A Study of the Use of Microneedle Patches to Deliver Topical Lidocaine in the Oral Cavity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Use of Microneedle Patches to Deliver Topical Lidocaine in the Oral Cavity (NCT03629041), a randomized phase 1 study. The primary outcome is VAS in Healthy Participants, When Topical 5% Lidocaine Dental Gel Was Applied to the Upper Palatal and Upper Anterior Buccal Sulcus Areas With a Microneedle Patch and a Patch With no Microneedles, Prior to Infiltration With Local Anaesthesia..

2. Clinical Question

3. Trial Design

The registry record identifies this as a randomized, double-masked, crossover Phase 1 study. It lists Innoture Ltd as the sponsor and enrollment as 16. The study is marked completed. Its recorded start date is 2018-07-31 and its primary completion date is 2018-08-22. These registry entries describe the study status and design, but do not establish how many participants contributed usable primary outcome measurements.

The two interventions were a microneedle patch and a patch with no microneedles. In both conditions, the intervention description specifies topical 5% lidocaine gel applied to an identified oral site for 3 minutes. The outcome description then identifies three tests involving a dental needle: penetration of the mucosa, insertion to contact bone, and injection of local anaesthetic into the site. Pain was recorded immediately after each test. The primary outcome title identifies the upper palatal and upper anterior buccal sulcus areas.

Because the registered model is crossover, the treatment comparison is intended to involve conditions evaluated within a crossover design rather than simply contrasting two unrelated parallel groups. The record does not report treatment order, allocation sequence, period structure, washout interval, or how the two oral sites and three tests were assigned across conditions. It also does not specify which people were masked. Those details should not be inferred from the labels randomized and double-masked.

The registry lists five outcome measures and zero analyses. It does not report primary outcome values, a treatment-effect estimate, confidence intervals, or a statistical test. Therefore the design and measurement procedure can be described, but the relative VAS results cannot be assessed from 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: Participants were healthy volunteers who have their regular dental care at Rhiwbina Dental Surgery.

Visit 1

Visit 2 (2 Weeks ± 3 Days From Visit 1)

Reasons for not completing this period:

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 VAS in Healthy Participants, When Topical 5% Lidocaine Dental Gel Was Applied to the Upper Palatal and Upper Anterior Buccal Sulcus Areas With a Microneedle Patch and a Patch With no Microneedles, Prior to Infiltration With Local Anaesthesia., measured over Following 3 minutes of application of topical anaesthetic using a patch, the 3 tests were performed and the pain score recorded immediately after each test..

The primary endpoint is pain measured with a visual analogue scale (VAS) after application of topical 5% lidocaine gel and subsequent tests at oral sites. Participants indicated pain by selecting a position along a continuous line anchored at no pain (0) and worst pain imaginable (100). The record states that lower scores indicate a better outcome. Scores were recorded immediately after each of three tests following 3 minutes of patch application.

The tests were designed to assess pain in connection with progressively different actions at the treated site: needle penetration through the oral mucosa, insertion through the mucosa to contact bone, and injection of local anaesthetic into the site. The endpoint title also names upper palatal and upper anterior buccal sulcus areas. The record does not give separate numerical results for each test or site, nor explain whether scores were combined into a summary endpoint.

VAS measures are used to represent a person's subjective experience on a continuous scale. In general, a continuous score can retain distinctions across a range of reported pain rather than reducing responses to a small set of categories. Interpretation depends on understanding the scale anchors, timing, and the exact test associated with each score. Here, the registry describes those elements, but does not report the observed means, standard deviations, or treatment comparison. The endpoint definition alone therefore cannot show whether scores differed between patch conditions or how precisely any difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized by a mean, with standard deviation as the measure of dispersion. These are descriptive statistics: they describe observed scores, not by themselves the strength of evidence for a treatment difference. The registry record does not report the primary means, standard deviations, treatment contrast, confidence interval, or test result. Its list of zero analyses means there is no reported analysis result to interpret.

What does a mean and standard deviation tell a reader?

In general, the mean is the arithmetic average of measured values. The standard deviation describes how much individual observations vary around that average. A mean can make a group of continuous measurements easier to summarize, but it can hide differences among participants or across measurement conditions. The standard deviation provides information about spread, but it is not the same as uncertainty in the estimated mean or uncertainty in a treatment contrast.

For this study, the VAS is anchored from no pain (0) to worst pain imaginable (100), and the record says lower scores indicate a better outcome. The measurement description includes multiple tests and oral areas. A reader would need to know which score or scores were used to calculate each reported mean, whether scores were summarized across tests or sites, and how any repeated measurements were accounted for. Those details are not reported in the registry record.

Why does the crossover design affect the analysis?

In general, crossover designs expose participants to more than one treatment condition, allowing a comparison that can use within-participant information. Since measurements from the same person tend to be related, an analysis should recognize that pairing rather than treating every condition's observations as independent. A paired analysis can be more informative than an unpaired comparison when it matches the design and assumptions.

Crossover interpretation can also depend on treatment sequence and period. A period effect is a difference associated with when a condition is given, rather than which condition is given. Carryover refers to an effect of an earlier condition that persists into a later one. These are general design considerations, not reported findings about this study. The treatment order, period structure, washout, and statistical handling of such issues are not reported in the registry record. The label crossover alone is not enough to establish which analysis was used.

What would a confidence interval contribute?

In general, a confidence interval conveys the precision of an estimated treatment effect. It expresses a range of values compatible with the observed data and statistical assumptions; it does not guarantee that the true effect lies in that range. If the interval includes effects in different directions or a wide range of magnitudes, the estimate may be imprecise. Without a reported treatment estimate and interval, neither the direction nor precision of the comparison can be assessed. A p-value, if reported, would address compatibility with a null hypothesis under a particular model, but would not replace an effect estimate and its interval.

The record gives no numerical inferential result. In particular, it does not report a p-value, confidence interval, model, or test for the primary outcome. It would be inappropriate to infer statistical significance from the study's randomized or masked design, its enrollment entry, or its completed status. Design descriptions and outcome results answer different questions.

How should multiplicity be considered?

Multiplicity arises when several outcomes, sites, tests, time points, or treatment contrasts are examined. In general, examining multiple comparisons can increase the chance that at least one result appears notable by chance. A prespecified analysis can identify a primary comparison and explain whether adjustments or a hierarchy are used. The registry identifies a VAS primary outcome but describes multiple tests and sites, and the registered outcome has not been reduced to one comparison. Multiplicity procedures and a statistical analysis plan are not reported in the registry record. It is therefore unclear how results across those measurements would have been prioritized or interpreted together.

What does the sample-size illustration mean?

The stated planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not the registry's reported rationale for the study design. The sample-size justification for the trial is not reported in the registry record. Any sample-size estimate based on those assumptions is a planning illustration, not observed power and not evidence that the trial had adequate precision. The record does not report the numerical planning estimates or an observed primary effect that could be used to judge the illustration.

These general methods explain what would be needed to interpret a continuous crossover comparison. They do not supply missing results or establish that a particular model or procedure was used in this study. The registry record gives the design labels and measurement description, but not the analysis needed to evaluate the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description encompasses more than one measurement context: it names upper palatal and upper anterior buccal sulcus areas and describes three tests after patch application. The registered outcome is identified as having several categories or time points and is not reduced to one comparison. Consequently, the record does not establish a single numerical primary contrast that can be interpreted independently of the other measurements. The multiplicity strategy, including any adjustment, hierarchy, or prespecified selection of results, is not reported in the registry record.

Missing outcome information is also difficult to assess. Enrollment is listed as 16, but the number with recorded VAS measurements at each site and test, the number included in any analysis, and the reasons for any missing data are not reported in the registry record. The record does not describe an intention-to-treat, per-protocol, or other analysis population. It also does not say how incomplete crossover data would have been handled.

These omissions limit interpretation even without knowing whether measurements were missing. In general, missingness can affect a comparison if the availability of measurements is related to participants' outcomes or treatment conditions. An analysis may use different assumptions or procedures to handle incomplete data, but no such approach is documented. The reader cannot determine whether all randomized participants were analyzed or whether results were based on a subset.

The registry lists five outcome measures and zero analyses. It does not report an analysis plan, a missing-data method, or a population definition. Therefore, the multiplicity and missing-data issues cannot be resolved by relying on the outcome labels or the crossover designation alone.

11. 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 lists four treatment groups. For each group, the number at risk for serious events is 4 and the number affected by serious events is 0. For each group, the number at risk for other events is 4 and the number affected by other events is 0. The recorded number of deaths is 0 in each group. The group labels are Treatment Group 1 through Treatment Group 4; the registry record does not map those labels to the two patch conditions, so that mapping should not be assumed.

These entries mean that no serious or other adverse events are recorded among the participants at risk in each listed group. They do not establish that an event could not occur, or that the patches are free of risk. With limited observations, zero recorded events can still leave substantial uncertainty about less common harms. The record does not report additional detail about event monitoring, duration of follow-up, severity categories beyond the serious and other groupings, or the relationship of any event to an intervention.

The adverse-event figures should also be kept separate from the VAS endpoint. They describe recorded safety outcomes, not comparative pain scores. The registry record's safety entries do not provide the primary efficacy-style comparison, and the absent VAS analysis cannot be inferred from the absence of recorded events.

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

The registry record establishes that this was a completed, randomized, double-masked, crossover Phase 1 study of topical 5% lidocaine gel applied to oral mucosa with either a microneedle patch or a patch without microneedles. It describes a VAS pain outcome after three local anaesthetic infiltration tests and names two oral areas. Those details define the comparison the study was designed to address, but they do not reveal what the measured pain scores were.

The primary outcome means and standard deviations, a treatment-effect estimate, a confidence interval, and an inferential test are not reported in the registry record. It is therefore not possible to say from this record whether the scores were higher or lower under either patch condition, whether the results varied by site or test, or how precise a difference might be. The absence of results is not evidence that the conditions produced the same outcome, and it is not evidence of a difference.

The safety entries record zero serious events, zero other events, and zero deaths in each of the four listed treatment groups, with 4 at risk for each event category in each group. This is a description of the recorded entries, not proof that no risk exists. The record does not identify which numbered safety groups correspond to which patch condition.

Enrollment is listed as 16, but the number analyzed and completeness of outcome measurements are not reported. The record also does not provide the statistical analysis approach or explain how multiple sites and tests would be considered. Those omissions prevent a complete assessment of outcome reliability and precision.

Accordingly, the defensible interpretation is limited: the registry describes the design, interventions, VAS measurement, and recorded safety counts, but does not report the primary comparison. No conclusion about the direction or magnitude of the pain-score results can be drawn from the available registry entries.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a crossover design with a subjective, continuous outcome measured after several tests at oral sites. Crossover designs can be useful when within-participant comparisons are appropriate, but their analysis needs to reflect the repeated measurements and treatment sequence. Without the sequence, period details, and analytic method, readers cannot tell how the design was translated into a treatment estimate.

The outcome structure also illustrates why clarity about the primary comparison matters. The record names two oral areas and describes three tests, yet does not reduce the primary outcome to one reported contrast. If several site-test measurements are examined, readers need to know which comparison was prespecified and how multiplicity was handled. Otherwise, selective attention to one measurement could give an incomplete account of the overall evidence.

Precision is especially important in an early-phase study. A mean and standard deviation can describe the observed scores, while a treatment estimate with a confidence interval would show how uncertain the comparison is. Those primary results are not reported in the registry record. The enrollment entry alone cannot establish that the study could detect a particular effect or that a result would be precise.

The record also offers a useful distinction between design information and evidence of an outcome. Randomization, masking, and a completed status tell readers about the registered study, but do not substitute for analyzed results. Similarly, the recorded absence of adverse events in the listed groups is informative as a description of those entries, but cannot establish absence of risk. The trial's statistical contribution cannot be judged fully without outcome estimates, uncertainty, and a transparent account of the analysis.

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.

A central limitation of the registry record is that it contains no reported analysis of the primary VAS outcome. Means, standard deviations, treatment contrasts, confidence intervals, and test results are not reported in the registry record. This prevents assessment of effect direction, magnitude, and precision.

The primary outcome description refers to two oral areas and three tests, but no single comparison or method of combining measurements is reported. The multiplicity strategy is not reported either. A reader cannot determine whether the measurements were considered separately, summarized, or prioritized according to a prespecified plan.

The crossover structure is identified, but the registry record does not report treatment order, period arrangement, washout, or how pairing and possible period or carryover effects were handled. The record also does not identify which individuals were masked. These missing design and analysis details make it difficult to assess whether the reported design was implemented and analyzed in a way that protects the intended comparison.

Enrollment is listed as 16, but the number contributing data to the primary outcome, the completeness of measurements, and the reasons for missing values are not reported. Neither an analysis population nor a missing-data method is described. It is therefore not possible to evaluate attrition or determine how incomplete observations could affect the results.

Safety information is recorded across four numbered groups, but the correspondence between those groups and the intervention conditions is not reported. The record also gives no further detail about event follow-up or attribution. Finally, the sample-size justification and statistical analysis plan are not reported in the registry record. These limitations concern what can be established from the registry entries; they do not demonstrate that the underlying study lacked procedures that were not recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Use of Microneedle Patches to Deliver Topical Lidocaine in the Oral Cavity — NCT03629041.
• Registry record last updated 2019-11-14; status last verified 2019-10.
• Results first posted 2019-11-14.
• 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 randomized, double-masked, crossover Phase 1 study sponsored by Innoture Ltd. Enrollment is listed as 16. The recorded start date is 2018-07-31 and the primary completion date is 2018-08-22.

The study compared topical 5% lidocaine gel applied to oral mucosa with a microneedle patch or a patch with no microneedles. The primary outcome was VAS pain after three tests at upper palatal and upper anterior buccal sulcus areas. Lower scores were defined as a better outcome.

The primary outcome results and statistical analysis are not reported in the registry record. The safety entries list zero serious events, zero other events, and zero deaths in each of four treatment groups. The number analyzed, missing-data approach, multiplicity strategy, and statistical analysis plan are not reported.