This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients. (NCT00545402), a randomized phase 4 study. The primary outcome is Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00545402 |
| Phase | Phase 4 |
| Condition | Liver Transplantation |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 180 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
De novo liver transplant patients. The primary endpoint was analyzed in the intention-to-treat population; its two reported arms each included 87 participants.
Intervention
Mycophenolate mofetil (MMF) starting at 3 g/day, with dose adjusted according to exposure, alongside tacrolimus and corticosteroids. The registry describes this as a corticosteroid-sparing regimen.
Comparator
Fixed-dose MMF 2 g/day with tacrolimus and corticosteroids. The registry summary describes corticosteroids being reduced over 6 months and discontinued after 6 months in this regimen.
Primary question
How did the percentage of participants with treated biopsy-proven acute rejection, classified according to Banff criteria, compare between the two regimens through 12 months post-transplant and the listed follow-up periods?
The question concerns the contrast between two combinations of immunosuppressive treatments, not MMF in isolation. The regimens differ in MMF dosing strategy and in the corticosteroid approach described in the registry. Tacrolimus is included in both arms.
The primary endpoint counts participants with treated biopsy-proven acute rejection. It is therefore a clinical event defined with a biopsy-based classification and treatment, rather than a laboratory measurement alone. The registry gives a follow-up schedule extending through Month 12 post-transplant, 28 days after Month 12 or the last study-treatment dose, and later follow-up after the last dose.
The main statistical comparison is the observed difference between the randomized groups. It does not by itself isolate the effect of one drug or one component of the regimen, because several treatment features form each assigned combination. The registry record does not report a separate component-specific comparison.
3. Trial Design
This was a Phase 4, randomized, open-label, parallel-group study sponsored by Hoffmann-La Roche. The registry lists liver transplantation as the condition and describes the participants as de novo liver transplant patients. Enrollment was 180. The study status is completed; the recorded start was 2007-11 and primary completion was 2011-07.
Participants were assigned to one of two CellCept-containing combination regimens. In the adjusted-dose group, MMF began at 3 g/day and was adjusted according to exposure, with tacrolimus and a corticosteroid-sparing regimen. In the fixed-dose group, MMF was 2 g/day with tacrolimus and corticosteroids. The brief summary describes corticosteroids in the fixed-dose regimen as being reduced over 6 months and then discontinued after 6 months. More detailed treatment information is not reported in the registry record.
The study had no masking, so participants and study personnel were not blinded according to the registry. Open-label assignment can matter when outcomes involve clinical decisions, assessment, or treatment. The primary endpoint required treated rejection with biopsy evidence, but the registry record does not report whether endpoint assessment was blinded or centrally adjudicated.
The primary outcome is reported for the intention-to-treat population. Each arm has 87 participants in that endpoint record. For the secondary endpoint records, each arm has 90 participants. The reasons for these different endpoint-specific sample sizes are not reported in the registry record. The planned sample-size justification and the trial's statistical analysis plan are not reported in the registry record.
The brief summary gives an anticipated study-treatment duration of 3–12 months and a target sample-size range of 100–500 individuals. Those are descriptions of the anticipated study and target range, not the number enrolled in the completed trial.
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.
Overall Study
| Stage | Adjusted Mycophenolate Mofetil (MMF)+Tacrolimus+Corticosteroid | Fixed-Dose MMF + Tacrolimus + Corticosteroid (CS) |
|---|---|---|
| STARTED | 90 | 90 |
| COMPLETED | 56 | 61 |
| NOT COMPLETED | 34 | 29 |
Reasons for not completing this period:
| Reason | Adjusted Mycophenolate Mofetil (MMF)+Tacrolimus+Corticosteroid | Fixed-Dose MMF + Tacrolimus + Corticosteroid (CS) |
|---|---|---|
| Discontinuation of treatment | 17 | 9 |
| Use of unauthorized immunosuppressant | 8 | 7 |
| Death | 5 | 7 |
| Graft loss | 2 | 4 |
| Withdrawal by Subject | 0 | 1 |
| Protocol Violation | 1 | 0 |
| Reason not specified | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: ITT population
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: Intent to treat (ITT) population includes all randomized participants who received at least 1 dose of MMF.
| Characteristic | Unit | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS | Total |
|---|---|---|---|---|
| Participants analysed | 90 | 90 | 180 | |
| Age, Continuous | years | 53.4 (SD 8.5) | 55.1 (SD 8.3) | 54.2 (SD 8.4) |
| Sex: Female, Male: Female | Participants | 16 | 19 | 35 |
| Sex: Female, Male: Male | Participants | 74 | 71 | 145 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR) According to Banff Criteria up to 12 Months Post-Transplant, measured over Days 0, 5, and 14, Month 1, 2, 3, 6, 9, and 12, 28 days after Month 12 or last dose of study treatment, and 6 and 12 months after the last dose of study treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with treated biopsy-proven acute rejection according to Banff criteria. The registry defines acute rejection using histopathological features: portal inflammation, bile duct inflammation, and venous endothelial inflammation. At least two of these three features were required for a histopathological diagnosis of acute rejection. Each feature was graded, and the combined scores formed the Rejection Activity Index (RAI).
The registry describes RAI values of 0, 1, or 2 as no evidence of rejection; 3 as borderline acute rejection; 4 or 5 as mild acute rejection; 6 or 7 as moderate acute rejection; and 8 or 9 as severe acute rejection. The endpoint is specifically treated biopsy-proven rejection, so it is not simply the percentage with any abnormal biopsy finding. It reflects the registry's defined histological criteria together with treatment of the event.
This type of endpoint is used to quantify an important post-transplant event in a way that is tied to tissue assessment and a stated grading framework. The percentage expresses how common the endpoint was among participants in each group. It does not describe the timing or duration of individual rejection episodes. The registry gives repeated assessment times from Days 0, 5, and 14 through Month 12, with additional listed follow-up after Month 12 or the last study-treatment dose.
The record does not report further operational details about how treated events were counted if a participant experienced more than one episode.
7. Results Posted in the Registry
- Fixed-Dose MMF + Tacrolimus + CS: 8.0% (7/87) versus 8.0% (7/87) on control; risk difference 0.0 percentage points (95% CI -8.1 to 8.1), risk ratio 1.00 (0.37–2.73); unadjusted two-proportion z-test p = 1.000.
Risk difference: Fixed-Dose MMF + Tacrolimus + CS
95% CI: -8.1 to 8.1 percentage points
Recalculated from the posted summary statistics
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.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| Percentage of Participants With Graft Loss | Binary Endpoint | Risk difference | +3.3 pts (-2.3 to 9.0) | 527 per arm |
| Overall Survival (OS) at Month 12 - Percentage of Participants With an Event | Binary Endpoint | Risk difference | +2.2 pts (-6.5 to 11.0) | 2,860 per arm |
Percentage of Participants With Graft Loss
- Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
- Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
- Result:
- Fixed-Dose MMF + Tacrolimus + CS: 5.6% (5/90) versus 2.2% (2/90) on control; risk difference 3.3 percentage points (95% CI -2.3 to 9.0), risk ratio 2.50 (0.50–12.55); unadjusted two-proportion z-test p = 0.247.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Fixed-Dose MMF + Tacrolimus + CS and the control. The interval gives the range of effects that remain compatible with the data.
Overall Survival (OS) at Month 12 - Percentage of Participants With an Event
- Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
- Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
- Result:
- Fixed-Dose MMF + Tacrolimus + CS: 11.1% (10/90) versus 8.9% (8/90) on control; risk difference 2.2 percentage points (95% CI -6.5 to 11.0), risk ratio 1.25 (0.52–3.02); unadjusted two-proportion z-test p = 0.619.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Fixed-Dose MMF + Tacrolimus + CS and the control. The interval gives the range of effects that remain compatible with the data.
The registry lists secondary outcomes covering graft loss, graft survival, overall survival, and graft histology. Detailed numerical comparisons are posted for graft loss and an overall-survival event outcome. Across the detailed binary outcomes, the estimates do not form a uniform pattern of clearly separated groups: the point estimates differ in direction and magnitude, and their intervals include zero. This overall pattern does not provide a consistent basis for treating the secondary findings as confirmatory evidence of a treatment difference.
These outcomes address related but distinct aspects of post-transplant follow-up. Graft loss and survival events are not the same endpoint as treated biopsy-proven acute rejection, and they need not move in parallel. The primary endpoint result therefore cannot be substituted for an interpretation of graft or survival outcomes, nor can the secondary outcomes redefine the primary result.
The registry reports Log Rank analyses for the detailed graft-loss and overall-survival outcomes. The method is generally suited to time-to-event comparisons, but the posted endpoint summaries also give percentages and simple risk-difference calculations. The record does not report detailed event-time information or explain how the reported analyses relate to one another. The listed Log Rank tests and unadjusted binary comparisons should not be treated as interchangeable.
Unadjusted secondary results carry less weight because testing multiple outcomes increases the chance of observing an apparently notable result by chance. In general, multiplicity procedures or a prespecified testing hierarchy can address that issue. Neither a multiplicity adjustment nor a hierarchy of secondary hypotheses is reported in the registry record. The secondary results are therefore best viewed as supportive or exploratory descriptions, not as stand-alone proof of a treatment effect.
The pattern across outcomes should be read with the endpoint-specific sample sizes and uncertainty in mind. The registry does not report a comprehensive analysis plan explaining how missing outcome data, competing events, or multiple outcomes were handled.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Percentage of Participants With Graft Loss
- Graft Survival
- Overall Survival (OS) at Month 12 - Percentage of Participants With an Event
- Overall Survival at Month 12
- Percentage of Participants by Graft Histology at 12 Months Post-Transplant - Central Review
9. Statistical Interpretation
In the primary outcome record, treated biopsy-proven acute rejection was reported for 8.0% of participants in the adjusted-MMF group and 8.2% in the fixed-dose group. The record lists 7 events in each arm, with 87 participants in each arm. The risk-difference estimate for fixed-dose versus adjusted-dose MMF is 0.0, and the unadjusted p-value is 1.0.
The reported interval for the risk difference extends on both sides of zero. In general, an interval that includes zero is compatible with no between-group difference as well as with differences in either direction at the interval's level of precision. It does not establish that the regimens are equivalent. No equivalence or non-inferiority margin is reported in the registry record, and the study's stated design objective is not reported as an equivalence analysis.
The observed primary outcome percentages are close, and the event counts are equal. Those features describe the posted results, but they do not prove that the regimens have the same underlying event risk. The interval is broad enough to include nonzero differences; its limits are given in the comparison record. The statistical evidence should therefore be read as an estimate with uncertainty, rather than as proof that a difference is absent.
The displayed endpoint percentages and the reported risk-difference estimate need not appear identical in their rounded form. The registry presents the percentages to one decimal place and the effect estimate separately. The report does not identify a discrepancy between the posted result and its comparison statistic.
The two regimens change more than one feature: MMF dosing strategy differs, and the corticosteroid approach is described as corticosteroid-sparing in one regimen and as a taper followed by discontinuation in the other. Consequently, the comparison addresses the assigned treatment combinations. It cannot identify which component accounts for any difference or similarity in outcomes.
The record also reports secondary outcomes, including graft loss and overall survival outcomes. Their analyses do not alter the primary endpoint result, and their estimates should be interpreted with their own uncertainty and with caution about multiple comparisons. The registry does not report a multiplicity adjustment or a hierarchy assigning confirmatory status to the secondary outcomes.
10. Statistical Methods Explained
The primary comparison is a randomized, two-arm comparison of percentages. Randomization is intended, in general, to make assigned groups comparable on average at baseline; it does not guarantee that every prognostic feature is balanced in a particular trial. The registry record does not report baseline characteristics or further details of the randomization procedure.
What does the risk difference describe?
In general, a risk difference is the event proportion in one group minus the event proportion in the other group. It is an absolute contrast: zero represents equal observed proportions, while positive and negative values indicate opposite directions according to the stated group ordering. Here, the comparison is fixed-dose MMF versus adjusted-dose MMF. The posted estimate is 0.0. The interpretation should retain that group ordering rather than treating the estimate as an unsigned measure of separation.
The estimate is based on the primary endpoint's binary outcome: a participant either met the registry definition of treated biopsy-proven acute rejection or did not. The record lists 7 events in each group. The comparison is unadjusted, meaning the posted estimate is not described as adjusted for other measured variables. The registry does not report an adjusted primary analysis.
What does the p-value say?
In general, a p-value describes how compatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The primary comparison lists an unadjusted p-value of 1.0. This is consistent with the equal event counts in the two reported groups, but it does not demonstrate equivalence or rule out effects that the study could not estimate precisely.
The record does not name a statistical test for the primary binary comparison. It does report Log Rank analyses for the secondary graft-loss and overall-survival outcomes. A log-rank test is generally used to compare time-to-event patterns while accounting for the timing of events and censoring. The registry record does not provide the event-time data, censoring details, or further specifications of those analyses.
How should endpoint sample sizes be read?
The primary outcome uses 87 participants per arm, while each of the two detailed secondary outcome records uses 90 participants per arm. These are the endpoint-specific sample sizes stated in the registry. They should not be assumed to represent the same analysis population or the same availability of outcome data. Reasons for the differing counts, missing-data handling, and participant flow for each endpoint are not reported in the registry record.
The primary outcome is identified as using the intention-to-treat population. In general, intention-to-treat analysis preserves participants in the groups to which they were randomized, regardless of treatment changes, according to the analysis definition. The registry does not describe how the intention-to-treat label was operationalized for this endpoint or how missing outcome status was handled.
What do planning illustrations mean?
The sample-size illustrations use an observed effect as their starting point and show hypothetical participants per arm for stated power levels and fractions of that observed effect. They are not the trial's observed power, and they are not evidence that the trial was designed around those estimates. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. For time-to-event illustrations, the stated quantity is total events; other illustrations give participants per arm.
Such calculations are planning illustrations only. In general, using an observed effect as the planning target can be unstable, particularly when event counts are small, and hypothetical sample sizes depend on the chosen effect and assumptions. The trial's own sample-size rationale, target effect, and formal power calculation are not reported in the registry record. No new power calculation is implied by the posted results.
The registry lists no discrepancy between the sponsor's analysis and the posted primary comparison. The primary result should therefore be read as reported in the registry, rather than replaced by a separate recalculation. The registry's other analysis choices, including any interim monitoring or adjustment procedures, are not reported in the registry record.
11. Confidence Intervals and Precision
Precision concerns how tightly the estimated effect is constrained by the data. The primary risk-difference interval spans values on both sides of zero. That means the observed estimate is compatible with no difference, but the interval also allows differences in either direction. The interval is the relevant complement to the point estimate: the point estimate alone does not convey how uncertain the comparison is.
The registry reports the interval limits for the primary comparison as -0.081 and 0.081. These limits are wider than the point estimate and include zero. The registry record does not state the confidence level alongside this comparison, so a confidence percentage should not be assumed from the posted information. The interval should not be interpreted as a range containing every plausible true effect with certainty.
The primary endpoint has 7 events in each arm and 87 participants per arm. In general, when a binary outcome has few events, the effect estimate may be imprecise even when the observed proportions look similar. The actual precision is represented by the interval, not by the visual closeness of the rounded percentages.
For the secondary binary outcomes, the risk-difference intervals also extend across zero. This indicates substantial uncertainty in those comparisons as well. Their point estimates should be read alongside their intervals and not as definitive evidence for a group difference. The registry's displayed intervals are not narrow enough to exclude effects in either direction for these outcomes.
Precision is distinct from statistical significance. A non-small p-value does not show that an effect is exactly zero, and a confidence interval crossing zero does not establish equivalence. Equivalence requires a prespecified margin and an analysis designed to assess whether the interval lies within that margin; such a margin is not reported in the registry record.
These intervals also do not address every uncertainty. They do not resolve possible limitations in outcome ascertainment, missing data, adherence, or generalizability. The registry record does not provide enough information to assess those issues in detail.
12. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary outcome and lists several secondary outcomes. It reports two detailed secondary analysis records, including Log Rank analyses for graft loss and an overall-survival outcome. The registry record does not report whether secondary hypotheses were ordered in a formal testing hierarchy or whether p-values were adjusted for multiple comparisons.
Multiplicity matters because evaluating several outcomes can increase the chance that at least one result appears statistically notable even when there is no corresponding underlying effect. In general, a prespecified hierarchy or an adjustment procedure can help control that risk. Without a reported procedure, secondary findings should be interpreted more cautiously than a single prespecified primary comparison. The available information does not establish whether multiplicity was considered elsewhere in the protocol or analysis plan.
The primary endpoint is labeled as analyzed in the intention-to-treat population. This is useful information about the intended analysis population, but the registry record does not explain how participants without an observed endpoint were handled. It also does not report the number or reasons for missing primary outcome assessments, imputation procedures, or sensitivity analyses.
For the primary endpoint, the registry reports 87 participants in each arm. The detailed secondary outcome records each report 90 participants per arm. The reason for the differing endpoint sample sizes is not reported in the registry record. The record also does not provide a participant-flow account that would explain exclusions, unavailable measurements, withdrawals, or other differences between the endpoint-specific counts.
The registry record does not report interim analyses, stopping rules, or procedures for monitoring accumulating outcome data. Their absence from the registry information should not be taken as proof that none occurred; their status is simply not reported in the registry record. The trial's full statistical analysis plan and sample-size justification are likewise not reported in the registry record.
13. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Adjusted MMF + Tacrolimus + CS | 70 | 91 | 76.9% |
| Fixed-Dose MMF + Tacrolimus + CS | 69 | 92 | 75.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Adjusted MMF + Tacrolimus + CS | 91 of 91 |
| Fixed-Dose MMF + Tacrolimus + CS | 91 of 92 |
Most frequent serious adverse event terms
| Event term | Organ system | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|---|
| Renal failure acute | Renal and urinary disorders | 14 of 91 | 5 of 92 |
| Renal failure | Renal and urinary disorders | 6 of 91 | 6 of 92 |
| Biliary anastomosis complication | Injury, poisoning and procedural complications | 5 of 91 | 6 of 92 |
| Hepatitis C | Infections and infestations | 3 of 91 | 7 of 92 |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | 5 of 91 | 4 of 92 |
| Diarrhoea | Gastrointestinal disorders | 6 of 91 | 2 of 92 |
| Multi-organ failure | General disorders | 5 of 91 | 3 of 92 |
| Sepsis | Infections and infestations | 3 of 91 | 4 of 92 |
| Inguinal hernia | Gastrointestinal disorders | 2 of 91 | 4 of 92 |
| Bile duct stenosis | Hepatobiliary disorders | 2 of 91 | 4 of 92 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Adjusted MMF + Tacrolimus + CS | Fixed-Dose MMF + Tacrolimus + CS |
|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 45 of 91 | 44 of 92 |
| Hypertension | Vascular disorders | 31 of 91 | 31 of 92 |
| Diarrhoea | Gastrointestinal disorders | 31 of 91 | 26 of 92 |
| Renal failure | Renal and urinary disorders | 24 of 91 | 23 of 92 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 22 of 91 | 25 of 92 |
| Cholestasis | Hepatobiliary disorders | 24 of 91 | 19 of 92 |
| Renal failure acute | Renal and urinary disorders | 22 of 91 | 16 of 92 |
| Thrombocytopenia | Blood and lymphatic system disorders | 16 of 91 | 13 of 92 |
| Hyperkalaemia | Metabolism and nutrition disorders | 15 of 91 | 14 of 92 |
| Urinary tract infection | Infections and infestations | 13 of 91 | 14 of 92 |
Serious events with the highest arm-level rate: renal failure acute (15.4%), hepatitis c (7.6%), diarrhoea (6.6%), renal failure (6.6%), biliary anastomosis complication (6.5%).
The registry reports serious adverse event information for 91 participants at risk in the adjusted-MMF group and 92 in the fixed-dose group. It records serious adverse events affecting 70 and 69 participants, respectively. It also reports other adverse events affecting 91 participants in the adjusted group and 91 in the fixed-dose group, among 91 and 92 participants at risk. These are registry counts; they are not the primary efficacy outcome.
The registry lists acute renal failure at 15.4%, hepatitis C at 7.6%, diarrhoea at 6.6%, renal failure at 6.6%, biliary anastomosis complication at 6.5%, and multi-organ failure at 5.5% among the leading serious adverse event terms. The record does not specify the arm for each listed percentage in the information, so these figures should not be assigned to a particular regimen.
In general, adverse-event counts describe events recorded during a study and do not by themselves establish that a treatment caused an event. The registry does not report death counts in the adverse-event record. These safety summaries should be interpreted separately from the primary rejection comparison.
14. What the Result Does, and Does Not, Mean
The results describe what was recorded for participants in the two randomized treatment groups. For the primary endpoint, the reported percentages and equal event counts are similar, and the risk-difference estimate is 0.0. The interval nevertheless spans possible differences in both directions. The evidence therefore does not establish that the regimens are equivalent, nor does it establish a difference between them.
The comparison concerns complete treatment strategies: adjusted-dose MMF with tacrolimus and a corticosteroid-sparing regimen versus fixed-dose MMF with tacrolimus and corticosteroids. It cannot determine the separate contribution of MMF dose adjustment, corticosteroid exposure, or another part of the combination. The registry does not report a component-specific analysis.
The result applies to the recorded study population and endpoint definitions. The primary outcome concerns treated biopsy-proven acute rejection according to Banff criteria, not every possible measure of graft function, survival, or safety. Secondary outcomes offer additional information, but their uncertainty and the unreported multiplicity approach limit how strongly they can support separate conclusions.
A non-significant comparison is not evidence that two treatments are interchangeable. Demonstrating equivalence or non-inferiority requires a suitable design, prespecified margin, and analysis. The registry record does not report such a margin or identify the primary comparison as an equivalence or non-inferiority test.
These findings are statistical descriptions, not medical advice. They do not determine which regimen should be used for an individual or establish the full balance of benefits and harms. Treatment decisions require clinical context and evidence beyond the registry outcome summaries.
15. Why This Trial Matters Statistically
This trial illustrates why a point estimate and a measure of uncertainty should be considered together. The primary percentages are close, the event counts are equal, and the risk-difference estimate is zero as posted. The interval still allows nonzero differences in either direction. A comparison that does not show statistical evidence of a difference is not automatically a demonstration of equivalence.
It also illustrates the importance of defining the treatment contrast. The randomized groups differed in MMF dosing strategy and corticosteroid approach, while both included tacrolimus. Any observed group contrast therefore belongs to the assigned combinations rather than to one component considered separately. This is a common interpretive issue in multi-drug regimen trials.
The endpoint itself combines histopathological criteria with treatment of rejection. That makes the endpoint more specific than an outcome based only on a laboratory measure or an unqualified clinical suspicion. At the same time, the registry record does not report whether outcome assessors were masked, a relevant consideration in an open-label study.
Finally, the differing endpoint-specific sample sizes and the absence of reported details about missing data, multiplicity, and the statistical analysis plan show how registry summaries can leave important interpretive questions unanswered. Numerical results can be read accurately while still recognizing that some design and analysis details are not reported. That distinction is central to careful evidence appraisal.
16. 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.
- Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.
The study was open-label. The registry record does not report whether biopsy review or endpoint adjudication was blinded, so the potential for knowledge of treatment assignment to influence assessment cannot be evaluated from the reported information.
The primary endpoint is a treated event. Treatment decisions may contribute to whether an event is recorded, in addition to the biopsy-based criteria. The registry provides the Banff criteria but does not report further operational rules for event counting, repeat episodes, or adjudication.
The primary endpoint record includes 87 participants per arm, while the detailed secondary outcome records include 90 per arm. Reasons for these different endpoint-specific counts and details about missing outcome data are not reported in the registry record. This limits assessment of whether the analyses could be affected by incomplete follow-up or outcome availability.
The primary confidence interval includes zero and allows differences in either direction. The registry record does not report an equivalence or non-inferiority margin, so the similar observed percentages should not be used to claim equivalence. The sample-size justification and the trial's own statistical analysis plan are not reported in the registry record.
Several secondary outcomes are listed, but no multiplicity adjustment or prespecified hierarchy is reported. Secondary findings should consequently be interpreted cautiously. The record also does not report interim analyses, stopping rules, or detailed participant flow. These limitations concern the information available in the registry record and do not establish that the unreported procedures or details were absent from study documents.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients. — NCT00545402.
- Registry record last updated 2014-07-14; status last verified 2014-06.
- Results first posted 2014-07-14.
- 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.
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20. Record Summary
NCT00545402 was a completed, randomized, open-label, parallel-group Phase 4 trial sponsored by Hoffmann-La Roche. It enrolled 180 liver transplant patients and compared an exposure-adjusted MMF combination regimen with fixed-dose MMF; both regimens included tacrolimus and corticosteroids, with different corticosteroid approaches described in the registry.
The primary endpoint was the percentage of participants with treated biopsy-proven acute rejection according to Banff criteria. The primary record reports 87 participants per arm, 7 events in each arm, percentages of 8.0% and 8.2%, a risk-difference estimate of 0.0, and an unadjusted p-value of 1.0. The interval includes zero and does not establish equivalence.
The registry lists secondary outcomes involving graft loss, survival, and graft histology. Detailed secondary information includes graft-loss and overall-survival analyses. Important details about multiplicity, missing-data handling, the sample-size rationale, and the statistical analysis plan are not reported in the registry record.