Comparison of Oral Aprepitant and Transdermal Scopolamine for Preventing Postoperative Nausea and Vomiting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Oral Aprepitant and Transdermal Scopolamine for Preventing Postoperative Nausea and Vomiting (NCT00659737), a randomized na study. The primary outcome is Number of Participants With Postoperative Nausea and Vomiting.

2. Clinical Question

The comparison concerns adding scopolamine to an aprepitant regimen, rather than comparing aprepitant with no active treatment. Both groups received oral aprepitant; the patch differed. The registry identifies postoperative nausea and vomiting as the condition of interest and lists the primary outcome as the number of participants with postoperative nausea and vomiting during 0-24 hours. The brief summary also names rescue medication, prolonged recovery-room time, and unplanned hospital admission as outcomes of interest, but the record does not post results for those outcomes. The posted comparison therefore addresses the recorded primary outcome, not every outcome mentioned in the summary.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group trial. The record lists an enrollment of 115 and a completed status. It lists the phase as NA. Drexel University College of Medicine is identified as the sponsor. The recorded start is 2008-04, and primary completion is recorded as 2010-03.

The two groups shared oral aprepitant and differed in the patch administered before surgery. One group received a placebo transdermal patch, while the other received a scopolamine transdermal patch. Each intervention description specifies administration at least 1 hour before the surgical procedure. The reported arm sizes are 57 for aprepitant with placebo patch and 58 for aprepitant with scopolamine patch. The registry does not report additional details about the randomization sequence, allocation concealment, or how masking was maintained.

Randomization is intended to create groups comparable, on average, with respect to factors that might affect the outcome. Double masking is intended to reduce the influence of treatment knowledge on participants’ experience or on outcome assessment. These are general purposes of the design; the record does not describe how those protections were implemented or assess whether masking was successful.

The primary endpoint is a binary participant-level outcome: whether postoperative nausea and vomiting was recorded during 0-24 hours. The results list 28 participants with the outcome in the aprepitant-plus-placebo-patch group and 34 in the aprepitant-plus-scopolamine group. The registry does not report an analysis population definition, such as whether the comparison followed an intention-to-treat approach, or details about participants with missing outcome data.

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

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 Postoperative Nausea and Vomiting, measured over 0-24 hours.

The primary endpoint is the number of participants with postoperative nausea and vomiting during 0-24 hours. It is expressed as a count of participants with the event, alongside the number of participants in each arm. The record reports 28 participants with the outcome among 57 in the aprepitant-plus-placebo-patch arm, and 34 among 58 in the aprepitant-plus-scopolamine arm.

This endpoint treats the outcome as binary at the participant level: a participant either had recorded postoperative nausea and vomiting during the stated timeframe or did not. Such an endpoint is useful for comparing how often an event occurs across treatment groups. It does not, by itself, describe how many episodes an affected participant experienced, when symptoms began, their severity, or how long they lasted. Those details are not reported in the registry record.

The outcome combines nausea and vomiting in one measure. The record does not provide separate counts for nausea and vomiting, nor does it specify the operational criteria used to determine that the endpoint occurred. The 0-24 hours timeframe defines the period covered by this primary result; it should not be read as a finding about outcomes outside that interval.

7. Results Posted in the Registry

• Aprepitant and Scopolamine Transdermal Patch: 58.6% (34/58) versus 49.1% (28/57) on control; risk difference 9.5 percentage points (95% CI -8.6 to 27.6), risk ratio 1.19 (0.85–1.68); unadjusted two-proportion z-test p = 0.307.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry gives a binary primary outcome, counts of participants with the outcome, a risk difference, relative measures, and an unadjusted p-value. It does not describe the statistical procedures used to produce those estimates, so the explanations below are general interpretations of the measures rather than a claim about the trial’s exact analysis method.

What does a binary outcome count?

A binary outcome records whether an event occurred for each participant during the defined observation period. Here, the event is postoperative nausea and vomiting during 0-24 hours. The reported counts are 28 participants with the event in the aprepitant-plus-placebo-patch group and 34 in the aprepitant-plus-scopolamine group. The arm sizes provide the denominators for those counts. A participant-level binary count does not preserve information about repeated episodes or symptom severity unless those are reported separately.

What does the risk difference express?

A risk difference contrasts the event risks in two groups by subtracting one group’s risk from the other’s. The reported value is 0.095 for the scopolamine-patch group compared with the placebo-patch group. A positive value indicates that the observed risk was higher in the group named first in that contrast. The risk difference is an absolute measure: it describes the distance between group risks on the risk scale. It does not indicate why the groups differed, and it can be interpreted only in the context of the endpoint, study population, and observation period.

How do relative measures differ?

A risk ratio compares the event risks as a ratio; an odds ratio compares the event odds. The registry reports a risk ratio of 1.193 and an odds ratio of 1.467 for the scopolamine-patch group relative to the placebo-patch group. Ratios above the null value of one indicate a higher observed outcome in the group in the numerator of the comparison. Risk ratios and odds ratios are not interchangeable, and an odds ratio is not the same as a risk difference. These relative measures can be less immediately intuitive when the outcome is not rare, so the underlying group counts and absolute contrast remain useful context.

What does a p-value tell the reader?

A p-value summarizes how unusual data at least as incompatible with a null hypothesis as the observed data would be, if the null hypothesis and the test’s assumptions held. The registry reports an unadjusted p-value of 0.307. “Unadjusted” indicates that the displayed value is not described as adjusted for other factors or for multiple comparisons. The exact test and its assumptions are not reported in the registry record. A p-value is not a measure of effect size, a measure of clinical importance, or the probability that the null hypothesis is true.

Whether a result crosses a conventional significance threshold is not the same question as whether the estimate is large, precise, or clinically important. Interpretation should consider the estimated contrast and its interval as well as the p-value. The registry’s p-value does not establish equivalence between the groups, and a result that is not statistically significant does not show that the groups are identical.

Why use an interval as well as an estimate?

A confidence interval represents uncertainty around an estimated effect under a statistical procedure and its assumptions. Wider intervals indicate less precision than narrower intervals. The reported interval for the risk difference includes values below and above zero, so it does not isolate a single direction of difference. The registry does not state the interval’s confidence level or method. Confidence intervals describe uncertainty in an estimate; they do not account automatically for every limitation, such as missing outcomes, outcome misclassification, or limits to generalizability.

The sponsor’s own analysis takes precedence if a discrepancy between that analysis and a simple recalculation is identified. No such discrepancy is flagged in this record. No statistical analysis details beyond the posted comparison are reported, so further claims about adjustment, model selection, or prespecified testing would be unsupported.

10. Confidence Intervals and Precision

The point estimate for the risk difference is 0.095, with the scopolamine-patch group having the higher observed event risk in this comparison. A point estimate is a single summary of the observed contrast; it does not convey how uncertain that summary is. The registry reports a confidence interval that extends from a negative value to a positive value, crossing zero, the null value for a risk difference.

That span means the interval is compatible with the data supporting differences in either direction, as well as no difference, under the interval procedure and its assumptions. It does not show that all values inside the interval are equally likely, and it does not establish that the true difference is zero. The interval is broad enough that the estimate should be treated cautiously rather than as a precise measure of the contrast. The registry does not state the confidence level or the method used to calculate it.

The relative estimates are also uncertain: the reported risk ratio is 1.193 and the reported odds ratio is 1.467. Their confidence intervals include the null value of one. These measures express the comparison on different scales from the risk difference, but they lead to the same caution against reading the point estimates as precise standalone conclusions.

Precision is distinct from statistical significance and from clinical importance. A p-value of 0.307 does not replace the interval, while the interval alone does not determine whether a difference would matter in practice. The registry record does not report a threshold for a clinically important difference. The event counts and interval should therefore be read together, with the limits of the recorded endpoint and analysis in mind.

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 planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not a report of the trial’s original design calculation. The trial’s own original sample-size assumptions are not reported in the registry record. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

The column for 80% power gives the planned participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect is the true one. The 90% power column uses a higher target chance of detection under the same planning framework. These are design targets, not guarantees about what a future trial will find. The figures are not observed power.

The entries describe planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For 100% of the observed effect, the figures are 432 participants per arm for 80% power and 577 participants per arm for 90% power. For 75% of the observed effect, they are 770 and 1,031 participants per arm. For 50% of the observed effect, they are 1,738 and 2,326 participants per arm.

Smaller effects are harder to distinguish from random variation, so detecting a smaller effect under otherwise similar assumptions requires more participants. These calculations use the observed estimate as their starting point, which can be an uncertain basis for planning. They should be treated as illustrations of how assumed effect size and power target affect planning, not as a recommendation or a claim about the trial’s design.

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 = 0.491; treatment proportion p₁ = 0.586; average p̄ = 0.539.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7050 = 1.3817.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7018 = 0.5906.
4. n = (1.3817 + 0.5906)² / (0.0950)² = 431.2, rounded up to 432 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 <- 0.491228070175439                          # control proportion
p1 <- 0.586206896551724                          # 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(659737)
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 = 432 (80% power), 577 (90% power)
 75% of observed effect: n per arm = 770 (80% power), 1,031 (90% power)
 50% of observed effect: n per arm = 1,738 (80% power), 2,326 (90% power)
power.prop.test: 431.2 
Simulated power at n = 432 per arm: 0.804 (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. Multiplicity, Missing Data and Analysis Populations

The registry posts one primary outcome measure, the number of participants with postoperative nausea and vomiting during 0-24 hours. The brief summary also refers to nausea, vomiting, rescue medication, prolonged recovery-room time, and unplanned hospital admission. However, the record reports no secondary outcome results. It therefore does not allow a reader to assess how those other outcomes compared between the groups.

Multiplicity arises when several outcomes, timepoints, or statistical comparisons are assessed. If many tests are conducted, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that issue. The registry record does not report whether there was a multiplicity adjustment, a hierarchy of outcomes, or a strategy for interpreting several tests. The posted p-value is described as unadjusted. With no secondary results or complete testing plan recorded, the extent of any multiplicity concern cannot be determined from this record.

The record lists no analysis entries. It does not report the statistical analysis plan, the exact method for the primary comparison, covariate adjustment, or whether any interim analyses were conducted. The original sample-size justification and the trial’s own design assumptions are also not reported in the registry record.

Missing-data handling and analysis populations are not described. The record does not state whether all randomized participants were included in the primary comparison, how participants with missing outcome information were treated, or whether any sensitivity analyses were performed. The arm sizes and outcome counts alone do not establish that there were no missing data. Details about the timing of outcome assessment, protocol deviations, and analysis exclusions are likewise not reported. These omissions limit assessment of whether the posted comparison reflects the intended analysis and how robust it is to alternative assumptions.

14. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry lists zero serious adverse events among 57 participants in the aprepitant-plus-placebo-patch group and zero among 58 participants in the aprepitant-plus-scopolamine-patch group. It also lists other adverse events in 29 participants in the placebo-patch group and 34 participants in the scopolamine-patch group. These are counts as recorded in the registry, not a complete description of the types, timing, severity, or duration of events.

Zero reported serious adverse events does not establish that no serious events occurred outside the recorded reporting process, nor does it show that the groups have identical safety profiles. The record does not identify the definition or ascertainment procedures for serious events. It lists no serious-event terms. Death counts are not reported in the registry record.

The other adverse-event counts should not be interpreted as evidence about comparative risk without fuller information about event definitions, follow-up, ascertainment, and missing data. The registry safety figures are descriptive and limited to the categories and counts posted.

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

The recorded comparison describes postoperative nausea and vomiting during 0-24 hours among participants assigned to oral aprepitant with either a placebo patch or a scopolamine patch. The observed event counts were 28 of 57 in the placebo-patch arm and 34 of 58 in the scopolamine-patch arm. The estimated risk difference was 0.095 in the direction of a higher observed risk in the scopolamine-patch group. The interval for this estimate crosses zero, and the unadjusted p-value is 0.307.

These findings do not establish that adding scopolamine increased the outcome, nor do they establish that the regimens were equivalent. The interval includes values on both sides of no difference, and the registry does not report an equivalence or non-inferiority framework. A statistically non-significant comparison is not proof that the treatments have the same effect. The point estimate, p-value, and interval each answer different statistical questions and should be considered together.

The result applies to the recorded endpoint and timeframe. It does not separately describe nausea and vomiting, symptom severity, repeated events, or outcomes beyond 0-24 hours. It also does not provide results for rescue medication, prolonged recovery-room time, or unplanned hospital admission, although these are named in the brief summary.

The registry entry is not enough to judge all aspects of trial conduct or applicability. Detailed eligibility criteria, outcome definitions, analysis populations, missing-data methods, and the full statistical plan are not reported in the registry record. The findings are therefore best read as an uncertain estimate from the posted randomized comparison, rather than as a definitive statement about treatment effects in other settings or populations.

16. Why This Trial Matters Statistically

This trial offers a useful statistical example of a comparison in which both groups receive a common treatment and differ by an additional intervention. That distinction matters for interpretation: the result concerns aprepitant with a scopolamine patch versus aprepitant with a placebo patch, not scopolamine as a standalone treatment or aprepitant versus no treatment.

The primary outcome is a participant-level binary event, which makes the observed counts easy to understand but limits the information captured. It reports whether postoperative nausea and vomiting occurred during the stated timeframe, not the burden or severity of symptoms. Separating the event count from its interpretation also helps prevent a common error: treating the number of affected participants as a complete account of the clinical experience.

The comparison illustrates why an estimate should be read alongside its uncertainty. The risk difference is positive, but its confidence interval extends across zero and the p-value is 0.307. Neither the observed direction alone nor the p-value alone answers whether the result is precise or whether a difference would matter. The relative estimates provide other scales for the contrast, but they do not remove the uncertainty.

The record also demonstrates the limits of registry outcome reporting. The brief summary mentions additional outcomes, while no secondary results or analysis entries are posted. Without the analysis plan, missing-data approach, and outcome definitions, readers cannot fully evaluate the statistical conduct or completeness of reporting. The sample-size illustrations show how the planning target changes with the assumed effect, but they are not evidence about the original design or the trial’s achieved power.

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 primary result is restricted to a combined measure of postoperative nausea and vomiting during 0-24 hours. The record does not give separate nausea and vomiting counts, a symptom severity scale, episode frequency, or a fuller operational definition of the event. This limits interpretation of what the event count represents and how much clinical burden it captures.

The brief summary identifies patients at high risk for postoperative nausea and vomiting, but detailed eligibility criteria and baseline characteristics are not reported. The registry therefore does not support a detailed assessment of which patients the results best describe. The record names additional outcomes, including rescue medication, prolonged recovery-room time, and unplanned hospital admission, but does not post results for them.

Although the trial is described as randomized and double-blind, details of sequence generation, allocation concealment, and masking procedures are not reported. The statistical analysis method, analysis population, handling of missing outcomes, and any sensitivity analyses are also not reported. The registry does not provide a detailed account of outcome ascertainment or protocol deviations.

The posted comparison includes an estimate and an unadjusted p-value, but the record does not state the exact testing procedure or confidence-interval method. The reported interval crosses the null, and its width indicates substantial uncertainty in the effect estimate. Safety reporting is limited to aggregate event counts, with no event-term details for serious events and no death counts reported in the registry record. These limitations constrain how fully the efficacy and safety findings can be assessed from the registry entry alone.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Comparison of Oral Aprepitant and Transdermal Scopolamine for Preventing Postoperative Nausea and Vomiting — NCT00659737.
• Registry record last updated 2014-05-15; status last verified 2013-09.
• Results first posted 2014-04-29.
• 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.

21. Record Summary

NCT00659737 is a completed, randomized, double-blind, parallel-group trial sponsored by Drexel University College of Medicine. The record lists enrollment of 115, a start of 2008-04, and primary completion in 2010-03. It compares oral aprepitant with a placebo transdermal patch against oral aprepitant with a scopolamine transdermal patch, with each administered at least 1 hour before surgery.

The primary outcome is the number of participants with postoperative nausea and vomiting during 0-24 hours. The registry reports 28 of 57 in the placebo-patch group and 34 of 58 in the scopolamine-patch group, with a risk difference of 0.095 and an unadjusted p-value of 0.307. The risk-difference interval crosses zero. No secondary results or analysis entries are posted. Important details about outcome definitions, missing data, analysis populations, and the statistical plan are not reported in the registry record.