Clinical Outcomes Mandible: Buffered 1% vs. Non-Buffered 1% Lidocaine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Outcomes Mandible: Buffered 1% vs. Non-Buffered 1% Lidocaine (NCT03127943), a randomized phase 4 study. The primary outcome is Mean Time to Pulpal Response After Mandibular Molar Anesthesia.

2. Clinical Question

The registry describes this as a pilot study assessing the clinical impact of buffered compared with non-buffered 1% lidocaine with epinephrine in dental and oral surgical procedures. In a crossover design, each subject receives both treatments, so the comparison concerns the two treatment periods within a study that enrolled 24 subjects. The arm-level summaries each list 24 observations, but the registry record does not report further detail about how the repeated observations were incorporated into the treatment comparison.

The primary outcome is based on pulpal testing of mandibular molar teeth. The registry says teeth were tested before anesthetic administration and every 30 minutes up to 120 minutes, using cold and electric pulp tests, with anesthesia reported by subjects as yes or no. The question is therefore about the recorded time-related outcome under these testing conditions, not about every aspect of anesthesia or every possible clinical outcome.

3. Trial Design

The registry describes a Phase 4, randomized, double-masked, crossover study sponsored by the University of North Carolina, Chapel Hill. It lists an enrollment of 24 and a completed status. The study began on 2017-05-01, with primary completion on 2018-04-01. The registry record does not report the specific randomization procedure or the details of how masking was maintained.

The two treatments were buffered 1% lidocaine with epinephrine and non-buffered 1% lidocaine with epinephrine. The arm descriptions say that subjects received one anesthetic in week One and the alternate anesthetic in week Two, with injections directed at the inferior alveolar, lingual, and buccal nerves. They also mention at least a week between injections for the same nerves. The descriptions are truncated, so the registry record does not fully report the treatment-period schedule or related procedural details.

In a crossover trial, participants receive both treatments at different times. This can make within-person comparisons relevant because each participant experiences both conditions. However, the statistical interpretation depends on how the study handles the paired observations and possible period or carryover effects. The registry record does not report those analysis details, nor does it state whether such effects were assessed.

The primary endpoint was mean time to pulpal response after mandibular molar anesthesia. Outcome testing was described as occurring before anesthetic and every 30 minutes up to 120 minutes, with cold and electric pulp tests and subject-reported yes-or-no presence of anesthesia. The record lists two outcome measures and no posted secondary outcomes. It does not report the original sample-size justification, the analysis population, the number of participants who completed both periods, or the handling of missing observations.

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.

First Intervention

Washout (1 Week)

Second Intervention

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 Mean Time to Pulpal Response After Mandibular Molar Anesthesia, measured over Every 30 minutes up to 120 minutes Total.

The primary endpoint is the mean time to pulpal response after mandibular molar anesthesia, measured in minutes. The registry describes testing before anesthetic administration and every 30 minutes up to 120 minutes, using cold and electric pulp tests. Subjects reported whether anesthesia was present, with a yes-or-no response. The posted group means are 100 minutes for buffered lidocaine and 106 minutes for non-buffered lidocaine, with standard deviations of 37.2 and 41.5 minutes, respectively.

A time-based endpoint can describe how long a measured response persists or when a specified response is observed. In this record, however, the operational definition of “time to pulpal response” is not fully explained. It does not specify exactly how the repeated yes-or-no test results were converted into each participant’s time value, or how results from cold and electric pulp testing were combined. Those details matter because they determine what the mean represents and how to interpret it.

Using a mean provides a summary of the central value of a continuous outcome, while the standard deviation describes variability among observations. The mean is useful for comparing average recorded times, but alone it does not show the distribution of individual values or how many participants had particular outcomes. The registry does not report those individual-level details. The endpoint therefore supports a comparison of the posted group summaries, while leaving aspects of its measurement and analysis definition unclear.

7. Results Posted in the Registry

• Non-buffered 1% Lididocaine, the Buffered 1% Lidocaine: mean 106.00 versus 100.00 on control; difference 6.00 (95% CI -16.30 to 28.30), standardized effect d = 0.15; z-test p = 0.598.

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a continuous measure reported as a mean and standard deviation. A mean is the arithmetic average of the recorded values; it gives a single summary of the group’s central level. The standard deviation describes how spread out the observations are around that mean. Neither statistic by itself describes the full distribution. Different sets of participant values can share the same mean and standard deviation, so group summaries cannot show patterns such as skewness, clusters, or outliers.

What does the mean difference represent?

The posted contrast is the non-buffered mean minus the buffered mean. Its estimate is 6.0 minutes. A positive estimate under this ordering means that the non-buffered group’s posted average is higher; it does not, on its own, establish that the difference is reliable or clinically important. The confidence interval gives a range of values compatible with the data and the calculation’s assumptions. Since the interval extends from -16.3 to 28.3 minutes, it includes zero and also allows differences in either direction.

The comparison lists a pooled standard deviation of 39.41 and a standardized effect estimate of 0.152. A standardized effect expresses a mean contrast relative to a measure of outcome variability, placing the contrast on a scale that is not in minutes. It can help describe the size of a contrast relative to spread, but it does not replace the original-unit estimate or establish clinical importance. The registry record does not state a threshold for an important difference.

Why does the crossover structure matter?

In a crossover study, the same participants receive each treatment in different periods. Their outcome values are consequently related: observations from one person may be more alike than observations from different people. A paired analysis accounts for this within-person relationship. An analysis that treats observations as independent may not represent the design appropriately. The registry record does not report the method used for the comparison, whether pairing was incorporated, or how period and possible carryover effects were considered. Those details should not be inferred from the word “crossover” alone.

Randomization concerns the assignment of treatment order or sequence. It can help reduce systematic differences in treatment allocation, but the registry record does not describe the randomization method, sequence concealment, or sequence balance. Double masking indicates that the study was recorded as double-masked, but the record does not explain who was masked or how masking was implemented. These labels describe the registered design; they do not resolve uncertainties about the reported statistical analysis.

How should the p-value be read?

The unadjusted p-value is 0.598. In general, a p-value quantifies how often a result at least as incompatible with a stated null hypothesis might occur if that null model and its assumptions held. It is not the probability that the null hypothesis is true, and it is not a measure of the size or clinical importance of a difference. The term “unadjusted” indicates that the reported value is not presented as adjusted for multiple comparisons. The record does not report a broader multiplicity plan.

Confidence intervals and p-values are related ways of conveying uncertainty, but the interval is especially useful because it shows a range and direction of compatible estimates in the outcome’s original units. The interval covers zero and values on both sides. The results therefore do not narrowly pinpoint the direction or magnitude of the average contrast. The confidence interval also depends on the assumptions used to calculate it, which are not fully detailed in the registry record.

What does variability add?

The group standard deviations are 37.2 and 41.5 minutes, while the estimated mean difference is 6.0 minutes. These are reported quantities, not a new calculation. Standard deviations describe variation among outcome values within each posted group; the confidence interval describes uncertainty about the estimated contrast. They answer different questions. A broad spread among observations does not itself tell how uncertain the mean difference is, because that uncertainty also depends on sample size and the analysis structure.

In general, over-dispersion means that observed variation is greater than a statistical model expects. It matters because a model that underestimates variability can produce confidence intervals that are too narrow and p-values that are too small. The registry record does not report an over-dispersion assessment, and the outcome is presented as a continuous mean, so no claim about over-dispersion is warranted for this trial. This general concept should not be confused with the reported standard deviations.

The record also does not report diagnostic checks, model assumptions, transformations, covariate adjustment, or sensitivity analyses. It is therefore not possible to assess from the registry entry whether the analysis accounted for distributional features or departures from assumptions. The descriptive summaries remain interpretable as posted, but the inferential comparison should be understood with that reporting limitation.

What is not established by these statistics?

The reported contrast does not establish equivalence. Demonstrating equivalence ordinarily requires a prespecified acceptable difference and an analysis designed to assess whether the uncertainty lies within that margin. The registry record does not report an equivalence margin or an equivalence analysis. Likewise, the absence of a statistically significant result is not proof that there is no difference. The confidence interval communicates the range of estimates compatible with the analysis more informatively than a binary significant-or-not label.

Finally, the registry lists 24 observations in each treatment summary and enrollment of 24, but does not state whether all randomized participants contributed complete data to both periods or whether the listed summary counts have a particular crossover interpretation. The record also does not describe missing-data handling or the analysis population. These omissions limit evaluation of how the posted results relate to all enrolled participants.

10. Confidence Intervals and Precision

The reported mean difference is 6.0 minutes, with a 95% confidence interval from -16.3 to 28.3 minutes. A confidence interval describes uncertainty around an estimated quantity under the analysis assumptions: narrower intervals indicate greater precision, while wider intervals leave more possible values compatible with the data. This interval includes zero, as well as differences in both directions, so the estimate does not precisely determine the direction of the average contrast.

The interval is expressed in minutes, the same unit as the outcome, which makes its range interpretable on the endpoint’s scale. It should not be read as containing a fixed percentage of individual participants’ values. Rather, it concerns uncertainty in the estimated mean difference. The two group standard deviations, 37.2 and 41.5 minutes, describe variation in observed values and are not confidence intervals for the means.

The width of an interval reflects the amount of information and the method used to calculate it. The trial enrolled 24 participants, and the registry lists 24 observations in each treatment summary. Because this is a crossover study, the relationship between observations from the same subject can affect the precision of a treatment contrast. The registry record does not describe whether the reported interval accounts for pairing or other design features, so its calculation cannot be fully evaluated from the record.

Precision is distinct from clinical importance. The registry does not report a threshold for an important difference, and the interval alone cannot define one. It does show that the point estimate should not be treated as an exact or highly certain value: a range of negative and positive contrasts remains compatible with the posted result under its assumptions.

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 illustrative, not the trial’s original design calculation. They use the observed effect as a starting point and consider scenarios targeting 100%, 75%, and 50% of that observed effect. The assumptions listed are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For this continuous outcome, the entries are participants per arm, not total events. The registry record does not report the assumptions used for the original trial design.

The 80% power column gives the estimated participants per arm under the stated assumptions for a planning scenario with an 80% chance of detecting the specified effect if that effect is the true one and the model assumptions hold. The 90% power column describes the corresponding planning target with a higher chance of detection. These are design illustrations, not guarantees of what a future study would achieve.

For planning based on 100% of the observed effect, the figures are 678 participants per arm for 80% power and 907 participants per arm for 90% power. For planning based on 75% of the observed effect, they are 1,204 and 1,612 participants per arm. For planning based on 50% of the observed effect, they are 2,709 and 3,627 participants per arm. The smaller-effect scenarios require more participants because smaller differences are harder to distinguish from variation under the same assumptions.

These figures are not observed power for the completed study. They do not show the probability that the trial’s result is correct, and they should not be used to reinterpret the confidence interval or p-value. They are planning illustrations based on the observed effect, which may itself be uncertain.

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 = 6.000; pooled standard deviation σ = 39.409.
2. n = 2 × (1.96 + 0.842)² × 39.409² / 6.000² = 677.2, rounded up to 678 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 <- 6                      # observed difference in means
sigma <- 39.4086919346481                     # 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(3127943)
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 = 678 (80% power), 907 (90% power)
 75% of observed effect: n per arm = 1,204 (80% power), 1,612 (90% power)
 50% of observed effect: n per arm = 2,709 (80% power), 3,627 (90% power)
power.t.test: 678.2 
Simulated power at n = 678 per arm: 0.804 (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 record lists two outcome measures and no posted secondary outcomes. It does not report a prespecified multiplicity strategy, such as a hierarchy of outcomes or an adjustment for testing multiple hypotheses. The p-value for the reported comparison is identified as unadjusted. No additional outcome analyses are listed, so the available record does not support a broader account of how multiple testing was handled.

Multiplicity matters when several outcomes, time points, subgroups, or analysis choices are examined. Repeated testing can increase the chance of at least one apparently unusual result under a null model. Whether and how this concern applies depends on the full analysis plan and the set of analyses actually conducted. The registry record does not report that complete set or a statistical analysis plan, so the extent of any multiplicity concern cannot be determined.

The record does not report an analysis population, such as whether the comparison included all randomized participants, only participants completing both treatment periods, or another defined group. It also does not report the number of participants with complete endpoint data, exclusions after randomization, or how missing observations were handled. In a crossover trial, missing data in either period can affect which participants contribute to a within-person comparison. Without these details, the relationship between the posted summaries and the enrolled population is unclear.

The registry record also does not report an interim analysis plan, stopping rules, or whether any interim analyses occurred. These should not be assumed from the study’s completed status. Likewise, no details are reported about protocol deviations, per-protocol analyses, intention-to-treat analyses, or sensitivity analyses. These reporting gaps limit assessment of robustness and analysis choices, but do not by themselves establish that any particular procedure was or was not performed.

14. 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 serious adverse events, other adverse events, and deaths separately for buffered and non-buffered 1% lidocaine. For each treatment, 24 participants are listed as at risk for serious events and 24 as at risk for other events. The reported counts are zero serious adverse events, zero other adverse events, and zero deaths in each treatment group.

These figures describe what was recorded in the registry for the listed categories and groups. They do not establish that no unrecorded symptoms or events occurred, and the record does not explain how events were collected, defined, attributed, or monitored. Since the design is crossover, the treatment-group entries should not automatically be interpreted as independent groups of people; each subject was described as receiving both anesthetics in separate periods.

The registry lists no serious adverse event terms. The adverse-event figures are a safety summary, not an estimate of comparative risk with a stated uncertainty interval. With zero events recorded in these categories, the posted counts alone cannot precisely quantify the possibility of uncommon events. They should be read as event counts in this study record, not as a general guarantee about safety in other circumstances.

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

The posted data describe a comparison of mean time to pulpal response after mandibular molar anesthesia with buffered and non-buffered 1% lidocaine. The means are 100 and 106 minutes, and the reported difference is 6.0 minutes in the non-buffered-minus-buffered direction. The 95% confidence interval, from -16.3 to 28.3 minutes, includes zero and allows values in either direction. The p-value is 0.598.

Those results support a cautious description: the estimate of the average contrast is uncertain, and the posted data do not sharply establish its direction or size. They do not demonstrate that the formulations are equivalent, because no equivalence margin or equivalence analysis is reported. Nor does the p-value mean there is a 59.8% chance that there is no difference. It is a statistical quantity interpreted under a null model and analysis assumptions.

The endpoint is specific: pulpal response measured by repeated cold and electric pulp tests and subject-reported presence of anesthesia, on a schedule described as every 30 minutes up to 120 minutes. The registry record does not fully define how those repeated responses became the reported time outcome. The result therefore should not be generalized to unreported endpoints or treated as a complete account of all aspects of anesthesia.

The study is described as a randomized, double-masked crossover pilot with enrollment of 24. That design provides a within-participant treatment sequence, but the posted record does not explain how the statistical analysis accounted for pairing, treatment period, possible carryover, or missing observations. These details affect interpretation of the uncertainty estimates. The record also does not report participant characteristics beyond the study context, limiting assessment of how broadly the result might apply.

The safety record lists zero serious adverse events, zero other adverse events, and zero deaths for each treatment group, with 24 at risk in each category. These are recorded counts, not proof that events are impossible or that the study can rule out rare events. Overall, the registry supports a description of the observed endpoint summaries and their uncertainty, while leaving clinical importance, broader applicability, and some analytic details unresolved.

16. Why This Trial Matters Statistically

This trial is statistically instructive because its design and result raise issues that occur in clinical research: interpreting a continuous outcome, understanding uncertainty, and distinguishing a lack of clear evidence from evidence of no difference. The reported mean difference is 6.0 minutes, but the confidence interval from -16.3 to 28.3 minutes spans both directions. Reading the interval alongside the point estimate makes the uncertainty more apparent than focusing on a single p-value.

The crossover structure is also important. Each participant was described as receiving both formulations in separate periods, which creates related observations within a person. The appropriate treatment comparison depends on how that relationship is handled. The registry identifies the design but does not report the analysis details, making it a useful example of why design labels alone do not fully explain a result.

The endpoint involves repeated assessments and subject-reported yes-or-no responses, while the reported statistic is a mean time. Clear operational definitions are essential when converting repeated measurements into a continuous outcome. The registry describes the testing schedule and procedures but does not fully report the derivation of the time value. This illustrates how endpoint definition contributes to interpretability, separately from statistical significance.

Finally, the planning illustrations show how assumptions about the target effect and desired power can produce substantially different sample-size requirements. Those figures are not observed power and are not the original study’s design rationale. Keeping planning calculations separate from trial results helps prevent a common interpretive error. The record’s reporting gaps also demonstrate why analysis populations, missing-data handling, multiplicity, and crossover methods are important to transparent reporting.

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 record leaves several trial-specific details unclear. Although the study is described as a randomized, double-masked crossover, the randomization method, treatment-sequence allocation, masking procedures, and full treatment schedule are not reported. The arm descriptions are truncated. They mention administration in week One and week Two, and at least a week between injections for the same nerves, but do not provide a complete account of the periods or procedures.

The posted outcome definition is also incomplete. The record describes testing before anesthetic and every 30 minutes up to 120 minutes, using cold and electric pulp tests and subject-reported yes-or-no presence of anesthesia. It does not say exactly how these repeated assessments were converted into each participant’s time to pulpal response, or how findings from the two tests were combined. That limits interpretation of what the reported mean represents.

For the analysis, the record does not report whether the comparison accounted for the crossover pairing, treatment period, sequence, or possible carryover. It also does not identify an analysis population, the number completing both treatment periods, missing-data procedures, protocol deviations, or sensitivity analyses. The original sample-size justification and statistical analysis plan are not reported. These omissions restrict evaluation of the inferential method and the representativeness of the posted summaries.

Participant characteristics and detailed enrollment flow are not reported in the results presented, limiting assessment of applicability. The record lists no posted secondary outcomes and does not provide a multiplicity plan. The adverse-event counts are recorded, but event definitions and collection methods are not described. These limitations are reporting limitations; they do not establish that a procedure was omitted or that an event was missed.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Clinical Outcomes Mandible: Buffered 1% vs. Non-Buffered 1% Lidocaine — NCT03127943.
• Registry record last updated 2019-02-06; status last verified 2018-04.
• Results first posted 2019-02-06.
• 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

The registry describes a completed, Phase 4, randomized, double-masked crossover pilot study sponsored by the University of North Carolina, Chapel Hill. Enrollment was 24. The study compared buffered and non-buffered 1% lidocaine with epinephrine for dental and oral surgical procedures involving mandibular nerve blocks.

The primary outcome was mean time to pulpal response after mandibular molar anesthesia. The posted means were 100 minutes for buffered lidocaine and 106 minutes for non-buffered lidocaine. The reported mean difference was 6.0 minutes, with a 95% confidence interval from -16.3 to 28.3 minutes and an unadjusted p-value of 0.598.

The registry reports zero serious adverse events, zero other adverse events, and zero deaths for each treatment group. It does not report the detailed crossover analysis, missing-data handling, analysis population, original sample-size justification, or complete endpoint derivation.