IVIG in Patients With VGKC Ab Associated Autoimmune Epilepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IVIG in Patients With VGKC Ab Associated Autoimmune Epilepsy (NCT02697292), a randomized phase 3 study. The primary outcome is Change in Seizure Frequency From Baseline to 5 Weeks.

2. Clinical Question

The clinical question is framed around a change in seizure frequency over a specified short-term interval, not a count of all seizures or a measure of seizure severity. It compares the participant-level response in the IVIG group with the response during the placebo-controlled phase. The record describes a randomized, double-blind, placebo-controlled study with quadruple masking, but does not identify which roles were masked or explain how masking was implemented.

The placebo group’s later IVIG infusions are part of the planned treatment sequence after the blinded phase. They are not part of the primary comparison described by the endpoint timeframe, which is baseline to 5 weeks. The registry record does not report a separate primary question about outcomes after the placebo group switched to IVIG.

3. Trial Design

The registry record describes a randomized, double-blind, placebo-controlled, parallel-group Phase 3 study. It lists 17 participants enrolled and identifies Mayo Clinic as the sponsor. The listed condition is autoimmune epilepsy. The study status is terminated; the reason for termination is not reported in the registry record.

The IVIG group was assigned intravenous immunoglobulin (Gamunex-C) for 4 infusions. The placebo/normal saline group was assigned placebo for 4 infusions during the blinded phase, followed by IVIG for 4 infusions after that phase. Both arm descriptions say participants would maintain a stable dose of antiepileptic medications. The registry record does not provide further details about infusion timing, dose, or the length of the blinded phase.

The posted primary outcome compares seizure frequency at baseline and 5 weeks, counting participants with at least a 50% reduction. The arm-level figures are 2 participants in the placebo/normal saline group, with 9 listed for the group, and 6 participants in the IVIG group, with 8 listed. These are the outcome counts and group sizes as reported; they do not by themselves explain how missing observations or withdrawals were handled.

The study also lists change in cognitive assessment as a secondary outcome. The registry record does not report the specific cognitive assessment instrument or its results in the registry record for this analysis. Further details about the protocol, eligibility criteria, planned analysis populations, and the reason the trial was terminated 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 Change in Seizure Frequency From Baseline to 5 Weeks, measured over baseline, 5 weeks.

The primary endpoint counts participants who experienced at least a 50% reduction in seizure frequency from baseline to 5 weeks. It is a binary participant-level outcome: each participant either meets the reduction threshold or does not. The reported arm values are counts, rather than mean seizure counts or a continuous measure of change.

A threshold-based responder outcome can make a change easier to interpret as a proportion of participants reaching a prespecified level of improvement. It also compresses the underlying seizure-frequency information: participants just short of the threshold and participants with no reduction fall into the same non-responder category, while participants who meet the threshold are counted together regardless of how much further their frequency changes. This is a general feature of thresholded endpoints, not a statement about what happened to any particular participant in this study.

The endpoint uses a baseline comparison and a 5-week timeframe. Those details define the period and reference point for the response count. The registry record does not report the underlying seizure counts, the method used to collect them, or the handling of incomplete measurements. It also does not report a separate endpoint result for the period after the placebo group received IVIG.

The group counts are useful descriptive information, but the count alone does not convey the uncertainty around a group comparison. The registry record reports an odds ratio analysis with a confidence interval and p-value; those statistics should be read with attention to the stated one-sided method and to the uncertainty reflected in the interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is binary at the participant level: the registry record counts whether a participant had at least a 50% reduction in seizure frequency from baseline to 5 weeks. The two possible categories are meeting that threshold or not meeting it. This kind of endpoint is often called a responder outcome. It turns a measured change into a category based on a cutoff, which can simplify group comparisons but discards detail about the size of changes within each category.

The arm summaries are counts of participants meeting the threshold. The registry record lists 2 in the placebo/normal saline group and 6 in the IVIG group. It lists 9 participants for the former group and 8 for the latter. These counts describe the posted result without requiring a model. They do not disclose whether any participants lacked a usable measurement, whether all randomized participants were included in the endpoint analysis, or how the analysis treated missing values. Those details are not reported in the registry record.

An odds ratio compares the odds of an event in one group with the odds in another. Odds are not the same as probabilities or proportions, so an odds ratio should not be translated directly into a multiple of the participant counts or into a difference in the proportion of responders. The registry record gives an odds ratio of 10.5 with a 95% confidence interval from 1.1 to 98.9. It does not specify the numerator and denominator convention for this estimate. The arm counts can be reported as stated, but assigning a direction to the odds ratio requires knowing how the groups were coded.

A confidence interval communicates uncertainty in an estimated parameter under the statistical method used. Its width matters: the interval from 1.1 to 98.9 is broad, so the estimate does not pin down the magnitude precisely. The interval is not a statement that a particular proportion of participants had odds within those bounds, and it does not cover uncertainty arising from every possible design or reporting issue. It reflects the analysis method’s uncertainty calculation and assumptions.

The record labels the reported method “t-test, 1 sided,” while identifying the parameter as an odds ratio. Those are the registry’s reported descriptors. The statistical procedure, test statistic, model details, and rationale for selecting a one-sided test are not reported in the registry record. General statistical practice calls for interpreting a test in light of its prespecified hypothesis, outcome coding, and assumptions. The record does not provide enough detail to assess those elements fully.

The p-value is 0.044. In general, a p-value describes how extreme the data, or data more extreme, would be under a specified null hypothesis and the assumptions of the test. It does not quantify the clinical importance of a difference, the chance that a treatment works, or the probability that the null hypothesis is correct. Because the reported test is one-sided, its interpretation depends on the direction specified for the test. That direction is not reported in the registry record.

Randomization is intended, in general, to support comparison of groups by allocating participants without choosing treatment based on prognosis. The registry record identifies the design as randomized, but does not report the randomization sequence method, concealment procedure, or any assessment of balance in participant characteristics. Masking is described as double blind and quadruple in the record; which people were masked and how the masking was maintained are not reported. These omissions prevent a detailed appraisal of implementation from the registry description alone.

Small group sizes are relevant to precision. With relatively few participants, each observed outcome can have substantial influence on the estimate, and the data may provide limited information about the range of plausible effects. For binary outcomes, sparse event counts can make estimates especially sensitive to the analysis method. This is a general statistical consideration; it does not imply that any particular participant’s outcome was influential. The broad confidence interval is consistent with imprecision in this posted comparison.

The record includes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations describe hypothetical sample sizes under stated assumptions; they are not observed power and should not be read as the trial’s own prospective design justification. The registry record does not report the trial’s sample-size justification or indicate that those illustrations were used to design the study.

Multiplicity concerns arise when several outcomes, time points, comparisons, or analyses are examined. In general, making multiple statistical tests can increase the chance of at least one apparently unusual result unless the analysis addresses that issue. The registry record lists a secondary outcome of change in cognitive assessment and reports two analyses, but does not describe an adjustment for multiplicity, a hierarchy of outcomes, or which analyses were prespecified. The effect of any multiplicity strategy therefore cannot be assessed from the registry record.

The record reports a terminated status and a primary outcome result. It does not report the reason for termination, the analysis population, missing-data procedures, interim monitoring, or a complete statistical analysis plan. These are distinct aspects of trial conduct and analysis; their absence from the registry description should not be filled in by assumption.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Placebo/Normal Saline Group", "Intravenous Immunoglobulin (IVIG) (Gamunex-C) Grou")
n      <- c(9, 8)
events <- c(2, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Placebo/Normal Saline Group  9  2  22.2  2.8  60.0  6.3  54.7  6.7  55.6
ARM  Intravenous Immunoglobulin (IVIG) (Gamunex-C) Grou  8  6  75.0  34.9  96.8  40.9  92.9  40.0  92.5

11. Analyses Reported by the Sponsor

The registry record reports the sponsor’s analysis as an odds ratio of 10.5, with a 95% confidence interval from 1.1 to 98.9 and p = 0.044. It labels the method “t-test, 1 sided” and the analysis as superiority. The posted arm summaries give the responder counts and group sizes, but the record does not state the odds-ratio coding convention or provide the full analysis procedure.

No recalculated comparison is available in the posted results. The registry record identifies values as missing or not estimable for a two-arm comparison of this binary endpoint. In keeping with that reporting, the sponsor’s odds ratio and test are the only inferential comparison; no new estimate has been calculated from the counts.

The reported confidence interval is wide, so the sponsor’s point estimate is not precise. The meaning and direction of the odds ratio also depend on its group coding, which is not stated in the registry record. The reported p-value belongs to a one-sided test, but the test direction and fuller analysis plan are not reported. These limitations affect how much can be concluded from the reported inferential statistics without replacing or reinterpreting the sponsor’s analysis.

The posted counts remain directly interpretable as counts: 2 participants in the placebo/normal saline group and 6 in the IVIG group met the primary threshold. The registry result does not provide the information needed for an independent recalculation with a different method or assumptions.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists change in cognitive assessment as a secondary outcome and reports two analyses. It does not state whether the analyses correspond to different endpoints, comparisons, or time points. It also does not report a prespecified hierarchy, a multiplicity adjustment, or a plan for interpreting multiple tests. Without those details, it is not possible to assess whether the reported p-value was considered alongside other tests or how any multiplicity was handled.

Missing-data procedures are not reported in the registry record. The primary outcome lists group sizes of 9 and 8, alongside responder counts of 2 and 6, but the record does not explain whether every participant had an endpoint measurement, how withdrawals or unavailable seizure-frequency data were treated, or whether the analysis used an intention-to-treat or another population. The listed group sizes alone do not establish the analysis population or how incomplete data were handled.

The registry record does not report interim analyses, stopping rules, or the reason the trial was terminated. Those details could be relevant to understanding how the final analysis was reached, but they cannot be inferred from the terminated status. The protocol’s statistical analysis plan and any prespecified handling of the one-sided test are also not reported in the registry record.

These omissions do not change the recorded endpoint counts or the sponsor-reported odds ratio. They do limit assessment of whether the analysis followed prespecified procedures, how the result relates to other outcomes, and whether missing observations or multiple testing affected the inference.

13. 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 lists serious adverse events for 0 participants in each group. It lists other adverse events for 4 participants in the placebo/normal saline group and 1 participant in the IVIG group. Deaths are listed as 0 in each group. The group sizes associated with the safety summaries are 9 and 8, respectively.

These are counts of participants affected, not counts of all event episodes. The record does not provide serious adverse event terms, and the serious-event term list is empty. It does not describe the other adverse events, their severity, timing, relationship to study treatment, or whether any participant had more than one event. The category “other adverse events” should therefore not be interpreted as a uniform type of event.

Zero reported serious adverse events and zero deaths are the posted counts for this study; they do not establish that the risk of such events is absent. A study with the group sizes offers limited information about uncommon events. Safety comparisons also need to be read in light of the exposure period and completeness of reporting, neither of which is fully described in the registry record. These figures are descriptive counts, not medical advice or a comprehensive safety assessment.

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

The primary result describes a threshold-based seizure-frequency outcome over baseline to 5 weeks. The posted counts are 2 participants meeting the threshold in the placebo/normal saline group and 6 in the IVIG group. The registry record also reports an odds ratio of 10.5, a 95% confidence interval from 1.1 to 98.9, and p = 0.044 from an analysis labeled one-sided. The interval is broad, and the record does not identify the odds-ratio coding direction.

These results do not establish the size of a precise or lasting difference. The confidence interval indicates substantial uncertainty in the estimated odds ratio, and the participant counts do not show the range of individual seizure-frequency changes. A threshold endpoint does not distinguish among participants who meet the cutoff to different degrees, or among those who do not meet it.

The primary comparison concerns the blinded phase and the 5-week endpoint. The placebo group’s planned IVIG infusions after the blinded phase do not provide a reported comparison of later outcomes in the registry record for this analysis. The registry record does not report longer-term seizure results, the cognitive assessment result, or individual-level outcome data.

The p-value is tied to a one-sided test, while the direction of the test and full analysis plan are not reported. The reason for termination, analysis populations, and missing-data handling are also not reported. These limits mean the posted result is best read as a small study’s reported outcome and sponsor analysis, with uncertainty and incomplete analysis detail—not as a definitive answer to every question about IVIG, seizures, or later outcomes.

No medical decision follows from these statistics alone. The data describe what was recorded for this trial; they do not establish an individual participant’s likely outcome or replace a broader assessment of evidence and clinical context.

15. Why This Trial Matters Statistically

This trial is statistically instructive because its primary outcome is a binary responder count, while the registry also reports an odds ratio and a one-sided test. Readers need to distinguish the observed counts from the model-based comparison. The counts are directly stated; the odds ratio depends on a coding convention that is not reported. The result illustrates why effect estimates need clear definitions of which group is in the numerator and which outcome is treated as the event.

The wide confidence interval is also important. A single point estimate can appear to give a definite answer, but the interval indicates that the estimated magnitude is uncertain. With the small group sizes listed in the registry, binary outcomes offer limited information for estimating a stable treatment contrast. The confidence interval helps make that uncertainty visible, although it does not resolve questions about methods or missing data.

The registry’s description of the analysis as one-sided makes prespecification especially relevant. In general, the direction of a one-sided test should follow a stated hypothesis rather than be selected after seeing the data. The registry record does not report the planned direction or complete analysis plan, so this feature cannot be fully evaluated.

The study also highlights the difference between an observed result and a planning calculation. Sample-size illustrations based on an observed effect are hypothetical planning exercises, not evidence that the trial had a particular probability of detecting an effect. The record does not report the trial’s own sample-size rationale. Clear separation of planning assumptions from observed results is essential when interpreting a small trial.

Finally, the reported terminated status, sparse safety counts, and absent details about missing data and multiplicity constrain what can be inferred. These are not reasons to discard the posted results; they are reasons to state carefully what the record establishes and what remains unknown.

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.

The registry record lists 17 participants enrolled and group sizes of 9 and 8. These small groups limit the amount of information available for estimating a binary outcome and make the reported odds ratio imprecise, as reflected in its broad 95% confidence interval from 1.1 to 98.9. The result is based on a threshold response and does not preserve the underlying seizure-frequency values.

The odds-ratio coding convention is not reported. Although the group order is listed, that alone does not establish which group’s odds form the numerator. The method is described as “t-test, 1 sided,” but the analysis details, test direction, and rationale are not reported. This makes the inferential result harder to assess independently.

The registry record does not report the analysis population, missing-data methods, randomization procedure, allocation concealment, or the roles included in quadruple masking. It does not report the reason for termination, a detailed protocol, or the statistical analysis plan. The listed secondary outcome is change in cognitive assessment, but its instrument and result are not reported in the registry record for this analysis. Multiplicity procedures are not reported.

The primary endpoint is limited to baseline to 5 weeks. The registry record does not report later seizure outcomes or a comparison after the placebo group received IVIG. Safety reporting gives counts, but does not provide event descriptions or exposure details. These trial-specific limitations restrict interpretation of precision, analysis conduct, longer-term outcomes, and safety beyond the posted counts.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: IVIG in Patients With VGKC Ab Associated Autoimmune Epilepsy — NCT02697292.
• Registry record last updated 2019-12-30; status last verified 2019-12.
• Results first posted 2019-12-30.
• 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.

20. Record Summary

The registry record describes a randomized, double-blind, placebo-controlled, parallel-group Phase 3 study of IVIG for autoimmune epilepsy associated with VGKC antibodies. Mayo Clinic is listed as the sponsor, enrollment is 17, and the status is terminated. The reason for termination is not reported in the registry record.

The primary outcome counts participants with at least a 50% reduction in seizure frequency from baseline to 5 weeks. The posted counts are 2 in the placebo/normal saline group and 6 in the IVIG group. The registry reports an odds ratio of 10.5, a 95% confidence interval from 1.1 to 98.9, and p = 0.044, with the method labeled “t-test, 1 sided.” The odds-ratio coding direction and fuller analysis details are not reported.

Change in cognitive assessment is listed as a secondary outcome. Serious adverse events and deaths are listed as 0 in each group; other adverse events are listed for 4 participants in the placebo/normal saline group and 1 in the IVIG group. Missing-data handling, analysis populations, multiplicity procedures, and the reason for termination are not reported in the registry record.