Optimal Bupivacaine Dose for Initiation of Labor Epidural Techniques: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optimal Bupivacaine Dose for Initiation of Labor Epidural Techniques (NCT04814537), a randomized phase 4 study. The primary outcome is ED90.

2. Clinical Question

3. Trial Design

This completed Phase 4 study is registered as NCT04814537 and is titled “Optimal Bupivacaine Dose for Initiation of Labor Epidural Techniques.” Brigham and Women's Hospital is the listed sponsor. The registry describes a randomized, triple-masked, parallel-group trial with planned enrollment of 100. The recorded start date is 2021-02-25, the primary completion date is 2022-03-23, and the status is COMPLETED.

The two arms are the Dural Puncture Epidural Technique and the Conventional Epidural Technique, called EPL in the arm description. Both descriptions specify bupivacaine 0.25% diluted to 20 mL with isotonic sterile 0.9% saline. Each says that the first subject in that arm would receive an initial dose of bupivacaine 25 mg. The listed intervention is bupivacaine hydrochloride.

The endpoint is framed as an ED90 dose estimate for each technique, rather than as a simple count of participants meeting a target or as a single average pain score. The registry lists 45 participants for the DPE arm and 50 for the EPL arm in the posted outcome. These arm-level counts should not be treated as a complete account of the analysis population: the population used for the endpoint and the handling of participants without evaluable endpoint data are not reported in the registry record.

Randomization and masking describe the trial's registered design, but the allocation procedure, who was masked, and how masking was maintained are not reported in the registry record. The registry also does not report the planned dose-allocation procedure, the statistical model, or a detailed analysis plan. Those omissions limit how fully the design and the derivation of the ED90 values can be reconstructed from the 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 ED90, measured over 30 minutes.

The primary endpoint is ED90, expressed in milligrams. It is defined as the bupivacaine dose with which 90% of participants achieve adequate analgesia, with adequate analgesia specified as NRS<3 at 30 minutes. It therefore combines a clinically defined response threshold with a dose estimate: the quantity of interest is the dose associated with a target response probability, rather than the response proportion at one fixed dose.

This type of endpoint is used when the research question concerns the dose corresponding to a chosen level of response. It can summarize a dose-response relationship in a way that is directly tied to a specified response target and assessment time. The target of 90% is part of the endpoint definition in this trial; it does not mean that 90% of the enrolled participants necessarily achieved the outcome.

The registry reports ED90 values of 29.3 mg for DPE and 45.25 mg for EPL. It does not report confidence intervals, standard errors, or other uncertainty measures for these values. Nor does it report the underlying participant-level dose and response data. Consequently, the precision of each estimate and the information supporting it cannot be assessed from the posted summary alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does ED90 represent?

ED90 is a dose-response quantity. In this trial, its definition is the bupivacaine dose associated with adequate analgesia in 90% of participants, where adequate analgesia means NRS<3 at 30 minutes. Unlike a mean pain score, ED90 is tied to a response threshold. Unlike a simple response percentage, it expresses the dose associated with a target probability of response.

In general, a dose-response analysis uses information about doses and whether the response criterion was met to estimate how response probability changes across dose levels. The ED90 is then a point on that estimated relationship. This is a general explanation of the endpoint concept; the registry record does not report the dose-response model or estimation procedure used in this trial. It is therefore not possible to say whether the posted estimates came from a particular parametric model, a nonparametric method, or another approach.

Why does uncertainty matter?

A point estimate is a single value used to summarize an estimated quantity. It does not show how much statistical uncertainty surrounds that value. In general, a confidence interval communicates a range of values compatible with the data and the method under stated assumptions. A narrow interval would indicate greater precision than a wide interval, although interpretation also depends on the validity of the model and the quality of the data.

The registry posts ED90 estimates of 29.3 mg for DPE and 45.25 mg for EPL, but it does not report confidence intervals or another uncertainty measure. The values therefore do not reveal how precisely each target dose was estimated. They also do not show whether the data support a sharply defined dose-response curve or whether the estimate is sensitive to modeling choices.

What would a comparison require?

In general, comparing two point estimates requires more than reading their numerical values side by side. A formal comparison should account for uncertainty in both estimates and the structure of the analysis. Depending on the analysis plan, this might involve an interval or test for a contrast, or a joint model of the dose-response relationships. The registry does not report such a contrast, a p-value, or its method. No formal claim about a difference between the two techniques can therefore be drawn from the posted point estimates alone.

The randomized, parallel-group design is relevant to the intended comparison, but it does not substitute for reporting the analysis. Randomization can help balance groups on average, while masking can reduce some opportunities for biased assessment or care. The registry labels the study randomized and triple masked; it does not give further details about allocation, which roles were masked, or the analysis used to estimate ED90. General design concepts should not be mistaken for confirmation that particular safeguards or analytic procedures were implemented beyond what the record states.

What do the arm counts tell us?

The outcome listing gives arm counts of 45 for DPE and 50 for EPL. Counts describe the reported outcome groups, but they do not establish how many observations entered the ED90 calculation, which doses were represented, or how missing response assessments were treated. A dose-response estimate can depend on the distribution of observations across dose levels and on the observed response pattern, not only on the total arm count. The underlying dose and response data are not reported in the registry record.

In general, over-dispersion can occur when observed response variability exceeds what a simple statistical model expects. If present and ignored, it can make uncertainty estimates too optimistic. The registry does not report whether over-dispersion was assessed or whether the chosen analysis addressed it; this is a general methodological consideration, not a claim that over-dispersion occurred in this trial.

What is not documented?

The registry lists one outcome measure and no posted analyses. It does not report the sample-size justification, statistical analysis plan, model form, estimation method, confidence intervals, interim analyses, or prespecified handling of missing data. These omissions prevent a detailed appraisal of model assumptions, precision, and the distinction between planned and exploratory analyses.

The registry's sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations are planning calculations, not observed power and not evidence about the trial's original design rationale. No numerical planning results are stated in the record used for this interpretation, so no additional sample-size values can be characterized.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, ED90, and reports no secondary outcomes. It lists no posted analyses. This limited outcome listing does not establish whether the trial protocol included additional outcomes or analyses that were not entered in the registry.

Multiplicity arises when several outcomes, treatment contrasts, time points, or subgroups are tested or estimated. In general, repeated inferential testing can increase the chance of a false-positive finding if the analysis does not account for the number and structure of the tests. Whether that concern applies, and whether any adjustment was planned, cannot be determined from the registry record. The statistical plan and any multiplicity strategy are not reported.

The record does not describe missing-data methods or identify an analysis population such as intention-to-treat or per-protocol. The outcome arm counts are 45 for DPE and 50 for EPL, while the registry enrollment is 100. These fields do not explain why their counts differ or whether any outcome measurements were missing, excluded, or otherwise unavailable. No reason for the count pattern should be inferred from the record.

For a dose-response endpoint, missingness may matter if the probability of missing an assessment is related to dose, response, or other participant characteristics. This is a general concern, not evidence that such a pattern occurred in this trial. Without participant flow, missingness details, and analysis-population definitions, the robustness of the ED90 estimates to incomplete outcome information cannot be assessed.

11. 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.

The registry reports zero serious adverse events in each arm. For serious adverse events, the listed number at risk is 50 in the DPE arm and 50 in the EPL arm; the number affected is 0 in each. The record also lists zero deaths in both arms.

These figures describe the safety counts entered in the registry. They do not show that the risk of serious adverse events is zero, nor do they establish that the techniques have equivalent safety. When no events are observed in a group, the true event risk remains uncertain; the amount of uncertainty depends in part on the number observed and the follow-up and ascertainment procedures. The registry does not report confidence intervals for these safety results or additional detail about event definitions, monitoring, or follow-up.

The serious-event counts should be read separately from the primary ED90 endpoint. They do not measure analgesic response, and the efficacy estimates do not summarize safety. The registry lists no top serious adverse-event terms. This is a description of the posted safety record, not a basis for medical advice or a complete assessment of harms.

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

The result provides one posted ED90 estimate for each registered epidural technique: 29.3 mg for DPE and 45.25 mg for EPL. Each value is intended to represent the dose associated with the specified response target, NRS<3 at 30 minutes in 90% of participants. The estimates make the trial's dose-focused question explicit and distinguish the target dose from a pain score measured in an individual participant.

The results do not report the proportion of participants who achieved the response at a particular dose, and the two values are not themselves a direct comparison test. The registry gives no interval or other measure of uncertainty for either estimate and no p-value or contrast between techniques. The numerical separation of two point estimates cannot establish the strength, precision, or statistical significance of a difference.

The record also does not document the model used to derive ED90, the analysis population, the handling of missing observations, or the dose-response data underlying the estimates. That means readers cannot judge from the summary whether alternative reasonable methods would yield similar values. The posted arm counts provide context but do not resolve these questions.

Interpretation should remain bounded by the registered population and endpoint: laboring women, the described epidural techniques, bupivacaine, and the NRS<3 threshold at 30 minutes. The registry does not establish how the estimates relate to other settings, later pain assessments, different thresholds, or other outcomes. Nor do the posted safety counts establish an absence of risk.

In short, the record reports two dose estimates tied to a clearly stated response target, but leaves their precision and comparative meaning uncertain. It supports a descriptive account of the estimates, not a definitive conclusion about which technique has a lower ED90 or about clinical benefit.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is a target dose derived from a response probability, rather than a conventional mean or a response rate at one fixed dose. ED90 translates a stated response goal into a dose estimate. That makes the analysis dependent on how the relationship between dose and response is represented and on how much information the data contain across the dose range.

Reporting only the point estimates leaves a central part of the statistical story unresolved: precision. Confidence intervals or other uncertainty measures would help readers understand how stable each ED90 estimate is. A direct contrast with uncertainty would also be needed to assess the evidence for a difference between techniques. Neither is reported in the registry record.

The randomized and triple-masked labels describe important design features, but sound interpretation also depends on clear reporting of the analysis population, missing-data handling, and estimation method. The registry does not report these details. Their absence is especially relevant for a modeled dose endpoint, because readers cannot evaluate assumptions or reproduce the estimates from the posted summary.

The study therefore illustrates a broader biostatistical point: a clinically interpretable target can still be difficult to assess without the model, uncertainty, and analysis details that produced it. The reported ED90 values offer a concise summary, while the missing methodological information limits what can be concluded about their reliability and comparability.

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 registry record leaves several trial-specific limitations that constrain interpretation. It does not report confidence intervals, standard errors, or another measure of uncertainty for either ED90 estimate. The two posted values are therefore point estimates without a stated indication of precision. No formal test or estimate of the contrast between DPE and EPL is reported.

The method used to estimate ED90 is not described. The record does not identify the dose-response model, estimation procedure, model checks, or assumptions. Participant-level dose and response data are also not reported, so the values cannot be independently reconstructed from the registry summary. The number of observations contributing to each estimate is not made explicit beyond the arm counts listed with the outcome.

There is no reported account of participant flow, missing outcome data, exclusions, or analysis populations. The record also does not describe how masking was implemented, how the randomized allocation was generated or concealed, or whether any interim analyses took place. These omissions do not demonstrate that such procedures were absent; they mean they are not reported in the registry record.

The endpoint is narrowly defined as NRS<3 at 30 minutes. The posted estimates do not address other assessment times or response thresholds. Finally, the safety summary reports no serious adverse events, but does not include uncertainty intervals or detailed monitoring information. These limitations call for a cautious reading of the posted estimates rather than a broader claim about comparative effects or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Optimal Bupivacaine Dose for Initiation of Labor Epidural Techniques — NCT04814537.
• Registry record last updated 2026-08-04; status last verified 2026-07.
• Results first posted 2026-08-04.
• 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.

18. Record Summary

NCT04814537 is a completed Phase 4 randomized, triple-masked, parallel-group trial sponsored by Brigham and Women's Hospital. It studied bupivacaine for labor epidural pain relief using the Dural Puncture Epidural Technique and the Conventional Epidural Technique, identified as EPL in the record. The registry lists enrollment of 100 and records the trial start as 2021-02-25 and primary completion as 2022-03-23.

The primary outcome is ED90 in milligrams: the dose associated with NRS<3 at 30 minutes in 90% of participants. The posted values are 29.3 mg for DPE and 45.25 mg for EPL. The registry does not report uncertainty intervals or a direct statistical comparison. It lists zero serious adverse events and zero deaths in each arm. The dose-estimation method, missing-data handling, and analysis population are not reported in the registry record.