Mycophenolate Mofetil in Patients With Progressive Idiopathic Membranous Nephropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mycophenolate Mofetil in Patients With Progressive Idiopathic Membranous Nephropathy (NCT01282073), a randomized phase 3 study. The primary outcome is Percentage of Complete Remission.

2. Clinical Question

3. Trial Design

The registry record identifies this as a randomized, phase 3, multicenter trial with no masking. It lists two active regimens: mycophenolate mofetil with low-dose steroid and cyclosporin with low-dose steroid. The official title describes a randomized controlled multicenter trial. The record gives an enrollment of 43 and marks the study as completed. The dates listed are a start in 2011-03 and primary completion in 2016-05.

The intervention entries and outcome arms describe a comparison between the two regimens. However, the registry record also classifies the model as single group, which does not align clearly with the two listed treatment arms and randomized allocation. The record does not explain this classification, so the design details should be read from the listed interventions and arms rather than assuming that the model label resolves the discrepancy.

There is no masking, so participants and study personnel were not blinded according to the registry entry. The registry record does not report how randomization was generated, whether allocation was concealed, how treatment adherence was assessed, or whether any protocol changes occurred. It also does not provide arm descriptions or detailed treatment schedules.

The primary outcome was the count of participants with complete remission at 48 week after treatment. Secondary outcomes are listed as estimated glomerular filtration rate, relapse, proteinuria, and side effects. Six outcome measures are indicated in the record, but only four secondary outcome categories are named. The record lists no analyses, and the sponsor’s statistical analysis details are not reported in the registry record.

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

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 Percentage of Complete Remission, measured over at 48 week after treatment.

The primary endpoint is the number of participants who achieved complete remission at 48 week after treatment. The registry defines complete remission as reduction in proteinuria to 200 mg per day with stable serum albumin with more than 3.5 g/dL. The result is therefore a binary outcome recorded as a count: each participant is classified according to whether the specified remission condition was met at the stated assessment time.

A remission endpoint captures a clinically relevant change in proteinuria together with a serum albumin condition. Using a defined threshold gives the outcome a consistent operational meaning for comparing treatment groups. Because the result is a count of participants meeting the definition, the analysis can compare the proportion with remission in each arm as well as report an absolute difference between those proportions. Those comparisons describe the posted outcome; they do not by themselves establish why any difference occurred.

The registry record names estimated glomerular filtration rate, relapse, proteinuria, and side effects as secondary outcomes, but their definitions, assessment schedules, and results are not reported in the registry record in the registry record for this analysis. The primary endpoint time point is explicitly given as 48 week after treatment. Details such as rules for handling participants without an assessment at that time are not reported in the registry record.

7. Results Posted in the Registry

• Cyclosporin, Low Dose Steroid: 16.7% (3/18) versus 19.0% (4/21) on control; risk difference -2.4 percentage points (95% CI -26.4 to 21.7), risk ratio 0.88 (0.22–3.40); unadjusted two-proportion z-test p = 0.847.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: participants either met the registry definition of complete remission at 48 week after treatment or did not. For this type of outcome, a group’s event count is interpreted alongside its denominator. The arm counts are 4 of 21.0 for mycophenolate mofetil with low-dose steroid and 3 of 18.0 for cyclosporin with low-dose steroid. These are the observed results, not estimates of what would happen in every future population.

What does a risk difference describe?

A risk difference subtracts the event proportion in one group from the event proportion in the comparison group. It is an absolute measure: it describes the difference in probability on the original scale rather than expressing one group as a multiple of another. The posted comparison is cyclosporin relative to mycophenolate mofetil, with a risk difference of -0.024. The negative sign indicates that the observed event proportion in the cyclosporin arm was lower under this subtraction order. The estimate is not a claim that the true difference is exactly this value.

Why are relative measures also reported?

A risk ratio compares event proportions by division, while an odds ratio compares the odds of the event. The registry comparison gives a risk ratio of 0.875 and an odds ratio of 0.85. These scales can be useful for different scientific questions, but they answer different formulations of the contrast. With few observed events, relative estimates can be sensitive to small changes in the counts. The risk difference remains directly interpretable as an absolute contrast, while the relative measures express the same comparison in ratio form.

What does the p-value test?

The unadjusted p-value is 0.847. In general, a p-value measures how compatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null hypothesis is true, and it is not a measure of the size or clinical importance of an effect. The registry record does not report the exact test used, so the p-value should be treated as the posted unadjusted result rather than attributed to a particular test procedure.

Why report a confidence interval?

A confidence interval communicates uncertainty around an estimated contrast. In general, it indicates the range of values that are compatible with the observed data and the interval method under repeated use of that method. The risk-difference interval runs from -0.264 to 0.217. Because it includes values on both sides of zero, the data do not precisely determine the direction of the difference. The ratio intervals are also broad: 0.225 to 3.403 for the risk ratio and 0.163 to 4.426 for the odds ratio. The interval method and confidence level are not reported in the registry record.

Why does event frequency affect precision?

Statistical precision depends on the amount of information in the data, not only on the total number enrolled. For a binary endpoint, the number of participants who experience the event is important to how precisely a group proportion and its contrast can be estimated. Here, the event counts are small in both arms. Small event counts generally leave a wider range of plausible effects, which is reflected in the broad intervals. This is a general statistical explanation, not an additional finding about the trial.

What is the role of an unadjusted analysis?

An unadjusted comparison contrasts the observed groups without accounting for other measured characteristics. It is straightforward to interpret but does not demonstrate that baseline factors were balanced, nor does it estimate a covariate-adjusted treatment effect. Randomization is intended to support comparability in expectation, but the registry record does not report baseline characteristics or an adjusted analysis. No sponsor analysis is posted in the record; the posted summary comparison is therefore the available numerical contrast.

The registry record does not describe its statistical model, interval construction, handling of missing endpoint data, or analysis population. Those details matter because different methods can yield different estimates or uncertainty, especially when counts are limited. The calculations labelled as recalculated are simple unadjusted re-calculations from posted summary statistics; no discrepancy is flagged for this comparison.

10. Confidence Intervals and Precision

The risk-difference estimate is -0.024, and its confidence interval extends from -0.264 to 0.217. This interval includes zero and values on both sides of it. In practical statistical terms, the point estimate alone does not convey the uncertainty: the data are compatible with a negative difference as well as a positive difference under the reported interval method. The interval is broad, so the direction and magnitude of the underlying contrast are not precisely determined.

The relative-effect intervals also show substantial uncertainty. The risk ratio is 0.875, with an interval from 0.225 to 3.403; the odds ratio is 0.85, with an interval from 0.163 to 4.426. The ranges include values below and above 1, the no-relative-difference value. These measures should not be interpreted as proving no effect simply because their intervals include that value.

A confidence interval is not a guarantee that the true effect lies within its particular endpoints. In general, it is a procedure for expressing uncertainty across repeated applications, under the assumptions and method used. The registry record does not report the confidence level or interval method, so those details cannot be assessed. The modest event counts, 4 and 3, are relevant to the limited precision, though the exact contribution of each design or analysis feature cannot be separated from the registry information.

The overall reading is that the estimate is not precise enough to sharply distinguish the possible directions or sizes of the remission contrast. The registry result should be read with its interval, not only its point estimate or p-value.

11. 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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculations. The registry record does not report the original sample-size assumptions or justification. The listed assumptions for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is specified as a stated fraction of the observed effect.

The figures are participants per arm for 80% power and participants per arm for 90% power. These columns describe the planned number of participants in each arm that would be required under the listed assumptions to have the stated probability of detecting the chosen effect, if that effect and assumptions were correct. They do not describe the number actually enrolled or analyzed in this trial. The event-count analysis is binary; these planning values are participants per arm, not total events.

The planning rows consider 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For those scenarios, the participants per arm for 80% power are 4,061, 7,314, and 16,666, respectively; for 90% power they are 5,436, 9,791, and 22,311, respectively. Smaller effects require more participants because a smaller separation between groups is harder to distinguish from random variation. The curve represents this same relationship across the planning scenarios.

These values are hypothetical design illustrations, not observed power. Observed power is not a useful substitute for interpreting the uncertainty in the actual result; the confidence intervals and event counts describe the posted evidence directly.

12. 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 = 0.190; treatment proportion p₁ = 0.167; average p̄ = 0.179.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5416 = 1.0616.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5414 = 0.4556.
4. n = (1.0616 + 0.4556)² / (-0.0238)² = 4,060.6, rounded up to 4,061 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 <- 0.19047619047619                          # control proportion
p1 <- 0.166666666666667                          # 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(1282073)
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 = 4,061 (80% power), 5,436 (90% power)
 75% of observed effect: n per arm = 7,314 (80% power), 9,791 (90% power)
 50% of observed effect: n per arm = 16,666 (80% power), 22,311 (90% power)
power.prop.test: 4060.6 
Simulated power at n = 4,061 per arm: 0.807 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcome categories, including estimated glomerular filtration rate, relapse, proteinuria, and side effects. It also indicates six outcome measures, while the named secondary categories number fewer than that. The record does not explain this difference or provide a full list of measure definitions and assessment times. Results for these secondary outcomes are not reported in the registry record in the information available for this analysis.

When a study examines multiple outcomes or multiple time points, the chance of obtaining at least one apparently notable result can increase. General statistical approaches to address this issue include prespecifying a primary endpoint, adjusting inference across comparisons, or clearly separating confirmatory from exploratory analyses. The registry record does not report whether any multiplicity strategy was planned or used. Therefore, the posted primary comparison should not be assumed to represent a complete testing strategy for every outcome.

Missing outcome data can affect the interpretation of a treatment comparison. The registry record does not report how many participants had an endpoint assessment, whether any primary outcome values were missing, or how missing values were handled. It also does not describe withdrawals, exclusions after randomization, or sensitivity analyses. The enrolled arm counts should not be assumed to equal the numbers included in a particular endpoint analysis unless the record explicitly states this.

The record does not name an intention-to-treat, per-protocol, or other analysis population, and it lists zero analyses. It does not report an adjusted statistical model, a prespecified analysis plan, or interim analyses. Without these details, it is not possible to assess whether the posted comparison follows a prespecified approach or how deviations from planned treatment and follow-up were handled. These absences limit assessment of the analysis process; they do not by themselves show that a specific problem occurred.

14. 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 non-serious adverse event terms

The registry record reports serious adverse events for 0 participants in the mycophenolate mofetil and low-dose steroid arm and 0 participants in the cyclosporin and low-dose steroid arm. The numbers listed at risk for serious adverse events are 21 and 18, respectively. Deaths are reported as 0 in each arm. These figures describe the serious-event and death counts posted in the record; they do not establish that no other harms occurred.

For other adverse events, the record reports 12 affected participants in the mycophenolate mofetil arm and 9 in the cyclosporin arm, with 21 and 18 at risk, respectively. The record labels these as other adverse events and does not provide terms or severity breakdowns in the registry record for this analysis. No percentages are calculated.

Adverse-event counts are descriptive. A count alone does not establish that an event was caused by a treatment, and differences between arms can be influenced by the event definitions, observation time, completeness of reporting, and chance. The registry record does not provide detailed event listings, exposure time, or rules for attributing events to treatment. The posted safety figures should therefore be interpreted as the recorded counts, not as a complete comparison of every possible harm.

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

The primary result describes complete remission at 48 week after treatment in a randomized comparison of mycophenolate mofetil with low-dose steroid and cyclosporin with low-dose steroid. The observed counts were 4 and 3, respectively. The posted risk difference comparing cyclosporin with mycophenolate mofetil is -0.024, with a confidence interval from -0.264 to 0.217, and the unadjusted p-value is 0.847.

These results do not provide a precise estimate of the direction or magnitude of the difference. The interval spans negative and positive values, and the relative-effect intervals are also broad. The p-value does not demonstrate equivalence or prove that the treatments have identical effects. A conclusion of equivalence or non-inferiority would require prespecified margins and a suitable analysis, neither of which is reported in the registry record.

The result applies to the recorded primary endpoint, at the stated assessment time, in the trial population described by the registry. It does not answer whether the regimens differ in estimated glomerular filtration rate, relapse, proteinuria, or side effects, because those outcome results are not reported in the registry record. Nor does this comparison determine how either regimen compares with placebo or no treatment; both listed arms received active treatment with low-dose steroid.

The registry information also leaves important analysis details unclear, including the endpoint analysis population, missing-data handling, and the statistical method used for the comparison. Those omissions prevent a full assessment of the analysis. The appropriate statistical reading is limited: the posted remission counts yield an uncertain between-arm contrast, and the record does not establish a definitive treatment advantage, absence of an effect, or equivalence.

16. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between an estimated effect and the precision of that estimate. The risk-difference point estimate is close to zero, but its confidence interval is broad and includes values on both sides of zero. A small or non-significant point estimate is not, by itself, evidence that the underlying difference is negligible. The interval makes the uncertainty visible.

The primary outcome is binary and the observed remission counts are limited. With relatively few events, the data may not tightly constrain the event probabilities or their contrast. This illustrates why outcome counts and interval estimates should be read together, rather than relying only on the p-value. It also illustrates the value of expressing a treatment comparison on both an absolute scale, through the risk difference, and relative scales, through the risk ratio and odds ratio.

The planning illustration connects the observed effect to prospective study size. Its assumptions show how the participant requirement rises when the target effect is smaller or the desired power is higher. Those calculations are not evidence about the trial’s original design and are not observed power. The original design assumptions are not reported in the registry record.

Finally, the record demonstrates why transparent reporting matters for interpretation. Randomization and the listed active comparators are clear, but the model classification is difficult to reconcile with the two arms, and the analysis population, missing-data approach, multiplicity strategy, and interval method are not reported. These gaps do not negate the posted result, but they limit how fully it can be evaluated or generalized.

17. 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 registry record gives limited information about eligibility, baseline characteristics, and the clinical features defining high-risk disease. It therefore does not allow assessment of how representative the enrolled participants were of a broader population with membranous nephropathy. The arm descriptions are blank, and treatment doses, schedules, adherence, and concomitant-care details are not reported in the registry record.

The record identifies randomization and no masking but does not describe sequence generation or allocation concealment. It also classifies the study model as single group while listing two randomized treatment arms. The reason for this classification is not reported in the registry record. This makes the design metadata internally difficult to interpret, even though the intervention and outcome entries describe a comparison.

The posted primary outcome includes small event counts and a broad confidence interval. The registry record does not specify the confidence level, interval method, exact test underlying the p-value, or whether the comparison was adjusted. It does not identify an analysis population or explain how missing outcome data, withdrawals, treatment changes, or protocol deviations were handled. No sponsor analysis is listed.

Secondary outcomes are named, but their detailed definitions, time points, and results are not reported in the registry record. The record’s count of outcome measures does not fully correspond to the named secondary categories, and the reason is not explained. Multiplicity handling is also not reported. Safety information is limited to the counts of serious and other adverse events and deaths, without event terms or exposure-time details.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Mycophenolate Mofetil in Patients With Progressive Idiopathic Membranous Nephropathy — NCT01282073.
• Registry record last updated 2025-08-27; status last verified 2025-08.
• Results first posted 2025-08-27.
• 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.

21. Record Summary

The registry record identifies NCT01282073 as a completed, randomized, phase 3 study sponsored by Kyungpook National University Hospital. Its title concerns mycophenolate mofetil in patients with progressive idiopathic membranous nephropathy. The listed interventions were mycophenolate mofetil with low-dose steroid and cyclosporin with low-dose steroid; masking was none.

The primary endpoint was complete remission at 48 week after treatment, defined using proteinuria and stable serum albumin criteria. Remission was recorded for 4 participants in the mycophenolate mofetil arm and 3 in the cyclosporin arm. The posted risk difference was -0.024, with a confidence interval from -0.264 to 0.217, and the unadjusted p-value was 0.847. The estimate is imprecise and does not establish equivalence or a definitive difference.

The registry record lists estimated glomerular filtration rate, relapse, proteinuria, and side effects as secondary outcomes, but their results and several analysis details are not reported in the registry record. Serious adverse events and deaths were recorded as 0 in both arms; other adverse events were recorded for 12 and 9 participants, respectively.