Mycophenolate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mycophenolate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis (NCT00843856), a randomized phase 4 study. The primary outcome is Number of Patient Who Gained Remission From the Nephrotic Syndrome.

2. Clinical Question

In statistical terms, the primary comparison asks whether the observed remission counts differ between the two randomized groups during the stated timeframe. The posted result is a comparison of counts, not a reported time-to-event estimate. The endpoint’s description mentions relapse after withdrawal, but the record does not give a separate time-to-relapse measure or explain in detail how remission and relapse were operationally defined.

3. Trial Design

The registry identifies NCT00843856 as a Phase 4 randomized study with a parallel-group model and no masking. The interventions were tacrolimus alone and tacrolimus combined with mycophenolate mofetil. The record lists an enrollment of 40, a start date of 2009-03-03, primary completion in 2018-03, and a status of completed. Imperial College Healthcare NHS Trust is listed as the sponsor.

The primary outcome is a participant count titled “Number of Patient Who Gained Remission From the Nephrotic Syndrome.” Its timeframe is 10-109 weeks. The primary outcome arms report 8 participants with the outcome among 16 in the tacrolimus group, and 8 among 19 in the combination group. The record’s overall enrollment and the group counts appearing for particular outcomes are not interchangeable: outcome records can use different available denominators, and the registry does not explain the difference between enrollment and those primary outcome denominators.

The arm descriptions provide dose and target-level details for both regimens. The tacrolimus-alone description states 2mg bd with adjustment to obtain levels of 5-12ng/L. The combination description states tacrolimus 2mgs bd, adjusted to obtain levels 5-12mg/L, alongside mycophenolate mofetil 500mg bd, adjusted to obtain levels 1.5-3mg/L. The difference in units as written in the two arm descriptions is reproduced in the record; a clarification is not reported in the registry record.

The registry lists 2 outcome measures and 1 analysis. It also posts a secondary remission outcome with a 6-12 months timeframe. The record does not report the randomization procedure, allocation concealment, eligibility criteria, protocol deviations, or a detailed analysis plan. It is therefore possible to describe the recorded design and outcomes, but not to reconstruct trial conduct or the complete prespecified statistical approach from this entry alone.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patient Who Gained Remission From the Nephrotic Syndrome, measured over 10-109 weeks.

The primary endpoint is a count of participants who gained remission from nephrotic syndrome, reported over 10-109 weeks. The registry description links the endpoint to the efficacy of mycophenolate in preventing relapse of nephrotic syndrome secondary to membranous glomerulonephritis on withdrawal of tacrolimus therapy. The posted result records 8 participants with remission in the tacrolimus group and 8 in the tacrolimus-and-mycophenolate-mofetil group; the denominators reported for this outcome are 16 and 19, respectively.

A binary participant outcome is useful because it allows a direct comparison of how many people in each group did or did not experience the recorded event. The risk difference expresses the contrast in event proportions as an absolute difference, while a risk ratio expresses the contrast as a relative ratio. These measures address different questions: an absolute difference describes how far apart the group proportions are, and a relative measure describes one in relation to the other.

In general, a remission endpoint can make a treatment comparison clinically interpretable when the event definition, assessment schedule, and analysis population are clear. Those details are not fully described in this record. In particular, the registry does not report an operational remission definition, whether all randomized participants were included in the posted primary counts, or how follow-up and treatment withdrawal were handled in the analysis. The primary count should therefore be read as the outcome posted by the registry, without assuming additional endpoint rules.

7. Results Posted in the Registry

• Tacrolimus and Mycophenolate Mofetil: 42.1% (8/19) versus 50.0% (8/16) on control; risk difference -7.9 percentage points (95% CI -41.0 to 25.2), risk ratio 0.84 (0.41–1.73); unadjusted two-proportion z-test p = 0.640.

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 Patients Achieved Remission

• 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:
  • Tacrolimus and Mycophenolate Mofetil: 95.0% (19/20) versus 80.0% (16/20) on control; risk difference 15.0 percentage points (95% CI -5.0 to 35.0), risk ratio 1.19 (0.93–1.51); unadjusted two-proportion z-test p = 0.151.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tacrolimus and Mycophenolate Mofetil and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary outcome: the number of patients who achieved remission, assessed over 6-12 months. Its corresponding group counts and unadjusted comparison are reported separately from the primary endpoint. The secondary outcome has a different stated timeframe, so it should be interpreted as additional information about remission rather than as a repeat measurement of the primary endpoint under an identical time definition.

Across the primary and secondary outcomes, the posted results do not tell a simple, fully resolved story about the treatment contrast. They address remission using different timeframes, and the registry does not report a sponsor analysis for the secondary outcome. These features limit direct comparison between outcomes and make the secondary result less suitable as a stand-alone basis for a broad conclusion about the overall treatment effect.

In general, secondary outcomes can help describe whether patterns are consistent across related measures and can identify questions for further study. Their evidential weight depends on whether they were prespecified, how many outcomes were examined, how outcomes were defined, and whether multiplicity was addressed. Those details are not reported in the registry record. When many outcomes or time points are tested, the chance of observing a nominally notable result by chance can increase; adjustment or a prespecified hierarchy can help manage that issue, but an approach cannot be assumed if none is recorded.

The secondary comparison is unadjusted, and its confidence interval includes the null value for the risk difference. It is therefore best treated as exploratory context rather than as confirmatory evidence. This does not mean the result is uninformative; it means that the interpretation should reflect its secondary status, the uncertainty of the estimate, the separate timeframe, and the absence of a reported sponsor analysis.

Primary and secondary outcomes should not be combined informally into a single overall conclusion. They may measure related but nonidentical aspects of remission, and the record does not explain how the outcomes relate analytically or whether one was intended to support the other. Taken together, the posted outcomes motivate attention to definitions, timing, and uncertainty, while leaving the overall effect on remission incompletely determined.

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

• Number of Patients Achieved Remission

9. Statistical Interpretation

10. Statistical Methods Explained

Several statistical ideas help interpret the posted comparison. The registry reports a randomized, parallel-group study, with one group receiving tacrolimus and the other receiving tacrolimus with mycophenolate mofetil. For the primary outcome, the event is a participant gaining remission. Because the outcome is recorded as a count of participants with an event, the comparison is binary: participants either meet the recorded outcome or do not. The registry does not report the detailed operational definition that determined this classification.

What does a risk difference describe?

A risk difference is an absolute contrast between the event proportions in two groups. The recalculated estimate is -0.079 for the combination group relative to the tacrolimus group. The sign depends on the comparison direction: a negative estimate indicates a lower observed event proportion in the first-named group under that subtraction convention. It is not a statement about the number of participants lost or gained, and it is not a relative percentage change. The interval around the estimate is needed to assess how uncertain that absolute contrast is.

The posted recalculation also gives a risk ratio of 0.842, with a confidence interval from 0.41 to 1.73, and an odds ratio of 0.727, with a confidence interval from 0.191 to 2.771. These are relative measures, but they are not interchangeable with the risk difference. A risk ratio compares event proportions; an odds ratio compares event odds. When event proportions are not small, an odds ratio can appear more extreme than a risk ratio. These relative estimates also have substantial uncertainty in this record, as reflected by intervals spanning values on either side of the null value for a ratio.

Why is Fisher’s exact test used?

The registry identifies Fisher Exact as the method for the primary comparison. In general, Fisher’s exact test evaluates the association between group assignment and a binary outcome using the observed counts, and it is commonly used when group counts are limited or expected cell counts may be small. It does not require the same large-sample approximation used by some other tests. The registry does not report why this particular test was selected or whether it was specified in advance.

A test result and an effect estimate answer different questions. The p-value is a measure of compatibility between the observed data and a null hypothesis under the test’s assumptions. The risk difference, risk ratio, and odds ratio estimate the size and direction of the observed contrast. Confidence intervals show the range of values compatible with the data and the interval procedure. Good interpretation considers all of these, rather than treating a p-value threshold as the only relevant result.

What does randomization contribute?

In general, random assignment aims to make groups comparable at baseline, on average, with respect to both measured and unmeasured factors. It supports a causal interpretation when allocation and follow-up are conducted as intended and analysis preserves the randomized comparison. This record says the study was randomized, but does not describe the sequence generation, allocation concealment, or analysis population. Therefore, the design label alone cannot establish whether all protections associated with randomization were achieved in conduct and analysis.

The registry identifies the study as unmasked. In general, lack of masking can influence behavior, treatment management, outcome assessment, or reporting when those processes involve judgment. The endpoint is a participant count, but the record does not state whether remission was assessed using objective criteria or how assessors were involved. It is not possible to quantify any impact of masking status from the registry record.

What is the role of recalculation?

The recalculated estimates are simple unadjusted analyses based on the posted summary counts. They offer a way to express the raw group comparison using common effect measures and intervals. They do not replace the sponsor’s analysis, do not adjust for covariates, and do not recreate an individual-participant analysis. Because the recalculation uses aggregate counts, it cannot account for participant-level follow-up, missingness, timing, stratification, or other analysis features that are not included in the posted summaries.

The registry’s primary test is reported with p = 0.7; the recalculated unadjusted p-value is 0.64. The record does not report a discrepancy flag, but the two values should still be described according to their source and method. The registry’s result is the sponsor-posted analysis, whereas the recalculation is a summary-statistic analysis. No adjustment method, covariate model, interim analysis, or prespecified hierarchy of outcomes is reported in the registry record.

Why does outcome timing matter?

The primary timeframe is 10-109 weeks, while the secondary remission timeframe is 6-12 months. In general, outcomes assessed at different time points may capture different phases of response or follow-up. A count across a broad or variable timeframe does not provide the same information as a time-to-event analysis, which incorporates when events occur and how long participants are observed. The registry does not post a time-to-event analysis for the primary endpoint, and the primary outcome should not be interpreted as one.

In general, a clear statistical interpretation depends on knowing the endpoint definition, assessment schedule, analysis population, missing-data handling, and analysis plan. For this record, several of those details are not reported in the registry record. That limits how far one can assess the assumptions behind the estimates, even though the posted counts and the registry’s named test make the basic comparison identifiable.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.079, with a 95% confidence interval from -0.410 to 0.252. This interval is wide and spans zero. It therefore includes a range of possible absolute differences, with the direction of the contrast varying across the interval. The interval does not support a precise estimate of the size or direction of the primary group difference.

In general, a confidence interval is a measure of statistical uncertainty around an estimate under the method’s assumptions. A 95% confidence interval is produced by a procedure that, over repeated comparable studies, would cover the fixed parameter at the stated rate. It is not a statement that there is a 95% probability that this particular fixed effect lies within these observed limits. The limits also do not account automatically for bias, incomplete follow-up, outcome misclassification, or unreported analytic choices.

The relative estimates reinforce the uncertainty. The risk ratio is 0.842, with a 95% confidence interval from 0.41 to 1.73. The odds ratio is 0.727, with a 95% confidence interval from 0.191 to 2.771. For each ratio, the confidence interval spans the null value of one, so the posted data are compatible with no relative difference as well as values on either side of it. The estimates should not be read as definitive evidence of either benefit or harm.

Precision is shaped by the information in the observed data and by the statistical method. Here, the primary outcome denominators are 16 and 19, and the event count is 8 in each group. The confidence interval communicates the resulting uncertainty more fully than a single point estimate or p-value. Additional detail about missing observations, analysis populations, and endpoint assessment could affect interpretation, but is not reported in the registry record.

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 figures are participants per arm, not total participants or total events. They are illustrations calculated from the observed effect, not the trial’s own original design assumptions. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The sample-size assumptions used in the trial’s original design are not reported in the registry record.

The column for 80% power gives the participants per arm needed, under those planning assumptions, for an 80% chance of detecting the stated effect if that effect were the true one. The 90% power column gives the corresponding planning count for a 90% chance. These are prospective planning concepts, not probabilities that the observed result is correct. The posted figures are not observed power.

The rows describe planning for 100% of the observed effect, planning for 75% of the observed effect, and planning for 50% of the observed effect. Because the smaller fractions represent smaller effects to detect, they require more participants per arm in the listed illustrations. For the primary outcome, the figures range from 625 participants per arm for 80% power and 836 for 90% power when planning for 100% of the observed effect, to 2,514 and 3,365 when planning for 50% of the observed effect. The intermediate row gives 1,115 and 1,492.

These projections depend on treating the observed effect as a useful planning anchor. In small studies, that estimate can be unstable, so the resulting counts are illustrative rather than a claim about a definitive future design. The curve should be read in the same planning context: as the effect to detect becomes smaller, the required participants per arm rise. The illustrations do not show the power achieved in this completed trial and do not supply the missing original design rationale.

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 = 0.500; treatment proportion p₁ = 0.421; average p̄ = 0.461.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7049 = 1.3816.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7027 = 0.5914.
4. n = (1.3816 + 0.5914)² / (-0.0789)² = 624.5, rounded up to 625 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 <- 0.5                          # control proportion
p1 <- 0.421052631578947                          # 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(843856)
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 = 625 (80% power), 836 (90% power)
 75% of observed effect: n per arm = 1,115 (80% power), 1,492 (90% power)
 50% of observed effect: n per arm = 2,514 (80% power), 3,365 (90% power)
power.prop.test: 624.5 
Simulated power at n = 625 per arm: 0.800 (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 the sponsor’s primary analysis as Fisher Exact, with p = 0.7, for the comparison of tacrolimus with tacrolimus and mycophenolate mofetil. The unadjusted recalculation from the posted group summaries reports a risk difference of -0.079, with a 95% confidence interval from -0.410 to 0.252, and p = 0.64. The recalculation is a simple analysis of the summary counts, while the registry result is the analysis identified in the record.

The recalculation does not replace the sponsor’s reported result. It adds effect-size estimates and confidence intervals that help describe the magnitude and uncertainty of the comparison. Both reported p-values are above conventional thresholds often used for hypothesis testing, but neither establishes equality or excludes a meaningful difference. The interval, which spans zero and is broad, is central to understanding the imprecision.

The record does not report enough detail to reproduce the sponsor’s analysis beyond its method label and p-value. It does not give an analysis statistic, a confidence interval for that test, or a more detailed statistical specification. No discrepancy is flagged in the registry data. The sponsor analysis and the unadjusted recalculation should therefore be presented distinctly, with the registry’s analysis treated as the posted trial result and the recalculation as supplementary descriptive context.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and a secondary remission outcome, but a complete multiplicity strategy is not reported in the registry record. It is not stated whether additional analyses or outcome measures were prespecified, whether a hierarchy was used, or whether any adjustment for multiple testing was planned. This matters because each additional test can create another opportunity for a result to appear notable by chance. Without the analysis plan, the role of the secondary finding in the confirmatory evidence structure cannot be established.

The handling of missing outcome data is also not reported in the registry record. The entry does not state how missing assessments were defined, whether participants without a recorded outcome were excluded, or whether any imputation or sensitivity analysis was used. The denominators attached to outcome summaries are reported, but the registry does not explain their relationship to overall enrollment or provide a participant-flow account. As a result, the impact of missingness on the estimates cannot be assessed from the posted summary counts alone.

The analysis population is not described in enough detail to determine whether the comparison followed an intention-to-treat principle, a per-protocol approach, or another population definition. The record reports randomized allocation, but that label does not answer which participants were included in the primary analysis. It also does not describe crossovers, treatment discontinuations, adherence, or how treatment withdrawal was incorporated into the outcome analysis.

The registry names Fisher Exact for the primary comparison but does not report the detailed statistical plan, any covariate adjustment, interim analyses, or stopping rules. The sample-size assumptions for the original study design are not reported in the registry record. These omissions do not invalidate the posted counts; they define the limits of what can be inferred about how the reported analyses were chosen and conducted. Interpretation should remain anchored to the information actually recorded, without assuming unreported methods.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: diarrhoe and vomiting (15.0%), acute kidney injury (15.0%), anemia (10.0%), haematuria (10.0%), haemorrhoidectomy (5.0%).

The registry’s adverse-event record lists 7 serious adverse events among 20 at risk in the tacrolimus group and 3 among 20 at risk in the tacrolimus-and-mycophenolate-mofetil group. Other adverse events are listed as 0 in each group, and deaths are listed as 0 in each group. These figures should be read as the registry reports them, with the stated at-risk denominators, rather than treated as a complete safety profile.

The serious adverse event terms listed include diarrhoe and vomiting and Acute kidney injury, each reported as 15.0%, as well as Anemia and Haematuria, each at 10.0%. Haemorrhoidectomy and Headache are each listed at 5.0%. The record does not clearly connect these term percentages to a particular treatment group in the summary, so they should not be assigned to a group without further information.

In general, adverse-event counts describe events recorded under the study’s collection and reporting procedures. They do not by themselves establish that an event was caused by a treatment. The registry record does not report event definitions, severity grading beyond the serious-event categorization, duration, exposure-adjusted rates, or a detailed account of how events were assessed. The figures are descriptive and should not be used alone to compare safety or infer causation.

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

The primary posted counts are 8 participants with remission in each group, with denominators of 16 for tacrolimus and 19 for tacrolimus with mycophenolate mofetil. The unadjusted risk-difference estimate is -0.079, and its 95% confidence interval ranges from -0.410 to 0.252. The registry’s Fisher Exact result is p = 0.7. Taken together, these results describe a comparison with considerable uncertainty rather than a precise estimate of a treatment difference.

The data do not establish that the groups are equal. A failure to reach a conventional statistical threshold is not a demonstration of no effect, and the confidence interval includes differences in either direction. Conversely, the point estimate alone does not establish that one regimen is superior. The study hypothesis is not a result: the posted outcome data must be interpreted on their own terms, with attention to uncertainty and the limitations of the registry detail.

The record also does not establish an effect on the timing of relapse, sustained remission, or outcomes beyond the stated assessment timeframes. Although the primary outcome description refers to prevention of relapse after withdrawal of tacrolimus therapy, no separate time-to-relapse result is posted. The secondary remission outcome has a 6-12 months timeframe and should not be treated as identical to the primary outcome over 10-109 weeks.

General statistical interpretation distinguishes absence of clear evidence from evidence of absence. To conclude that treatments are sufficiently similar would ordinarily require a prespecified equivalence or non-inferiority framework with an appropriate margin and analysis. Such a framework is not reported in the registry record. Nor does the posted result determine how findings would apply to people outside the study’s unreported eligibility and analysis populations.

The responsible reading is narrow: the registry reports the stated counts and a non-significant Fisher Exact analysis, while the unadjusted estimate is imprecise. The results can inform understanding of what this study recorded, but they do not by themselves support a definitive claim that adding mycophenolate mofetil improves, worsens, or leaves unchanged remission outcomes. This is a statistical interpretation of the record, not medical advice.

18. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between an observed point estimate and the certainty of that estimate. The primary groups each have 8 participants recorded with remission, but their outcome denominators are 16 and 19. The recalculated risk difference is -0.079, yet the confidence interval extends from -0.410 to 0.252. Reporting only the event counts or p-value would obscure how much uncertainty remains about the size and direction of the contrast.

The record also makes clear why effect measures and tests should be read together. Fisher Exact is the sponsor-reported method, while the recalculation presents risk difference, risk ratio, odds ratio, confidence intervals, and an unadjusted p-value. A test addresses compatibility with a null hypothesis; effect estimates describe the contrast, and intervals show its precision. Neither one p-value nor one effect estimate answers every relevant question.

Different outcome timeframes matter as well. The primary endpoint is recorded over 10-109 weeks, while the secondary remission endpoint uses 6-12 months. Those measures should not be collapsed into a single result without a defined analysis plan. The registry’s limited reporting on outcome definitions, missing data, analysis populations, and multiplicity further demonstrates why transparent methods are important for evaluating clinical trial evidence.

Finally, planning illustrations derived from the observed effect are not evidence about the study’s achieved power or its original design rationale. They show how assumptions about the effect to detect relate to the participants per arm needed for a future study. Distinguishing planning calculations from observed findings helps prevent a small, imprecise study from being interpreted as if it had ruled out effects it was not designed or able to estimate precisely.

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 primary outcome’s operational definition is not reported in the registry record. The entry does not explain the criteria for remission, the assessment process, or how the broad primary timeframe of 10-109 weeks was applied. Although the outcome description refers to relapse after tacrolimus withdrawal, a distinct relapse endpoint or time-to-relapse analysis is not posted. This limits the ability to connect the title and hypothesis to the exact event counted.

The primary outcome denominators are 16 and 19, while the overall enrollment is 40. The registry does not provide a participant-flow account explaining the denominator differences, exclusions, missing assessments, or analysis population. Therefore, the extent to which the primary counts preserve the randomized comparison cannot be determined from this entry. Missing-data methods, treatment discontinuation, adherence, and crossover handling are also not reported.

The record identifies randomization but does not describe sequence generation or allocation concealment. It lists no masking, and does not explain how outcome assessment was conducted. The registry’s brief reporting does not permit an evaluation of whether the outcome was assessed independently or according to objective criteria. The combination arm’s tacrolimus units are written differently from those in the tacrolimus-alone arm description; clarification is not reported in the registry record.

There is limited statistical detail beyond the named primary test and the posted outcome values. The original sample-size assumptions, analysis plan, multiplicity approach, interim analyses, and any covariate adjustment are not reported. The secondary outcome has no registry-reported sponsor analysis. These gaps mean that the summary estimates can be described, but their relationship to a full prespecified analysis strategy cannot be established. The trial’s status is completed, but completion alone does not resolve these reporting limitations.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Mycophenolate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis — NCT00843856.
• Registry record last updated 2019-12-12; status last verified 2019-11.
• Results first posted 2019-12-12.
• 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

NCT00843856 is a completed Phase 4 randomized, unmasked, parallel-group study sponsored by Imperial College Healthcare NHS Trust. It compares tacrolimus with tacrolimus plus mycophenolate mofetil for idiopathic membranous glomerulonephritis. The primary registry outcome is remission from nephrotic syndrome over 10-109 weeks.

The primary counts are 8 of 16 for tacrolimus and 8 of 19 for the combination. The sponsor-reported Fisher Exact result is p = 0.7. The unadjusted recalculation gives a risk difference of -0.079, with a 95% confidence interval from -0.410 to 0.252, indicating substantial uncertainty. A secondary remission outcome is posted for 6-12 months. The registry does not report the original design assumptions, detailed missing-data methods, analysis populations, or a multiplicity strategy.