This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Epidural Neostigmine for Labor Pain (NCT00779467), a randomized phase 1 study. The primary outcome is Amount of Drug Consumed Per Hour in Each Group(Arm).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00779467 |
| Phase | Phase 1 |
| Condition | Labor Pain |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 200 |
| Arms in the primary outcome | 4 |
| Lead sponsor | Wake Forest University |
| Results posted | Yes |
2. Clinical Question
Population
People receiving epidural analgesia for labor pain. The registry record gives an enrollment of 200, but does not report further eligibility details or a fuller description of the analyzed population.
Intervention
Bupivacaine infusions with epidural neostigmine at 8 mcg/ml, 4 mcg/ml, or 2 mcg/ml. Neostigmine was being assessed as an additive to the numbing medication used in an epidural during labor.
Comparator
The listed comparator arm received bupivacaine with fentanyl 2 mcg/ml, described in the registry record as the standard infusion. The primary outcome is reported for all four groups.
Primary question
How did median hourly total bupivacaine consumption until delivery vary across the four infusion groups? Although this outcome is reported by group, the registry record does not report a statistical comparison or an estimate of the difference between groups.
The study is titled “Epidural Neostigmine for Labor Pain,” and its official title describes a neostigmine dose-response study. That framing suggests an interest in comparing several concentrations, but the record does not report a formal dose-response model or a prespecified hypothesis about the shape of a dose pattern. The posted outcome is drug consumption, not a direct numerical measure of pain relief. Patient satisfaction and several other outcomes are listed as secondary outcomes, but most do not have numerical results in the record.
The primary group summaries are medians with interquartile ranges. The 8 mcg/ml group had a median of 16.2 milliliters per hour (interquartile range 12.0 to 23.0); the 4 mcg/ml group, 14.6 (12.0 to 18.0); the 2 mcg/ml group, 15.3 (13.0 to 19.0); and the fentanyl group, 16.0 (13.0 to 21.0). These are descriptive values. Without a reported comparison, they do not establish whether observed differences are distinguishable from chance variation or whether a particular dose is preferable.
3. Trial Design
The registry describes a Phase 1, randomized, double-masked, parallel-group study sponsored by Wake Forest University. Its status is completed. The listed study start is 2008-10 and the primary completion is 2013-11. The registry enrollment is 200. The four reported groups received bupivacaine with neostigmine 8 mcg/ml, 4 mcg/ml, or 2 mcg/ml, or bupivacaine with fentanyl 2 mcg/ml.
Random allocation means the study assigned participants to groups rather than relying only on treatment choices made outside the study. Double masking indicates that two categories of people were intended to be unaware of group assignment, but the registry record does not identify those categories or give operational details of masking. A parallel-group design assigns participants to a group and follows that assignment rather than having each participant receive several study regimens in sequence. The record does not report the allocation ratio, sequence-generation method, concealment procedures, or what happened if an assigned infusion was not received.
The recorded arm counts for the primary outcome are 38, 40, 38, and 35, respectively. These counts differ from the registry enrollment figure, but the record does not explain the difference or state how many participants were randomized, treated, excluded, or included in each analysis. The primary outcome timeframe is until delivery. The record does not report a detailed protocol, eligibility criteria, recruitment location, or a statistical analysis plan. It also does not report how the study handled changes in treatment, early discontinuation, or missing observations.
The study lists nausea, sedation, shivering, pruritus, Bromage Score, patient satisfaction scores, and cesarean delivery as secondary outcomes. Numerical results are posted for nausea, sedation, and shivering. Numerical results for pruritus, Bromage Score, patient satisfaction scores, and cesarean delivery are not reported in the registry record. The record also does not report a rationale for the chosen enrollment or a sample-size justification. No conclusions about the protocol’s design assumptions can be drawn from the registry entries 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
| Stage | Bupivacaine With Neostimgine 8 mcg/ml | Bupivacaine and Neostigmine 4 mcg/ml | Bupivacaine With Neostigmine 2 mcg/ml | BUPIVACAINE WITH FENTANYL 2 MCG/ML |
|---|---|---|---|---|
| STARTED | 53 | 45 | 48 | 54 |
| COMPLETED | 38 | 40 | 38 | 35 |
| NOT COMPLETED | 15 | 5 | 10 | 19 |
Reasons for not completing this period:
| Reason | Bupivacaine With Neostimgine 8 mcg/ml | Bupivacaine and Neostigmine 4 mcg/ml | Bupivacaine With Neostigmine 2 mcg/ml | BUPIVACAINE WITH FENTANYL 2 MCG/ML |
|---|---|---|---|---|
| Lack of Efficacy | 11 | 2 | 6 | 11 |
| failed inclusion criteria | 3 | 3 | 1 | 2 |
| missing data | 1 | 0 | 1 | 4 |
| technical issue | 0 | 0 | 2 | 1 |
| unavailable research staff | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: median hourly total bupivacaine consumption in each group, in ml/hr
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.
| Characteristic | Unit | Bupivacaine With Neostimgine 8 mcg/ml | Bupivacaine and Neostigmine 4 mcg/ml | Bupivacaine With Neostigmine 2 mcg/ml | BUPIVACAINE WITH FENTANYL 2 MCG/ML | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 38 | 40 | 38 | 35 | 151 | |
| Age, Continuous | years | 28 (SD 5) | 27 (SD 6) | 28 (SD 6) | 27 (SD 6) | 27.5 (SD 5.75) |
| Sex: Female, Male: Female | Participants | 38 | 40 | 38 | 35 | 151 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Amount of Drug Consumed Per Hour in Each Group(Arm), measured over until delivery.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | milliliters per hour |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is median hourly total bupivacaine consumption, measured in milliliters per hour until delivery. It describes the typical rate at which bupivacaine was consumed in each assigned group during the stated period. The reported summaries pair each median with an interquartile range, which gives the interval from the 25th to the 75th percentile of the observed distribution. This describes the middle half of the group’s values, not the uncertainty around the median.
Drug consumption can be used to describe how much of the background epidural medication was used under each infusion regimen. In a dose-response study, group consumption summaries may help characterize whether consumption varies across the assigned concentrations. However, consumption alone is not a direct measure of pain intensity, patient experience, or satisfaction. It can be affected by how medication was administered and by clinical decisions during labor; the registry record does not provide details on those factors.
The medians were 16.2, 14.6, 15.3, and 16.0 milliliters per hour for the 8 mcg/ml, 4 mcg/ml, 2 mcg/ml, and fentanyl groups, respectively. Their interquartile ranges were 12.0 to 23.0, 12.0 to 18.0, 13.0 to 19.0, and 13.0 to 21.0. These descriptive summaries permit a side-by-side account of the observed distributions, but they do not provide a formal test or an interval estimate for a difference between groups. The registry record does not report a primary endpoint comparison, p-value, or confidence interval.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary results describe median hourly bupivacaine consumption until delivery in four groups. The 8 mcg/ml neostigmine group had a median of 16.2 milliliters per hour, with an interquartile range of 12.0 to 23.0. Corresponding results were 14.6 (12.0 to 18.0) for 4 mcg/ml, 15.3 (13.0 to 19.0) for 2 mcg/ml, and 16.0 (13.0 to 21.0) for bupivacaine with fentanyl 2 mcg/ml. The observed medians are relatively close in scale, but that descriptive impression is not a test of equality or equivalence. The record does not report a primary statistical comparison, confidence interval, or p-value, so the precision of between-group differences cannot be assessed from the posted primary endpoint results.
The secondary outcomes with numerical summaries are means and standard deviations for nausea, sedation, and shivering until delivery. Recalculated, unadjusted comparisons use the 8 mcg/ml group as the reference for the posted 4 mcg/ml and 2 mcg/ml comparisons. For nausea, the estimated mean differences are 0.5 for each comparison, with unadjusted p-values of 0.423 and 0.43. For sedation, the estimated differences are 0.1 and 0.0, with unadjusted p-values of 0.883 and 1.0. For shivering, the estimated differences are 0.1 in both comparisons, with unadjusted p-values of 0.27 and 0.336.
The confidence intervals associated with these recalculated comparisons include zero. That means the estimates are compatible with a range of possibilities that includes no mean difference, as well as differences in either direction. The intervals are not narrow enough to establish that groups are alike. Nor should the estimated directions or magnitudes be treated as definitive evidence of a difference: these are secondary, unadjusted recalculations, and the registry does not report sponsor analyses for them. Their interpretation is further limited by the number of outcomes considered and the absence of reported multiplicity procedures.
The posted primary summaries and the available secondary results address different aspects of the study. The primary outcome is a median rate of bupivacaine consumption; the secondary comparisons concern means on scales for nausea, sedation, and shivering. These outcomes cannot be combined into a single treatment-effect conclusion. The registry record does not report an analysis linking symptom scores to consumption, nor does it provide numerical findings for all listed secondary outcomes. Overall, the record supports a descriptive account of the available group summaries, but does not establish a dose-related pattern or a precise between-group effect on the primary outcome.
9. Statistical Methods Explained
The primary outcome is summarized by a median and an interquartile range. The median is the center of the ordered observations: half of the observed values lie at or below it and half at or above it. Unlike the mean, it is less influenced by unusually high or low observations. The interquartile range describes the middle half of observed values, from the 25th percentile to the 75th percentile. It expresses variability in the participants’ measurements; it is not a confidence interval and does not, by itself, indicate how precisely the group median has been estimated.
For example, the 8 mcg/ml group’s median consumption was 16.2 milliliters per hour, and its interquartile range was 12.0 to 23.0. This says where the group’s central observation and middle half of observations lay. It does not quantify uncertainty about a contrast with another group. A formal comparison would need to specify an estimand and a method suited to the outcome and trial design. The registry record does not report such a primary comparison or identify a method for it. No inferential result for the primary endpoint should be inferred from overlap or non-overlap of interquartile ranges.
The numerical secondary results are means with standard deviations. A mean is the arithmetic average. A standard deviation describes how dispersed individual observations are around that average; it is not the uncertainty of the mean. The recalculated secondary comparisons contrast the 4 mcg/ml and 2 mcg/ml groups with the 8 mcg/ml group, using posted group means, standard deviations, and sample sizes. The mean difference is the contrast between the two group averages, expressed in the outcome’s original units. A positive estimate means the comparison group’s mean is higher than the reference group’s mean for the contrasts presented.
These calculations are labelled recalculated because the registry does not post sponsor-reported analyses for these comparisons. They are simple, unadjusted comparisons based on summary statistics, rather than analyses that account for additional covariates, repeated measurements, or a broader trial model. The registry record does not report whether a different analysis was prespecified or performed outside the posted record. If a sponsor analysis were available, it would take precedence over an unadjusted reconstruction for describing the study’s own analysis.
A confidence interval describes a range of values compatible with the observed data and the statistical assumptions used to construct it. In these comparisons, the intervals include zero. Zero represents no difference between group means. Because the intervals also extend to values on either side of zero, the data do not precisely determine the direction of the mean difference. A p-value measures how inconsistent the data are with a specified null hypothesis under the calculation’s assumptions; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. The posted secondary p-values are unadjusted, and the registry record does not identify a prespecified testing hierarchy or threshold for interpreting them.
General statistical consideration: estimates from smaller groups tend to be less precise than estimates from larger groups when other features are similar. The arm counts for the posted primary outcome range from 35 to 40. Precision also depends on variability, which is represented for secondary outcomes by the standard deviations and for the primary endpoint by the interquartile ranges. The record does not give confidence intervals for the primary medians, so their sampling precision cannot be read directly from the posted primary summaries.
General statistical consideration: multiple testing matters when many outcomes or comparisons are examined. Each additional test creates another opportunity for a result to appear unusual by chance, even when the underlying group effects are absent. Adjustments or a prespecified hierarchy can help control how such findings are interpreted. No multiplicity adjustment or analysis hierarchy is reported in the registry record. Consequently, the secondary p-values should be read as exploratory, individual comparisons rather than as a confirmatory family of tests.
The record includes planning illustrations based on observed secondary effects. These are not the trial’s design justification and are not observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set to a stated fraction of the observed effect. Such illustrations show how sample-size requirements depend on the assumed target effect and analysis assumptions; they do not show that a study had a particular probability of finding an effect after it was completed. The registry record does not report its own sample-size assumptions or justification.
Finally, the distinction between an observed summary and an inferential conclusion is central. Group medians, means, and dispersions describe the posted observations. A comparison estimate adds a contrast, while a confidence interval communicates its uncertainty and a p-value addresses compatibility with a null model under specified assumptions. For the primary endpoint, only group summaries are reported. For the available secondary outcomes, comparison estimates are recalculated, unadjusted results. Neither type of result establishes equivalence, and the record does not report a prespecified equivalence margin or non-inferiority analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical analysis plan, a prespecified hierarchy of outcomes, or procedures for controlling multiplicity. This matters because the study lists several secondary outcomes, and the available secondary comparisons involve more than one group contrast. When many tests are considered, some may appear unusual by chance. Without a stated plan, it is difficult to distinguish confirmatory tests from exploratory ones or to understand whether any adjustment was intended.
The primary endpoint is reported with group medians and interquartile ranges, but no primary comparison, confidence interval, or p-value is reported. The registry record also does not report the analysis population, such as whether analyses included all randomized participants, participants who received an infusion, or only those with an observed outcome. It does not explain how allocation, treatment received, or protocol deviations were handled in the analysis.
Although the registry gives an enrollment of 200, the arm-specific primary outcome counts are 38, 40, 38, and 35. The record does not account for the difference between the enrollment figure and the reported outcome counts. It does not state whether this reflects missing measurements, exclusions, participants not randomized, or another reason. Missing data methods, imputation, and sensitivity analyses are not reported in the registry record. The reason for missingness and its relationship to treatment or outcomes therefore cannot be assessed.
These omissions constrain interpretation rather than demonstrating that an inappropriate method was used. The registry record may not contain every detail from the full study documentation, but analyses or procedures not stated in the record cannot be assumed. Accordingly, the primary endpoint remains descriptive, while the secondary comparisons are unadjusted recalculations and should be read cautiously. No inference about the study’s internal analysis plan or handling of missing data is warranted from the reported summaries alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Bupivacaine With Neostimgine 8 mcg/ml | 0 | 38 | 0.0% |
| Bupivacaine and Neostigmine 4 mcg/ml | 0 | 40 | 0.0% |
| Bupivacaine With Neostigmine 2 mcg/ml | 0 | 38 | 0.0% |
| BUPIVACAINE WITH FENTANYL 2 MCG/ML | 0 | 35 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bupivacaine With Neostimgine 8 mcg/ml | 0 of 38 |
| Bupivacaine and Neostigmine 4 mcg/ml | 0 of 40 |
| Bupivacaine With Neostigmine 2 mcg/ml | 0 of 38 |
| BUPIVACAINE WITH FENTANYL 2 MCG/ML | 0 of 35 |
The adverse-event figures report zero serious adverse events and zero other adverse events in each of the four groups, using group counts of 38, 40, 38, and 35 at risk, respectively. These are the counts recorded in the registry. They should be interpreted as posted event counts, not as proof that no adverse events occurred outside the definitions, observation, or reporting captured by the record.
The registry record does not report deaths; the death entries are blank rather than reported as zero. It also provides no serious adverse-event terms. The listed secondary outcomes include nausea, sedation, shivering, pruritus, Bromage Score, patient satisfaction scores, and cesarean delivery, but the adverse-event figures do not replace those outcome results. Numerical results are posted only for nausea, sedation, and shivering.
The record does not describe the adverse-event collection period, definitions, severity grading, attribution procedures, or completeness of surveillance. The zero counts therefore require this reporting context to be understood, and that context is not reported in the registry record. These figures alone do not support a broad conclusion about comparative safety.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, double-masked, parallel-group Phase 1 study was completed and that group summaries for median hourly bupivacaine consumption were posted. It also provides numerical summaries for three secondary outcomes and adverse-event counts. Those details permit a careful description of the available results, but the primary endpoint is not accompanied by a reported inferential comparison.
The primary medians range from 14.6 to 16.2 milliliters per hour across the four groups, with overlapping interquartile ranges. These summaries show the observed central values and middle-half ranges. They do not establish that the groups differ, that they are the same, or that neostigmine dose caused a change in consumption. A claim of equivalence would require an explicit margin and an appropriate analysis, neither of which is reported in the registry record.
The secondary comparisons are unadjusted recalculations from posted summary statistics. Their confidence intervals include zero, so they do not precisely establish the direction of the group contrasts. They are not a substitute for an analysis reported by the study investigators, and the registry record does not post such analyses for these outcomes. The record also lacks numerical results for several listed secondary outcomes, leaving the secondary evidence incomplete.
These results do not directly quantify pain relief or establish an optimal neostigmine concentration. The primary endpoint measures medication consumption, not pain intensity, and the registry does not report the primary group comparison. Although the study’s stated purpose concerns identifying a dose to use as an additive, the posted results do not report a formal dose-response analysis or the statistical evidence needed to identify one dose as best.
More broadly, the record does not report key details needed to judge precision and potential bias, including missing-data handling, analysis populations, a multiplicity plan, and a primary endpoint analysis. The appropriate interpretation is therefore limited: the listed descriptive values and event counts can be reported as recorded, while comparative or causal conclusions remain unsupported by the information in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its title and stated purpose suggest a dose-response question, while its posted primary outcome consists of descriptive group summaries. Dose-response questions often require more than ranking observed group averages or medians. The analysis needs to define what pattern is being tested and quantify uncertainty around that pattern. The registry record does not report a formal dose-response model or a primary comparison, so readers should separate the study’s motivation from the statistical evidence that is actually posted.
The use of a median and interquartile range for hourly consumption also highlights how outcome summaries shape interpretation. A median describes the center of a distribution and is less sensitive to extreme values than a mean, while the interquartile range describes the central spread. Neither supplies the uncertainty of a between-group contrast. A visual or verbal comparison of these summaries cannot substitute for an estimate and confidence interval for the primary treatment contrast.
The record also illustrates why posted secondary summaries need to be distinguished from trial-reported analyses. The available secondary comparisons are recalculated from group-level summary statistics and are unadjusted. They are useful for descriptive context, but do not reveal whether the study’s investigators prespecified those comparisons or used a different model. They also do not address multiplicity across outcomes.
Finally, enrollment and analyzed group counts are not interchangeable. The record reports both an enrollment figure and smaller arm-specific outcome counts, without explaining the relationship. This does not identify the reason for the difference, but it shows why analysis populations and missing-data accounting matter. A transparent report of participant flow, analysis methods, and uncertainty would be needed to support stronger comparative conclusions.
14. 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 limitation for interpretation is that the registry record reports group medians and interquartile ranges but no inferential comparison for the primary outcome. No confidence interval, p-value, or formal dose-response result is reported. Consequently, the observed differences in median hourly consumption cannot be assessed for statistical precision from the primary results alone.
The record gives enrollment as 200, while primary outcome counts by arm are 38, 40, 38, and 35. It does not explain the relationship between these figures or report participant flow. The numbers do not establish why counts differ, and no assumptions about attrition or exclusions are warranted. Analysis populations, missing-data methods, and sensitivity analyses are not reported.
Only three listed secondary outcomes have numerical summaries in the record. Results for pruritus, Bromage Score, patient satisfaction scores, and cesarean delivery are not reported in the registry record. The available secondary comparisons are unadjusted recalculations and have no accompanying sponsor-reported analyses. The record does not report whether these analyses were planned in advance or how multiple outcomes and comparisons were handled.
Further limits include absent detail on eligibility, allocation procedures, masking implementation, outcome measurement procedures, and adverse-event ascertainment. The registry record also does not report the rationale for enrollment or its statistical design assumptions. The study is listed as Phase 1, but that label alone does not resolve these reporting gaps or establish what analyses were intended.
Finally, consumption is not itself a direct measure of pain relief or satisfaction. Without a reported primary comparison and fuller outcomes, the posted values cannot identify an optimal dose or establish comparative clinical effects. These limitations concern what can be concluded from the registry record; they do not show that unreported analyses or information do not exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Epidural Neostigmine for Labor Pain — NCT00779467.
- Registry record last updated 2018-09-11; status last verified 2018-08.
- Results first posted 2017-04-10.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00779467, “Epidural Neostigmine for Labor Pain,” is a completed Phase 1 randomized, double-masked, parallel-group study sponsored by Wake Forest University. The registry lists an enrollment of 200, a start of 2008-10, and primary completion in 2013-11. The four groups received bupivacaine with neostigmine 8 mcg/ml, 4 mcg/ml, or 2 mcg/ml, or bupivacaine with fentanyl 2 mcg/ml.
The primary outcome is median hourly total bupivacaine consumption until delivery. Group medians and interquartile ranges are posted, but a statistical comparison of the primary outcome is not reported in the registry record. Numerical secondary summaries are available for nausea, sedation, and shivering. Other listed secondary outcomes lack numerical results. Secondary comparisons discussed in the record are unadjusted recalculations, and the registry does not report a multiplicity plan, missing-data methods, or analysis populations. Adverse-event entries show zero serious and other events in each group; deaths are not reported.