Duration of Effect of Biotene Spray in Patients With Dry Mouth: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Duration of Effect of Biotene Spray in Patients With Dry Mouth (NCT03663231), a randomized na study. The primary outcome is Mean Duration of Action of Intervention.

2. Clinical Question

3. Trial Design

The registry describes a randomized, quadruple-masked crossover trial. Randomization means that treatment assignment is determined by chance; masking means that specified groups involved in the trial are not told which intervention is being given. The record does not identify which four groups were masked or explain how masking was maintained.

A crossover design evaluates interventions in the same trial participants across treatment conditions, rather than assigning each participant to only one condition throughout. However, the treatment sequence, the number of periods, the timing between treatments, and any washout procedure are not reported in the registry record. The posted outcome summaries list 26 participants for Biotene and 26 for placebo, but do not explain how those counts relate to the 37 enrolled participants or to the crossover structure.

The trial compared a single dose of Biotene with a single dose of a water control. The primary outcome was mean duration of action, assessed from baseline up to 2 hours. Participants were asked whether their mouth was dry, and the time at which dryness returned defined the duration. The registry also lists six secondary outcomes concerning product ratings or preferences, although numerical results are posted for only three of them.

The registry lists the study as completed and identifies the University of Rochester as sponsor. The phase is listed as not applicable. The original sample-size rationale, planned analysis model, treatment-sequence details, and any prespecified handling of crossover effects are 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: 37 subjects were enrolled. 8 subjects failed screening. 16 were randomized to either the Biotene then placebo arm and 13 were randomized to the water then Biotene arm.

First Intervention

Washout

Second Intervention

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 Mean Duration of Action of Intervention, measured over baseline up to 2 hours.

The primary endpoint was mean duration of action, measured in minutes. In the registry description, each participant received a dose of Biotene or placebo and was asked whether their mouth was dry during observation up to 2 hours. The time when the mouth became dry again was defined as the duration of action. The reported endpoint is a continuous measure summarized by a mean and standard deviation.

This endpoint translates the study question into a measurable time: how long it takes for a participant to report that dry mouth has returned after a dose. In general, measuring time in this way provides a direct summary of the duration being investigated, rather than relying only on a rating at one fixed point. The registry does not describe the exact questioning schedule, how times were recorded between questions, or how observations that reached the end of the 2-hour period were handled; those details are not reported in the registry record.

The endpoint should be interpreted as the recorded duration under the trial’s measurement procedure. It is not, by itself, a complete description of symptom intensity, participants’ experience over the entire follow-up, or the acceptability of the product. Those are distinct questions, some of which were addressed by secondary outcomes.

7. Results Posted in the Registry

• Biotene: mean 27.00 versus 26.00 on control; difference 1.00 (95% CI -12.59 to 14.59), standardized effect d = 0.04; z-test p = 0.885.

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.

Mean Acceptability of Product

• 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:
  • Biotene: mean 4.20 versus 3.90 on control; difference 0.30 (95% CI -0.26 to 0.86), standardized effect d = 0.30; z-test p = 0.291.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Biotene and the control. The interval gives the range of effects that remain compatible with the data.

Mean Continued Use of Project

• 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:
  • Biotene: mean 3.10 versus 2.90 on control; difference 0.20 (95% CI -0.38 to 0.78), standardized effect d = 0.19; z-test p = 0.501.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Biotene and the control. The interval gives the range of effects that remain compatible with the data.

Mean Purchase Product Rating

• 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:
  • Biotene: mean 2.90 versus 2.60 on control; difference 0.30 (95% CI -0.26 to 0.86), standardized effect d = 0.30; z-test p = 0.291.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Biotene and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes with numerical summaries cover acceptability, continued use, and purchase rating. Across these outcomes, the reported mean scores were numerically higher for Biotene than for placebo, but the estimated differences were modest and the reported confidence intervals include zero. The posted unadjusted p-values are 0.291 for acceptability, 0.501 for continued use, and 0.291 for purchase rating. The outcomes therefore do not provide clear statistical evidence of between-intervention differences in these summaries.

The overall pattern is directionally consistent with the primary point estimate: the Biotene group means are numerically higher, while the primary estimate also favors Biotene by a small amount. This resemblance does not make the secondary outcomes confirmation of the primary result. They measure different aspects of product ratings and are assessed on a score scale rather than as duration in minutes. The scales’ ranges and interpretation are not reported in the registry record.

The registry lists additional secondary outcomes on tolerability, ease of use, and preference for another product, but numerical results for these outcomes are not reported in the registry record. The reported analysis count is zero, and the record does not describe a prespecified analysis plan for the secondary outcomes.

In general, testing several outcomes creates more opportunities for chance findings. Unadjusted results do not account for that multiplicity, so a nominal p-value for any one secondary outcome should be interpreted cautiously. The registry does not report whether the outcomes were ranked, designated as exploratory, or subject to a multiplicity adjustment. Taken together, the posted secondary summaries offer context about participants’ product ratings, but they carry less weight than a prespecified primary analysis with a documented statistical plan.

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

• Mean Tolerability of Product
• Mean Acceptability of Product
• Mean Continued Use of Project
• Mean Purchase Product Rating
• Mean Ease of Use of Product
• Mean Preference for Another Product

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports continuous outcomes as means and standard deviations. The primary outcome is duration in minutes; the secondary outcomes with numerical summaries are scores on a scale. A mean is the arithmetic average of the recorded values. A standard deviation describes the spread of those values around the mean. These summaries give a compact description of each intervention group, but they do not show the full distribution or the pattern of individual observations.

What does the mean difference represent?

The primary contrast is reported as a mean difference, with the Biotene mean compared with the placebo mean. The estimated difference is 1.0 minute. A difference of zero would indicate equal group means. A positive difference indicates a higher mean for Biotene in this reported contrast, while a negative difference would indicate a higher mean for placebo. This direction describes the numerical comparison and does not, on its own, establish a meaningful or reliable effect.

The registry also reports an unadjusted p-value of 0.885. In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of a difference. The registry does not report an adjusted p-value or describe the model underlying this test; the analysis details are not reported in the registry record.

What does the confidence interval add?

In general, a confidence interval presents a range of values compatible with the data and the method used to calculate the interval. For the primary difference, the reported interval extends from -12.59 to 14.59 minutes. Because it crosses zero, it includes no mean difference as well as possible differences in either direction. The interval is more informative than the point estimate alone because it communicates uncertainty about the magnitude and direction of the contrast.

A confidence interval does not guarantee that the true value lies within its particular endpoints, and it does not show the probability that any one value is correct. Its interpretation depends on the analysis assumptions and method. The registry does not describe how the primary interval was calculated or whether the analysis accounted for crossover pairing, treatment sequence, or period effects. Those methods are not reported in the registry record.

Why does the crossover structure matter?

In general, a crossover study can compare interventions within the same participants. Measurements from one person may be more alike than measurements from different people, and an analysis that accounts for that pairing can use this information. The relevant statistical approach also depends on how treatment order and periods were arranged and whether effects could carry over between periods. The registry identifies a crossover model but does not report the sequence, periods, washout, or analysis of these features. The displayed group summaries do not reveal whether the comparison used paired observations.

How should variability be understood?

The primary standard deviation was 25.0 minutes in each group, while the mean difference was 1.0 minute. In general, a large spread of observations relative to a group contrast makes the contrast harder to estimate precisely, particularly when the number of observations is limited. The standard deviation describes variability among measurements; it is not the same quantity as the uncertainty in the estimated mean difference. The confidence interval is the registry’s reported expression of uncertainty for the contrast.

For a crossover trial, variability between participants and variability in the within-participant differences are distinct. A paired analysis may be more or less precise depending on the correlation between a participant’s measurements. That correlation and any paired standard deviation are not reported in the registry record, so the group standard deviations alone cannot show the precision that a crossover-specific analysis would achieve.

What is not available about the analysis?

The registry lists no reported analyses, despite posting numerical outcome results. It does not report an analysis population, an approach to missing observations, an adjustment for multiple outcomes, or a prespecified model. These details are not reported in the registry record. This absence limits assessment of whether the posted estimates follow a planned analysis and how robust they may be to analytic choices.

General statistical interpretation should therefore distinguish the posted estimates from undocumented methods. The mean difference, confidence interval, and unadjusted p-value describe the numerical comparison as recorded. They do not supply the missing details about how the original investigators selected participants for analysis, handled the crossover structure, or addressed multiple testing.

11. Confidence Intervals and Precision

The primary mean difference is 1.0 minute, with a 95% confidence interval from -12.59 to 14.59 minutes. The interval includes zero and extends in both directions. It therefore does not support a precise conclusion about which intervention had the greater mean duration, and it leaves substantial uncertainty about the magnitude of any difference.

In general, a confidence interval gives a range of estimates compatible with the observations and the statistical method. A narrower interval indicates greater precision under that method; a wider interval indicates greater uncertainty. The primary interval is broad relative to the point estimate, so the point estimate should not be read as a precise estimate of the difference that would be expected in a broader population.

The reported standard deviations are 25.0 minutes in both groups, and each primary group summary includes 26 participants. Those summaries describe spread and the number of observations reported, but they do not fully explain the precision of a crossover contrast. In general, the relationship between the two measurements from the same participant can affect the precision of a paired comparison. The registry does not report that relationship or the calculation method for the interval.

The confidence interval is not a range of individual participant durations. Nor does it mean that every value inside it is equally plausible. It is an uncertainty summary for the estimated mean difference, conditional on the analysis method. Since that method is not reported in the registry record, the interval can be interpreted as posted but cannot be independently assessed for its handling of the crossover design.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. They give participants per arm for 80% power and participants per arm for 90% power. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For these continuous outcomes, the figures are participants per arm, not total events.

The 80% power column describes the planned sample size at which a study would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and the assumptions were correct. The 90% column uses a higher target chance of detecting that effect and therefore generally requires more participants. These are planning concepts, not guarantees about what a particular study will find.

The rows apply the full observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects require more participants to detect with the same target power and significance level. In the primary-outcome illustration, planning for 100% of the observed effect gives 9,812 participants per arm for 80% power and 13,135 for 90% power. Planning for 75% gives 17,442 and 23,350; planning for 50% gives 39,245 and 52,538. These figures illustrate how strongly planning requirements depend on the effect assumed.

This is not observed power. The registry does not report the trial’s original sample-size justification or design assumptions, so these illustrations should not be used to infer what the original investigators planned.

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 = 1.000; pooled standard deviation σ = 25.000.
2. n = 2 × (1.96 + 0.842)² × 25.000² / 1.000² = 9,811.1, rounded up to 9,812 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                      # observed difference in means
sigma <- 25                     # 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(3663231)
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 = 9,812 (80% power), 13,135 (90% power)
 75% of observed effect: n per arm = 17,442 (80% power), 23,350 (90% power)
 50% of observed effect: n per arm = 39,245 (80% power), 52,538 (90% power)
power.t.test: 9812.1 
Simulated power at n = 9,812 per arm: 0.798 (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

The registry lists one primary outcome and six secondary outcomes. Numerical summaries are posted for three secondary outcomes, while numerical results for the other listed secondary outcomes are not reported in the registry record. The record reports zero analyses and does not describe an analysis plan, including whether the outcome comparisons were prespecified or how multiple comparisons were to be handled.

In general, multiplicity arises when several statistical hypotheses are evaluated. If each result is interpreted separately without adjustment, the chance of at least one apparently notable finding can increase. Adjustments or a prespecified hierarchy can help control that risk, but the registry does not report whether either approach was used. The secondary p-values are explicitly unadjusted, so they should not be treated as if they account for the full set of outcomes.

Details about missing data and analysis populations are also not reported in the registry record. Although the trial enrollment is 37 and the primary summaries list 26 participants for each intervention, the record does not explain the difference. It does not state whether participants withdrew, whether particular measurements were unavailable, or how missing observations were treated. It also does not identify whether the reported summaries include all randomized participants or a subset.

For a crossover study, these omissions matter because the analysis may depend on whether participants completed both treatment periods and had usable measurements under both interventions. The registry does not report whether such participants were analyzed as pairs, whether incomplete pairs were included, or how treatment order and period were handled. These are not grounds for assuming a particular problem; they are limits on what can be determined from the registry record.

Consequently, the posted estimates can be described, but the degree to which they reflect a prespecified approach to multiple outcomes, missing observations, and crossover data cannot be assessed from the available analysis details.

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 adverse-event record reports 29 participants at risk in each intervention group. It records zero serious adverse events, zero other adverse events, and zero deaths in the Biotene group, and the same counts in the placebo group. No serious adverse-event terms are listed.

These figures describe what was recorded in the registry for the stated groups. They do not establish that no adverse events occurred outside the recorded period or that every possible event was captured. The registry does not report definitions, collection procedures, observation duration for safety, or a detailed account of participants at risk. Those details are not reported in the registry record.

In general, a zero count in a study of this size is not proof that an event cannot occur. The safety counts should be read as registry-reported observations, not as a guarantee about safety or a comparison with enough precision to rule out uncommon events.

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

The posted primary result estimates a mean duration of 27.0 minutes with Biotene and 26.0 minutes with placebo. The estimated difference is 1.0 minute, with a 95% confidence interval from -12.59 to 14.59 minutes and an unadjusted p-value of 0.885. The data therefore do not establish a clear difference in mean duration, and the confidence interval indicates uncertainty in both the direction and size of the contrast.

This result does not show that the interventions have exactly equal effects. The interval includes zero, but it also includes possible differences favoring either intervention. Nor does the point estimate alone establish a meaningful difference. The registry does not state a threshold for what would count as an important change in duration, so the clinical importance of particular values cannot be determined from the record.

The outcome is based on the time until a participant reported that their mouth was dry again, during observation up to 2 hours. It does not represent every aspect of dry-mouth symptoms or product experience. The registry’s other outcomes concern product ratings, but numerical results are not reported for all listed secondary outcomes.

The trial is described as randomized, quadruple-masked, and crossover. However, the record does not describe treatment sequence, washout, the analysis model, participant flow, or handling of missing observations. Those gaps limit the ability to assess how the reported estimates account for the trial design. The findings should be understood as the registry’s posted comparison, with its stated precision and its unreported analysis details.

These results are not, by themselves, a treatment recommendation. They describe a trial comparison in the enrolled participants and do not establish what would happen in other populations, under other conditions, or over a different observation period.

17. Why This Trial Matters Statistically

This trial illustrates why an estimated difference should be read together with its uncertainty. The primary point estimate is 1.0 minute, but the confidence interval ranges from -12.59 to 14.59 minutes. A small point estimate does not by itself show that the underlying difference is small or precisely known; the interval communicates that the data are compatible with a range of effects.

The crossover design also highlights the importance of matching analysis to study structure. In general, crossover observations from the same participant may be related, and that relationship can affect precision. A description of the design alone is not enough to determine whether the reported comparison appropriately used within-participant information. The registry identifies the crossover model but does not report the analysis method, sequence, or period details.

The sample-size illustrations provide a further statistical lesson: planning depends on the effect a study is intended to detect. The displayed planning figures increase as the assumed effect becomes smaller. They are based on the observed effect and stated planning assumptions, not the trial’s original rationale, which is not reported in the registry record. They are planning illustrations rather than evidence about the trial’s observed power.

Finally, the record distinguishes posted numerical results from a documented statistical plan. With multiple outcomes, unadjusted secondary results require cautious interpretation, and absent information on missing data and analysis populations limits appraisal. These are general lessons in interpreting registry results: assess the estimate, its precision, the design, and the transparency of the analysis together.

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 are specific to the information recorded for this trial. The registry reports 37 participants enrolled but lists 26 participants in each primary outcome group. It does not explain this difference, provide a participant flow account, or state how many participants completed each treatment condition. The analysis population is not reported in the registry record.

The crossover design is identified, but treatment order, periods, washout, and possible carryover are not described. The analysis method and whether it accounted for within-participant pairing are not reported in the registry record. Without those details, the posted contrast cannot be evaluated against the design in full.

The primary outcome was assessed up to 2 hours, but the registry does not report the exact schedule for asking participants whether their mouth was dry, how a return time was assigned between assessments, or how observations at the end of follow-up were handled. The score ranges and interpretation for secondary rating outcomes are not reported in the registry record.

The registry lists six secondary outcomes, but numerical results are available for only three. It does not report whether the outcomes were prespecified in a hierarchy or whether multiplicity was addressed. Missing-data handling, original sample-size justification, and the trial’s planned analysis assumptions are also not reported in the registry record.

These reporting gaps do not change the numerical estimates, but they constrain interpretation of how those estimates were produced and how broadly they should be applied. The primary confidence interval itself is wide and includes values favoring either intervention.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Duration of Effect of Biotene Spray in Patients With Dry Mouth — NCT03663231.
• Registry record last updated 2021-01-20; status last verified 2020-12.
• Results first posted 2021-01-20.
• 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

The registry record describes a completed randomized, quadruple-masked crossover trial sponsored by the University of Rochester. It enrolled 37 participants with dry mouth and compared a single dose of Biotene spray with a water control.

The primary outcome was mean duration of action in minutes, defined as the time until participants reported that their mouth was dry again during observation up to 2 hours. The reported means were 27.0 minutes for Biotene and 26.0 minutes for placebo. The mean difference was 1.0 minute, with a 95% confidence interval from -12.59 to 14.59 minutes and an unadjusted p-value of 0.885.

The registry posts numerical results for three secondary outcomes and records zero serious adverse events, zero other adverse events, and zero deaths in each group. Details of the analysis plan, participant flow, missing-data handling, and crossover analysis are not reported in the registry record.