Does Valproate Increase Levels of Folate Receptor Autoantibodies in Women?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Does Valproate Increase Levels of Folate Receptor Autoantibodies in Women? (NCT01231646), a registered phase not stated study. The primary outcome is Levels of Folate Receptor Autoantibodies.

2. Clinical Question

3. Trial Design

This completed study record describes a comparison of women in Lamotrigine and Valproate groups. The registry lists enrollment of 38. The study start is recorded as 2010-10, and primary completion as 2013-04. The sponsor is Northwell Health. The record gives no further description of recruitment, eligibility, follow-up, or the process used to place participants in the groups.

The arms are described as having no intervention, and allocation is not stated. The record explicitly notes that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Consequently, the design information does not support treating the group contrast as if it arose from randomized assignment. The record does not explain whether group membership reflects prior clinical decisions, participant characteristics, or another process.

Serum samples from both groups were assessed using ELISA assays with immobilized folate receptor protein. The stated assessment occurred on the same day after informed consent was obtained. The record lists one primary outcome measure, but no analysis results are posted. Details such as a prespecified statistical model, adjustment variables, handling of missing measurements, and analysis populations 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 Levels of Folate Receptor Autoantibodies, measured over On the same day after informed consent was obtained.

The primary endpoint is Levels of Folate Receptor Autoantibodies, expressed in ug/mL. It is described as a continuous measure summarized by a mean and standard deviation. The assay description specifies serum titers of immunoglobulin G, immunoglobulin M, and combined immunoglobulin G and immunoglobulin M directed to folate receptor. These measurements characterize antibody levels in the sampled women; they are not themselves a direct measurement of folate function or a clinical outcome.

ELISA is an assay method used to quantify target substances through an enzyme-linked detection process. In this study description, immobilized folate receptor protein is used to assess binding antibodies in serum. As a general statistical point, a continuous endpoint preserves information about the measured level rather than reducing it to a category such as present or absent. Comparing group means can describe an average difference, while standard deviations describe variation among individual measurements.

The record specifies the timing as the same day after informed consent. It does not report actual titers, group means, standard deviations, or a numerical comparison. Therefore, the endpoint definition is available, but the magnitude and precision of any group contrast are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous, and the registry identifies the mean as its summary measure and the standard deviation as its measure of dispersion. In general, a mean describes the center of a set of measurements. A standard deviation describes how spread out individual values are around that center. These statistics answer different questions: the mean characterizes the group average, while the standard deviation characterizes variability among participants.

For a comparison of two group means, a statistical analysis can estimate the difference in averages and quantify uncertainty around that estimate. A confidence interval is a range generated by a statistical procedure to express the precision of an estimate. Narrower intervals generally indicate greater precision under the model assumptions; wider intervals indicate less precision. A confidence interval is not a guarantee that the true value lies in the particular interval. No interval or estimated difference is reported in the registry record, so those interpretations cannot be applied to this study’s results.

A p-value, when reported, describes how compatible the observed data are with a specified null model, given the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. No p-value or inferential analysis is reported for this outcome. The registry record therefore does not support a claim about statistical significance.

What does the design imply for a group comparison?

General statistical reasoning distinguishes randomized comparisons from comparisons in which allocation is not established as random. Randomization can help balance measured and unmeasured characteristics on average, while a nonrandomized comparison can retain differences between groups that complicate interpretation. Here, the record says allocation is not stated and that the arms are not a like-for-like control comparison. It does not describe adjustment for participant characteristics or other methods that might address group differences. No causal interpretation is established by the record.

The arm labels are Lamotrigine and Valproate, but both arm descriptions say “No intervention.” The registry does not explain the meaning of that wording or how the group labels relate to medicine use. It would be inappropriate to infer a treatment protocol, exposure duration, or assignment mechanism from the labels alone.

How should the sample-size illustrations be read?

The registry’s assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They also describe planning for stated fractions of the observed effect. These are illustrations under stated assumptions, not evidence that the original study was designed around those calculations. The registry record does not report the trial’s own sample-size justification. Actual planning values are not stated in the registry record.

As a general concept, a sample-size calculation asks how many participants would be needed under assumed conditions to detect an effect of a specified size with a chosen statistical approach. Its output depends on the effect targeted, variability, allocation, and analysis assumptions. A planning illustration based on an observed effect is especially dependent on that effect estimate; it should not be described as observed power. The registry’s assumptions do not make an unreported result available and do not establish how precisely the study estimated its endpoint.

What role do distributional assumptions play?

The sample-size assumptions specify a normal approximation. In general, such an approximation uses a model in which the relevant statistic is treated as approximately normally distributed. Whether an approximation is adequate depends on features of the data and the method, and the record does not report diagnostics or an analysis model. For continuous outcomes, unusual values or strongly asymmetric distributions can affect means and uncertainty estimates. The registry provides no distributional summaries with which to assess those issues.

Over-dispersion is a general concern when data vary more than a chosen model expects. It can make model-based uncertainty too small if not accommodated. The endpoint is described as continuous, but no model details or data distributions are reported; there is no basis to say that over-dispersion was present or that a specific correction was needed.

Finally, the assay description identifies three antibody quantities, while the registry lists one primary outcome measure. The record does not clarify whether these quantities were analyzed separately, whether one was designated as the principal contrast, or how any multiple comparisons were handled. The absence of posted analyses means that the statistical method actually used cannot be established.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, but its description refers to immunoglobulin G, immunoglobulin M, and combined immunoglobulin G and immunoglobulin M titers. The record does not explain whether these were treated as separate analyses, how the combined measurement was constructed, or whether one measurement was designated as the principal test. A multiplicity adjustment or other approach to interpreting multiple outcomes is not reported in the registry record.

The registry reports zero analyses. It does not provide group means, standard deviations, participant counts for the analyzed endpoint, confidence intervals, or p-values. No account of missing measurements, exclusions, or analysis populations is reported. The enrollment figure alone does not establish how many participants contributed endpoint data or how any incomplete records were handled.

In general, missing-data methods matter because the amount and pattern of missingness can affect the estimate and its uncertainty. Analysis populations also matter because results may depend on which participants are included and under what rules. Those are general considerations, not descriptions of procedures used in this study: the registry record does not report such procedures.

Adverse-event fields list zero participants at risk or affected in the displayed categories, while deaths are null and no serious-event terms are listed. These fields do not provide a detailed adverse-event analysis. They should not be read as a complete account of safety outcomes or as evidence that no events occurred.

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

The record establishes that the study was completed, enrolled 38, and assessed serum folate receptor autoantibody levels in women in Lamotrigine and Valproate groups. It describes ELISA testing of immunoglobulin G, immunoglobulin M, and combined immunoglobulin G and immunoglobulin M titers. It does not report the measured values or analyses.

As a result, the posted record does not show whether average antibody levels differed between the groups, how large any difference was, or how precisely it was estimated. It cannot establish that the groups were equivalent, and it cannot establish that they differed. A missing result is not a null result.

The outcome is a laboratory measurement of antibody titers. The description does not report a clinical outcome, a measure of folate function, or pregnancy outcomes. The brief summary provides context about folate and certain birth defects, but the endpoint described in the registry is autoantibody level. An antibody measurement should not be treated as direct evidence about a clinical outcome that was not measured in the reported endpoint.

The design note also limits interpretation. Allocation is not stated, and the arms are not a like-for-like control comparison. Even if a numerical group difference were available, the record would not by itself show that group membership caused the difference. The registry record does not report the information needed to assess potential group differences or any adjustment intended to address them.

Accordingly, the record supports a description of the research question, comparison groups, assay, and endpoint timing, but not a conclusion about the size, direction, statistical significance, or clinical implications of a group contrast. Those outcomes are not reported in the registry record.

12. Why This Trial Matters Statistically

This record illustrates a basic distinction in clinical-trial interpretation: a clearly described research question is not the same as an interpretable result. The registry identifies a comparison of folate receptor autoantibody levels between Lamotrigine and Valproate groups and describes the assay and endpoint. It does not report the outcome values or analyses needed to quantify the comparison.

That gap matters statistically because an endpoint definition alone gives no information about the observed group means, the spread of measurements, or the precision of an estimated contrast. Without those quantities, neither the size of a possible difference nor the uncertainty around it can be assessed. The absence of a reported test also means that no conclusion about statistical significance can be drawn.

The record is also a useful example of why design information matters alongside outcome statistics. Allocation is not stated, and the registry explicitly says the arms are not a like-for-like control comparison. A group contrast in that setting would need cautious interpretation even if numerical results were available, because differences between groups could contribute to the observed pattern.

Finally, the endpoint description names multiple antibody measurements while the registry lists one primary outcome measure. Clear reporting of which measurements were analyzed and how would help readers understand the role of multiplicity and the scope of any conclusion. Here, that information and the analysis results are not reported. The statistical lesson is not that the comparison has a particular outcome, but that valid interpretation depends on transparent reporting of both design and results.

13. 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 main trial-specific limitation is that the registry record does not report outcome results. No group means, standard deviations, effect estimate, confidence interval, or p-value are available. Thus, the magnitude, direction, and precision of the primary comparison cannot be assessed.

The study design description is limited. Allocation is not stated, and the record identifies the arms as not a like-for-like control comparison. The arm descriptions say “No intervention,” despite the group labels naming Lamotrigine and Valproate. The registry does not clarify treatment exposure, assignment, duration, or the reason for this wording. These omissions prevent a more detailed account of the comparison.

The description names three antibody titers, but does not explain their individual analysis or how the combined immunoglobulin measurement relates to the other two. Although one primary outcome measure is listed, no analysis plan or multiplicity approach is reported. The record also gives no endpoint-specific sample size, missing-data accounting, participant characteristics, or analysis-population definition.

The registry’s sample-size assumptions describe planning illustrations but do not provide their numerical outputs or the trial’s own sample-size justification. The adverse-event fields are not a detailed event summary. These limitations are specific to what the registry record reports and do not establish what procedures or analyses may have occurred outside the record.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Does Valproate Increase Levels of Folate Receptor Autoantibodies in Women? — NCT01231646.
• Registry record last updated 2015-11-20; status last verified 2015-10.
• Results first posted 2015-10-23.
• 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.

17. Record Summary

The registry record identifies NCT01231646 as a completed study sponsored by Northwell Health. It lists enrollment of 38, a start date of 2010-10, and primary completion in 2013-04. The conditions are epilepsy and psychiatric or mood diseases or conditions. The study compares women in Lamotrigine and Valproate groups; allocation is not stated, and the record notes that the arms are not a like-for-like control comparison.

The primary endpoint is folate receptor autoantibody levels in ug/mL, measured by ELISA in serum on the same day after informed consent. The description names immunoglobulin G, immunoglobulin M, and combined immunoglobulin G and immunoglobulin M titers. The registry reports no analyses and no outcome values, so no numerical group comparison or estimate of precision can be interpreted.