Comparison of Two Topical Anesthetics: Benzocaine Versus Pliaglis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Two Topical Anesthetics: Benzocaine Versus Pliaglis (NCT01951820), a randomized phase 4 study. The primary outcome is Measurement of Pain Associated With Injection, in Millimeters, According to Visual Analog Scale.

2. Clinical Question

The trial addresses a focused comparison of two topical anesthetics in the setting of a dental needle insertion. Its primary outcome is the participant-reported level of pain associated with injection, recorded in millimeters on a Heft-Parker visual analog pain scale. The record describes the scale as extending from 0 mm, meaning no pain, to 170 mm, meaning maximum pain. The outcome timeframe is 2.5 minutes.

The comparison concerns topical anesthetic applied before a local anesthetic injection; both arm descriptions specify injection of articaine in addition to the assigned topical gel. The registry title refers to needle insertion in the palate, while the arm descriptions refer to application to the gums. Those descriptions identify the general clinical context but do not provide additional procedural detail.

Mean pain was reported as 26.9 mm in the Pliaglis arm and 38.5 mm in the benzocaine arm. Those are descriptive arm results. The record does not include a confidence interval, p-value, or other inferential estimate comparing the arms. It also does not report a more detailed description of the participant population, such as eligibility criteria or baseline characteristics. The clinical question is therefore clear in broad terms, but its result cannot be fully evaluated as a comparative estimate from the posted figures alone.

3. Trial Design

The registry record describes a completed Phase 4, randomized, double-blind, parallel-group trial. It reports enrollment of 64 participants. The two named arms were benzocaine and Pliaglis; their reported outcome populations were 34 and 30 participants, respectively. The record does not explain the allocation procedure, the ratio intended at randomization, or whether the reported outcome populations match all participants randomized.

In both arm descriptions, a topical numbing gel was applied before injection with articaine. The intervention contrast is therefore Pliaglis versus benzocaine as the topical preparation in the context of an articaine injection. The record does not give further details about how the gels were applied, how long they were left in place, or the injection procedure. Although the trial is labeled double blind, the registry record does not specify which people were masked or how masking was maintained.

The primary outcome is titled as measurement of pain associated with injection, in millimeters, according to a visual analog scale. The description identifies the Heft-Parker scale and says participants indicated their discomfort upon needle stick. The assessment timeframe is 2.5 minutes. The record lists one outcome measure and no secondary outcomes. It reports arm means, but gives no arm-level measure of variability and no comparative analysis.

The trial status is completed. The registry record lists a start in 2013-08 and primary completion in 2014-06. It names the University of Michigan as sponsor. These details describe the registered study; they do not supply the underlying protocol, analysis plan, or a fuller account of trial conduct. Sample-size justification, participant flow, and the allocation and masking procedures 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.

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 Measurement of Pain Associated With Injection, in Millimeters, According to Visual Analog Scale, measured over 2.5 minutes.

The primary endpoint is mean pain associated with injection, measured in millimeters using the Heft-Parker visual analog pain scale. The registry description says the participant indicates the discomfort experienced upon needle stick. The scale is described as running from 0 mm, corresponding to no pain, to 170 mm, corresponding to maximum pain. The registered timeframe is 2.5 minutes.

A participant-reported pain scale captures an experience that may not be directly observable by another person. Expressing that response on a continuous scale preserves more gradation than a simple yes-or-no classification. Reporting the mean provides a summary of the group’s responses, but the mean alone does not show how widely individual responses varied or whether the distribution was skewed. Those features matter when interpreting an average, particularly when the record supplies no standard deviation, standard error, or other measure of variability.

The posted mean is 38.5 mm for benzocaine and 26.9 mm for Pliaglis. The record lists the full scale range as 0.0 to 170.0 for both arms. That is the instrument’s stated range, not a measure of the observed spread of participants’ scores. The registry record does not report an arm-level observed minimum and maximum, an estimate of the between-arm contrast, or an uncertainty interval.

Using the same defined pain scale for both arms makes the outcome directly relevant to the trial’s stated comparison. Still, the timing, wording, and administration of the rating can affect interpretation, and the registry record does not provide further administration details. The outcome describes reported pain in this study context; it does not by itself describe other aspects of anesthesia or establish a broader clinical effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

General: A mean is calculated by adding the observations in a group and dividing by the number of observations included. It offers a single summary of the group’s location on a measurement scale. A mean can be useful for a continuous outcome such as a pain rating in millimeters, but it does not reveal the shape of the data. The same mean can arise from tightly grouped scores or from scores spread widely across the scale.

For this trial, the registry reports a mean of 38.5 mm in the benzocaine arm and 26.9 mm in the Pliaglis arm. It does not report a standard deviation, standard error, median, or observed range of participant scores. The listed 0.0-to-170.0 range is the scale’s full range, not a description of the observed score distribution. Thus, the posted summaries do not show how representative either mean is of individual participants’ ratings.

Why does variability matter?

General: Variability describes how far individual observations tend to lie from a group summary. It is needed to understand how precisely a mean is estimated and to calculate many common confidence intervals and tests comparing means. When variability is not reported, the reader cannot independently evaluate uncertainty around an arm mean or a difference between arm means from the summary alone.

For outcomes with non-normal or highly uneven distributions, the mean may also be influenced by unusually high or low observations. General statistical practice considers the distribution and the study design when selecting and interpreting an analysis. The registry record does not report the score distribution or an analysis plan that would clarify how the investigators handled its shape.

What does randomization contribute?

General: Random allocation aims to make treatment groups comparable on average with respect to characteristics that could influence the outcome. It is a design feature, not a guarantee that the groups will be identical in a particular trial. Reporting participant flow and baseline characteristics can help readers understand the groups actually analyzed, while an analysis plan clarifies how outcomes were compared.

The registry identifies this study as randomized and parallel-group, with 34 participants reported for benzocaine and 30 for Pliaglis on the primary outcome. The record does not describe the randomization sequence, allocation concealment, participant flow, or baseline characteristics. It also does not identify the analysis population or state how participants with unavailable outcome data were treated.

What does double blinding mean for interpretation?

General: Masking can reduce the influence of expectations on trial conduct, outcome assessment, and participant reporting. The meaning of a double-blind label depends on which people were unaware of assignments and how the masking was protected. For a subjective outcome such as self-reported pain, expectations are one possible influence on a rating, so details about outcome collection and masking can be useful.

The registry labels the study double blind but does not describe who was masked or how masking was maintained. The label therefore communicates the registered design classification, but not the operational details needed to assess masking in depth.

What is the role of a between-arm estimate?

General: A comparison of randomized groups is usually expressed as an effect estimate, such as a difference in means, accompanied by an uncertainty measure such as a confidence interval. The estimate describes the magnitude and direction of the observed contrast; the uncertainty measure indicates how much precision the data provide under the analysis assumptions. A p-value, when reported, addresses compatibility with a specified null hypothesis under a statistical model. It does not describe the size or clinical importance of an effect.

The registry record posts arm-level means but no comparative estimate, confidence interval, or p-value. It also lists no analyses. Therefore, no inferential conclusion can be drawn from the posted results. The arm means should not be treated as a substitute for the absent comparative analysis, and the numerical ordering alone does not establish statistical significance.

What can a planning illustration tell readers?

General: Sample-size planning estimates how many participants may be needed to detect a chosen effect with specified assumptions about statistical error, allocation, and the analysis. A calculation based on an observed effect is a planning illustration, not evidence that a trial had a particular probability of detecting an effect after it was completed. Retrospective calculations do not replace the trial’s design rationale.

The registry describes a planning approach using a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of the observed effect. It explicitly characterizes that exercise as a planning illustration rather than the trial’s own design. The registry record does not report the trial’s sample-size justification. No numerical planning results are reported in the registry record, so no participant target for a specified power can be stated from the posted information.

Why should multiple outcomes and analyses be considered?

General: When researchers test many outcomes or make many comparisons, the chance of at least one apparently notable result can increase. Prespecified primary outcomes and analysis plans help readers distinguish confirmatory questions from exploratory ones. Adjustment methods and clear reporting can help address multiplicity, but the appropriate approach depends on the plan and the analyses conducted.

The registry lists one outcome measure and no secondary outcomes, and it reports no analyses. It does not describe any multiplicity strategy or specify whether additional analyses were planned. These omissions prevent assessment of the analysis strategy beyond the registered outcome description.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no secondary outcomes. That limits the multiplicity questions that can be assessed from the posted record, but it does not establish that no other outcomes or analyses were considered during the study. The record reports zero analyses, and a multiplicity plan is not reported in the registry record. It is therefore not possible to determine whether any adjustment for multiple testing was planned or used.

General: Multiplicity arises when several outcomes, time points, subgroups, or statistical comparisons are examined. Each additional test can create more opportunities for a result that appears notable by chance. Clear prespecification and reporting help readers understand which analyses were confirmatory and which were exploratory. The registry’s single listed outcome is the pain measurement in millimeters, assessed at 2.5 minutes, but the record does not provide a statistical analysis plan.

Missing-data handling is also not reported in the registry record. The record gives outcome counts of 34 for benzocaine and 30 for Pliaglis, but does not explain whether these are all randomized participants, whether any enrolled participants lacked an outcome, or how unavailable ratings were handled. Participant flow, analysis-population definitions, and imputation procedures are not reported in the registry record.

General: Missing observations can affect an estimate when their occurrence is related to participant characteristics or outcomes. The effect of missingness depends on its amount, pattern, reasons, and the assumptions used in analysis. Without those details, readers cannot assess whether the posted arm summaries represent all randomized participants or a subset with available pain scores.

The registry record also does not describe an intention-to-treat or per-protocol analysis population. The available counts should be read as the group sizes attached to the posted endpoint results, not as a complete account of participant disposition.

11. 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 posted adverse-event figures report zero serious adverse events among 34 participants at risk in the benzocaine group and zero among 30 participants at risk in the Pliaglis group. The record also reports zero participants affected by other adverse events among 34 at risk in the benzocaine group and zero among 30 at risk in the Pliaglis group. These are the counts recorded for the listed groups.

A zero count means that no events of the stated category were reported in the registry record for that group. It does not establish that the underlying risk is exactly zero. General interpretation of safety counts depends on the amount of exposure, how events were defined and collected, follow-up duration, and the completeness of reporting. Those details are not reported in the registry record.

The registry does not list serious adverse-event terms. Death counts are null for both groups, so deaths are not reported in the registry record; null should not be read as a posted count of zero. The adverse-event figures also do not provide event narratives, severity breakdowns beyond the serious category, or a statistical comparison between groups.

These safety counts are descriptive and should be interpreted alongside the limited reporting context. They do not by themselves establish equivalence in safety or support a comparative risk estimate.

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

The registry record documents a randomized, double-blind comparison of Pliaglis and benzocaine as topical anesthetics before articaine injection, with participant-reported pain on a Heft-Parker visual analog scale as the primary outcome. The posted arm means are 26.9 mm for Pliaglis and 38.5 mm for benzocaine. Those figures show the observed average pain ratings as recorded for the two groups; the Pliaglis arm’s reported mean is numerically lower.

That descriptive ordering is not the same as a statistically supported estimate of a treatment effect. The registry record does not report a between-arm estimate, confidence interval, p-value, or analysis method. Without a measure of within-arm variability and details of the analysis population, the precision of a comparison cannot be assessed from the posted results. The registry record also does not report a threshold for a clinically important difference on this scale.

The figures do not establish that either anesthetic is better or worse, and they do not answer how likely the observed contrast is to reflect chance variation. They also do not demonstrate that the two groups are equivalent. Such conclusions require an appropriate comparison and adequate uncertainty reporting, neither of which is posted in the registry record.

The endpoint is specific: a participant’s pain rating associated with needle insertion, assessed at 2.5 minutes. It does not measure every aspect of anesthesia, and the posted results do not establish effects in other settings or populations. Eligibility criteria and participant characteristics are not reported in the registry record, which further limits assessment of how broadly the findings might apply.

The adverse-event record lists no serious or other adverse events among the participants at risk in either group, but the safety data do not provide enough context to establish that no risk exists or to compare safety precisely. Overall, the record supplies a descriptive outcome and adverse-event counts, while leaving the comparative statistical inference and important details about study conduct unreported.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical-trial reporting: arm-level summaries are not the same as a comparative analysis. A mean in each group can show the direction of the observed numerical ordering, but a reader also needs an estimate of the contrast and information about its uncertainty to understand how precisely the groups differ in the data. In this record, the means are available, but the comparative analysis is not.

The distinction is particularly relevant for a participant-reported continuous outcome. A mean summarizes ratings on the pain scale, while the variation among individual responses affects how precisely that mean and any between-group contrast can be estimated. The record identifies the scale and posts its full range, but does not describe the observed distribution or provide an arm-level variability measure. This makes clear why reporting only a mean can leave the statistical interpretation incomplete.

The registered design also provides useful context. Randomization and double blinding are important design features, but labels alone do not describe allocation procedures, who was masked, or the analysis population. Those details help readers assess the strengths and limits of a result. Their absence does not negate the design labels; it limits how fully the design can be evaluated from the registry record.

Finally, the record highlights the difference between a trial’s own planning and a retrospective planning illustration. A calculation using an observed effect and stated assumptions is not evidence of observed power and does not substitute for a sample-size justification established before the trial. The registry describes an illustrative calculation approach, while the trial’s sample-size rationale is not reported in the registry record.

These statistical distinctions matter because readers need to separate what the data describe from what an analysis can support. Here, the posted means and event counts are informative summaries, but the record lacks the uncertainty estimates and methodological detail needed for a full comparison.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting the outcome is the absence of a posted comparative analysis. The registry gives an arm mean and group size for each arm, but no between-arm estimate, confidence interval, p-value, or analysis method. It also reports no measure of within-arm variability. Readers therefore cannot assess the precision of the numerical contrast or how much scores varied among participants.

The endpoint description has some detail, including the Heft-Parker scale, its 0 mm to 170 mm range, and a 2.5-minute timeframe. However, the record does not explain how the rating was administered, who collected it, or whether any ratings were unavailable. The trial title refers to needle insertion in the palate, whereas the arm descriptions refer to applying gel to the gums. Further procedural clarification is not reported in the registry record.

The registry labels the trial randomized and double blind, but does not describe the randomization method, allocation concealment, or which parties were masked. It does not post baseline characteristics or participant flow. Although outcome counts are reported for both arms, their relationship to the total enrolled population and the handling of any missing data are not explained. The analysis population is not reported in the registry record.

The record lists no secondary outcomes and no analyses. It does not include a statistical analysis plan, an approach to multiplicity, or the trial’s sample-size justification. A planning illustration is described, but it is explicitly not the trial’s own design and no numerical planning results are reported in the registry record.

The adverse-event summary reports zero affected participants in the listed categories, but does not provide further collection or follow-up details. Taken together, these gaps mean the posted record supports a limited descriptive reading, rather than a comprehensive assessment of comparative efficacy, precision, safety, or generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparison of Two Topical Anesthetics: Benzocaine Versus Pliaglis — NCT01951820.
• Registry record last updated 2016-07-22; status last verified 2016-06.
• Results first posted 2016-07-22.
• 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

The registry record describes a completed Phase 4 randomized, double-blind, parallel-group trial sponsored by the University of Michigan, with enrollment of 64 participants. It compared Pliaglis and benzocaine topical gels before articaine injection. The primary outcome was mean pain associated with injection on the Heft-Parker visual analog scale, assessed at 2.5 minutes.

The posted outcome means were 26.9 mm among 30 participants in the Pliaglis arm and 38.5 mm among 34 participants in the benzocaine arm. The scale’s full range was 0.0 to 170.0 mm. No comparative analysis, uncertainty interval, p-value, or measure of arm-level variability is reported. The registry lists no secondary outcomes and zero analyses.

The adverse-event record reports zero serious and zero other adverse events in each arm; death counts are not reported in the registry record. Details about missing data, analysis populations, sample-size justification, allocation procedures, masking, and participant flow are also not reported in the registry record. The posted figures therefore provide descriptive results, but not a complete inferential comparison.