Benzocaine Versus Placebo Spray for Pain Relief at Hysterosalpingogram: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Benzocaine Versus Placebo Spray for Pain Relief at Hysterosalpingogram (NCT01925469), a randomized phase 4 study. The primary outcome is Change in Pain Score.

2. Clinical Question

3. Trial Design

This was a completed, randomized, parallel-group Phase 4 trial sponsored by the University of Pennsylvania. The registry lists an enrollment of 30 and 15 participants in each arm for the primary outcome. The study compared benzocaine spray with saline spray during hysterosalpingogram. The record describes the masking as quadruple, but does not identify which roles were masked or explain how masking was maintained. Randomization is recorded; the sequence-generation and allocation-concealment procedures are not reported in the registry record.

The study start is listed as 2011-12, and primary completion as 2012-04. These dates describe the registry record and do not supply additional information about recruitment or follow-up. The study status is completed. The record does not report eligibility criteria, participant demographics, recruitment location, spray dose details beyond the benzocaine concentration, or the timing of spray administration. The exact procedures for data collection and follow-up are also not reported.

The primary outcome was change in pain score, with the stated timeframe of pre-procedure (baseline) and procedure (time 0). The registry also lists patient satisfaction and change in pain score from pre-procedure to 5 minutes post procedure as secondary outcomes. There are 3 outcome measures and 3 analyses recorded. The registry record does not establish whether all participants contributed data to every outcome or analysis, or describe any analysis population.

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 Pain Score, measured over Pre-procedure (Baseline) and procedure (Time 0).

The primary endpoint is change in pain score from the pre-procedure baseline to maximum pain during HSG, designated time 0. Pain was rated on a validated visual analog scale: the patient marked a line representing a range from no pain to extreme pain, and the mark was recorded in millimeters and converted to points on a 0 to 100 scale. A change score is intended to represent how pain differs between the specified assessment times, rather than pain at a single time alone.

The registry lists the endpoint parameter as a median and gives a 95% confidence interval for each arm. The benzocaine arm value is 50.6, with a confidence interval from -7.4 to 98.8; the saline spray arm value is 70.4, with a confidence interval from 19.8 to 100.0. The record describes subtracting the two pain scores but does not specify the subtraction order. That omission limits interpretation of the direction of a change score. Nor are the arm-level intervals a confidence interval for the difference between groups. The endpoint can describe pain-score change, but comparing treatment groups requires an explicit between-group contrast and its uncertainty.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a Wilcoxon (Mann-Whitney) test for the comparison of benzocaine and saline spray. This is a rank-based method: rather than relying on a comparison of group means under a normal-distribution model, it uses the ordering of observations across the groups. In general, the test assesses whether observations in one group tend to rank differently from those in the other. It is often described as a test of medians, but a median-specific interpretation requires additional assumptions about the distributions. If the groups differ in spread or shape, a result can reflect more than a shift in median.

The record identifies medians as the summary parameter for the primary endpoint. A median is the middle of the ordered observations and is less influenced by extreme values than a mean. That can be useful for pain scores, particularly when the distribution is not symmetric. The registry does not report the individual observations or distributional summaries that would show how the scores were spread, whether there were ties, or whether the group distributions had similar shapes. It also does not report whether the Wilcoxon procedure was prespecified or how any test assumptions were assessed.

What does a confidence interval convey?

A confidence interval represents uncertainty around an estimate under the method used to construct it. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The primary outcome record gives separate 95% confidence intervals for the arm-level medians: -7.4 to 98.8 for benzocaine and 19.8 to 100.0 for saline spray. These ranges do not directly quantify uncertainty in the difference between arms. A confidence interval for a treatment contrast would answer a different question and is not reported in the registry record.

Confidence intervals should also be interpreted in light of the outcome scale and the analysis method. The scale is described as 0 to 100 points, while the benzocaine interval extends below zero. The record does not explain how the interval was constructed or why it extends beyond the stated lower endpoint of the rating scale. The interval endpoints should therefore be reported as listed rather than treated as observed pain scores. The registry does not report a prespecified clinically meaningful difference against which to judge the intervals.

How should the p-value be read?

The reported p = 0.43 comes from the registry's Wilcoxon (Mann-Whitney) analysis. In general, a p-value is calculated under a null hypothesis and describes the probability, under that model and its assumptions, of obtaining a result at least as incompatible with the null as the observed result. It is not an effect size, does not give the probability that a treatment is beneficial, and does not state the probability that chance alone produced the data. Interpretation also depends on the hypothesis, analysis plan, and significance threshold. The registry record does not report the test statistic, a detailed hypothesis statement, or a prespecified analysis threshold.

The sample-size assumptions recorded for a planning illustration specify a two-sided significance level of 0.05, equal allocation, and a normal approximation. Those are assumptions for the planning illustration, not evidence about the trial's original design or a report of the analysis plan. The registry does not report the original sample-size justification. Planning calculations based on an observed effect are illustrations of hypothetical future study requirements, not observed power and not a retrospective measure of whether the trial could detect an effect.

What is missing from the reported comparison?

The registry gives group summaries and a p-value but does not give a numerical between-group effect estimate with a confidence interval. Without that contrast, readers cannot directly quantify the estimated separation between the arms or its precision from the posted analysis. A p-value cannot substitute for either quantity. The arm medians are not a substitute for a contrast, particularly when the analysis is rank based and the outcome is a change score.

The record does not report whether the analysis adjusted for any baseline variables, how missing observations were handled, or whether the analysis followed an intention-to-treat principle. It does not specify whether the primary test was one of several candidate analyses or whether any multiplicity procedure was used. These omissions do not invalidate the recorded result, but they limit assessment of how the analysis was conducted and how the p-value should be interpreted. The study's randomized, parallel design identifies the broad comparison; it does not supply the unreported details of the statistical plan.

10. Analyses Reported by the Sponsor

The registry records the primary comparison as a Wilcoxon (Mann-Whitney) analysis with p = 0.43. It also lists arm-level outcome values and confidence intervals, but not an estimated between-group contrast with its confidence interval. The posted analysis is therefore the clearest direct inferential result available for the primary outcome, while the arm summaries offer context about the distributions' reported central values and uncertainty.

No discrepancy is flagged between the registry's reported analysis and a recalculation. However, the registry record does not report a recalculated between-group estimate that can be compared with the recorded test result. The absence of such an estimate means that no separate recalculation can clarify the effect's size or precision. The sponsor's own analysis takes precedence when a discrepancy is flagged; no such discrepancy is flagged in this record.

The p-value should not be reinterpreted as an effect estimate, nor should the separate arm-level intervals be combined informally to construct a treatment contrast. The analysis method tests a rank-based comparison, while a direct estimate and confidence interval for the contrast would make the magnitude and uncertainty easier to assess. Those quantities are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 3 analyses. It names patient satisfaction and change in pain score from pre-procedure to 5 minutes post procedure as secondary outcomes, in addition to the primary change-in-pain outcome. The numerical results for those secondary outcomes are not reported in the registry record. The names and counts alone do not indicate whether each outcome was tested, whether additional analyses were considered, or which outcomes were treated as confirmatory.

When multiple outcomes or analyses are examined, the chance of finding at least one apparently notable result can increase. General methods for addressing this include prespecifying a primary outcome, controlling an overall error rate, or treating secondary analyses as exploratory. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or a detailed statistical analysis plan. It is therefore not possible to determine from the posted record whether multiplicity was addressed or how it should affect interpretation of the reported p-value.

Missing-data handling and analysis populations are also not reported in the registry record. The primary outcome lists 15 participants in each arm, but that does not establish whether every randomized participant contributed a usable outcome, whether any participants were excluded, or how incomplete measurements were treated. The record does not say whether analyses used all randomized participants, participants with available outcome data, or another population definition. It also does not describe imputation, sensitivity analyses, or reasons for missing data.

These omissions matter because missingness can affect both the estimated outcomes and the comparability created by randomization. The number enrolled and the number listed for each arm describe the posted group counts, but do not by themselves resolve how missing observations or multiple testing were handled. Conclusions should remain tied to the reported primary analysis rather than extending to unreported secondary results or presumed analysis populations.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event record lists 15 participants at risk in each arm. It reports 0 serious adverse events in the benzocaine arm and 0 in the saline spray arm. It also reports 0 other adverse events in each arm. These are the event counts posted for the registry record; they do not establish that no events occurred outside the reporting period or categories represented in the record.

The deaths fields are not populated with a count, so deaths are not reported in the registry record; they should not be interpreted as zero. No serious adverse-event terms are listed. The record does not provide details about event definitions, collection procedures, observation duration, severity grading, or how events were assessed for relation to the sprays.

With 15 participants at risk in each group, these counts describe the recorded safety experience in a small trial, not the full range of possible adverse outcomes. A zero count in the posted record is not proof that an event cannot occur. These figures should be read as registry-reported counts, with the limits of the event definitions and follow-up information left unresolved.

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

The registry reports a randomized comparison of benzocaine spray and saline spray, with a primary endpoint based on pain-score change around HSG. The posted results include arm-level median values and confidence intervals, along with a Wilcoxon (Mann-Whitney) p-value of 0.43. These data describe the recorded comparison, but they do not provide a direct estimate and confidence interval for the between-arm effect. Precision and effect magnitude therefore cannot be fully assessed from the reported statistics.

The result does not establish that the sprays are equivalent. A failure to show a statistically compelling difference is not the same as evidence that effects are sufficiently similar, and the record does not report an equivalence margin or a non-inferiority design. Nor does the p-value identify whether any observed difference is clinically important. The registry does not report a threshold for meaningful change on the pain scale.

The outcome definition leaves the subtraction order for the change score unclear. Without that direction, even the sign of a score change cannot be translated confidently into increased or decreased pain. The scale is described, and the comparison method is named, but the statistical plan, analysis population, and missing-data procedures are not reported in the registry record.

The record also lists secondary outcomes without posting their numerical results. Those outcomes cannot be inferred from the primary result. The safety counts report no serious or other adverse events in the recorded groups, but deaths are not reported and details about event monitoring are absent.

In general, a randomized trial can help compare assigned groups, but the strength of conclusions depends on the conduct, completeness, and reporting of the study. Here, the registry provides a limited account of the design and outcome summaries. The appropriate reading is restricted to those the registry entries, not a broad claim about pain relief or safety beyond this trial.

14. Why This Trial Matters Statistically

This trial offers a compact example of why an outcome summary, an inferential test, and an effect estimate answer different statistical questions. The arm-level medians describe central values, the confidence intervals describe uncertainty around those arm summaries, and the Wilcoxon (Mann-Whitney) p-value reports a rank-based comparison. None of these alone supplies the missing between-group estimate and its uncertainty.

The example also illustrates a common interpretive issue with change scores. A result depends on the measurement times and on the direction used to subtract the scores. Here, the endpoint is framed as baseline pain and maximum pain during the procedure, but the subtraction order is not stated. That makes a numerical change harder to translate into a direction of pain change. A clear endpoint definition is part of statistical interpretability, not merely a matter of presentation.

The trial enrolled 30 participants, with 15 listed in each arm. In a study of this size, estimates may be imprecise, and a non-significant result should not be treated as evidence of equivalence. The wide arm-level confidence intervals reinforce the value of reporting a direct contrast and its interval, rather than relying on a p-value alone.

Finally, the registry names secondary outcomes and provides safety counts, but leaves secondary numerical results and several analysis details unreported. This makes the record useful for understanding the broad design and what was measured, while also showing why transparent reporting of analysis populations, missing data, multiplicity, and effect estimates matters for evidence appraisal.

15. 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.

Several limitations specific to this record constrain interpretation. The primary endpoint description states that baseline and maximum-procedure pain scores were subtracted but does not specify the order of subtraction. The reported change values therefore cannot be assigned confidently to an increase or decrease in pain. The registry lists medians and 95% confidence intervals by arm, but not a between-group effect estimate with a confidence interval. That leaves the magnitude and precision of the comparative effect unclear.

The recorded enrollment is 30, with 15 participants listed in each arm for the primary outcome. The arm-level confidence intervals are broad, indicating considerable uncertainty in the reported summaries. The registry does not report a clinically meaningful threshold for the pain scale, so the practical importance of the values cannot be judged against a stated benchmark. The description also does not explain why the benzocaine confidence interval extends below the scale's stated lower endpoint.

Further limitations arise from incomplete methods reporting. The randomization and quadruple masking labels are present, but the sequence-generation method, allocation concealment, masked roles, and masking procedures are not described. Eligibility criteria and participant characteristics are also absent. The registry does not report how missing outcomes were handled, which analysis population was used, or whether any adjustment or sensitivity analysis was performed.

Patient satisfaction and pain change at 5 minutes post procedure are listed as secondary outcomes, but their results are not reported in the registry record. The statistical plan and multiplicity procedures are likewise not reported. Safety information consists of posted event counts without further detail on definitions or follow-up; deaths are not reported. These limitations concern what can be evaluated from the registry record and do not, by themselves, establish how the trial was conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Benzocaine Versus Placebo Spray for Pain Relief at Hysterosalpingogram — NCT01925469.
• Registry record last updated 2017-04-28; status last verified 2017-03.
• Results first posted 2017-04-28.
• 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.

19. Record Summary

NCT01925469 is a completed randomized, parallel-group Phase 4 trial sponsored by the University of Pennsylvania. It enrolled 30 participants and compared benzocaine spray, described as 14%, with saline spray. The stated primary outcome was change in pain score from pre-procedure baseline to maximum pain during HSG at time 0, rated on a 0 to 100 visual analog scale.

The registry reports arm-level median values of 50.6 for benzocaine and 70.4 for saline spray, with respective 95% confidence intervals of -7.4 to 98.8 and 19.8 to 100.0. A Wilcoxon (Mann-Whitney) comparison is reported with p = 0.43. The record does not report a between-group effect estimate with a confidence interval. Secondary outcomes are listed but their numerical results are not reported in the registry record. Serious and other adverse-event counts are 0 in each arm; deaths are not reported.