3M Oral Rinse Incidence and Patient Acceptance of Sloughing When Used With Sodium Lauryl Sulfate (SLS) Toothpastes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 3M Oral Rinse Incidence and Patient Acceptance of Sloughing When Used With Sodium Lauryl Sulfate (SLS) Toothpastes (NCT04601103), a randomized na study. The primary outcome is Number of Participants With Oral Mucosal Exfoliation (Oral Sloughing).

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group study with enrollment of 53 participants. The registry lists three arms: 18 participants in the no-SLS toothpaste group, 18 in the medium-SLS group, and 17 in the high-SLS group. Each arm description pairs the toothpaste condition with 3M Oral Rinse. The record also lists Anti-plaque as a device intervention, but does not describe its assignment or role in the three posted arms.

The study status is terminated. The start date is 2020-01-06, and the primary completion date is 2020-03-10. The primary endpoint timeframe is end of treatment (3 weeks). The reason for termination, whether the study ended as planned, and whether the treatment period was identical for all participants are not reported in the registry record.

Randomization and masking are identified, but the method used to generate or conceal assignments is not reported in the registry record. The record does not specify which people were masked. It lists phase as NA. It does not report the protocol, original design assumptions, planned enrollment rationale, or a fuller description of the study setting.

The primary objective was to evaluate oral tissue sloughing through self-report and professional dental examinations. The record also lists secondary outcomes concerning the number of participants within ranges of average Oral Mucosal Sloughing Index scores. Those entries do not supply additional results in the information reported for the primary comparison. The posted arm sizes are the denominators used for the primary outcome counts and pairwise recalculations.

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:

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 Number of Participants With Oral Mucosal Exfoliation (Oral Sloughing), measured over End of treatment (3 weeks).

The primary endpoint is the number of participants with oral mucosal exfoliation, or oral sloughing, at end of treatment (3 weeks). Its description defines a participant as having experienced sloughing if it was reported by the participant or determined by the dental evaluator. It is therefore a participant-level event outcome, rather than a continuous score of tissue condition. Although the endpoint title is expressed as a count, its description also refers to the percentage of participants with the event.

Using an event outcome allows the registry to report how many participants in each arm met the stated definition. The posted counts are 15 of 18 in the no-SLS arm, 14 of 18 in the medium-SLS arm, and 13 of 17 in the high-SLS arm. These counts do not describe how often sloughing occurred within an individual, how severe it was, or how long it lasted. Those details are not reported as part of this primary endpoint.

Combining self-report with a dental evaluator's determination can capture events identified through either route. The registry does not report how disagreements between the two sources were handled, how examinations were standardized, or whether assessors were masked to toothpaste assignment. Those details would matter when interpreting how consistently the endpoint was classified.

7. Results Posted in the Registry

• Comparator: Medium SLS Toothpaste: 77.8% (14/18) versus 83.3% (15/18) on control; risk difference -5.6 percentage points (95% CI -31.3 to 20.2), risk ratio 0.93 (0.68–1.29); unadjusted two-proportion z-test p = 0.674.
• Comparator: High SLS Toothpaste: 76.5% (13/17) versus 83.3% (15/18) on control; risk difference -6.9 percentage points (95% CI -33.4 to 19.7), risk ratio 0.92 (0.66–1.28); unadjusted two-proportion z-test p = 0.612.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a Fisher Exact analysis across the three groups for the primary binary outcome. The pairwise effect estimates discussed separately are unadjusted recalculations from the posted counts. They describe the observed difference between each SLS toothpaste arm and the no-SLS arm; they are not reported as the sponsor's pairwise analyses.

What does a risk difference describe?

General: A risk difference is the event proportion in one group minus the event proportion in a reference group. A value below zero means the observed proportion is lower in the first group under that subtraction order; a value above zero means it is higher. A value of zero represents no difference in the event proportions. In this analysis, the comparison is SLS toothpaste versus no-SLS toothpaste, and the recalculated estimates are -0.056 for medium SLS and -0.069 for high SLS.

The corresponding posted group proportions are 0.833 for the no-SLS group, 0.778 for the medium-SLS group, and 0.765 for the high-SLS group. These are direct summaries of the counts and denominators in the posted comparison. They should not be interpreted as precise estimates of what would occur in a broader population, especially given the wide intervals and the small groups.

What does Fisher Exact test?

General: Fisher's Exact test evaluates whether a categorical outcome is associated with group membership, using the observed counts in the groups. It is suited to count data arranged as event and non-event categories. The registry reports Fisher Exact for the overall comparison across no SLS, medium SLS, and high SLS, with p = .916. The record does not report an estimated effect or confidence interval alongside that overall test.

A test result and an effect estimate serve different purposes. The test addresses how compatible the observed counts are with a null hypothesis of no group association under its assumptions. The risk difference gives the direction and scale of a particular two-group contrast. Neither a p-value nor an effect estimate alone establishes equivalence or tells whether a difference matters clinically.

Why distinguish the overall test from pairwise recalculations?

The overall test considers the three-group distribution in one analysis. The pairwise recalculations compare the medium-SLS group with the no-SLS group, and the high-SLS group with the no-SLS group. Each pairwise estimate has its own uncertainty interval and unadjusted p-value. Those pairwise results cannot be treated as a numerical breakdown of the overall test: they use different comparisons and express effects in a different way.

Because the pairwise calculations are unadjusted, their p-values do not account for examining multiple contrasts. A multiplicity procedure can change how inferential claims are evaluated when several hypotheses are tested. The registry record does not report an adjustment or a planned hierarchy for these comparisons. This does not change the arithmetic of the posted unadjusted estimates, but it is relevant to interpreting them as a set.

What do the intervals contribute?

General: A confidence interval describes a range of effect estimates compatible with the data under a specified method. It communicates precision as well as direction. A narrow interval indicates more precision than a wide interval, while an interval spanning zero for a risk difference is compatible with no difference and with effects in either direction. The recalculated intervals in both pairwise comparisons span zero and are broad.

The confidence level and interval method for the pairwise recalculations are not reported in the registry record. The overall Fisher Exact analysis also has no interval reported. The intervals therefore should be read as the posted recalculated uncertainty ranges, not attributed to the sponsor's analysis or to an unspecified registry method.

The endpoint is binary: a participant either met the event definition or did not, according to the posted outcome. It does not preserve information about repeated episodes or graded severity. The registry separately lists average Oral Mucosal Sloughing Index score ranges as secondary outcomes, but the two posted secondary entries do not provide numerical results in the information reported for this analysis. The number of outcome measures is listed as 4, while the number of posted secondary entries is 2. The record does not explain this difference.

10. Confidence Intervals and Precision

The pairwise intervals are broad relative to their point estimates. For medium SLS versus no SLS, the recalculated risk difference is -0.056, with an interval from -0.314 to 0.202. For high SLS versus no SLS, it is -0.069, with an interval from -0.334 to 0.197. Both ranges cross zero, so the posted results are compatible with a lower event proportion in an SLS arm, little or no difference, or a higher event proportion.

The intervals indicate limited precision: the counts come from groups of 18, 18, and 17 participants, and the estimates allow a wide range of possible differences. The point estimates alone should not be treated as stable estimates of the size of a population effect. The data do not narrowly distinguish among effects on either side of zero.

The registry's overall Fisher Exact analysis reports p = .916 but no effect estimate or interval. That result cannot substitute for a precision interval. A p-value summarizes evidence against a specified null hypothesis under a test; an interval displays a range of effect values under an interval method. Neither is a direct measure of clinical importance.

The confidence level and calculation method for the pairwise intervals are not reported in the registry record. As a result, the intervals can be described by their posted limits, but their exact construction cannot be evaluated from the registry information. The small group sizes and the lack of reported detail about analysis populations and missing data further constrain interpretation of precision.

11. 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 sample-size estimates are planning illustrations, not the number enrolled in this trial. For these binary-outcome comparisons, each estimate is participants per arm, rather than total events. The calculation assumptions are a two-sided significance level 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial's own original design assumptions are not reported in the registry record.

The 80% power column means the planned number of participants per arm for a design with 80% power under those assumptions to detect the chosen effect. The 90% power column gives the corresponding number per arm for a design with 90% power. Power is a property of a proposed design under assumed conditions; it does not describe what happened in the completed study. These figures are not observed power.

For the medium-SLS comparison, planning for 100% of the observed effect gives 796 participants per arm for 80% power and 1,065 for 90% power. The corresponding estimates for 75% of the observed effect are 1,377 and 1,842, and for 50% are 3,009 and 4,028. For high SLS, the respective estimates are 535 and 715 at 100% of the observed effect; 920 and 1,231 at 75%; and 2,000 and 2,676 at 50%.

The pattern reflects a general planning principle: smaller effects are harder to distinguish from random variation and require more participants under otherwise unchanged assumptions. These estimates are sensitive to the observed effect used as their starting point. Since the observed effects are imprecise, the planning figures should be treated as illustrations rather than as a recommendation or a reconstruction of the original study design. The curve represents the same planning relationship, not an additional trial result.

12. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.833; treatment proportion p₁ = 0.778; average p̄ = 0.806.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5597 = 1.0970.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5583 = 0.4699.
4. n = (1.0970 + 0.4699)² / (-0.0556)² = 795.5, rounded up to 796 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
p0 <- 0.833333333333333                          # control proportion
p1 <- 0.777777777777778                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4601103)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 796 (80% power), 1,065 (90% power)
 75% of observed effect: n per arm = 1,377 (80% power), 1,842 (90% power)
 50% of observed effect: n per arm = 3,009 (80% power), 4,028 (90% power)
power.prop.test: 795.5 
Simulated power at n = 796 per arm: 0.800 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

13. Analyses Reported by the Sponsor

The registry reports one overall analysis using Fisher Exact across the no-SLS, medium-SLS, and high-SLS groups, with p = .916. It does not report a pairwise estimate or interval for either SLS group versus no SLS in that analysis. The recalculated risk differences, intervals, and p-values instead describe two separate, unadjusted comparisons based on the posted counts.

For medium SLS versus no SLS, the recalculated risk difference is -0.056 and the unadjusted p-value is 0.674. For high SLS versus no SLS, the recalculated risk difference is -0.069 and the unadjusted p-value is 0.612. These values do not conflict with the overall p = .916: the analyses test different comparisons and report different statistical quantities. A three-group test need not produce the same p-value as either two-group contrast.

No discrepancy is flagged between the reported analysis and the recalculations. The reported Fisher Exact result remains the registry's own overall analysis; the pairwise values are additional unadjusted recalculations and should not be presented as sponsor-reported findings. The registry does not report the method used for a sponsor-led pairwise analysis, or a sponsor-reported interval for these two contrasts.

14. Multiplicity, Missing Data and Analysis Populations

The registry reports one overall Fisher Exact analysis across three groups and lists two secondary outcome entries concerning ranges of average Oral Mucosal Sloughing Index scores. The two secondary descriptions are nearly identical, with a punctuation difference. Numerical results for those secondary entries are not reported in the registry information described for this analysis.

The pairwise risk differences are unadjusted recalculations for two comparisons against the no-SLS group. When several contrasts or outcomes are examined, multiplicity can increase the chance of at least one result appearing unusual by chance. Statistical approaches can address that issue through adjustment or a prespecified testing order. Whether any such approach was planned or used is not reported in the registry record. The unadjusted p-values should therefore be interpreted as individual comparison results, not as multiplicity-controlled evidence across all possible outcomes and contrasts.

The record does not report how missing primary outcome data were handled, whether every enrolled participant contributed to the analysis, or whether the analysis followed an intention-to-treat or another population definition. The posted arm denominators match the reported arm sizes, but that alone does not establish that all randomized participants were analyzed or that there were no missing data.

The analysis plan, prespecified endpoint hierarchy, interim analyses, and statistical stopping rules are not reported in the registry record. The study status is terminated, but the reason for termination and its relation, if any, to the analysis are not reported. No conclusions about the planned analysis or missingness mechanism can be drawn from the available record. These gaps matter because decisions about which participants and outcomes enter an analysis can affect both the estimate and its uncertainty.

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.

Most frequent non-serious adverse event terms

The registry's serious adverse event figures show 0 affected participants in each arm: the no-SLS group had 18 at risk, the medium-SLS group had 18 at risk, and the high-SLS group had 17 at risk. Deaths are reported as 0 in all three groups. No serious adverse event terms are listed.

These counts describe what the registry reports for serious adverse events; they do not establish that serious events are impossible or that no event went unrecorded. With the group sizes reported, the absence of a posted serious event is a limited observation about this study rather than a precise estimate of rare-event risk.

The record also lists other adverse event counts of 15, 15, and 16 in the no-SLS, medium-SLS, and high-SLS groups, respectively, with at-risk groups of 18, 18, and 17. These are a separate registry category from serious adverse events. The primary sloughing outcome counts are 15, 14, and 13, respectively; the record does not explain the difference between those outcome counts and the other adverse event counts, so they should not be treated as interchangeable measures.

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

The posted results describe oral sloughing counts at end of treatment (3 weeks) among participants assigned to 3M Oral Rinse with no SLS, medium SLS, or high SLS toothpaste. The primary counts are 15 of 18, 14 of 18, and 13 of 17, respectively. The overall reported Fisher Exact analysis has p = .916, while the two unadjusted pairwise recalculations have risk differences of -0.056 and -0.069. Their intervals cross zero and are broad.

These findings do not establish that the toothpaste groups are equivalent. A result that does not identify a clear difference can arise when the groups are similar, but it can also arise when the study is too small or the estimates are too imprecise to distinguish meaningful possibilities. The reported intervals include differences in either direction, so the results do not precisely settle the size or direction of a population difference.

The results also do not establish that one toothpaste condition causes more or less sloughing than another. Randomization is reported, but details of assignment, masking, adherence, missing data, and analysis populations are not. The trial status is terminated, and the reason is not reported. Those limitations make it difficult to assess how completely the posted outcome reflects the intended study design.

The primary measure records whether a participant experienced sloughing under the combined self-report or dental-evaluator definition. It does not by itself convey severity, frequency, duration, or participant acceptance. While the trial title refers to patient acceptance, a separate acceptance result is not reported in the primary outcome information. The numerical findings should therefore be read narrowly as the posted counts and comparisons for oral sloughing, not as a complete assessment of all questions named in the trial title.

17. Why This Trial Matters Statistically

This trial illustrates how a simple binary outcome can be easy to summarize but difficult to estimate precisely when the groups are small. The primary result is a count of participants with sloughing, and the three arm counts are close. Yet the pairwise intervals are broad and cross zero. The point estimates alone might suggest a direction, but the uncertainty indicates that much larger differences in either direction remain compatible with the posted data.

It also demonstrates why an overall test and a pairwise effect estimate should not be conflated. The registry's Fisher Exact analysis addresses the three-group comparison and reports p = .916. The separate recalculations quantify the risk difference for each SLS group versus the no-SLS group. Different hypotheses and summaries naturally yield different results; interpreting them correctly requires attention to the comparison each one represents.

The trial raises common reporting questions. Its terminated status is clear, but the reason is not reported. The primary outcome combines two ways of identifying sloughing, while details of classification and masking are absent. The registry does not describe missing-data handling, the analysis population, multiplicity control, or original sample-size assumptions. Each omission limits what can be inferred from otherwise straightforward event counts.

Finally, the planning illustrations show how estimates based on an observed effect can translate into much larger projected study sizes, especially when planning for smaller effects. They are not a record of the trial's original design and cannot repair the uncertainty in the observed data. Separating observed results, recalculated comparisons, and hypothetical planning quantities is essential to a disciplined reading of this study.

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.

The small arm sizes are a central limitation for interpreting the event comparisons: the groups contain 18, 18, and 17 participants. The resulting pairwise intervals are broad, so the observed differences are imprecise. The record does not report the reason the study was terminated, whether all intended procedures were completed, or whether termination affected enrollment or follow-up.

Important design and analysis details are not reported in the registry record. These include the randomization procedure, allocation concealment, which parties were masked, adherence, missing-data handling, analysis population, and any interim analyses. The registry also does not report original sample-size assumptions or a statistical analysis plan. The sample-size illustrations are based on the observed effects and should not be mistaken for the original design rationale.

The endpoint combines participant self-report and dental evaluation, but the record does not explain how conflicting assessments were resolved or how evaluator judgments were standardized. It does not provide severity or duration results for the primary outcome. Although patient acceptance appears in the trial title, a separate acceptance measure is not included in the primary results described in this record.

There is also limited information about the populations and comparisons beyond the three posted arms. The registry lists Anti-plaque as a device intervention but does not describe its role in those arm descriptions. The reason the primary sloughing counts differ from the listed other adverse event counts is not reported. These uncertainties do not invalidate the posted counts, but they restrict the conclusions that can be drawn from them.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: 3M Oral Rinse Incidence and Patient Acceptance of Sloughing When Used With Sodium Lauryl Sulfate (SLS) Toothpastes — NCT04601103.
• Registry record last updated 2024-10-01; status last verified 2024-09.
• Results first posted 2021-11-19.
• 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

NCT04601103 is a randomized, single-masked, parallel-group study of 3M Oral Rinse used with no-SLS, medium-SLS, or high-SLS toothpaste. The registry reports enrollment of 53 participants, study status terminated, and an end-of-treatment primary endpoint timeframe of 3 weeks.

The primary outcome counts are 15 of 18 in the no-SLS arm, 14 of 18 in the medium-SLS arm, and 13 of 17 in the high-SLS arm. The reported overall Fisher Exact result is p = .916. Unadjusted pairwise recalculations show broad intervals that cross zero. The registry does not report the reason for termination, original sample-size assumptions, or key details about missing data and analysis populations.