MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study (NCT02424097), a randomized phase 4 study. The primary outcome is Change in White Spot Lesions Count - Enamel Decalcification Index (EDI).

2. Clinical Question

The central comparison is between the two assigned care approaches, rather than between separate components of the combined MI Paste and MI Varnish intervention. The registry summary says the trial was prospective, controlled, and conducted over 12 months. Lesions were to be evaluated using EDI, ICDAS, Nyvad criteria, and fluorescence-based assessment. The posted primary result concerns EDI; the posted secondary result concerns ICDAS II. Results for other outcome measures are not reported in the registry record.

3. Trial Design

This was a Phase 4, randomized, single-blind, parallel-group clinical trial sponsored by the University of California, San Francisco. The registry lists an enrollment of 40 and a completed status. The recorded study dates are a start in 2013-05 and primary completion in 2016-10. The study summary describes a prospective, controlled comparison in orthodontic patients over 12 months.

The two groups were MI Paste & MI Varnish and Standard of Care. In the intervention group, the patient was to apply MI Paste every night, while MI Varnish was to be applied in the office every three months. The comparator description specifies nightly home toothpaste use and a fluoride mouth rinse recommendation. The registry also lists the intervention materials as CPP-ACP 5% sodium fluoride varnish and 900ppm fluoride paste, and 1,100pm fluoride toothpaste and 0.5% NaF rinse for the control. Further detail about treatment delivery or adherence is not reported in the registry record.

Single masking is recorded, but the masked party is not reported in the registry record. Details of the randomization sequence, allocation concealment, and procedures for maintaining masking are also not reported in the registry record. The posted primary endpoint is the change in white spot lesion count measured by EDI, with the timeframe stated as baseline and 12-months. A secondary ICDAS II score is also posted for the same timeframe. The record does not report the original statistical analysis plan or the trial's sample-size justification.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: enamel decalcification index (EDI)

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 Change in White Spot Lesions Count - Enamel Decalcification Index (EDI), measured over Baseline and 12-months.

The primary endpoint is titled Change in White Spot Lesions Count - Enamel Decalcification Index (EDI). It is a continuous measure based on the area evaluation of the buccal surface of each tooth. Each tooth surface is divided into four quadrants. Each quadrant is scored from 0, for no decalcification, to 3, for decalcification covering the full area or severe decalcification with cavitation. A score of 1 represents decalcification covering <50% of the area, and a score of 2 represents decalcification covering > 50% of the area. Thus each tooth can have a score from 0 to 12.

The registry states that 16 teeth per subject were evaluated and that the tooth values were added for each subject, producing an individual range from 0 to 192. A group mean was then calculated. Higher scores indicate a worse outcome. This area-based scoring approach gives a numerical summary of lesion presence and extent across the evaluated teeth, which permits comparison of group averages. It is used as the primary measure because the study objective concerns white spot lesion regression and prevention. The timeframe is baseline and 12-months. How the change score was calculated from those assessments is not reported in the registry record.

7. Results Posted in the Registry

• MI Paste & MI Varnish: mean 40.20 versus 41.30 on control; difference -1.10 (95% CI -9.29 to 7.09), standardized effect d = -0.09; z-test p = 0.792.

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.

Change in International Caries Detection and Assessment System (ICDAS II) to Score for Smooth Surfaces White Spot Lesions (WSL)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • MI Paste & MI Varnish: mean 22.30 versus 22.60 on control; difference -0.30 (95% CI -3.79 to 3.19), standardized effect d = -0.06; z-test p = 0.866.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between MI Paste & MI Varnish and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary endpoint is a change in the ICDAS II score for smooth-surface white spot lesions, measured at baseline and 12-months. Its group means are similar in direction and scale of separation to the primary comparison: the MI Paste & MI Varnish mean is slightly lower than the Standard of Care mean. The secondary confidence interval includes zero, as does the primary interval. Taken together, the posted results do not show a clear separation between groups on either reported score.

Agreement in broad direction across two measures can be informative because EDI and ICDAS II assess lesions using different scoring frameworks. However, similarity in direction does not make the secondary outcome an independent replication of the primary result. Both outcomes come from the same trial population and share the same treatment assignment and follow-up context. The registry does not provide details about correlations between measures or how each outcome was selected for reporting.

Secondary outcomes usually carry less weight than a prespecified primary outcome because they may be among several measures considered, and repeated testing can increase the chance of finding an apparently notable result by chance. Appropriate interpretation depends on the full set of planned outcomes, any hierarchy of hypotheses, and whether multiplicity adjustments were intended. Those analysis details are not reported in the registry record. The record lists five outcome measures overall, but only one secondary result is posted. Results for the other measures are not reported in the registry record.

The secondary result can therefore be treated as descriptive context for the primary finding, not as a basis for a separate confirmatory claim. Its broad pattern is compatible with the primary result's uncertainty, but neither outcome establishes equivalence or determines whether a difference of clinical importance is present.

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

• Change in International Caries Detection and Assessment System (ICDAS II) to Score for Smooth Surfaces White Spot Lesions (WSL)

9. Statistical Interpretation

10. Statistical Methods Explained

Continuous outcomes are commonly summarized with a mean and standard deviation. The mean describes the group average, while the standard deviation describes how spread out individual scores are around that average. In the EDI outcome, a higher score is defined in the registry as worse. The posted group means therefore describe average scores, while the standard deviations give context about variation among participants. Neither quantity alone describes every participant's score or the distribution's shape.

What does the mean difference represent?

The mean difference compares the MI Paste & MI Varnish mean with the Standard of Care mean. The posted estimate is -1.1. Its negative sign reflects a lower mean in the intervention group for this comparison. The estimate is an absolute difference on the EDI score scale, not a relative percentage change. It should be interpreted with the confidence interval, because an estimate from a trial is uncertain and may not equal the underlying group difference.

How should the confidence interval be read?

A confidence interval gives a range of estimates compatible with the observed data under the assumptions of the analysis. The primary interval runs from -9.292 to 7.092. Since that range includes zero, the data do not rule out no mean difference under the unadjusted comparison. The interval also extends to values on either side of zero, so it does not pin down the direction or size of a possible difference precisely. A confidence interval is not a range containing every individual participant's score, and it does not guarantee that the true difference lies within its endpoints.

What does the p value add?

The unadjusted p value is 0.792. A p value describes how unusual data at least as inconsistent with a specified null hypothesis would be under that hypothesis and the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. A large p value does not demonstrate equivalence or prove that no meaningful difference exists. The confidence interval is useful alongside the p value because it conveys the range and precision of the estimated difference.

Why are the comparisons called unadjusted?

The posted comparisons use group summary statistics and are not described as adjusted for baseline values or other covariates. An adjusted analysis can account for prespecified participant characteristics or design factors, potentially changing both the estimate and its precision. Whether such an analysis was planned or conducted is not reported in the registry record. The registry record lists no reported analyses, so the posted result should not be treated as a full account of the trial's analysis process.

What does randomization contribute?

In general, random assignment is intended to make groups comparable with respect to measured and unmeasured characteristics on average. It does not guarantee that groups are balanced in a particular trial, especially when the amount of information is limited. Baseline group summaries and details of the allocation process are not reported in the registry record, so the extent of balance cannot be evaluated from the posted results. Randomization also does not remove uncertainty, ensure adherence, or resolve missing outcome data.

Why does the score's scale matter?

EDI is a bounded score constructed from quadrant-level assessments and then aggregated across teeth for each subject. Its numerical range and scoring rules give meaning to the direction of the mean, but do not by themselves establish that every score difference has equal clinical importance. A mean comparison can also conceal variation in individual responses or differences in the distribution of scores. The registry does not report a threshold for a clinically important EDI change, nor does it provide distributional summaries beyond the standard deviations.

These explanations are general statistical concepts. The registry does not report the trial's detailed statistical analysis plan, including assumptions about score distributions, baseline adjustment, or handling of incomplete observations. Those omissions limit how fully the posted summary comparisons can be evaluated.

11. Confidence Intervals and Precision

Precision concerns how tightly an estimate is determined by the data. For the primary EDI comparison, the mean difference is -1.1 and the 95% confidence interval extends from -9.292 to 7.092. The interval crosses zero and includes estimates in both directions. It therefore does not identify a single direction of difference with confidence, and its span indicates that the estimated comparison is uncertain.

The confidence interval should be considered together with the group standard deviations: 13.6 for MI Paste & MI Varnish and 11.8 for Standard of Care. The standard deviations describe variation in individual scores, whereas the confidence interval concerns uncertainty in the group mean difference. They answer different questions. The reported group sizes are 19 and 18; the registry does not report why those numbers differ from the enrollment figure or how any unobserved outcomes were handled.

The interval is not a statement that all plausible values are equally likely, nor does it describe the range of participant scores. It is calculated under an analysis framework and assumptions; details of the trial's original analysis plan are not reported in the registry record. The posted comparison is unadjusted, so the interval does not communicate uncertainty from any adjustment that may have been considered elsewhere.

In practical terms, the estimate alone suggests only a small separation between the reported group means, but the interval is broad enough to include larger differences in either direction. The posted data therefore have limited precision for distinguishing between a small or absent difference and a difference of greater magnitude. A confidence interval that includes zero is not proof of no effect, just as an interval extending on both sides of zero does not demonstrate that every value within it is equally compatible with the data.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants and not total events. They are illustrations based on the observed effect, rather than the trial's original sample-size design. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row considers an effect to detect equal to the stated fraction of the observed effect.

The 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding planning figure for a 90% chance. These are design calculations, not guarantees about what a future study will achieve. Smaller effects require more participants because a subtler difference is harder to distinguish from random variation.

For the primary outcome, the figures range from 2,112 participants per arm for planning around 100% of the observed effect at 80% power, to 11,307 participants per arm for planning around 50% of the observed effect at 90% power. The intermediate rows plan for 75% of the observed effect. The accompanying curve should be read as another view of how the planning requirement changes with the effect assumed for design; it does not add evidence about the trial result.

This is not observed power. It is a prospective planning illustration calculated from the observed effect and the stated assumptions. The original trial's sample-size assumptions and justification are not reported in the registry record, so these figures should not be taken as a reconstruction of the design used for the trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.100; pooled standard deviation σ = 12.757.
2. n = 2 × (1.96 + 0.842)² × 12.757² / -1.100² = 2,111.5, rounded up to 2,112 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.09999999999999                      # observed difference in means
sigma <- 12.7574739998615                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2424097)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2,112 (80% power), 2,827 (90% power)
 75% of observed effect: n per arm = 3,754 (80% power), 5,026 (90% power)
 50% of observed effect: n per arm = 8,446 (80% power), 11,307 (90% power)
power.t.test: 2112.4 
Simulated power at n = 2,112 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, time points, groups, or statistical comparisons. Each additional test can increase the opportunity for a chance finding if results are interpreted without a plan for controlling that risk. The registry lists five outcome measures and posts one secondary outcome in addition to the primary EDI outcome. The registry record does not report whether the outcomes were ordered in a hierarchy, whether one was designated as confirmatory, or whether an adjustment for multiple testing was planned. The p values posted for the primary and secondary comparisons are unadjusted and should be read accordingly.

Missing data are also important for interpreting group comparisons. The primary result reports 19 participants in the MI Paste & MI Varnish group and 18 in Standard of Care, while the registry enrollment is 40. The reasons for the reported group counts, the amount and pattern of missing outcome information, and the methods used to handle incomplete data are not reported in the registry record. The available information does not establish whether missingness was related to treatment assignment, outcome values, or other participant characteristics.

The analysis population is not described in detail. The registry record does not state whether results follow an intention-to-treat approach, a per-protocol approach, or another population definition. It also does not describe exclusions after randomization or how participants with incomplete follow-up were treated in the analysis. These details matter because different analysis populations can produce estimates with different interpretation.

Finally, the registry record lists no reported analyses and does not include the original statistical analysis plan. Consequently, it is not possible to determine from the record whether the posted comparisons were the only analyses conducted, how baseline measurements were incorporated, or what sensitivity analyses were used. These reporting gaps limit assessment of multiplicity, missing-data assumptions, and analysis choices; they do not by themselves show that any particular method was inappropriate.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports serious adverse events for 20 participants at risk in each group, with 0 serious events reported in each group. It also reports other adverse events for 20 participants at risk in each group, with 0 other events reported in each group. Deaths are reported as 0 in both groups, and no serious adverse event terms are listed.

These are registry counts over the recorded safety reporting period; the record does not provide further detail about event definitions, collection procedures, or the duration of safety follow-up. A zero count means no events of that type were reported in the stated group figures. It does not establish that the treatments carry no risk, and it cannot rule out uncommon events or events not captured by the recorded reporting process. The safety figures should be read as descriptive information from this trial, not as a comprehensive assessment of safety.

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

The registry results describe average EDI and ICDAS II scores for the two assigned care groups at the stated baseline and 12-months timeframe. For the primary EDI outcome, the reported mean difference is -1.1, and the confidence interval includes zero. The secondary ICDAS II comparison also has a confidence interval that includes zero. These findings describe uncertainty in the observed comparisons; they do not establish that the groups are equivalent or that a clinically important difference is absent.

The results also do not establish a reliable difference between the groups. The estimates are based on the reported group summaries and are unadjusted. No detailed trial analysis plan or reported analysis is available in the registry record, and the record does not explain the reported analysis group counts or missing outcome handling. Those limitations affect how confidently the numbers can be interpreted as estimates of the full randomized comparison.

The outcome is a scored measure of lesion area and severity, with higher EDI scores defined as worse. A group mean is a summary and cannot show how many participants improved, worsened, or had no change. Nor does the mean alone tell whether a score difference is important to patients or clinicians; a threshold for clinically important change is not reported in the registry record. The registry's stated objective includes caries protection and remineralization, but the posted EDI and ICDAS II summaries should not be expanded into claims about outcomes that were not reported.

In general, randomized comparisons can help estimate differences between assigned approaches, but their interpretation depends on the conduct of randomization, follow-up, adherence, outcome measurement, and analysis. Several of those details are not reported in the registry record. The posted results are therefore best read as limited descriptive evidence from one completed trial, with substantial uncertainty around the mean comparisons and incomplete information about the analysis process.

17. Why This Trial Matters Statistically

This trial is statistically interesting because its primary outcome reduces lesion assessments across tooth surfaces to a continuous score that can be compared between randomized groups. The registry explains how the EDI score is constructed and makes the direction interpretable: higher values indicate a worse outcome. That scoring detail helps readers understand what the mean difference represents, rather than treating it as an abstract number.

The results also illustrate why an estimate and its precision need to be considered together. The primary mean difference is -1.1, but its confidence interval extends across zero and covers values on either side. A small difference between reported means is not, by itself, evidence of equivalence. The uncertainty interval shows why conclusions should remain cautious even when a point estimate appears close to zero.

The trial also highlights the distinction between a study's actual design and hypothetical planning illustrations based on its observed effect. The sample-size calculations show how planning requirements can increase when targeting a smaller effect. They do not describe the trial's original design rationale, which is not reported in the registry record, and they are not observed power.

Finally, the registry provides a useful example of the limits of results reporting. It records randomization, masking, endpoints, group summaries, and adverse-event counts, but does not report key analysis details such as the original statistical plan, missing-data methods, or multiplicity strategy. Readers can interpret the posted comparisons while recognizing that the available record does not answer every question needed for a complete assessment.

18. 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 limitations specific to this trial affect interpretation. The primary comparison is based on reported groups of 19 and 18 participants, while the registry lists enrollment of 40. The record does not explain the difference between those figures, describe participant flow, or state how incomplete outcome data were handled. It is therefore not possible to assess attrition or determine the analysis population from the posted results alone.

The registry describes the study as single-blind but does not identify who was masked or explain how masking was maintained. Details of random sequence generation and allocation concealment are not reported in the registry record. The study concerns orthodontic patients and scores lesions on anterior teeth with brackets, so the results pertain to that study context; the record does not establish how well they apply to other populations or settings.

The primary endpoint is a composite score across multiple tooth surfaces, and the registry provides the scoring rules but no threshold for a clinically important change. The reported means and standard deviations do not show individual trajectories or the distribution of changes. The precise method used to calculate the stated change from baseline and 12-months is not reported in the registry record.

Only one secondary result is posted, although five outcome measures are listed overall. The registry does not report a detailed statistical analysis plan, multiplicity handling, baseline adjustment, adherence results, or sensitivity analyses. These gaps limit assessment of the completeness and robustness of the posted comparisons. They are reporting limitations and do not, on their own, establish that the trial was conducted improperly.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: MI Varnish and MI Paste Plus in a Caries Prevention and Remineralization Study — NCT02424097.
• Registry record last updated 2020-04-22; status last verified 2020-04.
• Results first posted 2018-12-24.
• 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.

22. Record Summary

NCT02424097 is a completed, randomized, single-blind, parallel Phase 4 study sponsored by the University of California, San Francisco. It compared MI Paste & MI Varnish with Standard of Care in orthodontic patients over the stated 12-month timeframe. The registry lists enrollment of 40, with study start in 2013-05 and primary completion in 2016-10.

The primary endpoint was change in white spot lesion count assessed with EDI. The posted unadjusted mean difference was -1.1, with a 95% confidence interval from -9.292 to 7.092. One secondary ICDAS II result was also posted. Both comparisons have confidence intervals that include zero. Serious adverse events, other adverse events, and deaths were reported as 0 in each group's safety figures. Details of the original analysis plan, missing-data handling, and multiplicity strategy are not reported in the registry record.