This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Antitussive Effect of a Naturally Flavored Syrup Containing Diphenhydramine, Compared With Dextromethorphan and Placebo (NCT02062710), a randomized phase 4 study. The primary outcome is Change in Cough Reflex Sensitivity to Capsaicin.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02062710 |
| Phase | Phase 4 |
| Condition | Cough Reflex Sensitivity |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 22 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Montefiore Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The registry lists cough reflex sensitivity as the condition and reports enrollment of 22 participants. The endpoint description refers to subjects completing a capsaicin cough challenge. Further details about participant characteristics, eligibility criteria, or the clinical setting are not reported in the registry record.
Intervention
The experimental syrup combined diphenhydramine 25 mg and phenylephrine 10 mg in naturally flavored cocoa syrup. Each participant received the study treatments in a randomized sequence, according to the registry’s crossover design.
Comparator
The comparators were dextromethorphan syrup 30 mg and placebo liquid, described as dextrose in water, 20 mL. The record describes six possible sequences of the three treatments.
Primary question
The primary question was whether the treatments differed in change in cough reflex sensitivity, measured as log C5, 2 hours after study drug administration. C5 is the capsaicin concentration that induces 5 or more coughs during the challenge. The endpoint description defines an increase in C5 as a decrease in cough reflex sensitivity.
The posted group means were 0.97 log C5 for the diphenhydramine/phenylephrine/cocoa treatment, 0.8 for dextromethorphan, and 0.57 for placebo. Unadjusted mean differences versus placebo were 0.4 for the combination syrup and 0.23 for dextromethorphan. These summaries describe the observed endpoint; they do not by themselves establish a treatment effect. The record does not post a sponsor analysis or explain how the crossover structure was handled in the reported comparisons.
3. Trial Design
The registry describes a randomized, double-masked, phase 4 crossover trial sponsored by Montefiore Medical Center. Its status is completed. The record lists enrollment of 22 participants, with the study starting in 2014-01 and primary completion in 2014-06.
In a crossover design, participants receive multiple treatments in sequence rather than being assigned to just one treatment for the entire study. The record describes three treatment periods: diphenhydramine with phenylephrine in cocoa syrup, dextromethorphan syrup, and placebo liquid. It lists six sequences, covering different orders of those treatments. This design allows each participant to receive each treatment, although the registry record does not report details needed to assess period effects, carryover, or washout procedures.
The experimental treatment was a single oral dose of diphenhydramine 25 mg and phenylephrine 10 mg in naturally flavored cocoa syrup. Dextromethorphan was given as syrup 30 mg, and placebo was described as dextrose in water, 20 mL. The primary endpoint was measured 2 hours after study drug administration. The record does not describe the masking procedures or explain how the different syrups and placebo were made indistinguishable.
The registry lists one outcome measure and no posted analysis results. The outcome summary gives a mean and standard error for each treatment, with 22 participants listed in each group. Because all participants crossed through treatment sequences, those group counts should not be read as evidence of three separate parallel groups. The record does not report participant flow, period-specific attendance, or whether all randomized participants contributed data to every treatment summary.
Details such as the original sample-size justification, eligibility criteria, setting, study sites, washout duration, and prespecified statistical model are not reported in the registry record. The posted summary therefore supports a description of the randomized crossover structure, but not a complete reconstruction of the trial protocol or its analysis plan.
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
| Stage | Diphenhydramine/Phen/Cocoa, Dextromethorphan, Then Placebo | Diphenhydramine/Phenylephrine/Cocoa, Then Placebo, Then Dextro | Dextromethorphan, Diphenhydramine/Phenylephrine/Cocoa, Then pl | Dextromethorphan, Placebo, Then Diphenhydramine/Phenylephrine/ | Placebo, Diphenhydramine/Phenylephrine/Cocoa, Then Dextrometho | Placebo, Dextromethorphan, Then Diphenhydramine/Phenylephrine/ |
|---|---|---|---|---|---|---|
| STARTED | 3 | 4 | 5 | 3 | 3 | 4 |
| COMPLETED | 3 | 4 | 5 | 3 | 3 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
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.
| Characteristic | Unit | Diphenhydramine/Phenylephrine/Cocoa, Dextromethorphan,Placebo |
|---|---|---|
| Participants analysed | 22 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 22 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Cough Reflex Sensitivity to Capsaicin, measured over 2 hours after study drug administration.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | log C5 (uM) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change in cough reflex sensitivity to capsaicin, recorded as log C5 (uM), 2 hours after study drug administration. The challenge involved breathing incremental doubling concentrations of aerosolized capsaicin, 1 minute apart, until the concentration that induced 5 or more coughs was reached. That concentration is called C5.
The endpoint description states that an increase in C5 corresponds to a decrease in cough reflex sensitivity: a higher concentration was needed to reach the cough threshold. This makes C5 a measured response to a standardized stimulus, rather than a count of everyday coughs or a report of symptoms over time. It focuses the outcome on the sensitivity of the cough reflex during the challenge.
The registry reports treatment means of 0.97 for the diphenhydramine/phenylephrine/cocoa treatment, 0.8 for dextromethorphan, and 0.57 for placebo. The reported unit is log C5 (uM), and the outcome measure is described as a change. The record does not give baseline values, participant-level measurements, or an explanation of the exact transformation or calculation used to derive the change. Nor does it report a threshold for interpreting a change as clinically important.
As a general statistical point, an objective challenge outcome can make it possible to compare responses under a defined testing procedure. Its interpretation still depends on the endpoint definition, measurement quality, and analysis. The registry record does not report further validation or clinical interpretation details for this measure.
7. Results Posted in the Registry
- Diphenhydramine/Phenylephrine/Cocoa: mean 0.97 versus 0.57 on control; difference 0.40 (95% CI -0.04 to 0.84), standardized effect d = 0.53; z-test p = 0.077.
- Dextromethorphan: mean 0.80 versus 0.57 on control; difference 0.23 (95% CI -0.24 to 0.70), standardized effect d = 0.29; z-test p = 0.340.
Mean difference: Diphenhydramine/Phenylephrine/Cocoa
95% CI: -0.04 to 0.84
Recalculated from the posted summary statistics
8. Statistical Interpretation
The posted treatment means were 0.97 log C5 for diphenhydramine/phenylephrine/cocoa, 0.8 for dextromethorphan, and 0.57 for placebo. The registry’s unadjusted comparisons versus placebo give a mean difference of 0.4 for the combination syrup and 0.23 for dextromethorphan. The endpoint description says that an increase in C5 means decreased cough reflex sensitivity, so the direction of the reported means is consistent with a higher threshold in each active-treatment summary than in the placebo summary.
These are descriptive and unadjusted comparisons. For the combination syrup, the reported confidence interval extends from a value below zero to a value above zero, and the unadjusted p-value is 0.077. For dextromethorphan, the reported confidence interval also crosses zero, and the unadjusted p-value is 0.34. The posted results therefore do not establish that either mean difference is distinguishable from zero under these unadjusted comparisons. They also do not show that the treatments are equivalent: absence of evidence for a difference is not evidence that the effects are the same.
The registry record lists 22 participants for each treatment summary. Since this was a crossover trial, those are repeated treatment observations from the same study population, not independent groups of 22 different participants. The mean differences and confidence intervals displayed in the posted comparison summaries do not identify whether the crossover correlation, period, or sequence was accounted for. No sponsor analysis is posted, so the record does not offer a reported model-based estimate that addresses those design features.
The mean and standard error are reported for each treatment, but confidence intervals for the individual treatment means are not reported in the registry record. The comparison intervals are wide enough to include both a value below zero and a value above zero. That range signals uncertainty about the size and direction of the underlying difference. The trial’s small enrollment and missing details on analysis and participant flow further limit how specifically the results can be interpreted.
These endpoint results concern cough-reflex sensitivity during a capsaicin challenge at a defined time after administration. They do not directly describe cough symptoms in daily life, duration of any response, or clinical outcomes beyond the recorded challenge measure. The registry record does not report secondary outcomes. The results should therefore be read as limited evidence about the posted endpoint, not as a broad conclusion about treatment effects.
9. Statistical Methods Explained
The registry identifies the primary outcome as a continuous measure summarized by its mean, with standard error as the reported measure of spread. A mean is the arithmetic average of the recorded values. A standard error describes the estimated uncertainty in that mean; it is not the same as the spread of individual participant values. The outcome entries report means of 0.97 for diphenhydramine/phenylephrine/cocoa, 0.8 for dextromethorphan, and 0.57 for placebo, with standard errors of 0.16, 0.18, and 0.16, respectively.
The comparisons are stated as mean differences against placebo. The posted unadjusted mean difference is 0.4 for diphenhydramine/phenylephrine/cocoa and 0.23 for dextromethorphan. A mean difference expresses the contrast between the treatment summaries on the scale of the outcome. Positive values in these comparisons indicate that the active-treatment mean was higher than the placebo mean. For this endpoint, the registry description associates an increase in C5 with decreased cough reflex sensitivity.
The record also reports unadjusted p-values: 0.077 for the combination syrup comparison and 0.34 for dextromethorphan. A p-value measures how compatible the observed data are with a specified null model, under the assumptions of the statistical procedure. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry does not report an adjusted p-value, a sponsor-generated test, or details sufficient to identify the precise inferential procedure used.
The comparisons include confidence intervals. A confidence interval describes a range of values compatible with the data and the method’s assumptions; its width reflects precision. Both posted comparison intervals include zero. In a difference scale, zero corresponds to no difference between the two means. An interval that crosses zero does not prove there is no effect; it indicates that the data and interval method do not isolate a direction of difference at the represented level of uncertainty.
These method explanations are general. A crossover study has features that matter to analysis because each participant receives multiple treatments. Measurements from the same person are generally related, and the order of treatments can matter. Period effects, sequence effects, and carryover are possible considerations in crossover analysis. Whether and how these were addressed in this trial is not reported in the registry record. The posted unadjusted summaries should not be treated as a substitute for a reported crossover model.
The registry identifies random allocation and double masking, and lists six treatment sequences. Random allocation is a method for assigning sequences without a systematic choice based on participant characteristics. Double masking means that two categories of people were intended to be unaware of assignment, but the record does not identify those categories or describe implementation. Such design features can reduce some sources of bias, but their presence does not resolve uncertainty from small enrollment, missing analysis details, or incomplete outcome reporting.
The outcome description refers to change in C5, while the group entries provide means and standard errors without baseline summaries. The record does not state how change was computed, whether measurements were transformed before analysis, or how missing observations were handled. It does not provide participant-level data, model coefficients, degrees of freedom, or an analysis population definition. Consequently, the displayed summary statistics can be described, but the underlying statistical workflow cannot be reconstructed from the registry record.
For planning, the posted illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions for the illustrations and are distinct from the trial’s original design assumptions, which are not reported in the registry record. The planning values are not evidence about the trial’s actual power or about the probability that an effect exists.
In general, over-dispersion matters when observed variation exceeds what a chosen statistical model expects. A model that understates variation can produce intervals that are too narrow and tests that appear more decisive than warranted. The registry record does not report an over-dispersion assessment, and the posted endpoint is described as a continuous measure summarized by a mean and standard error; there is not enough information to say whether over-dispersion was relevant to the trial’s analysis.
The registry lists one outcome measure and zero posted analyses. Thus, the mean differences, confidence intervals, and p-values available in the results summary should not be attributed to a documented sponsor analysis. The record does not report a statistical analysis plan, adjustment for multiple comparisons, handling of the crossover structure, or a prespecified hierarchy of tests. Those omissions limit interpretation of the inferential summaries, even though the descriptive means can still be reported directly.
10. Confidence Intervals and Precision
Precision concerns how narrowly an estimate locates the value compatible with the data and the method used. The reported mean difference for diphenhydramine/phenylephrine/cocoa versus placebo is 0.4, and its confidence interval runs from a negative value to a positive value. The reported mean difference for dextromethorphan versus placebo is 0.23, with a confidence interval from -0.242 to 0.702. Each interval crosses zero, so neither comparison isolates a difference in one direction at the interval’s stated level of uncertainty.
The exact interval endpoints for the combination-syrup comparison are not repeated because the posted endpoints include more than three decimal places. The important interpretation is that its interval also crosses zero. Both intervals permit a range of plausible values that includes no difference and values on either side of zero. That uncertainty means the point estimates should not be treated as precise estimates of the treatment contrasts.
The registry reports standard errors of 0.16, 0.18, and 0.16 for the three treatment means. It does not report confidence intervals for those individual means. Standard errors describe uncertainty in estimated means, while a confidence interval gives an interval for a parameter under a stated method. Neither measure describes the full distribution of individual responses.
As a general statistical point, confidence intervals depend on the analysis model and its assumptions. In a crossover trial, treatment estimates can depend on accounting for repeated observations from the same participant and on handling period or sequence effects. The registry does not report the analysis model used to produce the comparison intervals. The intervals should therefore be read as posted unadjusted summaries, not as a complete account of uncertainty under a documented crossover analysis.
With 22 participants listed for each treatment summary, the estimates arise from a small study population. The record does not provide a basis for determining how much the intervals would change under a different model or with additional participants. Their width and their overlap with zero support a cautious reading of the size and direction of the contrasts.
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.
| Effect to detect | Participants per arm, 80% power | Participants per arm, 90% power |
|---|---|---|
| 100% of the observed effect | 56 | 74 |
| 75% of the observed effect | 99 | 132 |
| 50% of the observed effect | 222 | 296 |
The sample-size figures are planning illustrations, not counts observed in the trial. They give participants per arm for the two-arm planning comparisons. The calculations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.
The 80% power column describes the planned number of participants per arm under which the calculation would have an 80% chance of detecting the assumed effect, if the planning assumptions and effect were correct. The 90% power column uses a higher target probability of detecting that assumed effect. These are prospective planning quantities, not guarantees about results, and they depend on the assumptions used.
For the diphenhydramine/phenylephrine/cocoa comparison, planning for 100% of the observed effect gives 56 participants per arm for 80% power and 74 for 90% power. Planning for 75% of the observed effect gives 99 and 132 participants per arm, respectively. Planning for 50% of the observed effect gives 222 and 296 participants per arm.
For the dextromethorphan comparison, planning for 100% of the observed effect gives 190 participants per arm for 80% power and 254 for 90% power. Planning for 75% gives 337 and 451 participants per arm. Planning for 50% gives 758 and 1,014 participants per arm.
Smaller effects require more participants under the same planning assumptions, because a smaller contrast is harder to distinguish from random variation. These figures are not observed power: they are planning illustrations based on the observed effect and specified assumptions, not a retrospective measure of what the completed trial could detect.
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 z1−α/2 = 1.960) and the desired power (z1−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
- Observed difference Δ = 0.400; pooled standard deviation σ = 0.750.
- n = 2 × (1.96 + 0.842)2 × 0.7502 / 0.4002 = 55.3, rounded up to 56 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 <- 0.4 # observed difference in means
sigma <- 0.750466521571749 # 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(2062710)
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 = 56 (80% power), 74 (90% power)
75% of observed effect: n per arm = 99 (80% power), 132 (90% power)
50% of observed effect: n per arm = 222 (80% power), 296 (90% power)
power.t.test: 56.2
Simulated power at n = 56 per arm: 0.800 (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.
13. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and no posted analyses. It does not report a statistical analysis plan, a testing hierarchy, or any procedure for adjusting for multiple comparisons. The posted summaries include two comparisons against placebo, but the record does not explain whether these were the only planned comparisons or whether additional analyses were intended.
Multiplicity is a general concern when several hypotheses are tested. With more tests, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of comparisons. The registry record does not state whether multiplicity was addressed, so the unadjusted p-values should be read as unadjusted rather than as results from a documented family-wise procedure.
Missing-data handling is also not reported in the registry record. It does not say whether all 22 participants contributed data to all three treatment summaries, whether any measurements were unavailable, or how incomplete sequences were handled. In a crossover study, missing a period can affect which within-participant contrasts can be estimated. Without participant flow and an analysis population definition, the extent and consequences of missing data cannot be assessed.
The record does not identify an intention-to-treat population, a per-protocol population, or another analysis set. It also does not describe exclusions, protocol deviations, or the treatment of participants with incomplete outcome measurements. Those details matter for understanding which observations contributed to the posted means and comparisons.
The registry does not report whether the analysis modeled treatment, period, sequence, or within-participant correlation. These are general features that can be relevant to crossover trials; whether they were incorporated is unknown. The posted unadjusted comparisons are not enough to determine whether the original design was analyzed in a way that preserves its repeated-measures structure.
Finally, the record does not report how outcome transformations, baseline values, or any covariates were handled. These missing details prevent a full assessment of prespecification and analytic flexibility. They do not negate the descriptive results, but they limit the certainty with which inferential conclusions can be drawn from them.
14. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Diphenhydramine/Phenylephrine/Cocoa | 0 | 22 | 0.0% |
| Dextromethorphan | 0 | 22 | 0.0% |
| Placebo | 0 | 22 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Diphenhydramine/Phenylephrine/Cocoa | 0 of 22 |
| Dextromethorphan | 0 of 22 |
| Placebo | 0 of 22 |
The registry reports serious adverse events for 22 participants at risk in each treatment group and records 0 affected participants in each group. It also reports other adverse events for 22 participants at risk per group and records 0 affected participants in each group. No serious-event terms are listed.
These figures describe the adverse-event entries in the registry. They do not establish that no events occurred outside the reported categories or reporting period. The record does not give further details about how adverse events were collected, defined, or attributed, and the death counts are not reported in the registry record.
Because the study used a crossover design, participants received each treatment in sequence. The group-level risk counts should not be interpreted as three distinct groups of different people. The record does not describe whether adverse events were summarized by treatment period, whether any participants withdrew because of events, or whether there were missing safety data. These limits constrain comparisons across treatments.
The posted safety figures should therefore be read narrowly: the registry records zero affected participants for the listed serious and other adverse-event categories among 22 at risk for each treatment. They do not, on their own, provide a comprehensive assessment of safety.
15. What the Result Does, and Does Not, Mean
The posted results describe a capsaicin cough-challenge endpoint measured 2 hours after study drug administration. The treatment means were 0.97 for diphenhydramine/phenylephrine/cocoa, 0.8 for dextromethorphan, and 0.57 for placebo. The corresponding unadjusted mean differences versus placebo were 0.4 and 0.23. Under the endpoint definition, an increase in C5 represents decreased cough reflex sensitivity during the challenge.
The comparison confidence intervals both cross zero, and the unadjusted p-values are 0.077 and 0.34. The posted results are therefore compatible with a range of treatment contrasts that includes no difference. They do not establish that either treatment differs from placebo on this measure. They also do not demonstrate equivalence, since the record does not report an equivalence margin or a test designed to establish equivalence.
The outcome is a laboratory-style response to inhaled capsaicin, not a direct measure of cough symptoms during ordinary activities. The registry does not report symptom outcomes, duration beyond the stated assessment time, or secondary outcome results. Thus, the findings should not be extended to outcomes that were not reported.
The crossover structure and the small enrollment are important context. Each participant received treatment sequences, so treatment observations are related within participants. The registry does not report whether the posted comparisons accounted for that relationship or for period and sequence. This prevents a complete statistical interpretation of the contrasts.
The results do not establish clinical importance: no threshold for a meaningful change in log C5 is reported. The registry also does not provide enough detail to assess generalizability to populations or settings beyond the participants studied. A precise conclusion is limited to the posted means, standard errors, unadjusted comparisons, and their uncertainty for this challenge endpoint. No medical recommendation follows from these registry summaries.
16. Why This Trial Matters Statistically
This trial is statistically informative as an example of why design and analysis need to be considered together. It used a randomized, double-masked crossover design, with participants receiving the three treatments in different sequences. That arrangement can make within-participant comparisons useful, but it also means repeated measurements from the same person are not independent. The registry record does not report whether the posted comparisons used the crossover structure.
The results also illustrate why an estimated mean difference should be read alongside its confidence interval. The point estimates are positive, but both comparison intervals cross zero. The unadjusted p-values do not resolve the uncertainty about the contrast, and neither the means nor the p-values alone give a complete account of precision or clinical importance.
The planning illustrations highlight how assumptions affect sample-size needs. The calculations use fractions of the observed effects; when the assumed effect is smaller, the participant counts rise. That pattern is a general feature of statistical planning, not evidence that the original trial was designed for these targets. The original sample-size justification is not reported in the registry record.
Finally, sparse registry analysis details matter. A completed trial record with descriptive results can show what was reported, while still leaving unanswered questions about the prespecified model, missing observations, multiplicity, and analysis populations. Statistical interpretation depends on those details, especially for a crossover study with a single posted outcome measure and no posted analyses.
17. 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 registry reports enrollment of 22 participants, and the treatment summaries each list 22. This is a small study population, and the posted comparison intervals are broad enough to include zero. The record does not give participant characteristics or eligibility details, so the applicability of the results to other populations cannot be judged from the registry entry.
The design is crossover, but details needed to assess its implementation are missing. The registry lists treatment sequences but does not report washout duration, period-specific results, carryover assessment, or the analysis of sequence and period effects. The reported comparison results are unadjusted, and no sponsor analysis is posted. It is therefore unclear whether the contrasts reflect an analysis that accounts for repeated observations within participants.
The endpoint is a capsaicin challenge measure at 2 hours after study drug administration. The record does not report baseline values, the calculation details for change, a clinically meaningful threshold, or follow-up beyond that assessment. The challenge outcome does not by itself describe everyday cough or other clinical outcomes, and no secondary outcomes are posted.
Other important omissions include participant flow, missing-data handling, analysis population definitions, the statistical analysis plan, multiplicity procedures, and the original sample-size justification. Safety reporting is limited to the posted counts, with death counts not reported in the registry record. These limitations do not invalidate the reported summaries, but they constrain conclusions about treatment differences, precision, clinical significance, and generalizability.
18. Related Tutorials
19. Related Statistical Calculators
20. Sources
- ClinicalTrials.gov: Antitussive Effect of a Naturally Flavored Syrup Containing Diphenhydramine, Compared With Dextromethorphan and Placebo — NCT02062710.
- Registry record last updated 2018-02-28; status last verified 2018-02.
- Results first posted 2015-04-28.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
21. Record Summary
The registry describes a completed, randomized, double-masked, phase 4 crossover trial sponsored by Montefiore Medical Center. It enrolled 22 participants and compared diphenhydramine 25 mg plus phenylephrine 10 mg in naturally flavored cocoa syrup, dextromethorphan syrup 30 mg, and placebo liquid.
The primary endpoint was change in capsaicin cough-reflex sensitivity, recorded as log C5 (uM) 2 hours after study drug administration. The posted means were 0.97, 0.8, and 0.57 for the combination syrup, dextromethorphan, and placebo, respectively. The unadjusted mean differences versus placebo were 0.4 and 0.23; both confidence intervals cross zero.
The registry lists one outcome measure and no posted analyses. The original sample-size rationale, detailed crossover analysis, missing-data methods, and multiplicity approach are not reported in the registry record.