In Vivo Investigation of Initial Stages of Enamel Erosion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for In Vivo Investigation of Initial Stages of Enamel Erosion (NCT02533466), a randomized na study. The primary outcome is Change From Pre-acid Challenge (Baseline) Tooth Impression Grading Score Immediately Following an Acid Challenge.

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group study registered as NCT02533466. Its registry title is In Vivo Investigation of Initial Stages of Enamel Erosion, and the official title is Study to Investigate the Initial Stages of Enamel Erosion in Vivo. The study status is completed. The registry records enrollment of 30 participants and lists the condition as tooth erosion. The phase is listed as not applicable.

The two groups received different dentifrice products: sodium fluoride plus potassium nitrate in the Test Product group and potassium nitrate in the Reference Product group. The application instructions were the same for both groups. Randomization and masking are recorded, but the method used to generate the random sequence, the allocation concealment process, and who was masked are not reported in the registry record. The actual group counts in the primary analysis were 16 and 14; the reason for the difference between these counts is not reported in the registry record.

The registry gives a study start date of 2015-10-01 and a primary completion date of 2015-11-06. Its brief description characterizes the study as exploratory and says it was designed to help develop a clinical model for measuring earlier stages of dietary acid-mediated enamel loss. Fluoride was to be used as a positive control to explore the validity of the design. The record does not report a separate validation criterion or a conclusion about whether the model was validated.

The study measured tooth-impression grading and listed salivary calcium, salivary pH, and buffering capacity outcomes at specified post-challenge times. The registered overall number of outcome measures is 10. Detailed protocol information beyond the registry descriptions, including the full analysis plan and the rationale for the enrollment target, is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 30 participants were screened and all of them were randomized.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Per Protocol (PP) population was defined as those subjects in the ITT (intent to treat) population who have at least one assessment of efficacy considered unaffected by protocol violation. Assessments of efficacy considered affected by protocol violation were excluded from PP analyses. The primary population was the PP population.

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.

Population: The Per Protocol (PP) population was the primary population.

6. Primary Endpoint

The registry lists the primary outcome as Change From Pre-acid Challenge (Baseline) Tooth Impression Grading Score Immediately Following an Acid Challenge, measured over Baseline, 30 minutes post dietary acid challenge.

The primary endpoint was change in tooth-impression grading score from pre-acid challenge baseline to the post-challenge assessment. The registry describes impressions of the tooth surface analyzed with scanning electron microscopy, followed by visual image analysis of enamel-surface topography. The grading scale represents increasing signs of surface erosive change: its descriptions range from no signs of surface erosive wear through early, mild, moderate, and severe signs. The record also identifies a category for images that were not evaluable.

This type of endpoint is intended to capture visible surface changes in the early stages of erosion, rather than relying only on a later clinical outcome. In general, a graded endpoint converts an ordered set of categories into scores; the order conveys increasing severity, but the gaps between adjacent grades need not represent equal changes. That feature is relevant when interpreting averages or differences in scores. The registry reports the primary measure as a median with full range and identifies a rank-based test for the comparison.

The primary endpoint title says immediately following an acid challenge, while its timeframe specifies baseline and 30 minutes post dietary acid challenge. Both descriptions appear in the registry record, and the exact timing is therefore best read with that qualification. The listed change is from pre-challenge baseline; the reported analysis is described as a comparison of final values. The record does not explain that distinction further.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is an ordered grading score based on enamel-surface images. General: when an outcome consists of ordered categories, the ranking carries information even if the numerical spacing between categories is not known to be equal. A rank-based procedure can compare the distributions of observations without requiring the score to behave like a normally distributed continuous measurement. The registry reports a Wilcoxon Rank Sum test for the primary comparison.

What does the reported difference represent?

The registry describes the tested parameter as a median difference in final values. The arm summaries are reported as medians with full ranges. The reported estimate is -0.08, with a 95% confidence interval from -1.0 to 0.0. The record does not explain in detail how the difference was derived from the ranked data or how the interval was constructed. It is therefore appropriate to quote the registry’s reported estimate and interval, rather than assume they are a simple subtraction of the arm medians.

General: an estimate is the effect size calculated from the observed data, while a confidence interval conveys its statistical uncertainty under the method’s assumptions. A p-value assesses how compatible the data are with a specified null hypothesis under the test; it does not give the probability that the null hypothesis is true. Nor does a p-value alone indicate whether an effect is large enough to matter. These distinctions are especially important when a study has an exploratory goal and the registry does not state a margin for non-inferiority or equivalence.

Why is the endpoint scale important?

The grading descriptions distinguish levels of surface change, from no visible erosive wear to severe changes, and include a not-evaluable category. The scale is ordinal: a higher grade indicates a more pronounced category of change, but the record does not establish that the numerical distance from one grade to the next is constant. Summarizing with medians and comparing ranks respects the ordering of the categories. Treating the score as an ordinary continuous measurement would require assumptions about the meaning of score differences that are not established in the registry record.

The record gives the primary outcome unit as scores on a grading scale and the dispersion as full range. It reports values of 3.75 and 3.17 for the two groups, even though the endpoint is described as a median. No additional distributional detail is reported in the registry record. The posted ranges indicate the observed span but do not show how many participants had each grade or whether the observations clustered in particular categories. That limits how fully the pattern can be reconstructed from summary statistics alone.

How should the analysis label be read?

The registry labels the primary analysis type as non-inferiority or equivalence. General: these designs require a prespecified margin that defines the largest difference considered compatible with the stated objective. The margin and its justification are not reported in the registry record. A conventional test for a difference and its p-value cannot, by themselves, determine non-inferiority or equivalence. The confidence interval must be interpreted against the relevant margin, and that comparison cannot be made from the recorded information.

The same caution applies to the secondary analyses. The record describes ANCOVA for the posted secondary outcomes, but does not report the model covariates, the complete model specification, or the prespecified analysis plan. General: ANCOVA compares groups while adjusting for variables included in the model, often including a baseline measurement. Its adjusted estimate can differ from an unadjusted comparison because it uses additional information and depends on the model specification. The registry-reported adjusted estimates therefore need not equal simple differences calculated from the arm summaries.

What do planning illustrations mean?

The record includes sample-size planning illustrations for certain secondary comparisons. These are based on the observed effect and stated assumptions: two-sided significance level 0.05, equal allocation, and a normal approximation. They illustrate participant counts per arm for specified fractions of the observed effect and selected power targets. They are not the trial’s original sample-size justification, which is not reported in the registry record, and they are not observed power. Planning from an effect seen in a small study can be sensitive to random variation in that estimate. The illustrations should be understood as hypothetical planning scenarios, not as evidence that the study was adequately or inadequately powered.

10. Analyses Reported by the Sponsor

The registry-reported primary analysis is a Wilcoxon Rank Sum test, with a median difference in final values of -0.08, a 95% confidence interval from -1.0 to 0.0, and p = 0.267. The record does not provide a separate sponsor narrative explaining the estimate or its intended interpretation. It also does not report a non-inferiority or equivalence margin, so the analysis label alone does not establish that either objective was met.

The summary statistics describe the arms using medians and full ranges, while the registry’s reported estimate comes from the rank-based comparison. A simple subtraction of the posted arm medians would not necessarily reproduce that rank-based estimate. The record does not flag a discrepancy between its reported result and the available summary information. Accordingly, the registry-reported analysis is the appropriate result to emphasize; no recalculated result supersedes it.

For the secondary outcomes with reported ANCOVA analyses, the adjusted estimates and p-values are also the registry’s reported analyses. Unadjusted calculations based on arm summaries answer a different, simpler comparison and need not match an adjusted model. The covariates and full statistical specification for those ANCOVA models are not reported in the registry record. Thus the estimates should be described according to the analysis method recorded, without inferring the adjustments or treating the unadjusted comparisons as replacements.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and multiple secondary outcomes, including tooth-impression grades at later assessments and salivary measurements. It does not report whether the analyses were ordered in a hierarchy, whether particular secondary outcomes were designated as confirmatory, or whether any multiplicity adjustment was planned or applied. General: when many outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. If no correction or hierarchy is specified, isolated secondary p-values should not be treated as definitive evidence.

The record describes the primary population as per protocol and defines it as participants in the intent-to-treat population with at least one efficacy assessment considered unaffected by protocol violation. It also states that efficacy assessments considered affected by protocol violation were excluded from per-protocol analyses. The remaining text of the population description is incomplete, and the total intent-to-treat population, exclusions, and analysis-specific participant flow are not reported in the registry record. The primary result uses 16 participants in the Test Product group and 14 in the Reference Product group.

Although the registry provides a definition of the per-protocol population, it does not report a full account of missing data, the treatment of not-evaluable images, or sensitivity analyses for excluded assessments. It is not reported in the registry record whether missing observations were imputed, omitted, or handled through another method. These details matter because complete-case summaries can be affected if the availability of an assessment is related to its value or to group assignment.

The registry does not report an interim analysis plan, stopping rules, or a detailed protocol for handling deviations beyond the stated per-protocol definition. It also does not report the original sample-size justification or a prespecified statistical analysis plan. These absences do not establish that such procedures were not used; they mean their role cannot be evaluated from the registry record. Interpretation should therefore distinguish the methods explicitly recorded from choices that remain undocumented.

12. 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 counts show zero serious adverse events in the Test Product group, with 16 participants at risk, and zero in the Reference Product group, with 14 participants at risk. The registry also reports zero other adverse events in each group, with the same group-specific numbers at risk. No serious adverse-event terms are listed. Death counts are not reported in the registry record.

These are observed counts in a small study, not proof that no adverse events can occur. A count of zero means that no events of the listed type were recorded among the participants at risk in these groups during the period represented by the registry results. The adverse-event observation period and the completeness of event collection are not reported in the registry record, so the counts cannot be used to infer longer-term safety or to compare uncommon risks reliably.

The registry’s adverse-event figures should also be kept separate from the efficacy findings. They describe event reporting, whereas the primary endpoint concerns tooth-impression grading after an acid challenge. The available safety results do not support broad conclusions beyond the reported counts and groups.

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

The primary result describes a comparison of tooth-impression grading scores after a dietary acid challenge in a randomized, single-masked, parallel-group exploratory study. The reported median difference was -0.08, with a 95% confidence interval from -1.0 to 0.0 and p = 0.267. The interval and test do not show a statistically clear difference under the reported analysis. They also leave uncertainty about the size and direction of a possible difference within the range of effects compatible with the estimate.

This result does not establish that the products are equivalent or that one is non-inferior to the other. Although the registry labels the analysis as non-inferiority or equivalence, it does not report the margin or decision rule needed to assess that claim. A failure to show a statistically clear difference is not the same as showing that any difference is small enough to meet a prespecified standard.

The study was described as exploratory and intended to help develop a clinical model for measuring early dietary acid-mediated enamel loss. The reported endpoint and secondary measures provide observations relevant to that aim, but the registry does not report a separate validation threshold or a conclusion demonstrating that the model is validated. The posted outcomes should therefore be interpreted as evidence from an exploratory investigation, not as a complete validation of the measurement approach.

Nor can these results establish effects beyond the people, products, procedure, and assessment conditions recorded in this trial. The enrollment was 30, and the primary analysis included 16 and 14 participants in the two groups. The record does not provide enough detail about missing assessments, measurement reliability, or the full analysis plan to resolve all sources of uncertainty. The findings are best understood as estimates from a limited study, with their interpretation bounded by the registry’s reported methods and results.

14. Why This Trial Matters Statistically

This trial is statistically interesting because its central outcome is an ordered visual grading of enamel-surface impressions, rather than a straightforward continuous measurement. The grading scale captures categories of surface change, but the registry does not establish equal numerical distances between grades. That makes the choice to report medians and use a rank-based comparison relevant to how the result should be understood.

The study also illustrates the difference between a test for a group difference and a formal non-inferiority or equivalence analysis. The registry labels the primary analysis as non-inferiority or equivalence, yet does not report the margin needed to interpret the result that way. The confidence interval and p-value remain useful descriptions of the observed comparison, but do not supply the missing decision criterion.

A further statistical point is the exploratory purpose. Multiple outcomes were measured across impression grading and salivary parameters. Without a reported multiplicity strategy, secondary findings should be treated as supportive context rather than a collection of independent confirmations. This is particularly important when several measures represent related but nonidentical aspects of the response to an acid challenge.

Finally, planning illustrations derived from observed effects should not be mistaken for the original design rationale or for observed power. They can show how assumed effects and target power influence prospective sample-size planning, but the registry does not report its original justification. The record therefore provides a useful case for separating descriptive estimates, formal testing, model-development objectives, and prospective planning.

15. 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.

Several trial-specific limitations constrain interpretation. The total enrollment was 30, and the primary analysis groups contained 16 and 14 participants. The precision of the primary estimate is reflected in its confidence interval, which extends from -1.0 to 0.0. The record does not report a sample-size justification, so it is not possible to assess the planned precision or power from the registry information.

The endpoint depends on impressions, scanning electron microscopy, and visual image analysis. The registry describes the grading categories, but does not report grader blinding details, reliability between or within graders, image-quality procedures, or how disagreements were resolved. The record includes a not-evaluable category in the scale but does not explain how such observations were handled in the analysis.

The primary endpoint title describes an assessment immediately following the acid challenge, while the timeframe says baseline and 30 minutes post dietary acid challenge. The registry does not reconcile those descriptions. The per-protocol population definition is also incomplete in the recorded text, and participant flow into each analysis is not detailed. Missing-data methods and sensitivity analyses are not reported in the registry record.

The analysis is labeled non-inferiority or equivalence, but the margin and formal decision rule are not reported. The full statistical analysis plan, model specifications for secondary analyses, and multiplicity procedures are likewise not reported. These gaps limit assessment of whether the analyses followed prespecified choices and how the results should be interpreted under the intended study objective.

Finally, the stated exploratory purpose was to support development of a clinical model. The registry does not report a validation criterion or an independent evaluation of the model. The results therefore do not, on their own, establish measurement validity or generalizability beyond the study setting and its recorded procedures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: In Vivo Investigation of Initial Stages of Enamel Erosion — NCT02533466.
• Registry record last updated 2017-08-02; status last verified 2017-03.
• Results first posted 2017-06-15.
• 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.

19. Record Summary

NCT02533466 is a completed randomized, single-masked, parallel-group study of early enamel erosion. It enrolled 30 participants and compared sodium fluoride plus potassium nitrate with potassium nitrate. The primary outcome was change in tooth-impression grading score following a dietary acid challenge, assessed using scanning electron microscopy and visual image analysis. The registry reports a Wilcoxon Rank Sum comparison with median difference -0.08, 95% confidence interval -1.0 to 0.0, and p = 0.267.

The study was described as exploratory and intended to help develop a clinical model for measuring earlier stages of dietary acid-mediated enamel loss. The registry lists additional tooth-impression and salivary outcomes. The record does not report the non-inferiority or equivalence margin, full analysis plan, original sample-size justification, multiplicity strategy, or complete missing-data methods. The posted primary result does not establish equivalence, non-inferiority, or validation of the proposed measurement model.