Comparison of Two Application Techniques for LET Gel: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Two Application Techniques for LET Gel (NCT04203225), a randomized phase 4 study. The primary outcome is Visual Analog Scale Pain Score.

2. Clinical Question

The clinical question focuses on pain during the start of suturing after topical anesthetic gel has been applied. Both groups received LET; the tested contrast was whether the gel was applied once for 30 minutes or applied three times at 10-minute intervals. This makes the comparison relevant to the timing and repetition of application within the specific setting described in the registry record.

The primary outcome was self-rated pain on a visual analog pain scale. The scale is described as having a minimum of 0 and a maximum of 100, with higher scores indicating more pain. The score was assessed immediately on placement or attempted placement of the first suture. The record also lists need for additional local anesthetic during suturing as a secondary outcome. It does not report further eligibility criteria, the anatomical location or severity of lacerations, or a fuller description of the eligible clinical population.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group Phase 4 trial. It lists enrollment as 48 and status as completed. The study dates are recorded as starting on 2017-05-22, with primary completion on 2019-11-12. The sponsor is Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center.

The two groups received the same topical LET gel, containing lidocaine (4%), epinephrine (0.1%), and tetracaine (0.5%), but differed in how it was applied. The Single LET group received one application for 30 minutes. The Triple LET group received three applications, one every 10 minutes. The summary describes use before suturing simple lacerations in children aged 7–17 years.

The primary outcome was the child’s visual analog pain score at placement or attempted placement of the first suture. The registry reports an outcome group size of 21 for Single LET and 27 for Triple LET. It reports group means of 16.0 in both groups, with standard deviations of 17.0 and 24.0, respectively. The record also lists need for additional local anesthetic during the suturing procedure as a secondary outcome.

Randomization, double masking, and a parallel-group model are recorded, but the method used to generate the allocation sequence, conceal allocation, and maintain masking is not reported in the registry record. The record also does not describe the intended sample-size justification, recruitment procedures, or the analysis population. These omissions limit how fully the design can be assessed from the registry information alone.

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 Visual Analog Scale Pain Score, measured over Immediately on placement or attempt at placement of first suture.

The primary endpoint is the patient’s self-rated pain at the placement or attempted placement of the first suture. Pain was recorded on a visual analog pain scale described in the registry as a 100m scale, with a minimum value of 0 and a maximum value of 100. Higher scores indicate more pain and therefore a worse outcome. The assessment was made immediately at the start of suturing.

A patient-reported measure captures the child’s own experience at a clinically defined point in the procedure. It complements an observer’s assessment, which may not reflect how much pain the patient feels. Measuring pain when the first suture is placed also places the endpoint after the assigned application schedule and at the point when repair begins. These are general reasons such an endpoint can be useful; the registry record does not state why this particular measure or time point was selected.

The outcome is continuous, and the registry reports a mean and standard deviation for each group. A group mean describes the average score, while the standard deviation describes the spread of individual scores around that mean. Neither summary shows the full distribution of scores or how individual children experienced the procedure. The registry record does not report a threshold for a clinically important difference, so the clinical importance of a given mean difference cannot be determined from the record alone.

7. Results Posted in the Registry

• Triple LET: mean 16.00 versus 16.00 on control; difference 0.00 (95% CI -11.61 to 11.61), standardized effect d = 0.00; z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Need for Additional Local Anesthetic

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Triple LET: 18.5% (5/27) versus 19.0% (4/21) on control; risk difference -0.5 percentage points (95% CI -22.8 to 21.8), risk ratio 0.97 (0.30–3.18); unadjusted two-proportion z-test p = 0.963.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Triple LET and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary endpoint: whether additional local anesthetic was needed during the suturing procedure. This outcome provides a procedural complement to the primary patient-rated pain score. The primary endpoint captures reported pain at the first suture, while the secondary endpoint captures whether further anesthetic was used at any time during suturing, based on chart review immediately after the procedure.

Across the posted comparisons, there is no clear pattern of separation between the application schedules. This is broadly consistent with the primary comparison’s point estimate, which is centered at no difference. However, the secondary outcome is a separate measure and does not demonstrate that the pain outcomes or procedural experiences were identical. Its estimate is uncertain, and it should be interpreted as supporting context rather than as a substitute for the primary endpoint.

Unadjusted secondary findings generally carry less weight than a prespecified primary result because they may not have the same priority in the trial’s design and may be considered alongside other outcomes. When several outcomes are examined, the chance of observing an apparently notable result can increase unless the analysis plan accounts for multiple comparisons. The registry record does not report a multiplicity strategy or a hierarchy for interpreting secondary outcomes. It also lists no reported analyses.

Accordingly, the secondary result should not be elevated to a definitive conclusion about the two application schedules. Its meaning is constrained by the uncertainty in the estimate, the lack of a reported analysis plan, and the absence of a stated multiplicity approach. The registry record does not report additional secondary endpoints beyond need for additional local anesthetic.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Need for Additional Local Anesthetic

9. Statistical Interpretation

10. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure and reports the mean and standard deviation in each group. The comparison is expressed as a mean difference, defined in general as the first named group’s mean minus the comparator group’s mean, according to the stated comparison direction. A mean difference is measured in the original units of the outcome, which are millimeters for the pain score.

What does the mean describe?

A mean is the arithmetic average of the observed scores in a group. It gives a compact description of the group’s central level, but does not show whether scores cluster closely around that level or are widely dispersed. The standard deviation summarizes that dispersion. It is not the uncertainty in the mean itself; uncertainty in an estimated mean difference also depends on the amount of information in each group and the variability of the measurements.

For the primary outcome, the posted means are 16.0 in both groups. The comparison reports a mean difference of 0.0 and an unadjusted p-value of 1.0. The reported standard deviations are 17.0 for Single LET and 24.0 for Triple LET. These summaries support a comparison of average scores, but they do not reveal the score distribution, outliers, or the extent of overlap between individual participants’ scores.

How should the confidence interval be read?

A confidence interval describes the uncertainty around an estimate under the statistical method used. In general, a narrower interval indicates greater precision, while a wider interval leaves more possible values compatible with the data and method. The primary mean-difference interval runs from -11.61 to 11.61. It contains zero and includes estimates in either direction. It is therefore not evidence of a precisely established zero effect. Rather, the point estimate is zero while the interval reflects uncertainty around it.

The registry record does not report a clinically important difference for the pain scale. Statistical compatibility with zero does not answer whether all values in the interval would be clinically unimportant. That requires a prespecified threshold or other clinical context, neither of which is reported in the registry record.

What does the p-value add?

A p-value is a measure of how incompatible the observed data are with a specified null hypothesis, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not quantify the size or importance of a difference. The primary p-value is labelled unadjusted. In this setting, it should be considered alongside the mean difference and confidence interval rather than used alone to make a conclusion.

The record does not state the exact test or model behind a sponsor analysis, and it reports no analyses. The comparison shown is a recalculated, unadjusted comparison based on the posted group summaries. Since the discrepancy flag is false, no discrepancy between a sponsor analysis and this recalculation is indicated in the registry information. That does not supply details about an analysis plan or establish how any unreported analysis was conducted.

How does the secondary outcome differ?

Need for additional local anesthetic is a binary outcome: each participant is counted according to whether additional anesthetic was needed during suturing. Its comparison is expressed as a risk difference, the difference between the proportions with the outcome in the two groups. The posted unadjusted estimate is -0.005, with a confidence interval from -0.228 to 0.218 and an unadjusted p-value of 0.963. The interval includes zero and extends to both negative and positive values, so the estimate is imprecise and does not identify a clear difference between groups.

For a binary outcome, a risk difference is an absolute contrast in proportions. In general, this can be easier to interpret in the context of the observed event frequency than a relative measure, but its precision still depends on the number of observations and outcomes. The record also posts relative measures for this secondary outcome, but does not report adjusted analyses. These unadjusted estimates should not be treated as independent confirmation of the primary result.

What do the planning illustrations mean?

The registry includes planning illustrations based on the observed secondary-outcome effect, not on the trial’s original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The illustrations consider planning for 100%, 75%, and 50% of the observed effect, with participant requirements stated per arm for 80% and 90% power.

These values are hypothetical planning calculations. They are not the number of participants observed, do not describe the original trial’s sample-size justification, and are not observed power. Because the observed effect is used as the starting point, the illustrations should not be read as independent evidence that a future study would reproduce that effect. The trial’s own sample-size assumptions and justification are not reported in the registry record.

11. Confidence Intervals and Precision

The primary point estimate is a mean difference of 0.0, and its confidence interval extends from -11.61 to 11.61. The interval includes zero and values on either side of zero. In practical terms, the posted results do not determine the direction of any underlying difference in average pain scores with precision. The point estimate is neutral, but the interval leaves uncertainty about the size and direction of a difference.

Precision depends on the variability of the outcome and the amount of information available. The registry reports outcome group sizes of 21 for Single LET and 27 for Triple LET, alongside standard deviations of 17.0 and 24.0. The greater spread in the Triple LET scores is relevant because more variable measurements generally make group averages less precise, all else equal. This is a general statistical principle; it does not establish the reason for the interval width in this trial.

The interval should not be treated as a range containing every plausible individual response. It concerns uncertainty in the estimated group mean difference under the calculation method. The individual pain scores may vary more widely than the interval, and the record does not provide their distribution. Nor does it report a clinical threshold that would distinguish a negligible difference from an important one.

The secondary risk-difference interval is also broad and includes both directions. That imprecision matters because the outcome is binary and the posted number of events is limited. The planning illustrations use the observed effect and stated assumptions to show how sample-size requirements might vary across target fractions of that effect. They are planning examples only; they do not retrospectively measure the trial’s power or show that the original design was adequate.

Overall, the estimates are not precise enough to support a strong claim that the application schedules yield identical outcomes. They also do not establish that one schedule produces a better outcome. The best reading is that the point estimates show little separation, while the confidence intervals leave meaningful uncertainty that cannot be resolved from the registry record alone.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary pain-score outcome and one secondary outcome, need for additional local anesthetic. It does not report a prespecified hierarchy for interpreting these outcomes or explain whether any adjustment was planned for multiple comparisons. When more than one outcome is examined, unadjusted tests do not account for the possibility that the number of tests can affect the chance of a nominally unusual result. This is a general statistical concern, not evidence that a particular finding in this trial is false.

The posted comparisons are labelled unadjusted, and the record lists no reported analyses. The registry record does not state whether outcomes were analyzed according to a prespecified statistical analysis plan, whether covariates were included, or whether any alternative analyses were conducted. The method of randomization and allocation concealment is also not reported. These details are important for evaluating how planned comparisons were carried out, but cannot be inferred from the randomized and double-blind design labels.

The record does not describe missing data, the number of participants with unavailable outcome measurements, or how missing observations were handled. The primary outcome population field is blank. It is therefore not possible to determine from the registry information whether all randomized participants were included in the primary analysis, whether an intention-to-treat approach was used, or whether another analysis population was defined. The record also does not describe exclusions after randomization or any imputation methods.

These are reporting limitations, not proof that data were missing or that analyses were biased. Without information on missingness and analysis populations, however, readers cannot assess whether the posted outcome summaries represent all randomized participants or a subset with recorded outcomes. The absence of a stated multiplicity plan similarly limits interpretation of the secondary comparison. These uncertainties reinforce the need to treat the registry results as a limited account of the trial rather than a full statistical report.

13. 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 adverse-event record reports zero serious adverse events and zero deaths in both the Single LET and Triple LET groups. It also reports zero events in the other adverse-event category for each group. These are the recorded figures for the groups as entered in the registry.

A count of zero means that no events in that category were recorded in the registry for the listed participants. It does not prove that the risk is absent, particularly when the groups are limited in size, and it does not provide precise evidence about rare events. The registry record does not provide descriptions of non-serious events, event definitions, severity grading, relatedness assessments, or the methods used to collect safety information. No serious adverse event terms are listed.

These safety figures should be interpreted as a report of observed and recorded events, not as a broad guarantee about safety in other populations or settings. They are also separate from the pain and additional-anesthetic outcomes, which address efficacy and procedure experience rather than adverse events.

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

The results describe a specific comparison: the same LET gel applied once for 30 minutes versus three times at 10-minute intervals before suturing simple lacerations in children aged 7–17 years. The primary outcome is pain self-rated at placement or attempted placement of the first suture. The reported mean scores are the same, and the unadjusted mean difference is zero, but the confidence interval indicates uncertainty around that estimate.

These findings do not establish that the two application schedules are equivalent. Equivalence requires a prespecified margin defining what difference would be small enough to regard the approaches as equivalent, along with an analysis designed to test that question. No such margin or equivalence analysis is reported in the registry record. A non-significant result alone cannot demonstrate that outcomes are the same.

The results also do not establish that one application schedule is superior. The point estimate does not favor either schedule, and the interval includes differences in both directions. The registry record does not report a threshold for clinical importance, so it is not possible to determine whether any particular difference within the interval would matter to patients or clinicians.

The findings are limited to the measured outcomes and the population described in the record. They do not establish effects on other forms of pain, other procedures, other populations, or other anesthetic products. The additional-anesthetic outcome is based on chart review during suturing and is not a complete measure of every aspect of procedural experience. The safety record likewise describes only the adverse-event categories and counts entered in the registry.

The most defensible interpretation is that the posted data do not show a clear difference in average pain score between these schedules, while uncertainty remains about the possible size and direction of an underlying difference. This is a statement about the registry results, not medical advice or a recommendation about which application schedule to use.

15. Why This Trial Matters Statistically

This trial illustrates why a point estimate and its uncertainty should be read together. The primary means are identical as posted, and the estimated mean difference is zero. Considered alone, that could be mistaken for proof that the schedules produce identical pain scores. The confidence interval is essential because it shows that the estimate remains uncertain and permits differences in either direction.

The trial also demonstrates the distinction between statistical significance and clinical importance. A p-value describes compatibility with a statistical null hypothesis under a method’s assumptions; it does not tell readers whether a difference matters to patients. The registry record does not state a clinically important difference for the pain scale. Without that context, the clinical meaning of possible values within the interval cannot be fully judged.

Its two endpoints also illustrate that different outcome types answer different questions. A continuous, patient-rated pain score measures reported pain at the first suture. The binary secondary outcome records whether additional local anesthetic was needed during the procedure. Agreement in broad pattern can be informative, but the endpoints are not interchangeable and neither alone captures every aspect of the procedure.

Finally, the record highlights the importance of transparent reporting. Randomization and double masking are documented, but details of allocation methods, missing-data handling, analysis populations, sample-size justification, and multiplicity are not. These omissions limit assessment of the analysis and the strength of conclusions. The planning illustrations are explicitly based on the observed secondary effect and should not be mistaken for observed power or the original design rationale.

16. 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 available registry information has several trial-specific limitations. The outcome group sizes are 21 for Single LET and 27 for Triple LET, and the primary confidence interval remains wide enough to include differences in either direction. The group standard deviations also show appreciable variability in pain scores, especially in Triple LET. Together, these features limit how precisely the comparison identifies an underlying difference.

The record describes the population as children aged 7–17 years with simple lacerations, but does not report fuller eligibility criteria, laceration characteristics, or the setting in which participants were treated. This makes it difficult to assess how closely the enrolled population matches other clinical contexts. The findings concern the stated LET formulation and application schedules; the record does not support conclusions about other products or procedural settings.

Although the design is listed as randomized and double-blind, the methods used to generate and conceal allocation and to implement masking are not reported. The record does not describe missing outcomes, exclusions, analysis populations, or handling of missing data. It also does not report a statistical analysis plan, a clinical-importance threshold, or a multiplicity approach.

The registry reports no analyses, and the displayed comparisons are unadjusted recalculations from posted summaries. The planning illustrations use the observed secondary-outcome effect rather than documenting the trial’s original sample-size justification. The record therefore offers limited information about how the study was planned and analyzed. These reporting gaps should be distinguished from evidence that a particular method was not used; the registry simply does not report those details.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Comparison of Two Application Techniques for LET Gel — NCT04203225.
• Registry record last updated 2021-02-18; status last verified 2021-01.
• Results first posted 2021-02-18.
• 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.

20. Record Summary

NCT04203225 is a completed, randomized, double-blind, parallel-group Phase 4 trial sponsored by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center. The registry lists enrollment as 48, a start date of 2017-05-22, and primary completion on 2019-11-12.

The study compared one 30-minute application of topical LET gel with three applications given every 10 minutes before suturing simple lacerations in children aged 7–17 years. The primary outcome was patient-rated pain at placement or attempted placement of the first suture. The posted group means were 16.0 in both groups; the mean-difference estimate was 0.0, with a confidence interval from -11.61 to 11.61.

The registry also lists need for additional local anesthetic as a secondary outcome and reports zero serious adverse events and zero deaths in both groups. It does not report analyses, a sample-size justification, missing-data methods, or a multiplicity strategy.