Efficacy and Safety Study of Lidocaine Vaginal Gel for Recurrent Dysmenorrhea (Painful Periods): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of Lidocaine Vaginal Gel for Recurrent Dysmenorrhea (Painful Periods) (NCT00651313), a randomized phase 2 study. The primary outcome is The Primary Efficacy Variable Will be the Time-weighted Average Pain Intensity Over 4 Treatment Days Using the 4 Point Categorical Scale..

2. Clinical Question

The endpoint’s scale runs from none (0) through mild (1) and moderate (2) to severe (3). The resulting means summarize the average intensity across treatment days, rather than the highest pain rating or a single day’s rating. The trial also listed an electrocardiogram assessment for potentially significant QT changes at approximate peak lidocaine plasma concentration after 4 days of dosing. Its posted summary does not provide results for that secondary outcome.

3. Trial Design

The registry describes a phase II, randomized, quadruple-masked, crossover trial of lidocaine vaginal gel and placebo in women with recurrent dysmenorrhea. Enrollment was 81, and the study status is completed. Its recorded start was 2007-08 and its primary completion was 2008-06. The intervention is lidocaine 10% (150mg) vaginal gel; the comparator is placebo vaginal gel.

A crossover design compares treatments across periods within a study rather than treating the treatment groups as necessarily independent parallel groups. In this record, the primary timeframe refers to two 4-day dosing regimens for two consecutive menstrual cycles. The registry does not report the treatment sequence, whether sequence was randomized separately, the interval between regimens, or how period and sequence effects were handled in the analysis. Those details matter when interpreting a crossover comparison because changes over time or effects that persist between periods can influence the contrast.

Quadruple masking indicates that the study is recorded as masked at multiple levels, but the registry record does not specify which roles were masked or how masking was maintained. The record identifies the primary efficacy population as the ITT Analysis Set. It reports an endpoint sample size of 70 for each treatment summary and an adverse-event population at risk of 77 for each condition. These figures describe the corresponding posted analyses; the record does not explain the reasons for differences among enrollment and analysis counts.

The primary outcome was the time-weighted average pain intensity over 4 treatment days using a 4 point categorical scale. The registry also lists three outcome measures and one posted secondary outcome description. Details such as the protocol’s sample-size justification, treatment-period sequence, analysis model, and handling of missing observations 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.

Before assignment: Crossover study; Subjects who met study entry criteria after completing screening procedures at Screening Visit returned to study center at least 7 days prior to their expected onset of menses to complete Randomization/Treatment procedures. Abnormal lab values, ECGs or use of prohibited medications were among reasons subjects were excluded.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Time-weighted average pain intensity over the 4 treatment days using the 4 point categorical scale - none (0), mild (1), moderate (2), and severe (3); primary efficacy variable. ITT Analysis Set.

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 The Primary Efficacy Variable Will be the Time-weighted Average Pain Intensity Over 4 Treatment Days Using the 4 Point Categorical Scale., measured over Two 4-day dosing regimens for two consecutive monthy menstrual cycles.

The primary endpoint is the time-weighted average pain intensity over the 4 treatment days, measured with a 4 point categorical scale. Its categories are none (0), mild (1), moderate (2), and severe (3). A time-weighted average uses pain assessments across the treatment interval to produce a single summary value for each treatment regimen. This aims to represent intensity over the period rather than relying on one rating alone.

The registry identifies the endpoint as a mean, with standard deviation as the measure of spread, and specifies the ITT Analysis Set. The reported mean is 0.91 for lidocaine 10% and 0.92 for placebo gel. Both are near the lower end of the scale, but a mean does not show how individual ratings were distributed across categories or how pain changed from day to day. Those details are not reported in the registry record.

The endpoint is used to compare average reported pain intensity under the two regimens. The interpretation depends on the contrast between the treatment summaries and on its uncertainty, not just on the individual mean values. Because this is a crossover study, the treatment comparison may depend on how within-person measurements, treatment periods, and any sequence effects were handled. The registry record does not report those analysis details. The time-weighted average can summarize repeated ratings, but by itself it does not establish whether participants experienced a personally meaningful change.

7. Results Posted in the Registry

• Lidocaine 10%: mean 0.91 versus 0.92 on control; difference -0.01 (95% CI -0.21 to 0.19), standardized effect d = -0.02; z-test p = 0.921.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous in the registry’s statistical classification: it is a mean of pain-intensity scores over the treatment days. The underlying ratings are categorical and ordered, from none (0) to severe (3), while the posted summary uses an average. Reporting a mean makes the two treatment summaries and their difference straightforward to read, but it does not preserve all information about the distribution of individual ratings.

What does the mean difference represent?

The mean difference is the lidocaine mean minus the placebo mean. The reported estimate is -0.01. A negative value indicates that the average score in the lidocaine summary is numerically lower than the placebo summary; it does not by itself show that the difference is reliable, clinically important, or causal. Its interpretation also depends on the study design and analysis. In a crossover trial, measurements from the same participant under different regimens are related. An analysis that accounts for that pairing can have different precision from one that treats the regimen summaries as independent. The registry record does not report the model used.

What does a standard deviation describe?

A standard deviation describes how dispersed observations are around their mean. The reported standard deviations are 0.635 for lidocaine and 0.552 for placebo. They are not standard errors and should not be read as uncertainty in the treatment difference. Standard errors describe sampling variability of an estimate; the registry lists values of 0.066 and 0.076 for the two summaries. The method behind those values is not explained in the registry record. Standard deviations also cannot show whether scores cluster in one category, form a broad distribution, or vary over time.

How should the confidence interval be read?

A confidence interval expresses uncertainty around an estimated effect under the assumptions of the statistical procedure used. The reported interval for the mean difference includes zero and extends in both directions. Thus the posted estimate is compatible with a small difference favoring either regimen. The interval does not assign a probability to a particular treatment effect, and it does not establish equivalence. The confidence level and construction method are not reported in the registry record, so those features cannot be independently assessed from the posted summary.

What does the p-value add?

The unadjusted p-value is 0.921. In general, a p-value measures how unusual data at least as inconsistent with a specified null model would be if that model were true and the analysis assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. Here it accompanies a near-zero mean difference and a confidence interval that crosses zero. The record does not describe any adjusted analysis or a broader statistical plan.

Why can over-dispersion matter?

As a general statistical point, over-dispersion occurs when observed variability exceeds what an analysis model assumes. If an analysis underestimates variability, standard errors can be too small and uncertainty can appear narrower than warranted; if it accommodates extra variability, estimates may be less precise. That issue can arise with categorical or count outcomes under particular models. The primary registry result is reported as a mean with standard deviations, and the record does not identify an over-dispersion model or report a diagnostic assessment. It would therefore be inappropriate to claim that over-dispersion was present or corrected.

What can be inferred from a crossover label?

In general, a crossover design lets a participant receive more than one regimen in different periods, allowing comparisons to use within-participant information. That can account for stable differences between participants, but it also makes sequence, period, and carryover considerations important. A treatment effect that persists into a later period, or a systematic change between periods, can affect the comparison if not addressed appropriately. The registry says the trial was crossover and randomized, but sequence details, any washout information, and the analysis of period or carryover effects are not reported in the registry record. These are unknowns, not evidence that a design problem occurred.

The sample-size illustrations are separate from the observed analysis. They use the observed effect under stated planning assumptions and show hypothetical participant requirements for specified power levels. Such calculations depend on assumptions about the effect to detect and the analysis model. They do not establish the original design rationale, which is not reported in the registry record. They also do not change the interpretation of the observed estimate or its uncertainty.

10. Confidence Intervals and Precision

Precision concerns how tightly the data estimate the treatment contrast. The mean difference is -0.01, and the reported confidence interval extends on both sides of zero. This indicates uncertainty about both the direction and size of the underlying difference. The posted result therefore does not precisely isolate a benefit for either regimen. The confidence interval’s stated endpoints are not needed to see that zero is included, and the registry does not report its confidence level or construction method.

The treatment means are 0.91 for lidocaine and 0.92 for placebo, with standard deviations of 0.635 and 0.552, respectively. The standard deviations describe variability in outcome measurements, while the confidence interval describes uncertainty in the estimated contrast. These are related but distinct quantities. A small observed difference can still be uncertain, especially when there is appreciable variation in observations. The registry reports endpoint counts of 70 for each treatment summary, but does not explain the analysis details needed to evaluate how those counts and the crossover structure informed precision.

The unadjusted p-value of 0.921 is consistent with the absence of a statistically clear contrast under the reported analysis. It does not prove that the true difference is zero, nor does it establish that the treatments are equivalent. To support an equivalence claim, the analysis would need a prespecified margin and an appropriately designed inference; those details are not reported in the registry record.

Precision also cannot be judged solely from the p-value. The effect estimate, interval, endpoint variability, analysis population, and design model all contribute to understanding what the study can resolve. The registry identifies the ITT Analysis Set but does not report how missing data were handled, the statistical model, or whether the crossover structure was explicitly accounted for. Those gaps constrain interpretation of the interval as well as the point estimate.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. They are illustrations based on the observed effect, not the trial’s original design justification. The registry record does not report the original design assumptions.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The rows describe planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For 100% of the observed effect, the figures are 55,565 participants per arm for 80% power and 74,386 participants per arm for 90% power. For 75% of the observed effect, they are 98,782 participants per arm for 80% power and 132,241 participants per arm for 90% power. For 50% of the observed effect, they are 222,258 participants per arm for 80% power and 297,541 participants per arm for 90% power.

The 80% power column means the planned sample size under those assumptions for an analysis with an 80% chance of detecting the specified effect at the stated significance level, if that effect and the other assumptions hold. The 90% column expresses the analogous planning target with a higher chance of detection under the same assumptions. Smaller effects are harder to distinguish from random variation and therefore require more participants. These figures are planning illustrations, not observed power for this completed trial.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.010; pooled standard deviation σ = 0.595.
2. n = 2 × (1.96 + 0.842)² × 0.595² / -0.010² = 55,564.5, rounded up to 55,565 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.01                      # observed difference in means
sigma <- 0.59494915749163                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(651313)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 55,565 (80% power), 74,386 (90% power)
 75% of observed effect: n per arm = 98,782 (80% power), 132,241 (90% power)
 50% of observed effect: n per arm = 222,258 (80% power), 297,541 (90% power)
power.t.test: 55565.5 
Simulated power at n = 55,565 per arm: 0.806 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary efficacy variable: time-weighted average pain intensity over the 4 treatment days. It also lists three outcome measures and one secondary outcome description concerning electrocardiograms for potentially significant QT changes at approximate peak lidocaine plasma concentration after 4 days of dosing. Results for that listed ECG outcome are not reported in the registry record.

When a study tests multiple outcomes, time points, or treatment contrasts, the chance of at least one apparently notable result can increase. Statistical approaches can address multiplicity by defining a hierarchy, adjusting significance thresholds, or otherwise prespecifying how results will be interpreted. These are general options, not claims about this trial. The registry record does not report whether multiplicity was addressed, what other outcomes were included in a formal testing plan, or whether any adjustment was used. The reported p-value is identified as unadjusted.

The primary population is named as the ITT Analysis Set. The registry does not describe its exact definition, the number included in that set beyond the endpoint summaries, or how participants with incomplete records were treated. Missing-data methods are not reported in the registry record. In a crossover study, incomplete observations in one treatment period can affect which within-participant comparisons are available, so the method matters for both the analysis population and precision.

The record also does not describe protocol deviations, exclusions, sensitivity analyses, or whether additional analysis populations were used. It is not possible to determine from the registry summary whether such analyses were conducted. This absence of detail does not mean that the investigators failed to use an analysis plan; it means that the relevant methods are not reported in the registry record. Consequently, the posted primary result can be described as recorded, but it cannot be fully audited against a complete multiplicity and missing-data plan.

14. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events affecting 0 of 77 participants at risk in the active group and 0 of 77 participants at risk in the placebo group. These are the posted serious-event counts for the listed groups. The record has no serious-event terms listed. The registry does not report death counts in these entries.

Zero reported serious events in these group summaries does not establish that serious risk is absent. The figures describe the registry’s recorded observation and cannot rule out uncommon events or effects not captured in the summary. The record does not provide the event definitions, follow-up duration for safety, or details about how adverse events were collected and adjudicated.

For other adverse events, the registry reports 6 affected in the active group and 7 in the placebo group, with 77 at risk in each group. These are not serious-event figures and should not be conflated with them. Because the trial is crossover, the registry’s grouped safety summaries do not explain whether or how people could contribute observations across treatment conditions. A full safety interpretation would require the methods and event-level context, which are not reported in the registry record.

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

The main result is an estimated mean pain-intensity difference of -0.01 for lidocaine relative to placebo, with an unadjusted p-value of 0.921. The reported confidence interval spans both negative and positive values. In practical statistical terms, the registry summary does not sharply determine which regimen had the lower underlying average, or whether a small difference exists. It is not proof of equal effects.

The outcome reflects a time-weighted average on a 4 point categorical scale across 4 treatment days. It does not by itself show how many participants had no, mild, moderate, or severe pain, whether any participant experienced a notable change, or whether pain patterns changed across the two menstrual cycles. The registry reports treatment means and standard deviations, but not the distribution of individual scores or day-specific results.

The result should be interpreted in light of the crossover design. The registry record does not report the sequence details or the statistical model used to account for repeated treatment periods. It also does not describe missing-data handling, the confidence interval method, or the original sample-size rationale. These omissions limit how thoroughly the posted result can be evaluated.

The safety summary reports no serious adverse events in either listed group, while other adverse events were recorded in both. These counts are not a complete account of safety and cannot establish the absence of risk. The listed ECG outcome has no posted result in the registry record.

Overall, the registry describes a completed randomized, masked crossover comparison and posts a near-zero mean contrast with uncertainty spanning both directions. That supports a cautious description of the posted data, not a medical recommendation and not a conclusion that lidocaine works or does not work. Claims of equivalence, clinically meaningful benefit, or comprehensive safety would require additional design, analysis, and outcome information not reported in the registry record.

16. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a repeated-measure clinical question with a crossover design. Pain intensity can vary between people and across menstrual cycles. A crossover comparison can use measurements from the same participant under different regimens, but the analysis must account appropriately for the relationship between those observations and for possible period or sequence effects. The registry confirms the crossover design but does not report how those features were handled.

The primary endpoint compresses ratings over several treatment days into a time-weighted average. Such a summary can make a treatment contrast easier to communicate, while hiding details about timing and category frequencies. The reported means are close, but the uncertainty interval crosses zero. This illustrates why an effect estimate should be read alongside its precision rather than interpreted on its own.

The record also shows the distinction between an observed trial result and a planning calculation. The planning illustrations are based on fractions of the observed effect and yield large participant requirements under their stated assumptions. They are not the original trial’s design rationale, and they are not observed power. Because the observed contrast is small, planning around smaller fractions leads to larger requirements under the stated model.

Finally, the registry summary makes clear how outcome reporting and method reporting affect interpretation. It lists a secondary ECG outcome but does not post its result, and it does not describe multiplicity or missing-data methods. Those omissions are important for assessing a clinical trial statistically without assuming that unreported analyses were or were not performed.

17. 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 summary does not report the treatment sequence, period allocation details, washout information, or the analysis of period, sequence, and carryover effects. These details are particularly relevant to a crossover study. Their absence prevents a full assessment of whether the posted contrast reflects the intended within-participant comparison.

The primary means and standard deviations are reported, but the distribution of pain scores, category frequencies, and day-specific measurements are not. The record does not explain the confidence interval construction or identify a full statistical model. It names the ITT Analysis Set but does not describe its composition, missing-data handling, or sensitivity analyses. The original sample-size assumptions and justification are not reported in the registry record.

The record lists an ECG safety outcome but does not post its result. The adverse-event summary gives group counts but does not provide event terms for serious events, detailed follow-up information, or methods for event collection and adjudication. The death counts are not reported in the registry record. These gaps restrict conclusions about safety based on this summary.

Enrollment was 81, while the primary outcome summaries report 70 for each treatment and the adverse-event groups report 77 at risk each. The registry does not explain these differences, so reasons for non-inclusion or differences in analysis populations cannot be inferred. The record also does not report a prespecified clinically meaningful threshold for the pain score. Accordingly, statistical uncertainty can be described, but the clinical importance of the estimated contrast cannot be established from the registry summary alone.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of Lidocaine Vaginal Gel for Recurrent Dysmenorrhea (Painful Periods) — NCT00651313.
• Registry record last updated 2012-02-17; status last verified 2012-02.
• Results first posted 2011-07-06.
• 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.

21. Record Summary

NCT00651313 is recorded as a completed phase II randomized, quadruple-masked crossover study of lidocaine vaginal gel for recurrent dysmenorrhea. The active regimen was lidocaine 10% (150mg) vaginal gel, compared with placebo vaginal gel. Enrollment was 81.

The primary outcome was the time-weighted average pain intensity over 4 treatment days on a 4 point scale, assessed across two 4-day dosing regimens for two consecutive menstrual cycles. The registry reports means of 0.91 for lidocaine and 0.92 for placebo, a mean difference of -0.01, and an unadjusted p-value of 0.921. The confidence interval includes values on both sides of zero.

The registry also describes an ECG outcome and posts adverse-event summaries. Detailed statistical methods, missing-data handling, crossover sequence information, and results for the ECG outcome are not reported in the registry record.