Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy (NCT01120028), a randomized phase 2, phase 3 study. The primary outcome is Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy.

2. Clinical Question

3. Trial Design

The registry describes a randomized, open-label, multicentre factorial study, with phase listed as Phase 2 and Phase 3. Its official title identifies comparisons of CAMPATH-1H versus basiliximab induction treatment and sirolimus versus tacrolimus maintenance treatment. The study is completed. The registry lists a start of 2010-09 and primary completion of 2014-02.

The four listed treatment combinations pair alemtuzumab or basiliximab induction with sirolimus or tacrolimus maintenance. The primary endpoint concerns Period 1: alemtuzumab/tacrolimus compared with basiliximab/tacrolimus. Each of those groups has 426 participants in the posted primary outcome. For Period 2, the arm descriptions place maintenance allocation at 6 months post-transplantation; the posted maintenance outcome comparisons have 197 participants in each group.

Open-label means masking is listed as none. Random allocation can reduce systematic differences between comparison groups at baseline, but lack of masking can affect behavior, clinical decisions, outcome assessment, or reporting, depending on the outcome and study procedures. Biopsy-proven rejection is a defined clinical event, but the registry record does not describe the biopsy assessment procedures or whether outcome assessment was blinded.

The registry lists University of Oxford as sponsor and kidney transplantation as the condition. It does not report the original sample-size justification, detailed eligibility criteria, allocation procedures, or a full protocol description. Those details should not be inferred from the factorial label or from the number enrolled.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 852 participants were randomized for a comparison of Alemtuzumab (426) and Basiliximab (426) based induction therapies. After 6-months, 394 of those participants were re-randomized to either Sirolimus (197) or Tacrolimus (197) based maintenance therapies.

Period 1: Alemtuzumab or Basiliximab

Reasons for not completing this period:

Period 2: Tacrolimus or Sirolimus

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab). Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy, measured over 6 months post-transplantation.

The primary endpoint counts participants with biopsy-proven acute rejection at 6 months post-transplantation. The registry describes the endpoint as the occurrence of biopsy-proven acute rejection events at 6 months after transplantation during Period 1, when participants were randomized to induction therapy while receiving tacrolimus. In the posted results, 31 of 426 participants in the alemtuzumab/tacrolimus group and 68 of 426 in the basiliximab/tacrolimus group had the endpoint.

A binary participant-count endpoint records whether a participant had at least one qualifying event during the specified period; it does not, by itself, describe the number of repeated events, their timing, or their severity. The registry’s endpoint is therefore useful for comparing how many participants experienced biopsy-proven rejection, but it does not provide a complete account of all aspects of rejection or graft health.

Biopsy confirmation gives the endpoint a specified diagnostic basis. General statistical context: a clear endpoint definition helps make a comparison interpretable, while the quality and consistency of its ascertainment still matter. The registry record does not report detailed rules for biopsy, event adjudication, or handling of participants without an observed biopsy result.

7. Results Posted in the Registry

• Period 1: Basiliximab/Tacrolimus: 16.0% (68/426) versus 7.3% (31/426) on control; risk difference 8.7 percentage points (95% CI 4.4 to 12.9), risk ratio 2.19 (1.47–3.28); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Period 1: Basiliximab/Tacrolimus: 3.1% (13/426) versus 3.8% (16/426) on control; risk difference -0.7 percentage points (95% CI -3.1 to 1.7), risk ratio 0.81 (0.40–1.67); unadjusted two-proportion z-test p = 0.571.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Period 1: Basiliximab/Tacrolimus and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Period 2: Tacrolimus: 2.0% (4/197) versus 4.1% (8/197) on control; risk difference -2.0 percentage points (95% CI -5.4 to 1.4), risk ratio 0.50 (0.15–1.63); unadjusted two-proportion z-test p = 0.241.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Period 2: Tacrolimus and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Period 1: Basiliximab/Tacrolimus: 31.9% (136/426) versus 31.7% (135/426) on control; risk difference 0.2 percentage points (95% CI -6.0 to 6.5), risk ratio 1.01 (0.83–1.23); unadjusted two-proportion z-test p = 0.941.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Period 1: Basiliximab/Tacrolimus and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering graft failure, serious infection, cancer, and major vascular events, with outcomes assessed in the induction and maintenance periods. Numerical comparisons are available in the posted results for graft failure after induction, graft failure after maintenance, and serious infection after induction. For cancer and major vascular events, numerical results are not reported in the registry record. The record lists serious infection after maintenance among its secondary outcomes, but a numerical result for that outcome is not included in the posted comparisons.

The available secondary comparisons do not show the same clear statistical pattern as the primary rejection result: their reported uncertainty is broad, and their unadjusted p-values do not indicate a clear difference. This is a general reading of the available estimates, not evidence that the groups are equivalent. In particular, small event counts can leave substantial uncertainty, and the estimates do not rule out potentially relevant differences.

These outcomes address different aspects of transplant follow-up and should not be treated as substitutes for the primary endpoint. The primary result concerns biopsy-proven acute rejection at 6 months post-transplantation; graft failure and serious infection are distinct outcomes. The secondary findings therefore add context but do not directly confirm or negate the primary comparison.

Unadjusted secondary results carry less weight because multiple outcomes and comparisons create more opportunities for chance findings. The registry record does not report a multiplicity adjustment or a prespecified hierarchy that would establish which secondary tests should be considered confirmatory. General statistical context: when many hypotheses are examined, an isolated small p-value is less compelling unless the testing strategy is accounted for. Conversely, non-significant results do not establish no effect, particularly when precision is limited.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)
• Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)
• Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)
• Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)
• Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)
• Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)

9. Statistical Interpretation

10. Statistical Methods Explained

Statistical interpretation depends on the outcome scale and the analysis method. The posted primary outcome is a binary participant count: a participant either appears among those with biopsy-proven acute rejection during the specified period or does not. The recalculated comparison uses the two posted counts and group sizes without adjustment. Its risk difference compares the participant-level event proportions in the basiliximab/tacrolimus and alemtuzumab/tacrolimus groups, in that order.

What does the risk difference describe?

A risk difference is an absolute contrast between two event proportions. A value above zero in the stated comparison direction means the event proportion was higher in the basiliximab/tacrolimus group in these posted data. The recalculated estimate is 0.087. This scale is often straightforward to interpret because it expresses the size of the observed contrast in proportion units. It is not an adjusted estimate, and it does not account for covariates, differences in follow-up, or other design features beyond the two posted counts and group sizes.

The posted recalculation also gives a risk ratio of 2.194, with a 95% confidence interval from 1.466 to 3.282, and an odds ratio of 2.42, with a 95% confidence interval from 1.546 to 3.789. These are relative measures and use different mathematical scales from the risk difference. A risk ratio compares event proportions; an odds ratio compares event odds. Their numerical values should not be read as if they were the same quantity. The registry’s sponsor-reported analysis is a time-to-event analysis, not either of these unadjusted binary comparisons.

What does the p-value tell the reader?

The unadjusted p-value for the recalculated primary comparison is <0.001. In general, a p-value describes how incompatible the observed data are with a specified statistical model in which there is no difference, assuming that model and its conditions apply. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of the contrast. A small p-value also does not correct for bias, incomplete data, or multiple testing.

The sponsor’s reported primary analysis uses the log-rank method and gives a hazard ratio of 0.42, a 95% confidence interval from 0.28 to 0.64, and p < 0.001. In general, a log-rank analysis compares event-time patterns between groups, taking account of when events occur and the available follow-up information. A hazard ratio summarizes a relative event rate over time under the analysis framework; it is not an absolute difference in participant proportions. The registry record does not provide details of the model assumptions, censoring rules, or any covariate adjustment for this analysis.

Why are the confidence intervals important?

A confidence interval displays the range of estimates compatible with the observed data under a specified method and its assumptions. The primary recalculated risk-difference interval is 0.044 to 0.130. Its endpoints convey uncertainty around the point estimate, rather than an exact boundary for the true effect. General statistical context: a confidence interval’s width reflects both the amount of information and variability in the data, as well as the method used to calculate it. An interval should be interpreted on the scale of its estimate.

In a randomized study, random allocation supports comparison of groups, but does not guarantee identical groups or prevent all bias. Open-label conduct is relevant because treatment awareness can influence care and outcome ascertainment. Biopsy-proven rejection has a specified diagnostic basis, but the registry does not report whether biopsies were assessed under blinded procedures. These design and reporting considerations are separate from the arithmetic of the recalculated risk difference.

The registry lists a factorial model, which means the design addresses more than one treatment allocation dimension: induction and maintenance. The primary comparison presented in the posted primary outcome holds maintenance at tacrolimus and compares induction assignments. This outcome therefore does not, on its own, estimate the maintenance-treatment contrast or establish whether the effects of induction and maintenance interact. The registry record does not report the factorial analysis plan or interaction results.

Statistical significance is not the same as clinical importance. The primary endpoint measures biopsy-proven acute rejection, while the broader study description refers to preserving renal function and transplant survival. The relationship between this endpoint and those broader aims cannot be quantified from the primary counts alone. The record does not report a threshold for a clinically important difference or a formal sample-size justification.

11. Confidence Intervals and Precision

The recalculated primary risk difference is 0.087, with a 95% confidence interval from 0.044 to 0.130. The estimate compares the basiliximab/tacrolimus group with the alemtuzumab/tacrolimus group. The interval does not include zero, so the posted unadjusted data are compatible with a positive difference on this scale under the calculation method. The interval’s width still matters: it describes a range of values consistent with the data rather than a single exact effect.

General statistical context: a confidence interval is a method-based measure of uncertainty. Under repeated use of the same procedure and its assumptions, intervals constructed in this way would cover the underlying parameter at the stated rate. For a particular study, the interval is not a probability statement that the true value lies within these specific endpoints. Interpretation depends on the estimand, the analysis assumptions, and the quality of the underlying data.

The recalculated relative measures also have intervals: the risk ratio is 2.194, with a 95% confidence interval from 1.466 to 3.282, and the odds ratio is 2.42, with a 95% confidence interval from 1.546 to 3.789. These intervals use relative scales and should not be substituted for the risk-difference interval. The sponsor’s time-to-event estimate has a separate 95% confidence interval from 0.28 to 0.64 around the reported hazard ratio of 0.42; it describes a different analysis quantity.

Precision is not the same as freedom from bias. A narrow interval would not resolve problems in endpoint measurement, missing data, or analysis choices; a wider interval would indicate greater statistical uncertainty. The registry record does not report the missing-data procedures, analysis population, or enough time-to-event details to assess all assumptions behind the sponsor’s interval.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations show participants per arm for the binary outcomes, rather than total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used for planning is a stated fraction of the observed effect. For time-to-event outcomes, the general convention in the illustrations is total number of events, but the primary endpoint is binary and its figures are participants per arm.

The 80% power column gives the illustrated number of participants per arm for a design that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and assumptions were correct. The 90% power column uses a higher target probability of detecting that same specified effect. These are design-planning quantities, not estimates of the probability that the completed study found a true effect.

The rows that plan for 100%, 75%, or 50% of the observed effect illustrate how the assumed effect size changes the required sample size. A smaller effect is harder to detect and therefore needs more participants under the same planning assumptions. The values are planning illustrations calculated from the observed effect, not the trial’s original design calculation. The original design assumptions and sample-size justification are not reported in the registry record. This is not observed power.

Planning figures should not be interpreted as a verdict on whether the study was adequate for every outcome. The primary outcome, secondary outcomes, and time-to-event analyses may have different event frequencies and analysis requirements. The registry record does not report the trial’s original target sample size or any planned adjustment for the factorial design, loss to follow-up, or multiple comparisons.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.073; treatment proportion p₁ = 0.160; average p̄ = 0.116.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4532 = 0.8883.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4490 = 0.3779.
4. n = (0.8883 + 0.3779)² / (0.0869)² = 212.5, rounded up to 213 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0727699530516432                          # control proportion
p1 <- 0.15962441314554                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1120028)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 213 (80% power), 285 (90% power)
 75% of observed effect: n per arm = 348 (80% power), 465 (90% power)
 50% of observed effect: n per arm = 711 (80% power), 952 (90% power)
power.prop.test: 212.5 
Simulated power at n = 213 per arm: 0.810 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports a sponsor analysis of the primary outcome using the log-rank method. It gives a hazard ratio of 0.42, with a 95% confidence interval from 0.28 to 0.64 and p < 0.001. The posted re-calculation uses the group counts and sizes to produce an unadjusted risk difference of 0.087, with a 95% confidence interval from 0.044 to 0.130 and p <0.001.

These results are not duplicate estimates of the same quantity. The sponsor’s reported analysis is time-to-event based, while the recalculation compares binary participant counts over the endpoint period. The registry record does not report the additional detail needed to reconstruct the sponsor’s method, including event-time handling and model specifications. Differences in the estimates’ scale and method mean that their numerical values should not be compared directly.

The registry does not flag a discrepancy between its posted result and the recalculation. The recalculation is an unadjusted analysis from the posted summary counts; it does not replace the sponsor’s analysis or establish that one method is preferable. Both should be read with attention to their estimands and assumptions, and neither alone resolves questions about missing data, outcome assessment, or multiplicity.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint alongside multiple secondary outcomes and reports multiple analyses. It does not report whether the statistical plan adjusted for testing multiple endpoints, comparisons, or time points. Nor does it report a prespecified hierarchy or indicate which secondary analyses were intended to be confirmatory. Without that information, the posted secondary p-values should be treated as exploratory or supportive rather than as a family of independent confirmatory tests.

General statistical context: when researchers test many hypotheses, the chance of obtaining at least one apparently notable result by chance can increase. Adjustment methods or a prespecified testing hierarchy can address this issue, but the registry record does not identify such a method. This missing information does not change the reported values; it affects how confidently multiple results can be interpreted together.

The registry record also does not report how missing outcome data were handled, how participants who did not complete follow-up were treated, or which analysis population was used. It is therefore not possible from the record to determine whether the primary comparison was based on all randomized participants, participants with observed endpoint data, or another analysis set. The record does not give reasons for missingness or describe imputation or sensitivity analyses.

The sponsor’s primary result is described as a log-rank analysis, but detailed censoring rules, model assumptions, and any covariate adjustments are not reported in the registry record. For the recalculated binary comparison, only the posted summary counts and group sizes are used. The recalculation cannot recover information about participants whose outcome status is absent or determine how missing follow-up might affect the comparison.

The registry does not report interim analyses or stopping rules. It also does not report the original statistical analysis plan or the protocol’s sample-size justification. These omissions limit assessment of whether the analyses followed a prespecified plan and how the number of tests was considered. They should be treated as reporting gaps, not as evidence that a particular procedure was or was not used.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: infections and infestations (49.2%), surgical and medical procedures (44.6%), injury, poisoning and procedural complications (36.2%), investigations (32.9%), immune system disorders (16.8%).

The serious adverse event fields list 341 affected participants among 426 at risk in Period 1: alemtuzumab/tacrolimus, and 354 among 426 at risk in Period 1: basiliximab/tacrolimus. For Period 2, the record lists 140 affected among 197 at risk in the sirolimus group and 134 among 197 at risk in the tacrolimus group. These are registry serious-adverse-event counts, distinct from the primary endpoint and from the secondary serious-infection outcome.

The registry also lists deaths of 11 and 6 in the two Period 1 groups, and 11 and 9 in the Period 2 sirolimus and tacrolimus groups, respectively. The record does not provide a comparative statistical analysis for these safety counts in the registry record described. Counts alone do not establish whether events were caused by a treatment, and the groups represent different treatment periods and allocations.

Serious adverse event terms listed most often include infections and infestations (49.2%), surgical and medical procedures (44.6%), injury, poisoning and procedural complications (36.2%), and investigations (32.9%). These categories describe the registry’s reported terms; they do not by themselves quantify treatment-related risk or indicate that categories are mutually exclusive. Safety interpretation also depends on event definitions, follow-up, and attribution details, which are not reported in the registry record.

17. What the Result Does, and Does Not, Mean

The primary result describes a difference in the posted number of participants with biopsy-proven acute rejection by 6 months post-transplantation. The alemtuzumab/tacrolimus group had 31 events among 426 participants, compared with 68 among 426 in the basiliximab/tacrolimus group. The recalculated risk difference and its confidence interval indicate a higher observed event proportion in the basiliximab group on the stated comparison scale.

This result does not by itself establish what would happen for an individual transplant recipient. It is an estimate from a randomized, open-label study and remains subject to uncertainty and limitations in outcome ascertainment, missing-data reporting, and analysis details. A confidence interval characterizes sampling uncertainty under its method; it does not capture every possible source of bias.

The primary outcome is not the same as long-term kidney function, graft survival, or overall transplant success. The study’s broader description concerns preserving renal function and transplant survival, but the primary endpoint is biopsy-proven acute rejection during Period 1. The secondary graft-failure outcomes and other safety outcomes address different questions and have their own uncertainty.

The comparison also does not represent every combination in the factorial design. The primary endpoint compares induction assignments while both groups are listed with tacrolimus maintenance. It does not estimate the sirolimus-versus-tacrolimus maintenance contrast or establish whether induction and maintenance effects depend on one another. The registry record does not report the factorial interaction analysis.

Statistical evidence is not a treatment recommendation. The result should be understood as an estimate of the recorded group contrast, interpreted alongside its precision, endpoint definition, study conduct, secondary outcomes, and the limitations of the registry reporting. It does not prove that one treatment is universally better, or that the observed difference will recur unchanged in another population or setting.

18. Why This Trial Matters Statistically

This study illustrates why an endpoint and its analysis scale need to be read together. A participant count answers how many people experienced a defined event, while a time-to-event analysis uses information about when events occurred and follow-up. The registry reports both an unadjusted recalculation based on counts and a sponsor log-rank result. Their numerical estimates answer related but non-identical statistical questions.

The factorial design also highlights the importance of distinguishing treatment dimensions. Induction treatment and maintenance treatment are different allocations, and the primary comparison focuses on induction among participants assigned tacrolimus maintenance. A headline result from that comparison should not be generalized automatically to the maintenance comparison or to all four combinations.

Precision matters alongside statistical significance. The primary risk-difference interval helps readers judge the range of estimates compatible with the posted data, while the secondary outcomes show why a non-significant result should not be read as proof of equivalence. The planning illustrations further show how sample-size requirements depend on the effect chosen for detection; those illustrations are not the trial’s original design justification.

Finally, the registry’s reporting gaps matter for reproducibility and interpretation. The multiplicity strategy, missing-data handling, analysis population, and original sample-size rationale are not reported in the registry record. Recognizing these limits is part of sound statistical reading: the posted result can be described precisely without claiming more than the record establishes.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The study is listed as open-label, with no masking. Awareness of allocation can influence care decisions or outcome assessment. The primary endpoint requires biopsy confirmation, but the registry record does not describe biopsy criteria, assessment procedures, or whether adjudication was blinded. These details affect how consistently the outcome may have been measured.

The primary comparison covers the two tacrolimus-maintenance groups in Period 1, rather than all four treatment combinations. The registry record does not report results of an interaction analysis or explain how the factorial design was incorporated into the analysis. It also does not provide enough detail to assess whether the result generalizes across the separate maintenance allocations.

The registry record does not report missing-data procedures, reasons for missing outcomes, or the analysis population. The sponsor-reported time-to-event analysis is identified as log-rank, but its censoring rules and other model details are not reported. The recalculated risk difference is unadjusted and uses the posted counts and group sizes; it cannot address these gaps.

Multiple outcomes and analyses are listed, but the record does not describe a multiplicity strategy or a hierarchy of hypotheses. Numerical secondary results are not available for every listed secondary outcome in the results described. The original sample-size justification, interim analyses, and detailed protocol are also not reported in the registry record. These limits restrict assessment of the prespecification and completeness of the analysis, without changing the values that are posted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy — NCT01120028.
• Registry record last updated 2020-04-02; status last verified 2020-03.
• Results first posted 2019-10-01.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

The registry describes a completed, randomized, open-label, multicentre factorial study of induction and maintenance treatments in kidney transplant recipients. Enrollment is listed as 852, with University of Oxford as sponsor. The primary endpoint is the number of participants with biopsy-proven acute rejection at 6 months post-transplantation.

In the primary Period 1 comparison, 31 of 426 participants in the alemtuzumab/tacrolimus group and 68 of 426 in the basiliximab/tacrolimus group had the endpoint. The recalculated unadjusted risk difference is 0.087, with a 95% confidence interval from 0.044 to 0.130 and p <0.001. The sponsor reports a log-rank hazard ratio of 0.42, with a 95% confidence interval from 0.28 to 0.64 and p < 0.001.

The reported estimates describe different statistical measures. Interpretation is limited by open-label conduct and by registry entries not reported on multiplicity, missing data, analysis populations, and the original sample-size justification.