
Judge's note: Seen on the p8 image. The row label and its own footnote give different units.
Second check: another model agreed
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Wording Abstract conclusion says low-dose tacrolimus "may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine". Table 2 shows no significant allograft-survival difference against low-dose cyclosporine (P=0.18 censored, P=0.56 uncensored).
- p. 1 Abstract, Conclusions
may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction
- p. 8 Table 2, Allograft survival rows, P value for comparison with tacrolimus, low-dose cyclosporine column
0.18
- p. 13 Discussion, concluding paragraph
the low-dose tacrolimus regimen provided better allograft survival than did regimens with standard-dose cyclosporine or low-dose sirolimus
Only the authors can say what is right here.
Judge's note: Table 2 (p8 image), allograft survival, low-dose cyclosporine vs tacrolimus: 94.3 vs 96.4 (P=0.18) and 93.1 vs 94.2 (P=0.56). The Discussion conclusion on p13 restricts the allograft-survival advantage to "regimens with standard-dose cyclosporine or low-dose sirolimus". The abstract states the claim more broadly than the body. It is hedged with "may be", so I rate it as wording (S3).
Second check: another model agreed
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Wording Table 2 footnote † ("P values were calculated with the use of the Kruskal–Wallis test for the overall group comparison") covers the whole overall P column. That column includes Kaplan–Meier end points and delayed graft function, but the Methods say "group differences were assessed by the log-rank test" for time-to-event end points.
- p. 8 Table 2 footnote †
P values were calculated with the use of the Kruskal–Wallis test for the overall group comparison.
- p. 4 Statistical Analysis
group differences were assessed by the log-rank test
Only the authors can say what is right here.
Judge's note: P4 Methods give Kruskal–Wallis for GFR and log-rank for KM end points. The Table 3 footnote ¶ (p13) uses log-rank for overall KM comparisons. Table 2 footnote † (p8) is not limited to the GFR rows. Which test produced each overall P value in Table 2 needs clarifying.
Second check: another model agreed
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Wording Table 1 type of donor, low-dose tacrolimus: 62.8 + 31.7 + 5.2 = 99.7%; low-dose cyclosporine: 64.2 + 26.8 + 8.8 = 99.8%. Both are beyond rounding of three items, and no missing-data row is shown.
- p. 6 Table 1, Type of donor (%), low-dose tacrolimus column
Deceased 62.8 / Living related 31.7 / Living unrelated 5.2
Judge's note: Read from the p6 image. Three values each rounded to 0.1 can sum to between 99.85 and 100.15, so both columns fall outside that range. Back-calculation gives 252 + 127 + 21 = 400 of 401 for tacrolimus and 256 + 107 + 35 = 398 of 399 for low-dose cyclosporine. This suggests one patient with missing donor type, but unlike the ESRD cause rows the table has no missing-data row here.
Second check: another model agreed
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Wording P9: "significant between-group difference in the Kaplan–Meier estimates for new-onset diabetes ... (P=0.02 for all comparisons)". Table 3 gives this as a single overall log-rank P (P=0.02), not a P value for every comparison.
- p. 9
(P = 0.02 for all comparisons), with the highest rate
Judge's note: The p13 image of Table 3 shows "New-onset diabetes after transplantation (P=0.02)", and footnote ¶ says overall group comparisons used log-rank. "For all comparisons" misdescribes a single overall test.
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Typo Affiliation gives the Prague institute as "Institutu Klinické a Experimentální Medicíny" (inflected form "Institutu" rather than the nominative name).
- p. 1 Affiliations
Institutu Klinické a Experimen-tální Medicíny
- p. 1 Affiliations, S.V.
Institutu Klinické a Experimen-
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the institute's official name is "Institut klinické a experimentální medicíny" (IKEM). The crop of page 1 shows "Institutu Klinické a Experimen-tální Medicíny, Prague, Czech Republic (S.V.)". "Institutu" is a Czech genitive/dative form and does not fit an affiliation given in the nominative. This is cosmetic.
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Typo Table 1, age, standard-dose cyclosporine: "45.9±13. 8" has a stray space inside the SD (should be 13.8).
- p. 6 Table 1, Age row, standard-dose cyclosporine
45.9±13. 8
Judge's note: The crop of the p6 image shows the space printed between "13." and "8".
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Typo Table 1 footnote ‡: "cerebovascular accident as the cause of death" should read "cerebrovascular".
- p. 6 Table 1 footnote ‡
cerebovascular accident as the cause
Judge's note: Visible in the p6 image crop.
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Typo Figure 3 legend: "The analysis of data for patients who died with a functioning allograft were censored". Singular "analysis" takes plural "were"; it is the data, not the analysis, that were censored.
- p. 9 Figure 3 legend
The analysis of data for patients who died with a functioning allograft were censored.
Judge's note: Seen on the p9 image. The meaning is clear; this is grammar only.
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Typo Appendix, Turkey: "O. Oymak, U Erken, B. Erbay" has no period after the initial "U".
- p. 14 Appendix, Turkey
O. Oymak, U Erken, B. Erbay
Judge's note: Seen in the p14 crop. Every other initial in the list has a period.
Second check: none (judge only)